WO2017101111A1 - Système de régulation du rythme biologique et procédé de régulation du rythme biologique - Google Patents

Système de régulation du rythme biologique et procédé de régulation du rythme biologique Download PDF

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WO2017101111A1
WO2017101111A1 PCT/CN2015/097887 CN2015097887W WO2017101111A1 WO 2017101111 A1 WO2017101111 A1 WO 2017101111A1 CN 2015097887 W CN2015097887 W CN 2015097887W WO 2017101111 A1 WO2017101111 A1 WO 2017101111A1
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biological rhythm
data
biological
rhythm
intervention
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PCT/CN2015/097887
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English (en)
Chinese (zh)
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徐璎
杨凌
周飞
刘宇
田小粟
韩青
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苏州大学
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Priority to CN201580084846.0A priority Critical patent/CN108430314A/zh
Priority to PCT/CN2015/097887 priority patent/WO2017101111A1/fr
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/02—Detecting, measuring or recording pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography or electroauscultation; Heart catheters for measuring blood pressure
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06Q—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR ADMINISTRATIVE, COMMERCIAL, FINANCIAL, MANAGERIAL OR SUPERVISORY PURPOSES; SYSTEMS OR METHODS SPECIALLY ADAPTED FOR ADMINISTRATIVE, COMMERCIAL, FINANCIAL, MANAGERIAL OR SUPERVISORY PURPOSES, NOT OTHERWISE PROVIDED FOR
    • G06Q50/00—Information and communication technology [ICT] specially adapted for implementation of business processes of specific business sectors, e.g. utilities or tourism

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  • the present invention relates to a biological rhythm adjustment system and a biological rhythm adjustment method.
  • the present invention relates to a personalized and integrated biological rhythm adjustment scheme that solves attenuated or disordered biological rhythms, and uses physical and physiological means to regulate the biological rhythm of the human body based on scientific research related to biological rhythms.
  • the biological clock is an intrinsic mechanism used by organisms to predict time changes and adjust physiological homeostasis. It is an important basic feature of living organisms.
  • the biological clock regulates various levels of biological rhythms such as molecular, biochemical, cellular, physiological and behavioral.
  • the weakening or disorder of the biological clock can cause serious damage to the survival and health of the living organism.
  • the weakening or disorder of the circadian clock can lead to sleep disorders, affective diseases, increased tumor incidence, metabolic diseases, accelerated aging, affecting reproduction and immune system diseases, and even affecting the health of future generations.
  • Insufficient illumination can cause the amplitude of the circadian clock in the body to decrease and the rate of synchronization between the cells to be weakened, which can damage the circadian clock system and cause other problems such as sleep disorders.
  • the shift work system in modern society the frequent adjustment of the time difference (Jet-lag) and other factors will also have a negative impact on human normal circadian rhythm.
  • irregular diets, inappropriate exercise, and even incorrect administration times can cause a decrease or disorder in the biological rhythm. This leads to various diseases such as sleep, metabolism, obesity, cardiovascular disease, and mentally related diseases.
  • Attenuated or disordered biological rhythms can also cause changes in the reproductive system, changes in the pregnancy cycle, increased abortion rate, leading to decreased birth weight and other symptoms, while biological rhythms decay with age, and biological rhythms are known to be closely related to various aging diseases. Association.
  • the biological clock controls 43% of gene expression, which regulates almost all physiological processes.
  • the weakening or disorder of the circadian clock is the physiological root of many "modern diseases". Only by adjusting the biological clock through appropriate methods can we fundamentally achieve similar pathology or sub- Repair of health status. Therefore, through the regulation of biological rhythm, it has been the main driving force for the research of some diseases caused by the weakening or disorder of biological rhythm. Compared with drug intervention, it is a means of almost zero cost without side effects. With the deepening of the research on the biological clock, the scientific control of the biological clock has gradually become possible from the acquisition of the biological clock input system to the oscillation system to the control system.
  • the principle that the biological rhythm can be regulated by light people use the method of light compensation to give blue light treatment, the principle is to use light to regulate melatonin, and then adjust sleep.
  • This method has a long time for light and no scientific basis for the light time point. It is easy to produce excessive illumination while adjusting the biological clock weakening or disorder, and the light treatment time may just be in the body's refractory period of light, so that the treatment has no effect. It is also not universal for individuals with different physiological states.
  • the present invention will construct an integrated system that is systematic, personalized, adaptive, and includes expert consultation, and effectively monitors and intervenes individual biological rhythms, including systems such as cloud biological platforms.
  • the object of the present invention is to provide a biological rhythm adjustment system and a biological rhythm adjustment method, which are personalized and analyzed by personalized resource collection, and a personalized adjustment scheme is generated.
  • the biological rhythm adjustment system and the biological rhythm adjustment method adjust the human biological rhythm by using physical and physiological means according to the scientific research basis related to the biological rhythm.
  • the invention collects non-invasive and time-dependent systematic interventions by collecting data closely related to human rhythms, combining mathematical models, assessing the biological rhythm of human individuals, and using mathematical models or feedback expert consultations. Combine different wavelengths of light, diet, physical exercise, indoor temperature control and other interventions, individualized regulation of the biological clock, improve sleep, metabolism, immunity, reproduction, degenerative diseases and other related pathological or sub-health status caused by biological rhythm weakening or disorder, On the basis of obtaining big data, we will further improve the population bio-rhythm standards, improve the control parameters, and cooperate with other electronic biological platforms to establish a cloud biomedical platform.
  • One aspect of the present invention provides a biological rhythm adjustment system comprising:
  • the acquisition module acquiring at least one biorhythm data of the target object according to a time series
  • An optimization module that processes the biorhythm data acquired by the acquisition module, calculates and obtains a current biorhythm state and an ideal biorhythm state of the target object, and determines a mode of interfering with the biorhythm of the target object ;
  • An intervention module that inputs according to an intervention mode determined by the optimization module The corresponding intervention operation.
  • the optimization module extracts at least one of phase information, amplitude information, and period information from the biorhythm data, and calculates and obtains according to the at least one information.
  • the optimization module obtains statistical characteristics (mean, variance, symmetry, etc.) from individual data of the entire population or a specific population, and according to at least one data. Statistical characteristics are calculated and the population biorhythm criteria are obtained.
  • the optimization module calculates and obtains a preset rhythm standard of the crowd according to scientific common sense or literature data in the field of biological rhythm.
  • the optimization module extracts at least one of phase information, amplitude information, and period information from the biorhythm data, and calculates according to the at least one information. And obtaining a current biological rhythm state of the target object.
  • the optimization module calculates and obtains the target object from the current rhythm state of the target object, the biological rhythm standard or the preset rhythm standard of the comparison population.
  • the ideal biological rhythm state is the ideal biological rhythm state.
  • the optimization module determines an intervention of the target object from an individual rhythm state of the target object and an ideal biological rhythm state, against an ARC curve or a PRC curve.
  • the pattern of biological rhythms is a specific implementation manner of the biological rhythm adjustment system of the present invention.
  • the method further includes:
  • the obtaining module further acquiring at least one environment parameter related to the target object according to a time series;
  • An optimization module that processes the biorhythm data acquired by the acquisition module and calculates and obtains a current biorhythm state and an ideal biorhythm state of the target object from the environmental parameter, and combines the environmental parameter Determining a pattern of biological rhythms that interfere with the target subject;
  • An intervention module that outputs a corresponding intervention operation based on the intervention mode determined by the optimization module.
  • the optimization module obtains an ideal biological rhythm state of the target object based on comparing a current biological rhythm state of the target object with a population biorhythm criterion, thereby determining to intervene in the target object.
  • the pattern of the biological rhythm is a preferred embodiment of the biological rhythm adjustment system of the present invention.
  • the optimization module obtains statistical characteristics (mean, variance, symmetry, etc.) from individual data of the entire population or a specific population, and according to statistics of at least one data. Feature calculation and acquisition of population biorhythm standards.
  • the optimization module calculates and obtains a preset rhythm standard of the population according to scientific common sense or literature data in the field of biological rhythm.
  • the optimization module extracts at least one of phase information, amplitude information, and period information from the biorhythm data, and according to the at least one information combination
  • the environmental parameters are calculated, and the current biological rhythm state of the target object is calculated and obtained.
  • the optimization mode calculates and obtains an ideal biological rhythm state of the target object from an individual rhythm state of the target subject, a biorhythm criterion or a preset rhythm criterion of the population.
  • the optimization module determines an intervention site from the current rhythm state of the target object and the ideal biological rhythm state, in comparison with the ARC curve or the PRC curve, in combination with the environmental parameter.
  • the pattern of the biological rhythm of the target object is not limited to the biological rhythm adjustment system of the present invention.
  • the method further includes:
  • a storage module that stores the biorhythm data and the environmental parameters of the target object acquired by the acquisition module in a time series
  • the optimization module acquires the biorhythm data and the environmental parameters stored by the storage module at predetermined time intervals and performs the processing, calculation, and determination.
  • the intervention module may include at least one of a display device, an audio device, a light control device, and a temperature control device.
  • the biorhythm data may include at least one of blood pressure, pulse, body temperature, exercise, blood glucose, and diet data of the target subject; the environmental parameter includes illumination At least one of strength, illumination time, and temperature.
  • the biorhythm adjustment system includes a portable monitoring device, and specifically may include at least one of a wearable device or an implant device or a combination thereof.
  • the biorhythm adjustment system may further comprise at least one of a server, an expert system, a database, or a combination thereof, in communication with the portable monitoring device.
  • the acquisition module includes at least one of a biometric information sensor and an input interface disposed on the portable monitoring device, wherein the target object is capable of passing the input
  • the interface inputs data related to the biological rhythm.
  • Another aspect of the present invention provides a biological rhythm adjustment method comprising the steps of:
  • the biorhythm data includes at least one of blood pressure, pulse, body temperature, exercise, blood sugar, and diet data of the target subject.
  • Obtaining according to a time series further includes an environmental parameter related to the target object
  • the biorhythm data includes at least one of blood pressure, pulse, body temperature, exercise, blood glucose, and diet data of the target subject;
  • the related environmental parameter includes light intensity At least one of light time, temperature, and the like.
  • the intervention mode Determine to include one or more of the following methods:
  • the main method is used (a); for individuals whose current rhythm does not match the individual ideal rhythm, use method (b) for phase, amplitude and period, etc.
  • the aspect is corrected and the method (a) is also used to optimize the conditioning environment.
  • the steps (1) to (3) are each repeated at predetermined time intervals.
  • the intervention operation includes performing image prompting on the target object, performing an audible prompt on the target object, performing illumination adjustment on the target object, and changing the At least one of the temperatures of the environment in which the target object is located.
  • the prompt content includes at least one prompt of sleep time, wake-up time, eating time, dietary composition, exercise time, light adjustment, and temperature adjustment.
  • Intervention system for individuals Once set and output, the system will continue to follow up on the effectiveness of the evaluation intervention and make appropriate adjustments for different outcome feedback, which is an adaptive solution.
  • population rhythm big data with biological rhythm as the core key parameter can be gradually formed, which provides data support for the subsequent optimization and improvement of the system, including the addition of functional modules and solution upgrade.
  • Figure 1 is a flow chart showing the data processing of the biological rhythm adjustment system of the present invention.
  • Figure 2 Changes in body temperature under normal conditions in mice (PER3HA, PER3SG); and changes in body temperature phase in the case of mutations (PER1SG or PER2SG).
  • FIG. 3 Phase of wild-type mice with ERS1 protein S714G site mutation (PER1S714G) mice in food intake, oxygen consumption (VO2) and mouse activity.
  • FIG. 4 Effect of restrictive dietary intervention (NRF) on the phase of metabolism (VO2) and activity of mice.
  • Figure 5 Schematic diagram of the variation of the amplitude of the biological clock.
  • Figure 6 Schematic diagram of the circadian period of the biological clock for light stimulation.
  • Figure 7 Schematic diagram of the effect of the clock synchronization on amplitude.
  • Figure 8 Schematic diagram of PRC and ARC for the response of the circadian clock to stimulation.
  • Figure 9 Schematic diagram of the effects of exercise and no exercise on gene expression of a species.
  • Figure 10 Schematic diagram of the effects of morning exercise and evening exercise on the circadian clock.
  • Figure 11 Schematic diagram of the effect of a high-fat diet on the amplitude of biological rhythms.
  • Figure 12 Schematic diagram of the effect of changes in room temperature on changes in body temperature.
  • Figure 13 Schematic diagram of the relevant biorhythm data in Example 2.
  • biological rhythms means a pattern of changes in the consistency and regularity of the body activity expressed in a fixed period of time.
  • biological clocks as used in the present invention is a system for controlling biological rhythms.
  • circadian day time and circadian night time means the time scale of the intrinsic biological rhythm system, the time period corresponding to the inner day and night.
  • rhythm biorhythm criteria means a rhythm standard calculated and obtained from statistical characteristics of data of the entire population or a specific population.
  • preset rhythm standard means a rhythm standard derived from scientific common sense in the field of biological rhythm or literature data.
  • biorhythm state means that the biorhythm state calculated and obtained is extracted based on at least one of phase information, amplitude information, and period information extracted from individual biorhythm data.
  • the term "individual ideal biological rhythm state” as used in the present invention means that the rhythm state calculated and obtained from the current rhythm state of the target subject, the biological rhythm standard or the preset rhythm standard of the comparison population is a kind Nearly 24 hours with a certain oscillation The rhythm state of the appropriate phase difference between the amplitude and various physiological indicators.
  • phase of biological rhythm means a position at which a biological rhythm is in a changing law at a specific time.
  • period of biological rhythm means the length of time during which the biological rhythm changes regularly.
  • amplitude of the biological rhythm used in the present invention means the difference between the maximum value and the minimum value of the biological rhythm in the regularity change.
  • Phase Response Curve means a phase shift curve which is caused by giving a stimulus at different time points.
  • Amplitude Response Curve means an amplitude change curve which is caused by giving a stimulus at different time points.
  • rhythmic In normal organisms, temperature changes, heart rate changes, blood pressure changes, sleep activities, and feeding changes are rhythmic (as shown in Figure 2). Related studies have found that these rhythms not only have their corresponding physiological basis, but also have their corresponding biological basis. For example, regulatory molecules and genes associated with biological rhythms are being discovered one after another; and changes in the activities of these regulatory molecules or defects in these related genes may trigger changes in these biological rhythms. Taking mice as an example, as shown in Figure 2, the body temperature shows a rhythmic change (PER3HA and PER3SG) under normal conditions, but in the case of a mutation in the PER gene (PER1SG or PER2SG), the phase of the body temperature rhythm changes. , thereby causing corresponding physiological changes.
  • rhythmic change PER3HA and PER3SG
  • the inventors have found through a large number of studies and experiments that although the physiological parameters of the organism have their fixed rhythm cycle and phase, there is a correlation between the rhythm phases of the various physiological parameters. Maintain correlation between these rhythm cycles and phases, optimize organisms The state is also crucial.
  • Figure 3 shows the phase advance of the food intake (Food Intake) after the rhythm-related PER1 protein S714G site mutation (PER1S714G) compared to wild-type (PER1S714) mice, while the oxygen consumption (VO2) represents The phase of metabolism of the body also advances. After the phase changes between the two, the phase of the activity of the mouse is no longer coordinated, and eventually the mouse tends to become obese. In the same mouse model, when the human intervention restricts the eating time, the eating of the mutant mouse returns to the normal phase, that is, after returning to the phase of the metabolic cycle and the activity cycle, the tendency of the mouse to become obese disappears. As shown in FIG.
  • the present invention therefore provides a method of assessing a biological rhythm that combines the collection of rhythm information of a plurality of physiological parameters of an organism for evaluation while aligning the interrelationships between the rhythms of these physiological parameters. Based on the results of a large number of experiments, the inventors believe that there is a coordinated phase difference and mutual feedback between the rhythms of different physiological parameters, which can promote the stability of these rhythms, and in turn guide the rhythm of the whole body to be stable and regular. In order to optimize the physiological functions of biological individuals.
  • the present invention provides such a method of regulating biological rhythm: in a comprehensive analysis Based on the rhythm of each physiological parameter of the living body, based on the principle of phase coordination and feedback described above, the ideal biological rhythm of the living body is determined; and the actual rhythm of the obtained organism is compared with the determined ideal rhythm of the living body, Based on this, a suitable intervention scheme is proposed for the rhythm of the organism, and then the corresponding means are used to induce the adjustment of the rhythm of the organism to optimize it.
  • the circadian clock oscillation is adaptive to light stimulation, and after 0.5-1 hour of continuous light stimulation, the inhibition pathway is initiated, thereby greatly reducing the response of the Per1/Per2 gene to light. Therefore, in order to effectively modulate the circadian clock with illumination, it is necessary to choose to give a strong light stimulus at the initial non-refractory window of 0.5-1 hour, which is much more effective than stimulation during the subsequent refractory period.
  • the oscillating negative feedback mechanism that the biological clock depends on implies an unstable center of oscillation. Although it is difficult to directly observe this unstable center point during the experiment, it has a function of the biological clock system. big influence.
  • the oscillation period of the circadian clock in the cell is pushed (or moved away) from the center by external stimuli (such as light), it has a great influence on the synchronism between cells.
  • Fig. 8(1) a two-dimensional system is taken as an example (the system runs in a counterclockwise direction), indicating the difference in synchronism between adjacent cells caused by stimulation at different phases.
  • the red dot at the center of the limit cycle is an unstable center point, and a certain stimulation intensity is given at one place, so that two adjacent cells at one position move to a corresponding position away from the center point.
  • the phase difference between the two cells becomes smaller, the synchrony becomes better, and points 2 and 3 are the same.
  • a certain stimulation intensity is given, so that the two adjacent cells at 4 are close to the center point.
  • the direction moves to the vicinity of the corresponding red dot, at which time the phase difference between the two cells becomes larger, the synchronism becomes worse, and points 5 and 6 are similar.
  • Fig. 8(2) the left graph shows the PRC curve of the system.
  • the slope of each point on the curve represents the sensitivity of the phase change after giving a certain stimulus at the phase time corresponding to the point.
  • the absolute value of the slope The larger the phase is, the more easily the phase is changed after the corresponding phase is stimulated; the right picture shows the ARC curve of the system.
  • the magnitude of the ordinate of the curve is the magnitude of the biological rhythm after giving a certain stimulus to different phases. The larger the coordinate value, the stronger the biological rhythm.
  • the degree of synchronization of the enhancement (or attenuation) can be obtained, thereby more effectively changing the amplitude of the biological rhythm of the overall output, and finally Affect the output of various physiological indicators downstream of the circadian clock.
  • the time point coincident with the "non-refractory period" window of the aforementioned stimulation should be selected as much as possible, and the appropriate phase should be selected to give appropriate intensity of stimulation regulation to obtain a multiplier. effect. Synchronization and single cell amplitude can also be enhanced separately if the selected two time periods do not overlap. But if the two overlap, there may be further effects.
  • the present invention provides a related method for determining an optimal synchronization time point of a diet, an optimal synchronization time point of an activity amount period, and a non-refractory period window of light, etc., so that a plurality of superimpositions can be performed to obtain more Good results.
  • the biological clock has a temperature compensation mechanism under natural conditions, when the temperature changes, the phase of the biological clock changes. Therefore, it is also possible to use the indoor temperature change to make a traction change to the biological clock, as shown in FIG. Although the effect of temperature traction is weaker than light, the temperature traction is somewhat less disturbing to life and it is easier to produce traction in the "background". Therefore, for the individual's biological rhythm, different morning and evening temperature differences can be set to personalize the biological clock.
  • the present invention also provides a method of collecting the surrounding environment information of an individual in detail, and selecting an intervention at a suitable time point, thereby enabling an effective improvement of the in vivo clock rhythm cycle.
  • the individual parameters to be concerned are parameters capable of reflecting or affecting the individual's biological rhythm state, such as body temperature, heart rate, blood pressure, sleep, activity, diet, and the like.
  • the collection of individual parameter data can be completed by using a portable monitoring device such as a wristband, through built-in blood pressure detection, heart rate monitoring, temperature detection and the like; with the mobile app, the individual can also complete Active input of diet and activity data.
  • the collected body temperature, heart rate, blood pressure, sleep, activity, and diet data will be stored in a specific database format and then analyzed by the mobile app or uploaded to the server center for analysis.
  • environmental parameters such as light, temperature, etc. are also the focus of the present invention. Sensors such as temperature and light can be provided with separate sensing devices or built into the aforementioned portable devices for the environment. Monitoring of parameters.
  • the invention also provides a suitable algorithm program for evaluating the collected parameter data reflecting the individual's biological rhythm, and calculating the current biological rhythm of the specific individual based on the collected data, including but not limited to phase ( Phase), Period (Amplitude) and Amplitude (Amplitude).
  • the present invention also provides a suitable algorithm program for evaluating the validity of the collected parameter data reflecting the environment in which the individual is located, and evaluating the current environmental conditions of the individual based on the collected data, including but not Limited to light intensity, lighting time and temperature.
  • the inventors have found through experiments and calculations that the expression rhythm of intracellular genes (such as Per1) of the suprachiasmatic nucleus (SCN, Suprachiasmatic Nucleus) in the central region of the mammalian circadian clock is close to the cosine function (cos). As long as you know the three factors of amplitude, period and phase, you can completely determine the cosine function, which is to determine its rhythm. Although this is an imaginary rhythm at the cellular level, since the suprachiasmatic nucleus is the biological clock center of the organism, the various rhythms of the organism are regulated and influenced by it, and therefore the physiological data and activity/sleep, etc. measured by the external device.
  • intracellular genes such as Per1
  • SCN suprachiasmatic nucleus
  • Data through a certain processing method, can roughly reverse the three factors of amplitude, period and phase of the central cell rhythm activity, and thus determine the imaginary rhythm.
  • the current rhythm, individual ideal rhythm, and population rhythm criteria provided by the present invention are all based on the imaginary rhythm of the aforementioned counter-initiated central region cells.
  • physiological data measured by an external device and data such as activity/sleep do not necessarily have the shape of a cosine function.
  • data such as activity/sleep
  • waveform features such as symmetry, etc. Due to the different data reliability in each time period (for example, human social activities during the day are more likely to interfere with the data), the time segment will be further considered when processing the data.
  • the indicators of the individual data of the whole population or specific population can be counted.
  • the standard such as amplitude, period and phase indicators, and symmetry indicators
  • its distribution type Gaussian distribution or Poisson distribution, etc.
  • the mean of the three indicators of amplitude, period and phase can be used to reverse the rhythm of the population.
  • the criterion used by the algorithm to confirm the plausibility of each data is mainly to judge the periodic nature and amplitude of each group of data. Data that falls within the fluctuation range of the rhythm data of the normal population or within the corresponding extended range of the range will be considered valid. Otherwise, the data of the group is invalid and cannot be used.
  • data of ⁇ 200% of the fluctuation range of the rhythm data falling into the normal population may be regarded as valid data; preferably, the fluctuation range of the rhythm data falling into the normal population may be ⁇ 150% of the data is considered valid data.
  • the rhythm standard of the normal population can be given at the time of system setting or can be added later.
  • the range value of the environmental parameters can be given at system setup or later.
  • the present invention also utilizes a so-called population based human circadian rhythms or "crowd rhythm standard" for rhythm optimization.
  • the population biorhythm criterion may be based on population biorhythm data for a period of time.
  • the simple average can also be obtained after processing through a specific model.
  • the length of time is determined according to needs, for example, it can be 2 days, 3 days, 7 days, 15 days, 30 days, etc., or any other suitable The time period.
  • This rhythm standard can be obtained based only on some basic physiological data of the population, such as body temperature, blood pressure, heart rate, etc., or can be obtained based on basic physiological data of the population and activity data such as sleep, diet, activities, and the like.
  • the population rhythm standard can also be obtained based on the above various conditions, but based on data of a plurality of similar individuals, for example, 2, 3, 5, 10, 20, 50, 100, 500. , 1000, etc.; so-called similar individuals, can refer to age, gender, race, region, work, occupation, activity habits, drinking Individual aspects of habits similar, may be similar to any combination of the aforementioned aspects.
  • the acquisition of the population rhythm standard includes two steps, from the number of individual items of the crowd According to the mean, the corresponding rhythm and the corresponding rhythm using multiple data are combined into the population rhythm standard.
  • the mean value of the three indicators of amplitude, period and phase is obtained according to the processing method of the single item data, and the corresponding virtual virtual cell rhythm is reversed. Since the hypothetical virtual cell rhythms (in terms of amplitude, period, and phase) derived from the individual mean values may be different, it may be further weighted according to factors such as data reliability. After weighted averaging, the amplitude mean, period mean and phase mean of the population are finally determined, which is used as the population rhythm standard.
  • the above-mentioned crowd rhythm standard data may be updated from the obtained data from time to time after being calculated according to the corresponding algorithm.
  • the present invention can also obtain various data of the individual natural circadian rhythms of the responding individual through the collected data reflecting the individual's condition. According to the present invention, based on the obtained effective data of the individual, selecting data of the same time and the same time period, and superimposing the data according to a certain specific gravity and method, the current biological rhythm of the user can be obtained, including but not limited to Obtain three key indicators of phase, period and amplitude.
  • the acquisition of the current biological rhythm of the individual includes three steps, namely, comparing the individual individual data with the individual data of the crowd to determine the validity of the data, and inversely pushing the corresponding rhythm from the individual single item data and the corresponding rhythm of the plurality of data into the current current rhythm of the individual.
  • the reliability of the data and the health of the individual rhythm can be judged according to the comparison between the indicators of the individual data of the population and the indicators of the individual data of the corresponding individual. If each individual individual data is within the error threshold of each indicator of the population rhythm standard, the individual data collected by the individual is regarded as valid; otherwise, the data collection is invalid, and the data corresponding to the parameter is re-acquired.
  • three indicators of amplitude, period and phase are obtained according to the processing method of the single item data, and are used to reverse the corresponding hypothetical cell rhythm.
  • the individual body temperature phase is correspondingly translated to obtain the virtual phase of the cell rhythm; according to the general amplitude ratio of the body temperature rhythm and the cell rhythm (obtained by experimental data), the amplitude of the cell rhythm is reversed; the body temperature rhythm Cycle can be used directly as a cell festival The cycle of the law.
  • the hypothetical cell rhythms in terms of amplitude, period, and phase
  • the current amplitude, period and phase of the individual are finally determined as the current rhythm of the individual.
  • the inventors have found that, based on the obtained individual biorhythm information, the difference between the corresponding population rhythm standard information and the related environmental factors can be used to derive the ideal biological rhythm of the individual.
  • the so-called "individual synchronized circadian rhythms" is to compare the current biological rhythm of the individual with the human biorhythm standard, and to refer to the population biorhythm standard, and to convert the influence of external environmental parameters into
  • the theoretical parameter is the biological rhythm obtained by adjusting the phase, period and oscillation amplitude of the individual's current biological rhythm.
  • a suitable intervention plan can be calculated, and the effect of adjusting the biological rhythm can be obtained through an external intervention component and an activity performed by the individual according to the intervention plan.
  • the main comparison is three key indicators such as phase, period and amplitude of oscillation.
  • the present invention uses the phase standard of the crowd rhythm as the median value, allowing a certain difference interval to determine the individual ideal phase.
  • the effects of modern social environments often cause human rhythm oscillations to be at a lower level.
  • the present invention will be based on the amplitude criteria of the population rhythm, allowing a certain difference interval to determine the individual ideal amplitude.
  • the present invention directly takes the cycle of the population rhythm as the individual ideal cycle.
  • the individual ideal phase may also not be based on the crowd rhythm
  • the criteria eg, where the amount of data is small enough to establish a credible population rhythm standard
  • the criteria are directly established directly from scientific knowledge in the field and known data, such as literature data.
  • the rhythm can be strengthened by optimizing the environment and making the environment more adaptable to the individual rhythm of the individual.
  • the individual's current rhythm can be adjusted toward the individual's ideal rhythm.
  • the theoretical basis used is the rhythm of the biological clock day and the clock and the night, as well as the corresponding PRC curve and ARC curve. These two curves depend on both the phase of the stimulus and the intensity of the stimulus.
  • the PRC curve shows that giving a stimulus for a portion of the time period helps the phase advance, while another portion of the time period delays the phase.
  • the ARC curve shows that giving a stimulus for a portion of the time period helps to increase the amplitude, while another portion of the time period reduces the amplitude.
  • the present invention can comprehensively determine the best. Intervention model. Based on the slope of the PRC curve for a single intervention and the value of the ARC curve, the present invention provides an algorithm to determine the intervention operation for a single intervention. When comprehensively outputting multiple interventions, it is necessary to comprehensively process the individual biorhythm indicators (including but not limited to phase, amplitude, and period), and then give corresponding interventions at the time when the intervention effect is the strongest.
  • the corresponding intervention can be scientifically set according to the rhythm state of the individual's own parameters, combined with the environmental parameters, in order to finally realize the optimization of the individual rhythm state.
  • the outputs that can be used for this purpose include:
  • the individual circadian clock and the individual circadian clock can be obtained according to the current rhythm of the individual, and the individual circadian clock can be matched by optimizing the adjustment environment (light, brightness, temperature, etc.). Daytime and individual biological clocks and nights make the environment more adaptable to the individual's current rhythm, thus strengthening the current rhythm.
  • the PRC curve can be used to obtain the most favorable time points for synchronization, giving extra stimulation and helping to improve the synchronization between cells.
  • phase For the correction of the phase, it can be corrected in two ways: 1) By optimizing the adjustment environment, creating a daytime and a biological clock and night environment in accordance with the individual ideal rhythm; 2) Finding a suitable time point or time period based on the PRC and ARC curves. , give extra stimulation to correct the phase.
  • amplitude correction it can be corrected in three ways: 1) By optimizing the adjustment environment, creating a daytime and biological clock and night environment in accordance with the individual ideal rhythm; 2) Finding a suitable time point or time period based on the ARC curve (ARC) Additional time is given to correct the amplitude; 3) Since the ARC curve is difficult to obtain or the reliability is poor, the PRC curve can also be used to find the appropriate time point or time period (near the slope of the slope of the PRC curve) Time period), giving additional stimulation to correct the amplitude.
  • ARC ARC
  • the PRC curve can also be used to find the appropriate time point or time period (near the slope of the slope of the PRC curve) Time period), giving additional stimulation to correct the amplitude.
  • the main means is to strengthen the periodicity by optimizing the environment, creating regular day and night changes, and increasing amplitude.
  • the deviation from the population's biological rhythm standards is larger, and expert feedback can also be used to give personalized guidance.
  • the above scheme for strengthening or correcting the biological clock can be realized by a single stimulation intervention or a combination of multiple stimulation interventions.
  • the core algorithm of the data analysis provided by the present invention is designed according to the scientific experimental basis related to the biological rhythm, and the core thereof is to obtain the fitting rhythm index of each physiological parameter of the individual or the group by calculation, and obtain the phase,
  • the inventors have found from a large number of studies and calculations that the individual's biological rhythms are based on the cellular, genetic, and molecular levels, which are the basic biological basis of biological rhythms, and that the individual's biological rhythms are only based on the basic biological basis of these biological rhythms. Time is the most ideal. Of course, due to the differences between individuals, and also due to the influence of environmental factors, sometimes also need to consider the individual's particularity.
  • a core of the present invention is to determine the biorhythm state of the user and compare it with the standard state of the normal human body to determine the difference in phase and amplitude between the individual rhythm and the standard data, thereby formulating an intervention plan.
  • the inventors believe that this is the basis of the present invention over all known similar inventions.
  • the acquisition module includes two components: a data receiving and transmitting component and a data processing component.
  • the data receiving and transmitting component receives and transmits all data transmitted and transmitted by the instruction transmitting part through Bluetooth and/or the network; the data processing component calculates the current biological rhythm of the individual through the mathematical model by using the received individual data, and evaluates the individual's rhythm parameter
  • the best intervention plan is designed in combination with environmental parameters, and it is also responsible for continuous evaluation after the intervention plan is given, and the intervention plan is adaptively adjusted according to the results.
  • the acquisition module includes a data collection component that may include a portable monitoring data collection device that is worn by a person, or may include a non-portable monitoring data collection device for further supplementation.
  • the intervention module mainly includes information sending and receiving components.
  • the messaging and receiving components use Bluetooth and/or the network to send and receive data and program commands, and then interact with external intervention components such as lighting and temperature.
  • the wearable device is an exemplary embodiment consistent with the relevant needs of the present invention and is worn by the user for collecting the daily circadian rhythm parameters and environmental parameters of the individual.
  • Wearable devices that meet the relevant needs of the present invention can be smart bracelets, watches, rings, necklaces, glasses, heart rate belts, and the like, or combinations thereof.
  • Wearable bracelet with corresponding light, step, heart rate and body temperature detection components with corresponding light, step, heart rate and body temperature detection components; optional simple LCD display on the front, which can display basic information such as time and current heart rate;
  • the physical storage space and the Bluetooth data transmission module and may have a wired connection interface, such as a microUSB data interface commonly used in electronic products.
  • the wristband After the user wears the bracelet, the wristband performs full-time monitoring and data collection of the user's movement, heart rate and body temperature through the various sensing elements.
  • the light-sensing components of the bracelet can be Ambient lighting for data collection, and other components to collect other environmental related data such as ambient temperature, humidity, air quality, etc.
  • the collected data is stored in the built-in storage space of the bracelet in a preset format before being synchronized with the terminal.
  • the external button of the wristband can be easily switched between the display contents of the ring display.
  • the bracelet can charge the internal battery via the microUSB interface.
  • the wearable device can transmit data with other smart devices including a smart phone, a smart tablet or a personal computer, such as a Bluetooth transmission module and corresponding software, or communicate via a wireless network connection, or transmit data through a microUSB interface. Wait.
  • other smart devices including a smart phone, a smart tablet or a personal computer, such as a Bluetooth transmission module and corresponding software, or communicate via a wireless network connection, or transmit data through a microUSB interface. Wait.
  • the user can also actively input personal diet-related data through a smart device, and the entry method includes text and photos.
  • the smart device can synchronously transmit the data of the opponent ring, or the user can also set the data to be automatically synchronized.
  • the frequency options include, but are not limited to, every minute, every 15 minutes, every 30 minutes, every hour, every time. 3 hours, every 6 hours, every day, etc., or you can also open the settings to let users customize the data synchronization frequency.
  • the smart device and supporting software can also define and save the user's personal information (including but not limited to age, gender, height and weight, etc.), and visually display the relevant parameters of the individual. At the same time, it can perform simple data statistics, initiate data transmission to the server, accept the data of the server and implement corresponding Output.
  • personal information including but not limited to age, gender, height and weight, etc.
  • the portable monitoring device there are other supporting hardware to help with data collection, such as sleep pads (for monitoring sleep activity), infrared sleep measurement devices, and more.
  • sleep pads for monitoring sleep activity
  • infrared sleep measurement devices and more.
  • These supporting hardware can upload data to the portable monitoring device for integration, or can be further uploaded to the smart device with a dedicated program or application through the network for further integration with the portable monitoring device.
  • the smart device After the smart device synchronizes the device data, it can perform further processing, and the data can be transmitted to the data server center of the system through the network for further data analysis and long-term storage.
  • the core data server center will be set up in a centralized location, connected to other hardware through the network, software, and the data is saved in a database format, including but not limited to Access, SQL, and the like.
  • the data transmitted by the smart device to the server includes: data related to the user's biological rhythm, and may also include the user's personal information (in the case of requesting the user's consent); the data transmission is performed according to a preset format.
  • the software is turned on, after the smart device completes the data synchronization with the portable monitoring device, the data synchronization with the server can be completed directly in the background.
  • the user can set the frequency of synchronizing data with the server through software.
  • the frequency options include, but are not limited to, hourly, every 3 hours, every 6 hours, every day, every week, every month, and the like.
  • the data server After the data server receives the user's data, it uses an optimized algorithm to process and analyze the data.
  • Data analysis can be initiated by the user or automatically after a predetermined data collection cycle is completed, such as automatically after one day, three days, or one week of data collection.
  • the process of data analysis is to judge the time format of the data and make necessary adjustments. Start the analysis with the correct format data.
  • the analysis will use the system optimization algorithm or program.
  • the algorithm or program will accumulate according to the different individual data obtained. Update to obtain the optimal algorithm or program, and compare the user's personal results obtained by the analysis with the standard results of the system to develop a suitable intervention.
  • the portable monitoring device records the data in a format preset by the software, but data recording interruption caused by user's human or hardware problems may occur. In this case, the judgment and adjustment of the data format are also necessary. This process can be done initially within the portable monitoring device or at the smart device and server center.
  • the system will return information requesting more data and emphasizing the integrity of the data collection to the user.
  • the server center sends the intervention output solution to the relevant hardware through the network, including smart devices (software), portable monitoring devices, and other downstream hardware.
  • the relevant hardware including smart devices (software), portable monitoring devices, and other downstream hardware.
  • smart devices software
  • portable monitoring devices such as lighting adjustment equipment.
  • the intervention output can be implemented by both software and hardware outputs.
  • Software interventions include: After the software installed on the smart device receives the intervention, the user can be alerted by the smart device at a specific time according to the solution.
  • the software reminder content may include a reminder to the user to eat, exercise or sleep, thereby achieving a reasonable adjustment of the user's biological rhythm. whole.
  • the software reminder can be directly implemented by a smart device such as a mobile phone, or can be further synchronized to an indirect implementation such as a wristband and the like.
  • the software can include user-defined features such as music sleep, lighting/music timer wake-up.
  • Hardware interventions including but not limited to lighting interventions, temperature regulation, etc. Interventions can be sent to individual hardware either directly or through software.
  • Illumination hardware is used to implement lighting interventions, such that lighting of a specific wavelength and intensity is turned on or off at a specific time.
  • the temperature regulation can be realized by the intelligent air conditioner. After the built-in module of the air conditioner receives the intervention plan or specific instructions, the ambient temperature is controlled accordingly.
  • the biorhythm adjustment system of the present invention can also be coupled to other smart home devices and control the output of interventions other than illumination intervention and temperature regulation.
  • the biorhythm adjustment system provided by the invention further comprises a feedback optimization mechanism.
  • the recording of relevant parameters is always in progress, and the changes in the data will be used as a reference to evaluate the effectiveness of the intervention.
  • the operation of the feedback system includes the process of data collection, data analysis/comparison, and intervention adjustment, which can be understood as corresponding to the three aspects of data collection, data storage and analysis, and intervention output as described above.
  • the data analysis processing of the intervention is performed only at the server center for analyzing the current biorhythm state of the user and evaluating the effectiveness of the current intervention protocol.
  • the data collection of the feedback system can also be actively input by the user.
  • the user can input the subjective feeling after receiving the intervention, and further help the system to judge the effectiveness of the intervention.
  • the effectiveness of the intervention program is mainly to determine whether the individual biorhythm of the user after the intervention has migrated to the normal standard (and the biological clock traction effect of the intervention program). Based on the effectiveness of the identified intervention, the server will determine whether to continue the current intervention or adapt the intervention.
  • Example 2 Example of a biological rhythm adjustment method
  • phase is CT20
  • amplitude 30.6, period is 25h.
  • Cycle The period of the individual's current rhythm.
  • the observed object is an elderly person, and the relevant corresponding data is detected by the portable detecting device as shown in Fig. 13 (1).
  • the phase of the body temperature in the current rhythm of the observed object is CT20, the amplitude is 1 °C, the period is 20h; the active phase is CT16, the amplitude is 60, and the period is 25h.
  • phase of the current hypothetical cell rhythm of the observed object from the body temperature is CT18, amplitude 18, the period is 20h;
  • the phase of the current hypothetical cell rhythm of the observed object is CT16, the amplitude is 45, and the period is 25h;
  • the weighted average of the body temperature and the phase, amplitude and period of the activity can be obtained, and the current phase of the individual is CT17, the amplitude is 30, and the period is 23h.
  • the comprehensive curve of the current biological rhythm of the observed object can be obtained, as shown in Fig. 13(2). Shown.
  • the amplitude of the current rhythm of the observed object is within the threshold of the ideal rhythm; the phase is earlier than the phase of the preset rhythm standard by 3 h, beyond the range of the ideal rhythm, and the phase is too advanced, therefore, according to the present invention, the observed object
  • the phase is adjusted to the lower limit of the ideal rhythm, CT18, that is, the phase of the observed object must be delayed by 1 h.
  • the observation object is another old person.
  • the relevant corresponding data is detected by the portable detection device.
  • the integrated curve phase of the individual's current biological rhythm is analyzed as CT20, the amplitude is 10, and the period is 25h.
  • the amplitude of the current rhythm of the observed object is too low to reach 80% of the amplitude of the crowd. Therefore, according to the present invention, the amplitude of the observed object should be increased as much as possible.
  • the one-time blue light stimulation can be achieved at the maximum point of the ARC value (CT7) and the time point near it to achieve the optimal amplitude improvement effect;
  • CT7 maximum point of the ARC value
  • the stimulation can be performed at the time point of optimal synchronization (CT7) and the nearby time point in combination with the PRC curve shown in the left column of FIG. 8(2) to make the synchronization better and the amplitude higher. If the purpose of correction cannot be achieved within one day, Repeat the stimulation for several consecutive days.

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Abstract

L'invention concerne un système de régulation du rythme biologique et un procédé de régulation du rythme biologique. Un état du rythme biologique de corps humain est évalué par la collecte de données relatives au corps humain étroitement liées au rythme biologique et combinées à des modèles mathématiques, une analyse personnalisée est effectuée au moyen de schémas, tels que les modèles mathématiques ou une consultation d'expert du type à rétroaction, etc., et par l'accumulation de ressources personnalisées pour obtenir une intervention systémique numérique, non effractive, en fonction du temps. En combinaison avec des lumières de différentes longueurs d'onde, un régime alimentaire, de l'exercice physique, un réglage de températures intérieures et d'autres rappels électroniques ou des moyens d'intervention à réglage automatique, l'horloge biologique est individuellement régulée, et le sommeil, le métabolisme, l'immunité, les maladies de l'appareil reproducteur et les maladies dégénératives ainsi que d'autres états pathologiques ou de mauvaise santé causés par l'affaiblissement du rythme biologique et de troubles sont améliorés.
PCT/CN2015/097887 2015-12-18 2015-12-18 Système de régulation du rythme biologique et procédé de régulation du rythme biologique WO2017101111A1 (fr)

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