CN110403569A - Method and application of comprehensive judgment of stroke based on left-right asymmetry and intensity increase of autofluorescence at multiple body surface locations - Google Patents

Abstract

The invention provides a detection method for detecting the acute phase and the recovery phase of stroke based on comprehensively judging the increase in the intensity of autofluorescence in multiple parts of the human body surface and the asymmetry of the intensity between the left and right sides of the body and its application. This method comprehensively analyzes and calculates the autofluorescence intensity of multiple parts detected and the asymmetry of the left and right sides of the autofluorescence, so as to determine the high risk of stroke, the possibility of stroke, and the degree of rehabilitation of stroke. make judgement. The method is noninvasive, efficient, simple, high in accuracy and good in repeatability.

Description

Comprehensive judgment based on left-right asymmetry and intensity rise of autofluorescence at multiple body surface locations Method and Application of Diagnosing Cerebral Apoplexy

technical field

The invention provides a detection method for comprehensively judging cerebral apoplexy based on comprehensively judging the autofluorescence of multiple parts of the human body surface. Specifically, it refers to the comprehensive analysis and calculation of the total number of positions where the autofluorescence intensity of the detected multiple parts increases, and the total number of positions where the left and right sides are asymmetrical, and the high risk of stroke and whether the stroke is determined based on the sum of these two totals. There is a stroke, and the degree of recovery from a stroke.

Background technique

In my country and other countries in the world, stroke is one of the most serious diseases that cause death and lifelong disability. Ischemic stroke is a type of disease with the highest incidence rate of stroke. At present, the main means of diagnosis is to carry out imaging analysis through nuclear magnetic resonance technology. This method can only be detected by more expensive methods such as nuclear magnetic resonance in the hospital, which is very inconvenient for patients, takes a relatively long time and is expensive. So far, there is no non-invasive, fast, economical method that can be used at home to determine whether a stroke has occurred, nor a non-invasive, fast, and economical method that can be used to screen out stroke patients during physical examination. At the same time, there is no non-invasive, fast, economical, and home-usable method for judging the prognosis of stroke. Therefore, a non-invasive, fast, economical, and home-usable method for judging the onset of stroke has been invented, which can be used to screen patients during physical examination. A non-invasive, fast, and economical method for detecting stroke patients, and a non-invasive, fast, economical, and family-usable method for judging the prognosis of stroke have extremely important socioeconomic significance and clinical value.

Contents of the invention

The purpose of the inventor is to break through the problems of the prior art, and to propose a non-invasive and fast method and its application that can be used to judge the high risk of stroke, the possibility of stroke, and the degree of rehabilitation of stroke .

The inventors found that if the sum of the total number of increases in the intensity of autofluorescence specific positions of the test subject and the total number of positions with asymmetric degrees of autofluorescence intensity on the left and right sides of the body is greater than 2, it can be judged that the subject has a high risk Have had a stroke, or are likely to have had a stroke.

The present inventors invented a method for judging the degree of risk, possibility of onset, and degree of recovery of stroke, which includes the following steps: Exciting multiple human body surfaces of the subject to receive light between 420nm and 800nm with excitation light between 400nm and 750nm of autofluorescence. The intensity of autofluorescence at specific locations and the degree of asymmetry of the intensity of autofluorescence on the left and right sides of the body are then analyzed. The sum of the total number of rises in the intensity of autofluorescence specific locations of the test subject and the total number of locations with asymmetric degrees of these autofluorescence intensities on the left and right sides of the body is then calculated.

The present inventors found that if the sum of the total number of increases in the intensity of autofluorescence specific positions of the tester and the total number of positions having asymmetry degrees of these autofluorescence intensities on the left and right sides of the body is higher, the possibility that the tester will suffer from stroke is higher. big.

The present inventors found that if the sum of the total number of rises in the intensity of autofluorescence specific positions of the test subject and the total number of positions having asymmetry degree of these autofluorescence intensities on the left and right sides of the body is higher, the possibility that the test subject has suffered from a stroke bigger.

The present inventors found that if the sum of the total number of increases in the intensity of autofluorescence specific positions of the tester and the total number of positions having asymmetry in the left and right sides of the body of these autofluorescence intensities is higher, the possibility that the tester has a stroke is higher. big.

The present inventors have found that if the tester is a stroke patient in the recovery period, the total number of increases in the intensity of his autofluorescence specific positions is greater than the sum of the total number of positions where the autofluorescence intensity has asymmetry on the left and right sides of the body. The higher the level, the worse the recovery level of the stroke patient.

In one aspect, the present invention provides an application of a molecular marker in the preparation of products for judging the high risk of stroke, the possibility of stroke, and the degree of recovery from stroke, wherein the molecular marker uses The excitation light between 400nm and 750nm excites the intensity of autofluorescence and its left-right asymmetry around the body surface of the subject, and the wavelength range of the autofluorescence is between 420nm and 800nm.

In a specific embodiment, the autofluorescence intensities of left and right nails, palms, fingers, arms, and faces of the acute stroke population and the stroke recovery population are significantly higher than those of the high-risk population. Among them, the autofluorescence of fingers, arms, and face was significantly higher in the acute stroke group than in the stroke recovery group.

In a specific embodiment, the detected body surface parts are 5 places on the skin of the face, the back and ventral sides of the left and right arms, the palms and backs of the left and right palms, the fingers of the left and right hands, and the nails of the left and right hands.

In a specific embodiment, the detected body surface parts are the dorsal and ventral sides of the left and right arms, the palms and backs of the left and right palms, the fingers of the left and right hands, and the fingernails of the left and right hands.

In a specific embodiment, when the fluorescence intensity value of a certain part of the subject's body surface excited by the excitation light is 1.5 times higher than the measured average body surface autofluorescence of the part of the non-stroke tester, the body surface fluorescence of the part is considered high strength.

In a specific embodiment, when there are two or more parts with high fluorescence intensity on the surface of the subject, it is determined that the subject has a high possibility of stroke.

In a specific embodiment, when there are two or more parts with high fluorescence intensity on the subject's body surface, it is determined that the subject has a stroke.

In a specific embodiment, when the fluorescence intensity value of a certain part of the subject's body surface excited by the excitation light is 0.75 times lower than the measured average body surface autofluorescence of the part in the acute stage of cerebral apoplexy, the body surface of the subject is considered to be Low fluorescence intensity.

In a specific embodiment, when there are two or more parts with low fluorescence intensity on the subject's body surface, it is determined that the subject's stroke is highly likely to be in the recovery period.

In a specific embodiment, when there are two or more parts with low fluorescence intensity on the subject's body surface, it is determined that the subject is in the recovery period of stroke.

In a specific embodiment, the asymmetry of autofluorescence and autofluorescence of left and right nails, palms, fingers, arms, and faces of the acute stroke population and the stroke recovery population is significantly higher than that of the high-risk population. Among them, the autofluorescence asymmetry of fingers, arms, and face was significantly higher in the acute stroke group than in the stroke recovery group.

In a specific embodiment, the detected body surface parts are 5 places on the skin of the face, the back and ventral sides of the left and right arms, the palms and backs of the left and right palms, the fingers of the left and right hands, and the nails of the left and right hands.

In a specific embodiment, the detected body surface parts are the dorsal and ventral sides of the left and right arms, the palms and backs of the left and right palms, the fingers of the left and right hands, and the fingernails of the left and right hands.

In a specific embodiment, when the difference between the left and right sides of the fluorescence of a certain part of the subject's body surface excited by the excitation light is 1.5 times higher than the measured average body surface autofluorescence difference of the part of the non-stroke test person, then it is considered that the High asymmetry of surface fluorescence.

In a specific embodiment, when there are two or more parts with high fluorescence asymmetry on the subject's body surface, it is judged that the subject has a high possibility of stroke.

In a specific embodiment, when there are two or more parts with high fluorescence asymmetry on the subject's body surface, it is determined that the subject has a stroke.

In a specific embodiment, when the fluorescence asymmetry difference of a certain part of the subject's body surface excited by the excitation light is lower than 0.75 times of the measured average body surface autofluorescence difference of the part in the acute stage of stroke, then It is considered that the degree of surface fluorescence asymmetry in this area is low.

In a specific embodiment, when there are two or more parts with low fluorescence asymmetry on the subject's body surface, it is determined that the subject's stroke is highly likely to be in the recovery period.

In a specific embodiment, when there are more than or equal to 2 parts with low fluorescence asymmetry on the body surface of the subject, it is determined that the subject is in the recovery period of stroke.

In another aspect, the present invention discloses a method for judging acute stroke and stroke recovery period, which includes the following steps:

(1) Exciting the surface of the patient's body with excitation light between 400nm and 750nm;

(2) Receive autofluorescence between 420nm and 800nm;

(3) Analyze the intensity of autofluorescence to determine whether it is a stroke.

(4) Further analyze the intensity of the specific position of autofluorescence. Judgment of acute stroke and stroke recovery period.

(5) Analyze the left and right symmetry of the intensity of autofluorescence to determine whether it is a stroke.

(6) Further analyze the left-right-side symmetry of the intensity of the specific position of autofluorescence. Judgment of acute stroke and stroke recovery period.

Further, when the fluorescence intensity of the skin in a specific region of the subject's body surface excited by the excitation light is higher than the measured average body surface autofluorescence of non-stroke test subjects, it is determined to be a stroke.

Further, wherein, the specific area for judging stroke by using the fluorescence intensity is preferably the skin on the ventral side of the arm, the palm, and the skin on the back side of the finger. More preferably, the ventral side of the arm

Further, after a stroke is determined, when the fluorescence intensity of the skin in a specific region of the subject's body surface excited by the excitation light is lower than the fluorescence intensity at this position of the acute stroke population in the database, the population in the recovery period of stroke is determined. Otherwise, it is the acute stroke population.

Further, specific areas on the body surface of acute stroke and stroke recovery period are determined, preferably ventral skin of fingers, nails, and dorsal skin of arms.

Furthermore, high-risk groups, acute stroke groups, and stroke recovery groups can be judged by the fluorescence intensity of a specific part of the body surface. High-risk populations, acute stroke populations, and stroke recovery populations can also be determined based on the combination of fluorescence intensities of multiple body surface sites.

Furthermore, the combined analysis of autofluorescence intensity and morphological distribution at multiple positions on the body surface can distinguish high-risk groups, people in the acute stage of stroke, and people in recovery from stroke.

Furthermore, the joint analysis of the left and right asymmetry of autofluorescence at multiple positions on the body surface can distinguish high-risk groups, people in the acute stage of stroke, and people in recovery from stroke.

Further, the autofluorescence intensity and morphological distribution at multiple positions on the body surface, as well as the asymmetry of fluorescence on the left and right sides, were jointly analyzed to distinguish high-risk groups, people in the acute stage of stroke, and people in recovery from stroke.

Description of drawings

Figure 1 is a schematic diagram of real-time non-invasive imaging of skin green autofluorescence using instruments for the symmetrical fingers of the left and right hands of stroke or non-stroke patients.

Fig. 2 is a comparison chart of the number of the inventor's joint self-fluorescent bright spots and the number of asymmetric parts, the number of high fluorescent parts and the number of fluorescent asymmetric parts.

Detailed ways

The present invention will be further illustrated by specific description below.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

As used herein, the terms "autofluorescence", "autofluorescence", "autofluorescence", and "auto-fluorescence" are used interchangeably and refer to tissues, cells, biological substances, after being irradiated with excitation light of appropriate wavelength, The phenomenon of absorbing the energy of the excitation light to enter the excited state, and emitting light with a longer wavelength than the excitation light when exiting the excited state, wherein autofluorescence is light with a longer wavelength than the excitation light.

As described herein, the term "exciting light" refers to light that can excite biomolecules to undergo autofluorescence, and its wavelength should be shorter than that of autofluorescence.

As used herein, the term "acute stroke" refers to within 1 week of stroke occurrence.

As described herein, the term "stroke recovery period" refers to a stroke occurring for more than one week and within one year.

In this paper, body surface fluorescence refers to the whole surface skin tissue of the human body except nails.

Example 1: The excitation light is in the blue light band, and the relationship between the autofluorescence intensity of various parts of the body surface and the acute stage of stroke and the recovery stage of stroke is combined.

According to the present invention, real-time non-invasive imaging of green autofluorescence of the skin is performed on the symmetrical fingers of the left and right hands of the stroke or non-stroke population ( FIG. 1 ).

According to the present invention, real-time non-invasive imaging of skin autofluorescence is performed on the arms, palms, belly of fingers, dorsal side of second knuckles of fingers, and back of hands of high-risk groups, people in the acute stage of stroke and people in the recovery stage of stroke. The experimental results show that, compared with the autofluorescence intensity of each body surface position in the non-stroke population, the autofluorescence intensity of the corresponding position of the stroke patients is significantly increased. We considered the position with high fluorescence as the autofluorescence intensity 1.5 times higher than that of the high-risk group.

We found that when the location of high fluorescence is greater than 2, the possibility of the subject having a stroke is high.

Example 2: The excitation light is in the blue light band, and the relationship between the autofluorescence intensity of various parts of the body surface and the acute stage of stroke and the recovery stage of stroke is combined.

According to the present invention, real-time non-invasive imaging of skin autofluorescence is performed on the arms, palms, finger belly, dorsal side of the second knuckle of the finger, and back of the hand of people in the acute stage of stroke and people in the recovery stage of stroke using an instrument. The experimental results show that compared with the autofluorescence intensity of each body surface position in the acute stroke population, the autofluorescence intensity of the corresponding position in the stroke recovery population is significantly lower. We considered the position with low fluorescence as the autofluorescence intensity lower than 0.75 times of the autofluorescence intensity in the acute stroke population.

We found that when the location of low fluorescence is more than 2, the possibility of the subject is recovering from stroke is high.

Example 3: The blue light band as the excitation light is the relationship between the difference in autofluorescence intensity at the left and right symmetrical positions on the subject's body surface and cerebral apoplexy.

According to the present invention, for patients with stroke or non-stroke, the left and right sides are symmetrically positioned, and the instrument is used to perform real-time non-invasive imaging of skin autofluorescence. The experimental results show that the autofluorescence intensity of the non-stroke population is symmetrical on the left and right sides, but the autofluorescence intensity on the left and right sides of the stroke patients is asymmetrical. The detected body surface parts are the dorsal and ventral sides of the left and right arms, the palms and backs of the left and right palms, the fingers of the left and right hands, and the fingernails of the left and right hands. When the difference between the left and right sides of the fluorescence of a certain part of the subject's body surface excited by the excitation light is 1.5 times higher than the average surface autofluorescence difference of the part of the non-stroke test subjects, it is considered that the surface fluorescence of the part is asymmetric. high. When there are two or more parts with high fluorescence asymmetry on the subject's body surface, it is judged that the subject has a high possibility of stroke.

Example 4: The excitation light is in the blue light band, and the relationship between the left and right asymmetry of autofluorescence in various parts of the body surface and the acute stage of stroke and the recovery stage of stroke.

When the fluorescence asymmetry difference of a certain part of the subject's body surface excited by the excitation light is lower than 0.75 times of the measured average body surface autofluorescence difference of this part of the test subjects in the acute stage of stroke, it is considered that the body surface fluorescence of this part is not good. Low degree of symmetry. When there are two or more parts with low fluorescence asymmetry on the subject's body surface, it is likely that the subject's stroke height is in the recovery period.

Combining the number of autofluorescent bright spots and the number of asymmetric parts, the inventors found that the number of high fluorescent parts and the number of fluorescent asymmetric parts in stroke patients were significantly higher than those in healthy people (Figure 2).

The inventor also used the autofluorescence intensity of a single location on the body surface, or the asymmetry of the autofluorescence of a single location to diagnose stroke, and found that the false positive rate and false negative rate were significantly higher than the joint detection method.

Based on the technology of the present invention, it will be applied (including but not limited to): 1. Screening of stroke period in population physical examination. 2. Used for family self-screening during stroke. 3. It is used for the diagnosis of stroke in hospitals at all levels (including community hospitals and hospitals at other levels). 4. It is used to detect the rehabilitation degree of stroke patients in families and hospitals at all levels.

Those skilled in the art will appreciate that, although specific embodiments of the invention have been described herein for purposes of illustration, various modifications can be made thereto without departing from the spirit and scope of the invention. Therefore, the detailed description and examples of the present invention should not be considered as limiting the scope of the present invention. The invention is limited only by the appended claims. All documents cited in this application are hereby incorporated by reference in their entirety.

Claims (8)

1. The application of comprehensive judgment of stroke based on the left-right asymmetry and intensity increase of autofluorescence at multiple body surface locations is the application of biomarkers in the preparation of products for detecting the occurrence of acute stroke and the onset of stroke in the recovery period , characterized in that if the sum of the total number of increases in the intensity of autofluorescence specific positions of the tester and the total number of positions with asymmetric degrees of autofluorescence intensity on the left and right sides of the body is greater than 2, it can be judged that the subject has a high risk Have had a stroke, or are likely to have had a stroke; Wherein, the body surface part refers to the whole surface of the human body. 2. A method for judging acute stroke and stroke recovery period, comprising the following steps: (1) Exciting multiple human body surfaces of the subject with excitation light between 400nm and 750nm; (2) Receive autofluorescence between 420nm and 800nm; (3) Analyze the intensity of autofluorescence at a specific position; (4) Analyze the degree of asymmetry of the intensity of autofluorescence on the left and right sides of the body; (5) Calculate the total number of increases in the intensity of the autofluorescence specific positions of the test subject and the intensity of these autofluorescence The sum of the total number of positions with a degree of asymmetry on the left and right sides of the body; If the sum of the total number of increases in the intensity of the tester's autofluorescence specific positions and the total number of positions with asymmetric degrees of these autofluorescence intensities on the left and right sides of the body is greater than 2, it can be judged that the testee has a high risk of stroke, Or very likely to have had a stroke. 3. The method as claimed in claim 2, if the sum of the total number of increases in the intensity of the autofluorescence specific positions of the tester and the total number of positions with asymmetry in the left and right sides of the body of these autofluorescence intensities is higher, the tester will suffer from more likely to have a stroke. 4. The method as claimed in claim 2, if the sum of the total number of increases in the intensity of the autofluorescence specific positions of the tester and the total number of positions with asymmetry in the left and right sides of the body of these autofluorescence intensities is higher, the tester has suffered from more likely to have a stroke. 5. The method as claimed in claim 2, if the stroke tester is in the recovery period, the higher the sum of the total number of autofluorescence intensity rises and the total number of positions with asymmetry in the left and right sides of the body, the higher the autofluorescence intensity. , the worse the recovery level of the stroke patient. 6. The method according to claim 2, wherein the human body surface is the whole surface of the human body, preferably the ventral side of the arm, the palm, and the skin on the dorsal side of the finger; more preferably the ventral side of the arm. 7. A method based on judging the acute stroke and the recovery period of the stroke to establish an instrument for detecting the occurrence of acute stroke and the recovery period of the stroke. 8. An application for comprehensively judging cerebral apoplexy based on left-right asymmetry and intensity rise of autofluorescence at multiple body surface positions according to claim 1, which is to detect whether subjects suffer from acute stroke in families and hospitals at all levels. Stroke or stroke recovery period, or screening to detect whether the subject has acute stroke or stroke recovery period during physical examination.