CN109513006A - It is a kind of to treat metabolic syndrome morbidity drug and its measuring method - Google Patents
It is a kind of to treat metabolic syndrome morbidity drug and its measuring method Download PDFInfo
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- CN109513006A CN109513006A CN201811548146.4A CN201811548146A CN109513006A CN 109513006 A CN109513006 A CN 109513006A CN 201811548146 A CN201811548146 A CN 201811548146A CN 109513006 A CN109513006 A CN 109513006A
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- 208000001145 Metabolic Syndrome Diseases 0.000 title claims abstract description 64
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 title claims abstract description 64
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- 230000035790 physiological processes and functions Effects 0.000 description 1
- 235000002378 plant sterols Nutrition 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
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- HCXVJBMSMIARIN-PHZDYDNGSA-N stigmasterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)/C=C/[C@@H](CC)C(C)C)[C@@]1(C)CC2 HCXVJBMSMIARIN-PHZDYDNGSA-N 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/0004—Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
- A61K49/0008—Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Urology & Nephrology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Gastroenterology & Hepatology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Zoology (AREA)
- Vascular Medicine (AREA)
- Biomedical Technology (AREA)
- Pathology (AREA)
- Rheumatology (AREA)
- Toxicology (AREA)
- Emergency Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
The invention belongs to pharmaceutical technology field, disclose it is a kind of treat metabolic syndrome morbidity drug and its measuring method, show phytosterol and blood pressure, BMI, fasting blood-glucose, total cholesterol, triglycerides, LDL cholesterol level and hs-CRP negatively correlated (equal P < 0.01).Phytosterol and waistline and waist-to-hipratio are negatively correlated (P < 0.01), but with smoking, drink, HbA1c non-correlation.In addition, phytosterol and metabolic syndrome are positively correlated (r=0.15, P=0.03).Present invention demonstrates that phytosterol is horizontal and body mass index, waistline, total cholesterol and high-sensitive C-reactive protein are negatively correlated, but with high-density lipoprotein cholesterol, take in phytosterol and be positively correlated;It is proposed that phytosterol plays an important role during metabolic syndrome.
Description
Technical field
The invention belongs to pharmaceutical technology field more particularly to a kind of treat metabolic syndrome morbidity drug and its measurement side
Method.
Background technique
2 times of metabolic syndrome (MetS) and All-cause death risk increase, 2 times of mortality risk increase, and 2 type glycosurias
Sick risk increases by 3 times.MetS is defined as 3 kinds or more in following 5 kinds of metabolic risk factors: abdominal obesity, sweet
Oily three esters increase, and high-density lipoprotein (HDL) cholesterol reduces, and blood pressure increases and/or fasting blood-glucose raising phytosterol is knot
It is similar to cholesterol height on structure.Campesterol and sitosterol are two kinds of the most abundant phytosterols, they are not closed in human body
At.Their plasma concentration is closely related, they are the Substitute Indexes of cholesterol absorption.It has been confirmed that the increased plant of moderate
Sterol intake may also reduce the blood lipid of general population.Epidemiological study about this problem always exists dispute.One
A little researchers have checked blood plasma phytosterol in the participant that Ludwigshafen risk and cardiovascular health (LURIC) are studied
With the relationship of cholesterol metabolic and CAD severity.Some researchers have confirmed that phytosterol can reduce blood lipid.So
And never studied the relationship between MetS and phytosterol.
In conclusion problem of the existing technology is:
Not yet explore the risk of the shortage phytosterol of reflection metabolic syndrome feature completely;Metabolic syndrome is in recent years
It is increasingly taken seriously, has previously ignored the effect of phytosterol in food, so never specific data.
Summary of the invention
In view of the problems of the existing technology, metabolic syndrome morbidity drug and its measurement are treated the present invention provides a kind of
Method.
The invention is realized in this way a kind of treat metabolic syndrome morbidity drug, the treatment metabolic syndrome morbidity
Drug is object sterol.
It is described another object of the present invention is to provide a kind of measuring method for the treatment of metabolic syndrome morbidity drug
Treat metabolic syndrome morbidity drug measuring method the following steps are included:
Step 1, progress Chi-square Test or t examine the feature with comparative studies sample in MetS state aspect;Use MetS
Replicate analysis;
Step 2 calculates Pearson correlation coefficients to assess the pass between intake phytosterol and clinic and laboratory measurement
Connection;The odd number ratio OR of the existing adjustment of metabolic syndrome, and the result analyzed are calculated using multiple logic regression analysis
Indicate that there is 95% confidence interval CI with OR;
Step 3, statistical analysis is considered significant using SPSS19.0 editions progress value < 0.05 P.
Further, the standard of the measuring method diagnosis metabolic syndrome of the treatment metabolic syndrome morbidity drug: (1) abdomen
Portion is fat, waistline: male > 90cm, women > 85cm or BMI > 30Kg/m2;(2) Serum Triglyceride increase > 1.7mmol/L or
150mg/dl;(3) LDL-C increases: male < 0.9mmol/L, < 35mg/dl, women < 1.0mmol/L, < 1.0mg/d1;(4) blood
Press raising > 140/90mmHg or treatment anti-hypertension;(5) fasting blood glucose level is high;Or glucose tolerance reduces or insulin supports
Anti- or diabetes;(6) ratio of urinary albumin and kreatinin: > 30mg/g or albumin excretion rate 20g/min.
Further, the T2DM or IFG of the measuring method of the treatment metabolic syndrome morbidity drug are determined by following all
Justice determines: (1) fasting blood glucose level < 100mg/dl;(2) oral hypoglycemic agents or insulin therapy;(3) diabetic history is reported.
Advantages of the present invention and good effect are as follows: present invention demonstrates that phytosterol and blood pressure, BMI, fasting blood-glucose, total gallbladder are solid
Alcohol, triglycerides, LDL cholesterol level and hs-CRP negatively correlated (equal P < 0.01).Phytosterol is in waistline and waist-to-hipratio
Negatively correlated (P < 0.01), but with smoking, drink, HbA1c non-correlation.In addition, phytosterol is positively correlated with metabolic syndrome
(r=0.15, P=0.03).Diabetic's (HbAlc > 6.5% or the patient for receiving diabetes drug treatment) (n=36)
Phytosterol value is lower than nothing and suffers from patient's diabetes (n=64) (259 ± 31vs.367 ± 13, P=0.0268).In addition, plant steroid
Alcohol level and body mass index, waistline, total cholesterol and high-sensitive C-reactive protein are negatively correlated, but and high-density lipoprotein cholesterol,
Intake phytosterol is positively correlated;It is proposed that phytosterol plays an important role during metabolic syndrome.
Detailed description of the invention
Fig. 1 is the measuring method flow chart that the present invention implements the treatment metabolic syndrome morbidity drug provided.
Fig. 2 is that the present invention implements provide BMI (-): BMI < 24kg/m2, BMI (+): BM >=24kg/m2;HP (-): < 140/
90mmHg, HP (+): >=140/90mmHg;DM (-): aglycosuria medical history, fasting blood-glucose < 6.1mmol/L now.DM (+) before this:
Previously there is diabetic history (A);Antidiabetic drug or insulin .TG (-):<150mg/dl is used now, TG (+):>=150mg/
dl;TC (-):<200mg/dl, TC (+):>=200mg/dl;LDL-C (-):<100mg/dl, LDL-C (+):>=100mg/dl,
HDL-C (-): < 40mg/dl;HDL-C (+): >=40mg/dl;Hs-CRP (-):<0.3mg/dl, Hs-CRP (+):>=0.3mg/dl
(B) schematic diagram.
Specific embodiment
In order to make the objectives, technical solutions, and advantages of the present invention clearer, with reference to embodiments, to the present invention
It is further elaborated.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, it is not used to
Limit the present invention.
Application principle of the invention is further described with reference to the accompanying drawing.
Treatment metabolic syndrome morbidity drug provided in an embodiment of the present invention is object sterol.
As shown in Figure 1, the measuring method for the treatment of metabolic syndrome morbidity drug provided in an embodiment of the present invention includes following
Step:
S101: carrying out Chi-square Test or t is examined with comparative studies sample in terms of MetS state (be not present or exist)
Feature;Then MetS replicate analysis is used;
S102: Pearson correlation coefficients are calculated to assess the pass between intake phytosterol and clinic and laboratory measurement
Connection;The odd number ratio (OR) of the existing adjustment of metabolic syndrome, and the knot analyzed are calculated using multiple logic regression analysis
Fruit indicates have 95% confidence interval (CI) with OR;
S103: statistical analysis is considered using SPSS19.0 editions (SPSS, Chicago, IL, USA) progress value < 0.05 .P
It is significant.
The present invention provides the standard of diagnosis metabolic syndrome: (1) abdominal obesity (waistline: male > 90cm, women > 85cm)
Or BMI > 30Kg/m2;(2) Serum Triglyceride increase > 1.7mmol/L or 150mg/dl;(3) LDL-C increases: male <
0.9mmol/L (< 35mg/dl), women < 1.0mmol/L (< 1.0mg/d1);(4) blood pressure increases (> 140/90mmHg) or treats
Anti-hypertension;(5) fasting blood glucose level is high;Or glucose tolerance reduces or insulin resistance or diabetes;(6) urinary albumin with
The ratio of kreatinin: > 30mg/g or albumin excretion rate 20g/min;
T2DM or IFG is determined by following all definition: (1) fasting blood glucose level < 100mg/dl;(2) oral hypoglycemic agents
Or insulin therapy;(3) diabetic history is reported.
Application effect of the invention is explained in detail below with reference to test.
1, method
Metabolic syndrome used to be diagnosed by the World Health Organization (WHO), because existing in following six kinds of ingredients
Two or more are based on T2DM (diabetes B) or the standard of IFG (glucose tolerance reduction): (1) abdominal obesity (waistline: male
Property > 90cm, women > 85cm) or BMI > 30Kg/m2;(2) Serum Triglyceride increase > 1.7mmol/L or 150mg/dl;(3)
LDL-C increases: male < 0.9mmol/L (< 35mg/dl), women < 1.0mmol/L (< 1.0mg/d1);(4) blood pressure increase (>
140/90mmHg) or treatment anti-hypertension;(5) fasting blood glucose level is high;Or glucose tolerance reduces or insulin resistance or sugar
Urine disease;(6) ratio of urinary albumin and kreatinin: > 30mg/g or albumin excretion rate 20g/min.T2DM or IFG is by following institute
Some definition determine: (1) fasting blood glucose level < 100mg/dl;(2) oral hypoglycemic agents or insulin therapy;(3) diabetes are reported
History.Dietary Investigation is carried out using 24 hour diets of the retrospective approach to all metabolic syndrome patients, so as to even
Continue three days acquisition dietary intakes.Then the mean intake of sterol in daily ration was calculated according to Chinese food component list in 2002.
2, it statisticallys analyze
Unless otherwise stated, all data are indicated with ratio, SD or ratio are indicated.Firstly, carrying out Chi-square Test
Or t examines the feature with comparative studies sample in terms of MetS state (be not present or exist).Then the present invention uses MetS weight
Complex analysis, because dichotomy is edvariable, (quantity is MetS standard and each ingredient of MetS to a continuous variable
(waistline, triglycerides, HDL cholesterol levels, blood pressure and blood glucose etc.).Pearson correlation coefficients are calculated to assess intake plant steroid
Being associated between alcohol and clinic and laboratory measurement.The existing tune of metabolic syndrome is calculated using multiple logic regression analysis
Whole odd number ratio (OR), and the result analyzed is indicated with OR, is had 95% confidence interval (CI).All tests are all two-sided
's.All statistical analysis are considered significant using SPSS19.0 editions (SPSS, Chicago, IL, USA) progress value < 0.05 .P
's.
3, result
The baseline characteristic of 3.1 all subjects and correlation analysis with phytosterol
As shown in table 1, the average BMI of subject, blood glucose level, blood pressure and blood lipid level are slightly above standard value, reflect
The characteristic feature of metabolic syndrome patient.It is analyzed by phytosterol data, according to BMI, hypertension, diabetes, total cholesterol
(TC) it is grouped with triacylglycerol (TG) exponent pair metabolic syndrome.The present invention observes that phytosterol has accumulated all fingers
Mark, such as BMI, TC, the blood pressure (table 1) of TG and metabolic syndrome.
The baseline clinical and biochemical characteristics of table 1- subject and correlation analysis with phytosterol
Phytosterol and blood pressure, BMI, fasting blood-glucose, total cholesterol, triglycerides, LDL cholesterol level and hs-CRP are in
Negatively correlated (equal P < 0.01).Phytosterol and waistline and waist-to-hipratio are negatively correlated (P < 0.01), but with smoking, drink, HbA1c without
Correlation.In addition, phytosterol and serum phytosterol are positively correlated (r=0.15, P=0.03).(table 1)
3.2 take in the comparison of study subject according to the phytosterol of MS
Overweight (BMI24 >=kg/m2) (n=57) subject intake phytosterol level be higher than non-BMI (BMI <
24kg/m2) (n=43) (have .374 ± 18mg, P in the subject of 423 ± 23vs hypertension (>=140/90mmHg) (n=61)
=0.0025).Diabetic (glycosylated hemoglobin >=6.5% or receiving treating diabetes) (n=36), phytosterol are horizontal
Lower than non-diabetic patients (n=64) (259 ± 31vs.367 ± 13mg, P=0.0268) and horizontal the height (>=150mg/ of TG
Dl subject)) (n=73), it is higher than TG normal level (< 150mg/dl) (n=27) (401 ± 20vs.381 ± 22mg, P=
0.0047).In the subject of LDL cholesterol horizontal high (LDL-C) (>=100mg/dl) (n=53), phytosterol add value
Lower than the people (n=47) (345 ± 18vs.396 ± 30mg, P=0.0034) of LDL-C horizontal normal (< 100mg/dL), TC is horizontal
The subject of high (>=200mg/dl) is lower than subject (392 ± 22vs.405 ± 37) mg, P=0.0317 of normal level).Separately
On the one hand, the phytosterol value of the subject of HDL cholesterol levels low (HDL-C) (< 40mg/dL) (n=26) is higher than HDL-C water
Straight and even normal person (>=40mg/d) dl) (n=74) (411 ± 33vs.395 ± 19mg, P=0.0422).In addition, the present invention selects height
Index of the sensitivity c reactive protein (hs-CRP) as assessment MS.The subject's of high hs-CRP (>=0.3mg/dl) (n=60)
Phytosterol value is lower than subject (336) ± 22vs.383 ± 27mg, P=of low hs-CRP (< 0.3mg/dl) (n=40)
0.0039).(table 2, Fig. 2)
Table 2: according to the feature and phytosterol of the study subject of MS
The analysis of 3.3 multivariate logistic regressions, the presence of Negative selection metabolic syndrome
Whether the present invention has studied phytosterol independent related to the presence of metabolic syndrome.Including age, blood pressure, glycosuria
Disease, BMI, WC, FBG, TG, TC, LDL-C, HDL-C, hs-CRP and phytosterol level are as independent variable.BMI (or every 1-SD
(95%CI), 1.95 (1.14-2.40);P < 0.01), waistline environment (the every 1-SD of OR (95%CI), 1.45 (1.09-2.12);P<
0.01), TG (or every 1-SD (95%CI), 2.97 (1.73-3.33);P < 0.01) and hs-CRP (OR=1-SD (95%CI),
3.45(1.84-4.03);P < 0.01) it is independent related to the increase of metabolic syndrome risk.The presence of HDL-C and metabolic syndrome is in
Negative correlation (the every 1-SD of OR (95%CI), 0.46 (0.27-0.80);P<0.01).Finally, phytosterol and metabolic syndrome are deposited
In negatively correlated, blood pressure unrelated with the age, diabetes, BMI, WC, HbA1c, FBG, TG, TC, LDL-C, HDL-C and hs-CRP
It is independent variable.(OR1-SD (95%CI), 0.37 (0.22-0.64);P < 0.01) (table 3).
The analysis of 3. multivariate logistic regression of table, the presence of Negative selection metabolic syndrome
Including age, blood pressure, diabetes, BMI, WC, FBG, TG, TC, LDL-C, HDL-C, hs-CRP and phytosterol water
It is flat to be used as independent variable.
3.4 result
Phytosterol only enters sterol in the mammalian body by diet comprising one group.Vegetable oil, in nut and avocado
There are relatively great amount of phytosterols.Research of the invention also demonstrates, BMI is the high BMI of metabolic syndrome patient, hypertension,
High TG, hs-CRP, like food oil, and nut and investigation result of the invention also indicate that their phytosterol intake is higher.
Phytosterol has many important physiological functions.Effect in censored human health and disease.Meanwhile
Many experiments show that, rich in phytosterol and its saturated derivatives in diet, such as stanols can inhibit the absorption of cholesterol, make
Blood plasma LDL concentration reduces 10-14%.
Some researchers have confirmed that the structure and cholesterol of phytosterol are closely similar.The area of they and cholesterol
It is not only that C24 additional methyl groups (campesterol) or ethyl (sitosterol), or in C22 other double bond (difference
For brassicasterol, stigmasterol).But this small architectural difference leads to the metabolism of phytosterol and cholesterol in mammal
Destiny is very different.Cholesterol and phytosterol all pass through Niemann-PickC1-Like1NPC1L1) transport protein glued by intestines
Theca cell internalization.Cholesterol is transported to endoplasmic reticulum, it passes through acyl-CoA there: cholesterol O-acyl transferase 2
(Acat2) effect is sterilized, for mixing chylomicron.
In recent years, the research of phytosterol and its derivative causes of the invention since it reduces the effect of cholesterol
Note that also interested in the potential association between circulation phytosterol and CVD risk.Phytosterol can undergo oxidation and be formed
Xyphytolsols, this is proved to be the potential medium of CVD risk, because it shows about 1.4% in phytosterol patients serum
Circulation sitosterol with its oxidised form presence.However, phytosterol is poor Acat2 substrate, therefore pass through heterodimer
ATP combination box (Abc) half transport protein g5 and g8 are transported back chamber film to be secreted into enteric cavity again.Abcg5 and Abcg8 are present in
The teleblem of enterocyte, is also expressed in liver.Discovery phytosterol may participate in anti-oxidant, cancer recently, and maintain just
Normal nervous function and other effects.But the combination of few paper concern phytosterols and metabolic syndrome.
According to known to the present invention, this report shows the correlation of phytosterol with metabolic syndrome for the first time.As it appears from the above, plant
Sterol levels and blood pressure, BMI, fasting blood-glucose, total cholesterol, triglycerides, LDL cholesterol level and hs-CRP are negatively correlated
(equal P < 0.01).Phytosterol and waistline be negatively correlated and waist-to-hipratio (P < 0.01), but with the age, smoking drinks, HbA1c without
Correlation.In addition, phytosterol and serum High Density Lipoprotein Cholesterol are positively correlated (r=0.15, P=0.03).
In result of study of the invention, this report shows that phytosterol has accumulated all indexs, such as BMI, TC, TG for the first time
With the blood pressure of metabolic syndrome.It has also been found that the consumption figure of high sugar patient is lower than the normal consumption of metabolic syndrome patient,
This may be related with strict control of diet, reduces food, especially oily, preferred treatment method of the nut as diabetes.This hair
Bright experiment is also clear that confirmation high-density lipoprotein cholesterol and phytosterol are positively correlated with intake phytosterol.Other grind
Study carefully confirmation, the intake of phytosterol can reduce low density lipoprotein cholesterol (LDL-C) concentration.Phytosterol and metabolic syndrome
There are negatively correlated, blood pressure unrelated with the age, diabetes, BMI, WC, HbA1c, FBG, TG, TC, LDL-C, HDL-C and hs-
CRP is included as independent variable.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all in essence of the invention
Made any modifications, equivalent replacements, and improvements etc., should all be included in the protection scope of the present invention within mind and principle.
Claims (4)
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