1.Preliminary evaluation of the effect of comprehensive health management on the prevention and treatment of ischemic stroke
Shuai ZHU ; Genming ZHAO ; Yiying ZHANG ; Dongni LIANG ; Hongjie YU ; Qian PENG ; Fang XIANG ; Na WANG
Journal of Public Health and Preventive Medicine 2026;37(2):89-93
Objective To evaluate the short-term effects of comprehensive health management interventions for stroke high-risk population screening on the prevention and treatment of ischemic stroke, and to provide reference and basis for improving and exploring health management and prevention strategies for stroke high-risk population. Methods From 2018 to 2022, 13 community health service centers in Jiading District, Shanghai were selected in the present study. Based on information push platform, stroke risk assessment and health intervention follow-up were conducted for community residents through convenience sampling. The residents were divided into a full course intervention group (intervention group) and a routine intervention group (control group) according to different health intervention measures and forms. The incidence of ischemic stroke in the two groups of survey subjects was tracked within 36 months. Results A total of 52144 subjects were included in the study. The total number of patients in the full course intervention group was 14227, with an incidence density of 577.32/100 000 (556.49/100 000-598.12/100 000), which was lower than that of the conventional intervention group (37 917), with an incidence density of 1 485.47/100 000 (1 464.99/100 000-1 505.94/100 000) (χ2=2490.212, P<0.001). The relative risk of the full course intervention group was 0.39, and the relative risk of stroke risk factors in the full course intervention group from low to high was 0.33, 0.43, 0.45, and 0.49, respectively. The incidence density of males in the full course intervention group was 660.76 (627.46/100 000 - 694.05/100 000), with a relative risk of 0.43, and the incidence density of female patients was 509.71/100 000 (483.37/100 000 - 536.05/100 000), with a relative risk of 0.35. The overall incidence density of the population under 62 years old gourp, 62-75 years old group and over 75 years old group was 197.45/100 000 (173.09/100 000 -221.80/100 000), 608.36/100 000 (580.19/100 000-636.54/100 000), and 1 025.06/100 000 (958.51/100 000-1 091.61/100 000), with relative risks of 0.51, 0.44, and 0.38, respectively. Conclusion Comprehensive health management measures can effectively reduce the short-term risk of ischemic stroke, and should be further promoted and improved to enhance the effectiveness of stroke prevention and control.
2.Effect of Tongxinluo Capsules on TCM Syndrome Elements in Patients with Chronic Coronary Syndrome of Qi Deficiency and Blood Stasis Type: A Multicenter and Prospective Cohort Study
Jia WANG ; Xilun TAN ; Xuesen WANG ; Xiaohe YANG ; Meili GAO ; Yiying LIU ; Chenhao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):170-177
ObjectiveTo investigate the effects of Tongxinluo capsules on traditional Chinese medicine (TCM) syndrome elements and major adverse cardiovascular events (MACEs) in patients with chronic coronary syndrome of Qi deficiency and blood stasis type. MethodsA multicenter and prospective cohort study was conducted. The intervention of Tongxinluo Capsules was used as the exposure factor, and the patients were divided into an exposure group (integrated traditional Chinese and western medicine treatment group) and a non-exposure group (western medicine treatment group). The patients were followed up for one year. The TCM syndrome element scores were assessed by using a syndrome element diagnosis scale on the day of enrollment and in the third, sixth, and twelfth months, and the incidence of MACE within one year was recorded. ResultsA total of 186 patients were included, with 128 patients in the exposure group and 58 patients in the non-exposure group. There was no significant difference in baseline data between the two groups. Compared with those in the pretreatment period for each group, the Qi deficiency and blood stasis syndrome scores in the treatment and follow-up period were significantly improved (P<0.05). Compared with the non-exposure group, the exposure group exhibited significantly decreased Qi deficiency syndrome scores in the treatment and follow-up period (P<0.01) and significantly reduced blood stasis syndrome scores in the sixth month (P<0.05). In the remaining follow-up period, there was no statistically significant difference between the two groups. Compared with that of the non-exposure group, during the treatment period (the third month), the difference in Qi deficiency and blood stasis syndrome scores of the exposure group was statistically significant (P<0.05, P<0.01). At the end of the follow-up period, patients in the non-exposure group had a MACE probability of 6.90% (4/58), higher than 3.13% in the exposure group (4/58). Compared with patients with angina pectoris who used conventional medicine, patients administered with Tongxinluo Capsules had a relative risk(RR) of 0.45 [95%confidence interval(95%CI) 0.12-1.75, P=0.26]. There was no significant difference in the incidence of MACE within one year between the two groups. ConclusionTongxinluo capsules can improve the degree of Qi deficiency in patients with chronic coronary syndrome in the short term, and the improvement effect of blood stasis syndrome appears in the medium and long term. They can better improve the Qi deficiency syndrome in the long term. Within one year, the incidence of MACE in the exposure group was lower than that in the non-exposure group.
3.Effect of Tongxinluo Capsules on TCM Syndrome Elements in Patients with Chronic Coronary Syndrome of Qi Deficiency and Blood Stasis Type: A Multicenter and Prospective Cohort Study
Jia WANG ; Xilun TAN ; Xuesen WANG ; Xiaohe YANG ; Meili GAO ; Yiying LIU ; Chenhao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):170-177
ObjectiveTo investigate the effects of Tongxinluo capsules on traditional Chinese medicine (TCM) syndrome elements and major adverse cardiovascular events (MACEs) in patients with chronic coronary syndrome of Qi deficiency and blood stasis type. MethodsA multicenter and prospective cohort study was conducted. The intervention of Tongxinluo Capsules was used as the exposure factor, and the patients were divided into an exposure group (integrated traditional Chinese and western medicine treatment group) and a non-exposure group (western medicine treatment group). The patients were followed up for one year. The TCM syndrome element scores were assessed by using a syndrome element diagnosis scale on the day of enrollment and in the third, sixth, and twelfth months, and the incidence of MACE within one year was recorded. ResultsA total of 186 patients were included, with 128 patients in the exposure group and 58 patients in the non-exposure group. There was no significant difference in baseline data between the two groups. Compared with those in the pretreatment period for each group, the Qi deficiency and blood stasis syndrome scores in the treatment and follow-up period were significantly improved (P<0.05). Compared with the non-exposure group, the exposure group exhibited significantly decreased Qi deficiency syndrome scores in the treatment and follow-up period (P<0.01) and significantly reduced blood stasis syndrome scores in the sixth month (P<0.05). In the remaining follow-up period, there was no statistically significant difference between the two groups. Compared with that of the non-exposure group, during the treatment period (the third month), the difference in Qi deficiency and blood stasis syndrome scores of the exposure group was statistically significant (P<0.05, P<0.01). At the end of the follow-up period, patients in the non-exposure group had a MACE probability of 6.90% (4/58), higher than 3.13% in the exposure group (4/58). Compared with patients with angina pectoris who used conventional medicine, patients administered with Tongxinluo Capsules had a relative risk(RR) of 0.45 [95%confidence interval(95%CI) 0.12-1.75, P=0.26]. There was no significant difference in the incidence of MACE within one year between the two groups. ConclusionTongxinluo capsules can improve the degree of Qi deficiency in patients with chronic coronary syndrome in the short term, and the improvement effect of blood stasis syndrome appears in the medium and long term. They can better improve the Qi deficiency syndrome in the long term. Within one year, the incidence of MACE in the exposure group was lower than that in the non-exposure group.
4.Guide on Methodological Standards in Pharmacoepidemiology in China(2nd edition)and their series interpretation(5):classic study designs and derivative approaches
Yiying ZHANG ; Shiwenqian YIN ; Shuhan MENG ; Shanjie WANG ; Siyan ZHAN ; Feng SUN
Chinese Journal of Pharmacoepidemiology 2025;34(5):485-493
Pharmacoepidemiology is an interdisciplinary field that applies epidemiological methods to study drug use,effectiveness,and associated risk in populations.Standardizing research methods in this field is crucial for ensuring research quality and promote the development of the discipline.Based on the Guide on Methodological Standards in Pharmacoepidemiology in China(2nd edition),this article interprets the relevant contents about classic research types and their derivative designs.It aims to clarify the types of study methodological designs in pharmacoepidemiology,systematically describe the characteristics and applications classical derivative designs,and compare these with research design frameworks outlined in international pharmacoepidemiological guidelines.Compared to the first edition,the second edition of the guideline has updated and detailed the types of research,updating the research design to original research(interventional research and non-interventional research),secondary research(systematic review,Meta-analysis,economic analysis,etc.),and tertiary research(umbrella review,etc.).Additionally,a variety of derivative designs have been added,including target trial emulation,nested case-control and case-cohort studies,case-crossover designs,self-controlled case series and self-controlled risk interval designs,case-population studies,interrupted time-series analysis,and case-coverage(ecological)designs for vaccine surveillance.This article strengthens the operability of the theoretical guidance of pharmacoepidemiological research methods in practice and provides a reference for conducting high-quality pharmacoepidemiological research.
5.Incidence and influencing factors of frailty in elderly patients with hematologic malignancies: a meta-analysis
Jinying ZHAO ; Zhongfan KAN ; Longting MA ; Qianqian ZHANG ; Yating LIU ; Rui MA ; Chunyan PING ; Yiying ZHANG ; Yayun CAO ; Qian YANG ; Qingyan GAO ; Xin WANG ; Wenjun XIE
Chinese Journal of Modern Nursing 2025;31(30):4144-4151
Objective:To systematically analyze the incidence and influencing factors of frailty in elderly patients with hematologic malignancies.Methods:Research on frailty in elderly patients with hematologic malignancies was retrieved from Chinese and English databases such as China National Knowledge Infrastructure, Wanfang Data, PubMed, and Web of Science. The search period was from database establishment to August 23, 2024. Two researchers screened the included studies, conducted quality assessment, and extracted data. Meta-analysis was conducted using Stata 18 and RevMan 5.4.Results:A total of seven studies were included, encompassing 19 076 elderly hematologic malignancy patients, with a frailty incidence of 59% [95% CI (0.48, 0.69) ]. Meta-analysis revealed that age [ MD=4.31, 95% CI (3.67, 4.96) ], gender [ OR=0.88, 95% CI (0.83, 0.93) ], alcohol consumption [ OR=1.67, 95% CI (1.15, 2.44) ], self-care ability [ MD=-1.79, 95% CI (-3.17, -0.41) ], anemia [ OR=6.67, 95% CI (2.94, 15.14) ], infection [ OR=1.81, 95% CI (1.16, 2.84) ], and neuropathy [ OR=2.52, 95% CI (1.38, 4.61) ] were the influencing factors of frailty in elderly patients with hematologic malignancies. Conclusions:The incidence of frailty is high in elderly patients with hematologic malignancies. Elderly patients with hematologic malignancies who are older, female, consume alcohol, have low self-care ability, anemia, infections, and neuropathy are prone to frailty. Healthcare providers can conduct early screening and intervention for high-risk populations of frailty based on risk factors to improve the quality of life for elderly hematologic malignancy patients.
6.Association between aldehydes and hyperuricemia based on Bayesian kernel machine regression
Shuang BING ; Ru HUANG ; Yiying ZHANG
Chinese Journal of Pharmacoepidemiology 2025;34(8):855-866
Objective To analyze the complex relationships between individual or combined exposures to six aldehydes and hyperuricemia(HUA)and serum uric acid(SUA)levels in adults by Bayesian kernel machine regression(BKMR),and to explore the factors associated with aldehyde exposure leading to HUA.Methods Participants aged 20 years and older with available aldehyde data were selected from the National Health and Nutrition Examination Survey(NHANES)2013-2014.The study employed BKMR to explore the complex associations between individual or combined exposure to multiple aldehydes and both HUA and SUA.Multivariable Logistic regression analysis was performed to evaluate the association between aldehydes and HUA,while multiple linear regression models were used to examine the linear relationship between aldehydes and SUA.Stratified analysis was conducted to explore the association between aldehydes and HUA across populations with different characteristics.Results A total of 1,952 participants were included in the analysis,of whom 346(17.73%)were diagnosed with HUA.Butyraldehyde[OR=1.59,95%CI(1.23,2.07)],heptaldehyde[OR=1.58,95%CI(1.18,2.13)],and hexaldehyde[OR=1.68,95%CI(1.15,2.45)]were significantly associated with HUA.For each one-unit increase in the concentration of butyraldehyde,heptaldehyde,or hexaldehyde,the risk of developing HUA increased by approximately 59%,58%,and 68%,respectively.The results from the BKMR model indicated that the combined effect of aldehyde exposure was positively associated with both HUA and SUA.Among the individual aldehydes,hexaldehyde showed the highest posterior inclusion probability(PIP=0.324),suggesting the greatest contribution to the observed association.Six aldehydes were also significantly positively correlated with reduced glomerular filtration rate(GFR)and elevated levels of triglycerides(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C).Conclusion Individual or combined exposure to aldehydes was positively associated with HUA.This association may be attributed to factors such as reduced GFR,as well as elevated levels of TG and LDL-C.
7.A preliminary study on the development and application of the risk assessment scale for early venous thromboembolism in patients under emergency observation
Lyuzhao LIAO ; Zhufeng ZHANG ; Maokuan TIAN ; Xiangxiang CHEN ; Ruomeng LI ; Yiying XIAO ; Ronglin JIANG
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2025;32(2):191-195
Objective To develop and validate an early venous thromboembolism(VTE)risk assessment scale for emergency observation patients.Methods ① Based on the characteristics of emergency observation patients,the Delphi expert consultation method and literature review were used to determine scale items and construct a scoring system.②The newly developed VTE scale and its scoring system were analyzed for reliability and validity.③Primary application:collect non acute traumatic observation and rescue patients admitted to Zhejiang Hospital from June 2022 to June 2023 as the research subjects.Patients were divided into survival and non-survival groups based on 28-day outcomes.Differences in VTE scores between the two groups using the new scale,Caprini,and Padua models were compared.The optimal cut-off point was determined using the receiver operator characteristic curve(ROC curve),according to the optimal cut-off value of the new scale score,patients were divided into two groups,and Kaplan-Meier survival curves were used to analyze the 28-day cumulative survival of the two groups of patients.Results ①The preliminary version of the early VTE risk assessment scale for emergency observation patients was developed,comprising 8 items:age,pre examination triage level,underlying diseases,D-dimer levels,activities of daily living(ADL)assessment,coagulation-related indicators,anticoagulants and(or)antiplatelet drugs use,and unhealthy habits.② A total of 121 emergency observation patients were included in the analysis.The test-retest reliability correlation coefficient(R)of the new scale was 0.945(>0.850),split-half reliability was 0.741(>0.700),and Cronbach'sαcoefficient was>0.700.KMO value was 0.715(>0.700),and Bartlett's sphericity test yieldedχ2=167.079,P<0.001,confirming the suitability of the scale for factor analysis.Three factors were identified:basic information,initial assessment,and blood test indicators.Pearson correlation analysis showed the correlation coefficients between the new scale and the Caprini and Padua scores were 0.842 and 0.307,respectively,both P<0.01.③Area under the curve(AUC)of the new scale was 0.566,95%confidence interval(95%CI)was 0.444-0.688,with an optimal diagnostic cut-off value of 13.5 points based on the maximum Youden index.The results of the Kaplan-Meier regression indicated that survival analysis using the 13.5-point cut-off revealed that patients with scores≥13.5 had significantly lower 28-day survival rates than those with scores<13.5(Log-Rank test:χ2=5.609,P=0.018).④The survival group had significantly lower scores than the non-survival group across all scales(new score:10.06±2.84 vs.12.69±3.06,Caprini model:7.22±2.48 vs.9.41±2.64,Padua model:2.91±1.97 vs.4.59±1.07,all P<0.05).Conclusion The early VTE risk assessment scale for emergency observation patients was successfully developed,demonstrating good reliability and validity through statistical analysis.The new scale effectively predicts disease severity and prognosis in emergency observation patients.
8.Comparison of IBUCy and FABC conditioning regimens followed by allogeneic hema-topoietic stem cell transplantation in medium-to-high risk acute myelocytic leukemia:an analysis of efficacy and safety
Zhang LINYI ; Wang LI ; Liu LIN ; Xiong YIYING
Chinese Journal of Clinical Oncology 2025;52(12):610-616
Objective:To evaluate the efficacy and safety of IBUCy(idarubicin,busulfan,and cyclophosphamide)and FABC(fludarabine,cyta-rabine,busulfan,and cyclophosphamide)conditioning regimens followed by allogeneic hematopoietic stem cell transplantation(allo-HSCT)for the treatment of medium-to-high risk acute myelocytic leukemia(AML).Methods:We retrospectively analyzed data of 49 patients with medium-to-high risk AML who received IBUCy(n=17)or FABC(n=32)conditioning regimens followed by allo-HSCT between January 2015 and December 2021 at The First Affiliated Hospital of Chongqing Medical University.Hematopoietic reconstruction time,adverse events,and survival outcomes were compared between the two groups to assess the efficacy and safety of the two regimens.Additionally,we analyzed factors that may be associated with prognosis.Results:Hematopoietic reconstruction was successful in all 49 patients.No significant differ-ences were observed between the two groups in terms of hematopoietic reconstruction time.Similarly,no significant differences were ob-served in the 5-year progression-free survival(PFS)and overall survival(OS)rates between the two groups.The incidence rates of oral mu-cositis,nausea and vomiting,diarrhea(≥grade 3 based on CTCAE v5.0),and chronic graft-versus-host disease(GVHD)were significantly high-er in the IBUCy group than that in the FABC group.However,the incidence rate of hemorrhagic cystitis in the FABC group was significantly higher than that in the IBUCy group.The time from diagnosis to allo-HSCT>6 months and being minimal residual disease(MRD)-positive be-fore transplantation were identified as the risk factors for PFS(P=0.019 and P=0.048,respectively).Patients who were MRD-negative before transplantation had significantly longer PFS when treated with the IBUCy conditioning regimen(P=0.039).Conclusions:Both IBUCy and FABC conditioning regimens prior to allo-HSCT are safe and effective for treating medium-to-high risk AML.Allo-HSCT should be performed as soon as possible when patients achieve their first complete remission.Patients with an MRD-negative status before transplantation tend to have longer PFS.Compared with the FABC regimen,the IBUCy regimen has some advantages;however,attention should be given to the prevention and management of gastrointestinal adverse events and chronic GVHD.
9.Impact of initial screening strategies on compliance with colonoscopy for colorectal carcinoma in residents aged 50 years and above
Fang XIANG ; Zhihao HU ; Yawei WANG ; Yiying ZHANG ; Fang HUANG ; Qian PENG ; Hongjie YU ; Chaowei FU
Shanghai Journal of Preventive Medicine 2025;37(2):140-144
ObjectiveTo compare colonoscopy compliance rates under different screening strategies, to explore ways to enhance colonoscopy compliance among residents with colorectal carcinoma. MethodsResidents aged between 50‒80 years were recruited through extensive community outreach and voluntary participation. A total of 210 630 residents who participated in the colorectal carcinoma screening program in Jiading District, Shanghai, between 2013 and 2019 were selected as the research subjects. All subjects underwent a colorectal carcinoma risk assessment questionnaire survey and two fecal occult blood tests (FOBT). Positive results in the initial screening were defined as a positive questionnaire survey or a positive result in at least one FOBT. Participants with positive initial screening results were advised to undergo colonoscopy screening in a hospital. Colonoscopy results were collected from hospital reports and physician follow-ups. Compliance with colonoscopy was analyzed under different screening strategies to identify possible factors influencing residents’ willingness to undergo the procedure. ResultsA total of 21 403 individuals (10.16%) were identified as positive with the questionnaire survey, 31 595 individuals (15.00%) tested positive with at least one FOBT. Combined questionnaire and FOBT positivity was observed in 3 501 individuals (1.66%). Among the 48 453 individuals with positive initial screening results, 17 230 (35.56%) underwent colonoscopy, and a total of 315 cases of colorectal cancer were detected. The sensitivity, specificity value of FOBT initial screening were 83.81% and 84.66%, respectively. According to the combined risk assessment and FOBT initial screening preliminary screening, the lowest colonoscopy compliance rate (25.63%) was observed among individuals with only a positive questionnaire, and the highest compliance rate (52.55%) was among those with both positive questionnaire survey and two positive FOBT results. Multivariate analysis revealed that FOBT positivity had the greatest impact on colonoscopy compliance. Those with one positive FOBT test result were 2.64 times more likely to undergo colonoscopy screening than those with negative FOBT results, while individuals with two positive FOBT results were 3.18 times more likely to do so. After adjusting for FOBT results, individuals with positive questionnaire survey results were 1.43 times more likely to undergo colonoscopy screening than those with negative results (95%CI: 1.34‒1.52). Compared to questionnaire-based risk assessment, FOBT results were more influential in determining compliance with colonoscopy. ConclusionThe choice of initial screening method significantly impacts residents’ compliance with colonoscopy. While implementing colorectal carcinoma screening programs, it is necessary to strictly adhere to screening protocols, including risk assessment and FOBT. Additionally, efforts should be made to raise public awareness, encouraging residents to actively participate in risk assessments and FOBT, thereby improving their compliance with colonoscopy.
10.A prospective randomized clinical study of folic acid in the intervention of radiation esophagitis induced by concurrent chemoradiotherapy in lung cancer
Hao ZHANG ; Yiying ZHU ; Weiwei OUYANG ; Shengfa SU ; Zhu MA ; Qingsong LI ; Yichao GENG ; Wengang YANG ; Xiaxia CHEN ; Bing LU
Chinese Journal of Radiation Oncology 2025;34(1):65-72
Objective:To investigate the efficacy of oral folic acid intervention in lung cancer patients with radiation esophagitis (RE) caused by concurrent chemoradiotherapy.Methods:In this randomized, controlled, single-center clinical trial, a total of 82 patients with stage N 2-N 3 lung cancer including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to October 2023 were prospectively included. All enrolled patients were randomly divided into the experimental group (folic acid group) and control group according to 1 vs. 1 of simple random method, and patients in both groups were required to receive radiation therapy for lung lesions and mediastinal metastatic lymph nodes [≥2 cycles of chemotherapy were completed during the same period of radiotherapy (≥40 Gy / 20 F) or targeted drugs were given simultaneously]. The severity of RE was evaluated using the modified common terminology criteria for adverse events criteria of the National Cancer Institute in both groups weekly at the onset of radiation esophagitis symptoms and thereafter until 1 week after the end of radiotherapy. Conventional treatment of RE was delivered according to the grading criteria of the Radiation Therapy Oncology Group. Patients in the folic acid group were given with folic acid tablets 30 mg/d orally at the beginning of radiotherapy until the end of radiotherapy, while those in the control group did not receive any drug intervention. The onset time, severity and duration of RE, and changes in the severity of esophageal toxicity after conventional treatment were recorded and analyzed. Serum folate value, serum vitamin B 12 value and homocysteine value were measured before and after radiotherapy. For continuous quantitative variables, independent sample t-test or independent sample rank-sum test was used for comparison among different groups. For categorical data, Chi-square test or Fisher's exact probability method was used for comparison among different groups. Results:During the observation period, no grade 4 or above RE was reported between two groups. The incidence of grade 0, 1, 2 and 3 RE in the folic acid and control groups was 10% (4/40) and 5% (2/41), 70% (28/40) and 42% (17/41), 15% (6/40) and 51% (21/41), 5% (2/40) and 2% (1/41), respectively. The differences were not statistically significant between two groups ( P=0.456). However, the incidence of grade 0-1 RE in the folic acid group was significantly higher than that in the control group ( Z=2.72, P=0.006). The median time of RE in the folic acid group and control group was 12 d (range 7-52 d) and 15 d (range 11-56 d) after the start of radiotherapy, respectively, with no statistically significant difference ( χ2=-0.75, P=0.456). However, median duration of the individual's most severe RE was 12 d (range 4-36 d) and 21 d (range 7-38 d) in the folic acid group and control groups, respectively, and the differences were statistically significant ( χ2=2.10, P=0.039). In the folic acid group, the grades of swallowing with pain and dysphagia were significantly declined after folic acid intervention, especially at 2 weeks after the occurrence of RE ( P=0.001, P=0.002). The remission rate of RE after 1 week in the folic acid group was higher than that in the control group, and the difference was statistically significant ( χ2=7.36, P=0.012). Conclusion:Oral intake of folic acid during concurrent chemoradiotherapy for lung cancer cannot reduce the incidence of RE, but it may reduce its severity, shorten the duration of the most severe RE in individuals, and have a certain protective effect.


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