1.Traditional Chinese Medicine Regulates JAK/STAT Signaling Pathway to Treat Colorectal Cancer: A Review
Mingxing WANG ; Wanhui DONG ; Baorui ZHANG ; Tong LAI ; Aixin LIU ; Qingming SUN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):278-287
Colorectal cancer (CRC) ranks as the second leading cause of cancer death worldwide. Although preventive colonoscopy screening has improved the survival rate of CRC patients in the past few years, there are still many patients diagnosed after symptoms appear. The surgery for CRC carries high risks and high recurrence, and ideal therapies remain to be developed. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway has become a focus of research due to its central role in cellular activities. As a classic oncogenic pathway, the JAK/STAT signaling pathway offers new possibilities for diagnosing and treating various malignancies, and it paves a new way for developing therapies for CRC. This pathway not only participates in basic cellular processes, such as proliferation, differentiation, and apoptosis but also plays a crucial role in immune responses and inflammation. Abnormal activation of the JAK/STAT signaling pathway is closely related to the occurrence and development of CRC. Studies have shown that the active components and compound prescriptions of traditional Chinese medicine (TCM) can inhibit the proliferation, invasion, migration, and angiogenesis while promoting the apoptosis and autophagy of CRC cells by interfering with the JAK/STAT signaling pathway. Furthermore, this pathway may also play a role in regulating the sensitivity of tumor cells to chemotherapy and radiotherapy, thus influencing the effectiveness of tumor treatment and impeding the progression of CRC. In recent years, research results have been updated rapidly, and previous literature summaries have failed to incorporate the latest findings, creating obstacles to accessing current literature. Therefore, this article supplements and summarizes information from the definition of the JAK/STAT pathway, association of this pathway with CRC, and TCM intervention of CRC. This review aims to provide references for future development of molecular biology regarding CRC and the research and development of new drugs.
2.Expression of enolase and laminin in the vagina of bacterial vaginosis of mice
Rui Zhang ; Yiqing Wu ; Haixu Yin ; Chang Li ; Aixin Ma ; Junzhu Wang ; Huihui Bai ; Zhaohui Liu ; Qinping Liao
Acta Universitatis Medicinalis Anhui 2024;59(11):1939-1943
Objective:
To investigate the differences in enolase and laminin levels in vaginal epithelial tissues between mice successfully infected withGardnerellaand mice not infected with Gardnerella, providing information for further exploration of the correlation between enolase and laminin levels and the incidence of bacterial vaginosis.
Methods:
Gardnerella strains isolated, purified, and identified from vaginal secretions of patients with bacterial vaginosis were used to infect the vagina of mice and establish a mouse model of bacterial vaginosis. Successful and failed mice was defined as successful and failed groups, respectively. Differential expression of enolase and laminin in the vaginal epithelial tissue of two groups of mice was detected by Western blot. Modeling success rate was statistically analyzed, and the expression differences of enolase and laminin was compared between two groups.
Results:
One strain of Gardnerella vaginalis infected 10 SPF grade KM mice, 7 mice met the diagnostic criteria for bacterial vaginosis, and 3 mice failed to model, with a success rate of 70%. Western blot was used to detect protein expression levels, and the levels of laminin and enolase in the successfully modeled mouse vaginal epithelial tissue were significantly higher than those in the failed modeling group, with statistical differences between the two groups(P<0.05).
Conclusion
Enolase and laminin may be involved in the occurrence of bacterial vaginosis, however, further research is needed to determine the mechanisms through which they trigger the occurrence and development of the disease.
3.Status quo and influencing factors of drug resistance of tuberculosis in Inner Mongolia
Jinqi HAO ; Lan ZHANG ; Yanqin YU ; Mingyuan HAO ; Aixin WANG ; Fumin FENG
Acta Universitatis Medicinalis Anhui 2024;59(3):515-520
Objective To investigate the status quo of drug resistance and influencing factors of tuberculosis in In-ner Mongolia,and to provide reference for accurate prevention and control of drug-resistant tuberculosis.Methods Random sampling was used in this study.TB patients from Tuberculosis designated hospital in Inner Mongolia were included,according to the rules and drug-resistant strains were identified and tested according to relevant norms.Composition ratio or rate was calculated for statistical description,and Logistic regression model was used to analyze the influencing factors of drug resistance in TB patients.Results Among 1 321 patients,there were 936 males and 385 females,with an average age of(52.65±18.09)years.The rates of mono-resistant,multidrug-resistant(MDR),extensively drug-resistant(XDR)and total drug resistance were 19.00%,11.58%,11.66%and 42.24%,respectively.The highest resistance rates were observed for streptomycin(7.27%),isoniazid(4.69%),and isoniazid+streptomycin(4.47%).The drug resistance spectrum presented diversity and com-plexity.Compared to females,males had a higher proportion of drug resistance,and the difference was statistically significant(P<0.001).The proportion of patients who were sensitive to anti-tuberculosis drugs increased with age(P<0.05).Among different age groups,the proportion of drug-resistant patients was higher in the 20-40 age group,40-60 age group,and 60 and above age group compared to the 0-20 age group(P<0.05).Addi-tionally,the proportion of drug-resistant patients was higher in the 20-40 age group and 40-60 age group com-pared to the 60 and above age group(P<0.05).Moreover,the proportion of drug-resistant and multi-drug re-sistant patients was higher among patients undergoing retreatment compared to those undergoing initial treatment(P<0.001).Multivariate Logistic regression analysis showed that male gender(OR=1.48,95%CI:1.02-2.14),age 20-40 years(OR=2.64,95%CI:1.05-6.60),retreatment(OR=2.34,95%CI:1.70-3.22),and outpatient follow-up(OR=1.56,95%CI:1.05-2.33)were independent risk factors for drug-resistant tuber-culosis.Conclusion Inner Mongolia has a high prevalence of MDR and overall drug-resistant tuberculosis among patients.The drug resistance profile exhibits diversity and complexity.Risk factors that contribute to drug resist-ance include being male,aged between 20 and 40,undergoing retreatment,and receiving outpatient follow-up.Therefore,it is necessary to further improve clinical diagnosis and treatment,promote rational use of first-line anti-tuberculosis drugs,prioritize individualized treatment,enhance health education,improve the medical insurance system,and optimize patient management approaches in order to enhance patient compliance.
4.Factors influencing malnutrition in tuberculosis patients based on analysis of nutritional status in different populations
Jinqi HAO ; Pengfei GAO ; Yanqin YU ; Lan ZHANG ; Jiafu QI ; Mingyuan HAO ; Aixin WANG ; Fumin FENG
Acta Universitatis Medicinalis Anhui 2024;59(5):903-908,913
Objective To investigate the nutritional status and dietary structure of tuberculosis patients among dif-ferent populations, analyze the factors influencing the nutritional status of tuberculosis patients, and provide theo-retical basis for improving clinical nutrition and related issues in tuberculosis patients.Methods Tuberculosis pa-tients, non-tuberculosis patients, and healthy individuals were randomly selected for a questionnaire survey.De-scriptive analysis was conducted using SPSS 20.0 software.Statistical description was performed using rates and composition ratios, and qualitative data were described using relative numbers.Chi-square test was used to compare overall rates and composition ratios among different health conditions groups, with a significance level of α=0.05.Independent factors analysis of nutritional status body mass index (BMI) was conducted using multiple Logistic re-gression analysis for variables with statistically significant differences in the univariate analysis.Results There were differences in the nutritional status (x2 =62.184, P<0.05) and dietary diversity score (x2 =64.049, P<0.05) among tuberculosis patients, non-tuberculosis patients, and healthy individuals.Univariate analysis of nutri-tional status BMI showed statistically significant differences in gender, smoking, meat-based diet, vegetable-based diet, moderate diet diversity score, and 6 other variables for tuberculosis patients (P <0.05) , and in gender, age, ethnicity, marital status, occupation, education level, smoking, drinking white wine, drinking beer, meat-based diet, moderate diet, and 11 other variables for healthy individuals (P<0.05) .The variables with statisti-cally significant differences in the univariate analysis were included in the multiple ordinal logistic regression analy-sis model for both tuberculosis patients and healthy individuals.The results showed that the level of education, veg-etable intake, moderate food diversity score (DDS) of 4-6 were independent influencing factors of nutritional sta-tus BMI among tuberculosis patients (P<0.05);marital status was an independent influencing factor of nutritional status BMI among non-tuberculosis patients (P<0.05);while gender and occupation were independent influencing factors of nutritional status BMI among healthy individuals (P<0.05).Conclusion The dietary nutritional status of the three population groups varied.Targeted health education should be conducted, especially for tuberculosis patients, to address the issue of uneven dietary intake and promote good dietary habits among local tuberculosis pa-tients.
5.Effect and mechanism of safflower yellow on wound healing of diabetic foot ulcers in mice
Jie ZHANG ; Zixin LIU ; Bingxue JIA ; Aixin ZHANG ; Zhuo ZHANG
Journal of Xinxiang Medical College 2024;41(5):412-418
Objective To investigate the effect and molecular mechanism of safflower yellow(SY)on wound healing of diabetic foot ulcer(DFU)in mice.Methods Forty-five C57BL/6 mice were injected intraperitoneally with streptozotocin to establish diabetic models.The diabetic mice were randomly divided into the sham operation group,model group,low-dose SY intervention group,high-dose SY intervention group,and high-dose SY combined with insulin-like growth factor-1(IGF-1)group,with 9 mice in each group.Before modelling,mice in the model group were not given any intervention,mice in the low-dose SY intervention group and high-dose SY intervention group were injected intraperitoneally with 5 and 20 mg·kg-1 SY,respectively,and mice in the high-dose SY combined with IGF-1 group were injected intraperitoneally with 20 mg·kg-1 SY and 0.03 mg·kg-1 IGF-1.Except for the sham operation group,the DFU model was established by incising the dorsal skin of the foot in the remaining four groups of mice.No wound on the dorsal skin of the foot was made in the sham operation group,and the remaining surgical steps were the same as those in the model group.The body mass of mice in each group was measured on day 14 after modelling using an electronic scale,tail vein blood was collected for fasting blood glucose measurement,and the wound width was measured using a small vernier caliper.Then,the mice were executed to collect the wound tissues.Hematoxylin-eosin staining was used to detect the histopathological changes in the wound tissues of mice in each group.Reverse transcription-quantitative real-time polymerase chain reaction was used to measure the relative expression levels of platelet-derived growth factor(PDGF),vascular endothelial growth factor(VEGF),alpha-smooth muscle actin(α-SMA),type Ⅰ collagen(collagen Ⅰ),protein tyrosine phosphatase 1B(PTP1B)and advanced glycation end products(AGEs)mRNA in the wound tissues of mice in each group.Western blot was used to detect the relative expression levels of proliferation marker Ki-67,proliferating cell nuclear antigen(PCNA),apoptosis-associated proteins(caspase-3,caspase-6,and caspase-7),p85 phosphatidylinositol-3-kinase(PI3K)and phosphorylated protein kinase B(p-AKT)protein in the wound tissues of mice in each group.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,and IL-6 in the wound tissues of mice in each group.Results The differences in blood glucose and body mass of mice among the sham operation group,model group,low-dose SY intervention group,high-dose SY intervention group,and high-dose SY combined with IGF-1 group were not statistically significant(P>0.05).The healing rate of wound tissues in the high-dose SY intervention group was significantly greater than that in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P<0.01).There was no statistically significant difference in the healing rate of wound tissues among the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P>0.05).In the high-dose SY intervention group,a large number of collagen fibers were densely and orderly arranged in the wound tissues,accompanied by a large number of neovessels;in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group,the wound tissues were sparsely populated with collagen fibers,accompanied by a small number of neovessels.The relative expression levels of PDGF,VEGF,α-SMA and collagen Ⅰ mRNA in the wound tissues of mice in the high-dose SY intervention group were significantly higher than those in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P<0.01);the relative expression levels of PTP1B and AGEs mRNA in the wound tissues of mice in the high-dose SY intervention group were significantly lower than those in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P<0.01).The relative expression levels of PDGF,VEGF,α-SMA,collagen Ⅰ,PTP1B and AGEs mRNA showed no statistically significant difference among the model,low-dose SY intervention,and high-dose SY combined with IGF-1 groups(P>0.05).The relative expression levels of Ki-67 and PCNA protein in the wound tissues of mice in the high-dose SY intervention group were significantly higher than those in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P<0.01);the relative expre-ssion levels of caspase-3,caspase-6,caspase-7,p85 PI3K,and p-AKT protein were significantly lower than those in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P<0.01).There was no statistically significant difference in the relative expression levels of Ki-67,PCNA,caspase-3,caspase-6,caspase-7,p85 PI3K and p-AKT protein among the model,low-dose SY intervention,and high-dose SY combined with IGF-1 groups(P>0.05).The levels of TNF-α,IL-1β and IL-6 in the wound tissues of mice in the high-dose SY intervention group were significantly lower than those in the model,low-dose SY intervention,and high-dose SY combined with IGF-1 groups(P<0.01).There was no statistically significant difference in the levels of TNF-α,IL-1β and IL-6 in the wound tissues of mice in the model,low-dose SY intervention and high-dose SY combined with IGF-1 groups(P>0.05).Conclusion High-dose SY intervention promotes DFU wound healing in mice by increasing angiogenesis,collagen formation and cell proliferation and reducing insulin resistance,inflammatory response and cell apoptosis,which may be related to the inhibition of the PI3K/AKT pathway.
6.Analysis of risk factors for metabolic syndrome complicated by retinopathy
Zuxu YUAN ; Suhua LI ; Yan ZHANG ; Aixin LIU ; Guangxiu HE
Journal of Xinxiang Medical College 2024;41(9):880-883
Objective To explore the risk factors for retinopathy in patients with metabolic syndrome.Methods A total of 120 patients with metabolic syndrome admitted to Nanyang Central Hospital from July 2021 to July 2023 were selected as the research subjects,and the patients were categorized into the retinopathy group(n=58)and the non-retinopathy group(n=62)according to the results of fundus examination.The clinical data of patients with metabolic syndrome in both groups were collected and compared.10 mL of blood was collected from the elbow vein of patients in both groups,and the hemoglobin level was measured using a fully automatic blood cell analyzer.The levels of total cholesterol(TC),triacylglycerol(TG),high density lipoprotein-cholesterol(HDL-C),and low density lipoprotein-cholesterol(LDL-C)in the two groups were measured using an automatic biochemical analyzer.The glycosylated hemoglobin(HbA1c)level was determined by high-performance liquid chromatography.The estimated glomerular filtration rate(eGFR)was calculated using the chronic kidney disease epidemiology collaboration equation.Multivariate logistic regression analysis was used to determine the risk factors for retinopathy in patients with metabolic syndrome.Results There were no statistically significant differences in smoking history,drinking history,usage rates of hypoglycemic drugs,lipid-lowering drugs and antihypertensive drugs,systolic blood pressure,cataract,TC,TG,HDL-C,LDL-C,and eGFR between the two groups(P>0.05).The age,disease duration,insulin usage rate,diastolic blood pressure,HbA1c level,and anemia incidence of patients in the retinopathy group were significantly higher than those in the non-retinopathy group(P<0.05).Multivariate logistic regression analysis showed that older age,longer disease duration,insulin injection,higher diastolic blood pressure,higher HbA1c level,and lower hemoglobin level were independent risk factors for retinopathy in patients with metabolic syndrome(P<0.05).Conclusion Old age,long disease duration,insulin injection,high systolic blood pressure,high HbA1c level,and low hemoglobin level are independent risk factors for retinopathy in patients with metabolic syndrome.
7.Risk factors and risk prediction model of retinal detachment in myopic pa-tients
Zuxu YUAN ; Suhua LI ; Yan ZHANG ; Aixin LIU ; Guangxiu HE
Recent Advances in Ophthalmology 2024;44(7):554-557
Objective To investigate the risk factors and risk prediction model of retinal detachment in patients with myopia.Methods The clinical data of myopic patients treated in our hospital from January 2021 to December 2023 were retrospectively analyzed.A total of 128 patients(128 eyes)with myopic retinal detachment who met the requirements were selected as the retinal detachment group,and 128 myopic patients(128 eyes)without retinal detachment were selected as the control group.The clinical data of patients in the two groups were collected and compared,including age,gender,di-opter,education level,affected side,whether to bear load or not,whether to vibrate or not,whether to have cataract or not,whether to have asthenopia or not,blood pressure,history of diabetes,history of ocular trauma,history of ophthal-mic surgery,and retinal thickness.Risk factors related to retinal detachment in myopia were determined through the multi-variate logistic regression analysis,and based on these factors,the risk prediction model was established.The receiver op-erating characteristic(ROC)curve was used to evaluate the predictive value of the model.Results The age,diopter,systolic blood pressure,cataract incidence,asthenopia incidence,ocular trauma and ophthalmic surgery rates of myopic patients in the retinal detachment group were significantly higher than those in the control group(all P<0.05).The retinal thickness and choroidal thickness of myopic patients in the retinal detachment group were significantly smaller than those in the control group(both P<0.05).The risk factors for retinal detachment in myopic patients were older age,higher diopter(absolute value),accompanied by ocular diseases or discomfort such as cataract,asthenopia and ocular trauma,thinner choroid,and thinner retina(all OR>1,P<0.05).The areas under the ROC curve(0.95CI)for predication of retinal de-tachment based on age,ocular disease or discomfort,diopter,choroidal thickness,and retinal thickness alone and their combination were 0.668(0.382-0.936),0.645,0.676(0.407-0.942),0.731(0.503-0.933),0.745(0.499-0.983),and 0.844(0.692-0.983),respectively.The area under the curve(0.844),sensitivity,specificity,and accuracy of the prediction model based on the combination of the five indicators were higher,indicating that this model had a better predic-tion effect.Conclusion The risk factors for retinal detachment in myopic patients are older age,higher diopter(abso-lute value),accompanied by ocular diseases or discomfort such as cataract,asthenopia and ocular trauma,thinner cho-roid,and thinner retina.The risk prediction model constructed based on these factors has a high evaluation effect.
8.Satisfaction analysis of elderly outpatient experience of public hospitals in China
Caixia SUN ; Jingyou ZHANG ; Junli GUO ; Aixin SHEN ; Meng SUN ; Shijing CHU
Chinese Journal of Hospital Administration 2024;40(6):426-430
Objective:To analyze the satisfaction of elderly outpatient experience, based on a satisfaction questionnaire survey of outpatients in public hospitals, for references to improve the medical experience of elderly patients.Methods:This study extracted the satisfaction survey questionnaires for outpatients in second level and above public hospitals nationwide from the National Health Commission′s satisfaction survey platform from 2019 to 2022. The questionnaire content included six dimensions: registration experience, doctor-patient communication, nurse-patient communication, environment and labeling, privacy protection, and medical staff response, as well as overall satisfaction. The satisfaction, relative satisfaction, and dissatisfaction rates of elderly outpatients were analyzed using standardized assignment of question options, etc; T-test was used for inter group comparison.Results:A total of 10.095 7 million outpatient satisfaction questionnaires were included in this study, including 0.576 3 million questionnaires for elderly outpatients. From 2019 to 2022, the overall satisfaction of outpatients had been increasing year by year, and the overall satisfaction scores of elderly patients were significantly higher than that of non-elderly patients( P<0.01). The satisfaction scores of elderly patients in the nurse communication dimension(86.55 to 91.03 points) and relative satisfaction(1.000) were the higher in each year, while the satisfaction scores in the environment and identification dimension(81.05 to 86.03 points) and relative satisfaction(0.935 to 0.955) were lower. In 2019 and 2022, elderly patients had higher dissatisfaction rates in the two dimensions of registration experience(2.26%, 1.91%) and doctor communication(0.80%, 0.53%). Conclusions:From 2019 to 2022, the overall satisfaction of elderly patients in secondary and above public hospitals in China was relatively higher with a steady increasing tendency. However, there was still room for further improvement in the environment and labeling, cultural construction, and registration experience for elderly patients.
9.Screening of Lactobacillus that inhibit Gardnerella vaginalis and preliminary study on its bacteriostatic mechanism
Rui Zhang ; Aixin Ma ; Junzhu Wang ; Chang Li ; Haixu Yin ; Huihui Bai ; Zhaohui Liu
Acta Universitatis Medicinalis Anhui 2023;58(11):1962-1965
Objective :
To select and obtain vaginal Lactobacillus strains with inhibitory effect on Gardnerella vagi⁃
nalis , and to explore the possible mechanism of inhibition of Gardnerella vaginalis by Lactobacillus vaginalis strains , so as to provide a prerequisite for the development of dominant strains for human disease treatment.
Methods :
Gardnerella vaginalis and vaginal Lactobacillus strains were isolated from vaginal secretions of patients with bacterial vaginosis (BV) and healthy women , respectively. The Lactobacillus strains with the ability to inhibit the proliferation of Gardnerella vaginalis were screened by spot on lawn. Double agar diffusion method was used to compare the inhibitory effects of Lactobacillus solutions , cell⁃free culture supernatants (CFCs) and bacteria on Gardnerella vaginalis.
Results :
Sixty⁃two strains of vaginal Lactobacillus strains were isolated and purified from vaginal vaginal secretions of 10 patients with bacterial vaginosis. Among the 62 strains of vaginal Lactobacillus , 18 strains could inhibit the proliferation of Gardnerella vaginalis. The vaginal Lactobacillus solutions , the CFCs , and bacteria all had inhibitory effect on Gardnerella vaginalis. The inhibitory effects of vaginal Lactobacillus solutions were higher than those of the CFCs. After the CFCs were treated with proteinase K , the inhibitory effect of eight samples disappeared , and that of 10 samples weakened obviously.
Conclusion
In this paper, 62 vaginal Lactobacillus strains are purified and identified , of which 18 strains can inhibit the proliferation of Gardnerella vaginalis. The production of antimicrobial protein may be involved in the mechanism that vaginal Lactobacillus inhibits the proliferation of Gardnerella vaginalis.
10.An open-label evaluation of safety and tolerability of coformulated bictegravir/emtricitabine/tenofovir alafenamide for post-exposure prophylaxis following potential exposure to human immunodeficiency virus-1
An LIU ; Ruolei XIN ; Hongwei ZHANG ; Lili DAI ; (Esther) Ruojun WU ; Xi WANG ; Aixin LI ; Wei HUA ; Jianwei LI ; Ying SHAO ; Yue GAO ; Zhangli WANG ; Jiangzhu YE ; A bu dou re xi ti Gulimila ; Zaicun LI ; Lijun SUN
Chinese Medical Journal 2022;135(22):2725-2729
Background::Single-tablet regimen (STR) provides a convenient once-daily regimen for the prevention of human immunodeficiency virus (HIV) infection. Here, we investigated the safety and tolerability of coformulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a three-drug, STR for post-exposure prophylaxis (PEP) in Chinese individuals.Methods::This was a prospective, open-label, single-arm trial conducted in a sexually transmitted diseases and acquired immunodeficiency syndrome clinic of a tertiary hospital in Beijing, China. Adults requiring PEP were prescribed BIC/FTC/TAF one pill once a day for 28 days. Clinical and laboratory data were collected and analyzed at baseline, weeks 2, 4, 8, 12, and 24.Results::Of 112 participants enrolled in the study, 109 (97.3%) were male and the mean age was 30 ± 8 years. PEP completion was 96.4% (95% confidence interval: 91.1-99.0%). Two participants stopped PEP after 2 days because the source partner was identified as HIV uninfected. One participant was excluded due to hepatitis B virus infection according to the exclusion criteria. One discontinued due to the participant’s decision. No participant acquired HIV through week 24. Adherence was 98.9% (standard deviation [SD]: 3.3%) by self-reporting and 98.5% (SD: 3.5%) by pill count. Only five participants experienced mild clinical adverse events attributed to the study drug (including headache, diarrhea, and nausea) and four participants had elevated serum creatinine (grade 1).Conclusions::A once daily, STR of BIC/FTC/TAF used as PEP was safe and well-tolerated with a high rate of completion and adherence in Chinese. BIC/FTC/TAF may be a good option for PEP.Trial Registration::ChiCTR.org.cn, ChiCTR2100048080


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