Objective To explore the value of endothelial dysfunction assessment in predicating major adverse cardiac and cerebrovascular events (MACCE) in peritoneal dialysis (PD) patients.Methods A prospective cohort study included 136 end stage renal disease (ESRD) patients from Jan 1,2009 to Dec 31,2011 was conducted.Endothelial function was assessed by flowmediated dilation (FMD) of brachial artery.Kaplan-Meier method was used to estimate survival rate.The survival difference between the two groups was compared by the log-rank test.Multivariate Cox proportional hazards regression was used to determine the independent risk factors of MACCE.Results In the follow-up period,18 patients in low FMD (FMD≤2.7％) group occurred MACCE,and 13 patients in high FMD (FMD ＞ 2.7％) group occurred MACCE.Compared with high FMD group,MACCE-free survival rate in the low FMD group had a significantly decreased (x2=4.190,P=0.041).Multivariate Cox proportional hazards regression analysis showed that higher level of total cholesterol,lower FMD,longer PD time and higher levels of hs-CRP were all independent predictors of MACCE.Conclusion Reduced brachial artery FMD is an independent risk factor of MACCE,and the application of FMD contributes to the risk stratification of cardiac and cerebrovascular disease in PD patients.

Objective To investigate the effects of Yitangkang on browning of white adipose and PINK1/Parkin pathway of mitophagy in adipose tissue of db/db mice.Methods Totally 30 six-week db/db mice were randomly divided into model group,Yitangkang Group(30 g/kg)and liraglutide group(200 μg/kg),and another 10 C57BL/6 mice of the same age were set as normal group.All groups were treated with corresponding drugs or normal saline for 5 weeks.During the period of administration,the body mass and fasting blood glucose(FBG)of mice in each group were detected regularly,the samples of liver,white and brown adipose of mice were weighed,the contents of serum triglyceride cholesterol(TC),triacylglycerol(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were detected by biochemical analyzer,HE staining was used to observe the pathological changes of inguinal white adipose tissue(iWAT),immunohistochemical staining was used to detect the expression of browning marker protein uncoupling protein-1(UCP1)in iWAT,Western blot was used to detect the expressions of browning-related proteins UCP1,PRDM16,PGC-1α and mitophagy-related proteins PINK1,Parkin,Beclin-1,p62 in iWAT.Results Compared with the normal group,the body mass,liver,white adipose and brown adipose mass of the model group significantly increased(P<0.01),the FBG and serum TG,TC and LDL-C contents significantly increased(P<0.01),and the content of HDL-C significantly decreased(P<0.01);large vacuoles in iWAT adipocytes,the diameter of adipocytes increased obviously,some adipocytes were extruded and deformed,and the edge of adipocytes was not clear,the expressions of iWAT UCP1,PRDM16,PGC-1α and p62 proteins decreased(P<0.01),while the expressions of PINK1,Parkin and Beclin-1 proteins increased(P<0.01).Compared with the model group,the body mass,liver and white adipose mass significantly decreased in Yitangkang group and the liraglutide group(P<0.01),FBG and serum contents of TC,TG and LDL-C were significantly decreased(P<0.05,P<0.01),while HDL-C content significantly increased(P<0.01);the diameter of iWAT adipocytes decreased,the number increased,and the morphology was regular,the expressions of iWAT UCP1,PRDM16,PGC-1α and p62 proteins increased(P<0.01),while the expressions of PINK1,Parkin and Beclin-1 proteins decreased(P<0.05,P<0.01).Conclusion Yitangkang can improve glucose and lipid metabolism and promote browning of white adipose in db/db mice,which may be related to mitophagy mediated by PINK1/Parkin pathway.

Objective To optimize the synthesis of photosensitizer chlorine e6‐C15 monomethyl ester (1) .Methods Tar‐get compound 1 was synthesized through E ring cracking of pheophorbide a (3) in methanol solution of potassium hydroxide followed by adding H2 O for ester hydrolysis with“one‐pot” process .Four main factors that influencing the synthetic yield of target compound 1 are ring cleavage reaction time (A) ,reflux hydrolysis reaction time (B) ,alkali concentration (C) and weight ratio of material 3 to alkali (D) .Each of the four factors was chosen at three levels and evaluated by the orthogonal ex‐perimentaldesignofL9(34).Results Theoptimizationtermsofthesynthesisoftargetcompound1wereB1C2A2D1 .Theyield of compound 1 was raised from 43 .0% to 56 .5% .Conclusion The developed process has the advantages of simple operation , good safety and high reaction yield ,and is suitable for industrial production .

The dysfunction of qi, blood, and fluid underlies the pathology of diabetes mellitus. The symptoms, signs, and physical and chemical indexes of diabetes mellitus patients reflect the duration, degree, primary and secondary pathological state of the abnormal metabolism of qi, blood, and fluid. It is necessary to construct a three-dimensional syndrome differentiation system of diabetes mellitus based on spatial and temporal dimensions. According to the four stages of depression, heat, deficiency, and damage, the location of the disease can be locked into qi, ying, and blood levels. The process reflects the pathological trend of the abnormal metabolism of qi, blood, and fluid: qi depression (prodromal stage: asymptomatic metabolic disorder/early stage of qi level) → qi heat (initial stage: index stage/late stage of qi level) → deficiency of both qi and yin (middle stage: symptom stage of three more and one less/stage of ying level) → damage of zang-fu viscera and meridians (late stage: complication stage/stage of blood level). According to the time process, the treatment principles are proposed as follows: during the early stage of qi level, treatment should focus on strengthening the spleen to regulate qi flow, to prevent the accumulation of glucose; during the late stage of qi level, treatment should focus on clearing heat and resolving turbidity, to remove the stagnated heat caused by glucose; during the stage of ying level, treatment should focus on benefiting qi and nourishing yin, to improve the symptoms about deficiency of both qi and yin; during the stage of blood level, treatment should focus on promoting blood circulation and removing blood stasis, to remove the complication. According to the etiology and pathogenesis of diabetes mellitus, the sequential treatment strategy is thus proposed, which is strengthening the spleen to regulate qi flow, clearing heat and resolving turbidity, benefiting qi and nourishing yin, and promoting blood circulation and removing blood stasis. The compound prescriptions such as Houpo Sanwu Decoction, Baihu Jia Renshen Decoction, Danggui Liuhuang Decoction, and Taohong Siwu Decoction are used with modification in the stage-based treatment.

Objective To make a system evaluation regarding the effect and safety of the"Nourishing Kidney and Activating Blood"method in the treatment of diabetic cognitive impairment.Methods According to the requirements of evidence-based medicine,the domestic and foreign databases were searched comprehensively,and the time limit was from the establishment of databases to June 2022,so as to find out the clinical randomized controlled trials of"Nourishing Kidney and Activating Blood"method in treating diabetic cognitive impairment.Revman5.3 was used for meta-analysis and risk bias evaluation,TSA0.9 for sequential analysis,Stata15.0 for publication bias evaluation,and GRADE3.6 for evidence quality evaluation.Results Eventually,14 RCTs were included with a sample size of 1126 cases.Meta-analysis showed that compared with conventional western medicine treatment,the"Nourishing Kidney and Activating Blood"method could significantly improve the effective rate of treating cognitive dysfunction in diabetes[OR=5.06,95%CI(3.38,7.57),P<0.00001],and significantly improve the total MoCA score of patients[MD=2.11,95%CI(1.76,2.47),P<0.00001],MMSE score[MD=1.86,95%CI(1.13,2.59),P<0.00001],MQ score[MD=13.40,95%CI(11.23,15.57),P<0.00001]and HDS score[MD=-3.36,95%CI(2.61,4.11),P<0.00001].Meanwhile,the"Nourishing Kidney and Activating Blood"method could reduce the level of glycosylated hemoglobin in DCI patients[MD=-0.84,95%CI(-1.37,-0.32),P=0.002].However,since the drugs used in the control group have no hypoglycemic effect,this conclusion needs to be further verified.In addition,the ability of the"Nourishing Kidney and Activating Blood"method to improve CDR score[MD=-0.01,95%CI(-0.08,0.07),P=0.84],ADL score[MD=2.10,95%CI(-1.62,5.82),P=0.27],TCM syndrome score[MD=-4.46,95%CI(-10.94,2.02),P=0.18]and reduce adverse reactions[OR=0.36,95%CI(0.08,1.60),P=0.18]was equivalent to that of conventional western medicine.Begg's test and Egger's test suggested that there might be some publication bias in the research.Metaninf command chart and sequential analysis of experiments indicated that the stability of research results was relatively good.The quality evaluation of evidence showed that the evidence of effective rate,glycosylated hemoglobin,MoCA scale score,MMSE score and MQ score was medium quality,the evidence of fasting blood glucose,CDR score and HDS score was low quality,and the evidence of ADL score,TCM syndrome score and adverse reactions was extremely low quality.Conclusion The existing literature evidence showed that the"Nourishing Kidney and Activating Blood"method had a good clinical effect in treating diabetic cognitive impairment,and it could reduce the blood glucose level and improve the cognitive function of patients,with certain safety.However,the above conclusions still needed more large samples and multi-center RCT to be further verified due to the limitation of the quality and quantity of the included literature.

By analysing the conceptual connotations of phenotype and traditional Chinese medicine （TCM） symptoms， the relationship between TCM symptoms， phenotypes and diseases is explained. It is believed that phenotypes and TCM syndromes have certain similarities， both of which elaborate the physiological and pathological mechanisms of the human body through external manifestations， and have the temporal and spatial characteristics of both phases and wholeness， as well as focusing on the connection between the innate and the acquired. Summarising the current status of the application of phenomics technology in the studies of TCM syndromes， it is concluded that the study of the intrinsic biological mechanisms of TCM syndromes with the help of phenomics technology has achieved certain results， but there are still problems such as difficulties in matching between traditional Chinese medicine syndromes and phenotypes， the incompleteness of the existing disease phenotype system， and the inconsistency of the understanding about "syndromes". It is proposed that in the future， large-scale clinical databases could be used to collect a wide range of TCM syndromes and phenotypes that are closely related to specific diseases. The phenomics technology could make preliminary correspondence and identification between a single syndrome and the corresponding phenotype， and then further carry out a more accurate phenotypic detection of the composite syndromes， and finally realise the standardization and intelligence of the diagnosis of TCM syndromes with the help of the artificial intelligence technology. By elaborating the modern scientific connotation of TCM syndromes from the perspective of phenotypes， we can provide scientific basis for the determination of TCM syndromes and the clarification of modern biomarkers of syndromes， as well as ideas for the modernisation research of TCM syndromes.

AIM: To investigate the clinical value of serum vitamin A(Vit A)and basic fibroblast growth factor(bFGF)levels predicting retinopathy of prematurity(ROP).METHODS: Prospective cohort studies. A total of 411 premature or low birth weight infants with gestational age less than 37 wk or birth weight less than 2 500 g who were delivered in Hainan Branch, Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine from January 2020 to December 2022 were selected as subjects. The Vit A and bFGF levels in peripheral blood were detected at 7 d and 35 d after birth, respectively.RESULTS: A total of 392 premature infants or low birth weight infants completed clinical study, including 51 cases in stage 1-2 ROP group, 23 cases in stage 3-5 ROP group and 318 cases in the group without ROP. At 7 d postnatal, the serum Vit A(0.44±0.17 μmol/L)and bFGF(0.53±0.16 ng/L)levels in stage 1-2 ROP group were lower than those in the group without ROP(0.50±0.12 μmol/L and 0.63±0.15 ng/L; all P<0.05). The serum Vit A(0.34±0.18 μmol/L)and bFGF(0.44±0.18 ng/L)levels in stage 3-5 ROP group were lower than those in the group without ROP(P<0.05). The serum Vit A and bFGF levels in stage 3-5 ROP group were lower than those in stage 1-2 ROP group(P<0.05). At 35d postnatal, the serum Vit A(0.33±0.19 μmol/L)and bFGF(0.39±0.19 ng/L)levels in stage 3-5 ROP group were lower than those in stage 1-2 ROP group(0.43±0.16 μmol/L and 0.48±0.17 ng/L; all P<0.05). According to the ROC curve drawn by serum Vit A, the AUC value was 0.853, the maximum Youden index was 0.68, the best sensitivity was 73%, and the best specificity was 95%. According to the ROC curve drawn by serum bFGF, the AUC value was 0.828, the maximum Youden index was 0.58, the best sensitivity was 90%, and the best specificity was 68%. According to the ROC curve drawn by serum Vit A combined with bFGF, the AUC value was 0.917, the maximum Youden index was 0.70, the best sensitivity was 70%, and the best specificity was 100%.CONCLUSION: Serum Vit A and bFGF levels are sensitive and effective indicators for predicting ROP. If the serum Vit A or bFGF levels are lower in premature infants or low birth weight infants, it may indicate the higher probability of ROP and its pathological stages. In addition, the clinica value of serum Vit A combined with bFGF in the diagnosis of ROP is higher than that of Vit A or bFGF alone, and the misdiagnosis rate is reduced.