Cognitive impairment （CI） is a clinical syndrome characterized by progressive decline in advanced cognitive functions such as memory， thinking， and judgment. Its etiology and pathogenesis are complex， and there is currently a lack of specific drug interventions. Metformin， as a first-line hypoglycemic drug for type 2 diabetes， not only lowers blood glucose levels but also improves CI. This article reviews and summarizes the pharmacological effects and mechanisms of metformin in improving Alzheimer’s disease， diabetes cognitive impairment， cognitive impairment after chemotherapy， in order to provide novel insights and approaches for the treatment of CI-related diseases. Studies have shown that the mechanism by which MET intervenes in CI mainly includes regulating β-amyloid protein and tau protein metabolism， reducing insulin resistance， inhibiting neuroinflammation， improving synaptic plasticity， improving mitochondrial dysfunction， regulating gut microbiota and lipid metabolism， etc. Future research needs to be conducted through interdisciplinary collaboration， fully integrating multiple omics data， and combining advanced technologies to further reveal their mechanisms of effect.

Purpose To study the relationshiPbetween CD88 expression and clinicopathologic features and epithelial-mesenchymal transition(EMT)in esophageal squamous cell carcinoma.Methods TCGA and TIMER database were used to analyze the expression level of CD88 in esophageal squamous cell carcinoma and adjaecnt esophageal squamous cell epithelium and its relationship with epithelial-mesenchymal transition.Par-affin specimens were collected from 199 patients with clinically diagnosed esophageal squamous cell carcinoma.Immunohisto-chemical EnVision method was used to detect the expression of CD88 and EMT-related proteins in esophageal squamous cell carcinoma and adjacent tissues,the relationship between CD88 expression and clinicopathological features,prognosis and EMT in ESCC tumors was analyzed.Results There were 86 cases with high CD88 expression and 113 cases with low CD88 expres-sion.The expression level of CD88 in esophageal squamous cell carcinoma was significantly higher than that of paracancerous tis-sue(P＜0.001).The group with high CD88 expression had lower ESCC differentiation level(P＜0.001)and higher T stage(P=0.03).The 5-year survival of patients with high CD88 ex-pression was significantly lower than that of patients with low CD88 expression(P=0.002).Cox univariate and multivariate analysis showed that CD88 expression was an independent prog-nostic factor for overall survival of patients with esophageal squa-mous cell carcinoma(P=0.013).The high expression of CD88 was negatively correlated with E-cadherin(r=-0.146,P=0.039),and positively correlated with vimentin(r=0.387,P=1.61e-08)and N-cadherin(r=0.304,P=1.3e-05).Con-clusion CD88 is highly expressed in esophageal squamous cell carcinoma.CD88 may affect the occurrence,development,in-vasion and metastasis of esophageal squamous cell carcinoma through EMT,and it might be used as a prognostic marker for e-sophageal squamous cell carcinoma patients.

Objective:To explore the relationship between serum uric acid trajectory and the progression of renal function in individuals aged 60 and above.Methods:This study was a retrospective cohort study. Individuals aged 60 years and above who received health checkups in Beijing Friendship Hospital, Capital Medical University, from March 2015 to December 2023 and met the criteria of baseline estimated glomerular filtration rate (eGFR)≥60 ml·min -1·(1.73 m 2) -1, were selected as the research subjects. The serum uric acid data of multiple measurements were collected and identified as different serum uric acid trajectories by group-based trajectory modeling (GBTM). According to the serum uric acid trajectories, the subjects were divided into a low trajectory group (101 cases), a middle trajectory group (176 cases), and a high trajectory group (86 cases). Cox regression analysis was used to examine the effect of serum uric acid trajectory on the progression of renal function in the elderly. Results:A total of 363 elderly were included. The mean follow-up time was 8.1 years. At the end of the follow-up, a total of 50 elderly individuals had experienced varying degrees of renal function decline. After adjusting for multiple confounding factors by Cox regression analysis, the risks of eGFR<60 ml·min -1·(1.73 m 2) -1, eGFR reduction rate ≥25% and composite endpoints [eGFR <60 ml·min -1·(1.73 m 2) -1, eGFR reduction rate ≥25% or >3 ml·min -1·(1.73 m 2) -1·year -1] in the high trajectory group were significantly higher than those in the low trajectory group, with an HR of 4.54 (95% CI:1.47-20.76), 3.75 (95% CI:1.06-21.21), and 3.74 (95% CI:1.44-115.59), respectively. In addition, there was no significant difference between baseline serum uric acid and renal function progression (all P>0.05). Conclusion:The high serum uric acid trajectory increases the risk for the progression of renal function in individuals aged 60 and above.

Purpose: Platelet-related indices, including mean platelet volume (MPV) and plateletocrit (PCT), have been reported as new prognostic factors of overall survival (OS) in many cancers, but not yet in biliary tract cancer (BTC). We intended to assess these indices in predicting OS in BTC patients with the aim to build a new prognostic model for patients with BTC after surgical resection. Materials and Methods: Survival analysis and time receiver operating characteristic analysis were applied to screen the platelet indices. Univariate and multivariate Cox analyses were used to identify independent prognostic factors and develop a new prognostic model. Harrell’s C-statistics, calibration curves, and decisive curve analysis were used to assess the model. Results: MPV and platelet distribution width (PDW)/PCT showed the best prognostic accuracy among the platelet indices. In multivariable analysis, factors predictive of poor OS were presence of nodal involvement, Non-radical surgery, poor tumor differentiation, carbohydrate antigen 19-9 > 100 U/mL, MPV > 8.1 fl, and PDW/PCT > 190. The new model was found to be superior to the TNM staging system and our new staging system showed higher discriminative power. Conclusion MPV and PDW/PCT have high prognostic value in BTC patients, and the novel staging system based on these two indices showed good discrimination and accuracy compared with the American Joint Committee on Cancer 7th TNM staging system.

Purpose: Platelet-related indices, including mean platelet volume (MPV) and plateletocrit (PCT), have been reported as new prognostic factors of overall survival (OS) in many cancers, but not yet in biliary tract cancer (BTC). We intended to assess these indices in predicting OS in BTC patients with the aim to build a new prognostic model for patients with BTC after surgical resection. Materials and Methods: Survival analysis and time receiver operating characteristic analysis were applied to screen the platelet indices. Univariate and multivariate Cox analyses were used to identify independent prognostic factors and develop a new prognostic model. Harrell’s C-statistics, calibration curves, and decisive curve analysis were used to assess the model. Results: MPV and platelet distribution width (PDW)/PCT showed the best prognostic accuracy among the platelet indices. In multivariable analysis, factors predictive of poor OS were presence of nodal involvement, Non-radical surgery, poor tumor differentiation, carbohydrate antigen 19-9 > 100 U/mL, MPV > 8.1 fl, and PDW/PCT > 190. The new model was found to be superior to the TNM staging system and our new staging system showed higher discriminative power. Conclusion MPV and PDW/PCT have high prognostic value in BTC patients, and the novel staging system based on these two indices showed good discrimination and accuracy compared with the American Joint Committee on Cancer 7th TNM staging system.

The Chinese Pharmacopoeia 2020 edition was reviewed and approved by the National Medical Products Administration and the National Health Commission of the People's Republic of China in July 2020.The current edition was officially implemented on December 30,2020.The general chapters of the Chinese Pharmacopoeia discuss the general testing methods and guidelines,which are the common re-quirements and basis for the implementation of drug standards in the Chinese Pharmacopoeia.Owing to adherence to the principles of scientificity,versatility,operability,and sustainable development,there is an improvement in the general chapters of the 2020 edition over those of the previous editions.Further,the application of advanced and mature analytical techniques has expanded,the development of testing methods for exogenous pollutants in traditional Chinese medicines has been strengthened,and technical requirements are now better harmonized with international standards.The updated edition provides technical and methodological support to ensure safety,effectiveness,and control of pharmaceuticals in China and will play an important and active role in encouraging the application of advanced technolo-gies,improving the quality control of medicines,and strengthening the means of drug regulation in China.This review provides a comprehensive introduction of the main features of and changes to the general chapters in the Chinese Pharmacopoeia 2020 edition and aims to provide reference for its correct understanding and accurate implementation.

OBJECTIVE: To determine the carrier rate of Fragile X mental retardation 1 gene (FMR1) mutants in women with a history of adverse pregnancy or childbirth, and to provide prenatal diagnosis for the carriers. METHODS: Peripheral blood samples were collected from women with a history of adverse pregnancy or childbirth, and the FMR1 gene cytosine-guanine-guanine repeat number (CGG)n was determined by triple-repeat primer polymerase chain reaction (TP-PCR) combined with capillary electrophoresis. Prenatal diagnosis was provided for the carriers during pregnancy. RESULTS: Among 819 samples, 9 gray zone repeats carriers and 10 premutation carriers were detected, which gave a prevalence of 1 in 91 and 1 in 82, respectively, with a total prevalence of 1 in 43. Prenatal diagnosis was provided during 7 pregnancies for 6 carriers. A female fetus with premutation (n = 30/57) and an affected male fetus with full mutation (n = 336) were detected. CONCLUSION FMR1 gene testing in women with a history of adverse pregnancy or childbirth can facilitate genetic counseling and reproductive guidance for carriers of gray zone repeats and premutations. Prenatal diagnosis for carriers of premutation can facilitate reduction of the birth of children with fragile X syndrome.

Purpose: The systemic inflammation response index (SIRI) has been reported to have prognostic ability in various solid tumors but has not been studied in gallbladder cancer (GBC). We aimed to determine its prognostic value in GBC. Materials and Methods: From 2003 to 2017, patients with confirmed GBC were recruited. To determine the SIRI’s optimal cutoff value, a time-dependent receiver operating characteristic curve was applied. Univariate and multivariate Cox analyses were performed for the recognition of significant factors. Then the cohort was randomly divided into the training and the validation set. A nomogram was constructed using the SIRI and other selected indicators in the training set, and compared with the TNM staging system. C-index, calibration plots, and decision curve analysis were performed to assess the nomogram’s clinical utility. Results: One hundred twenty-four patients were included. The SIRI’s optimal cutoff value divided patients into high (≥ 0.89) and low SIRI (< 0.89) groups. Kaplan-Meier curves according to SIRI levels were significantly different (p < 0.001). The high SIRI group tended to stay longer in hospital and lost more blood during surgery. SIRI, body mass index, weight loss, carbohydrate antigen 19-9, radical surgery, and TNM stage were combined to generate a nomogram (C-index, 0.821 in the training cohort, 0.828 in the validation cohort) that was significantly superior to the TNM staging system both in the training (C-index, 0.655) and validation cohort (C-index, 0.649). Conclusion The SIRI is an independent predictor of prognosis in GBC. A nomogram based on the SIRI may help physicians to precisely stratify patients and implement individualized treatment.

Objective To explore the diagnostic value of MR elastography and diffusion?weighted imaging in patients with liver fibrosis in the context of chronic hepatitis B. Methods Twenty?four patients with chronic hepatitis B, whose course of liver disease was more than 6 months and hepatitis B surface antigen was positive, were prospectively enrolled in the First Affiliated Hospital of Soochow University from July to December 2017. All of the patients underwent abdominal transient elastography (TE), routine MRI, magnetic resonance elastography (MRE) and DWI examination, TE and MRI were performed within one week. TE liver stiffness was measured, the MRE liver stiffness and ADC value were measured on MR imagings. All patients were divided into three groups: mild and non fibrosis (F0 to 1), significant fibrosis(F2 to 3) and cirrhosis (F4), according to the recommended standard of FibroTouch. Correlation between TE liver stiffness, MRE liver stiffness and ADC values were identified by using Spearman correlation test. The difference of the MRE liver stiffness and ADC value among the three groups was tested using independent sample t test. The overall predictive ability of MRE and DWI in assessment of liver fibrosis and cirrhosis was analyzed by constructing ROC curve. Results TE and MRI were successfully performed in all subjects, and the image quality was good. The MRE liver stiffness in mild and non fibrosis, significant fibrosis and cirrhosis was (2.32±0.31),(3.43±1.05),(4.77±0.68) kPa with statistically significant difference(F=61.690, P<0.01). The ADC values in three groups were (1.31 ± 0.14)×10-3, (1.23 ± 0.15)×10-3,(1.22±0.12)×10-3mm2/s without significant difference(F=1.074,P=0.360). The TE liver stiffness in three groups was (5.61±1.05),(9.56±0.57),(17.25±3.55)kPa, respectively, there was significant correlation between the MRE liver stiffness and the TE liver stiffness(t=0.858, P<0.01), but no significant correlation between the TE liver stiffness and the ADC value was found (r=-0.326,P=0.120). The area under ROC of MRE liver stiffness in diagnosing liver fibrosis grade (≥F2 and F4) was 0.96 and 1.00 respectively, while the AUC of ADC value was less than 0.70, which were 0.67 and 0.62 respectively. Conclusion MRE is a non?invasive promising tool for assessing liver fibrosis with chronic hepatitis B, while DWI has limited role.

Objective: To analyze the subjective and objective misdiagnostic reasons of brucellosis in Suzhou City. Methods: The clinical data of inpatients with brucellosis from the department of infectious diseases, the First Affiliated Hospital of Soochow University from 2016 to 2018 were collected. The main onset methods, the first consultation department, the diagnosis and treatment process, and the main diagnosis were analyzed. Simultaneously, a questionnaire survey was conducted among doctors from different departments in Suzhou City. To investigate the knowledge and diagnosis of brucellosis by electronic questionnaire, and analyze the results. Results: Totally 24 brucellosis cases were collected. Fever (13 cases, 54.17%), lumbago/arthralgia (6 cases, 25.00%) or both (3 cases, 12.50%) were the main initial symptoms, while a patient with fever, arthralgia and orchitis(1 case, 4.17%) and another with purpura (1 case, 4.17%) were also admitted. The 24 patients were distributed among 10 different departments, in which the department of infectious diseases (6 cases, 25.00%) and orthopedics (5 cases, 20.83%) dominated. Brucellosis was considered in only 2 patients (8.33%) before pathogen results, and the main suspected diagnosis were malignant hematopathy/lymphoma (7 cases, 29.17%), sepsis (5 cases, 20.83%), and tuberculosis (4 cases, 16.67%). Totally 124 questionnaires were collected and analyzed. We divided them into 2 groups: department of infectious diseases (52/124, 41.94%) and other departments (72/124, 58.06%). The proportion of answer "yes" for the question Suzhou is the epidemic area of brucellosis, question whether brucellosis is considered in suspected patients, question whether the epidemiology is collected and question how and where to conduct the serological test was 38.71% (48/124), 32.26% (40/124), 53.23% (66/124) and 29.84% (37/124), respectively. The positive answer in the department of infectious diseases (24/52, 46.15%) was significantly higher than those of others (16/72, 22.22%, χ²=7.913, P < 0.05). The respondents thought the serological test could not be conducted, because of that the non-pasture doctors were not familiar with the test procedure, which was complex (93/124, 75.00%) and the disease was not considered (85/124, 68.55%). And the respondents thought measures helpful to reduce misdiagnosis should include setting up serological test or simplifying the procedure (96/124, 77.42%), massed learning organized by related administrations (95/124, 76.61%) and learning by books, papers and classes (72/124, 58.06%). Conclusion There is obvious clinical misdiagnosis of brucellosis in Suzhou City, which may be caused by Suzhou doctors not paying enough attention to brucellosis, being unfamiliar with the inspection process and complicated inspection process.