19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.

ObjectiveBased on the Huangdi Neijing，a traditional Chinese medicine（TCM）identification scale of five human qualities was constructed and applied in elderly people to evaluate its reliability and validity. MethodsBased on the original text of the Huangdi Neijing and a review of relevant ancient and modern literature， an identification scale of five human qualities was developed through Delphi expert interviews. Offline surveys were conducted to evaluate the feasibility，reliability，and validity of its application in elderly people，and the scale was evaluated and revised. ResultsThe scale of five human qualities is divided into five subscales：wood，fire，earth，metal，and water. Each subscale is divided into four dimensions：morphological structure，psychological characteristics，tolerance，and physiological characteristics，with a total of 75 items. The survey results in elderly people show that：（1） The recovery rate and completion rate are 100%，and the average filling time is 23.3 min. 85.5% of the samples are completed within the preset time. （2） Reliability analysis results：The homogeneity reliability of each subscale，Chronbach's α，ranges from 0.702 to 0.793. The scores of each subscale in the split-half reliability range from 0.758 to 0.841， indicating that the internal consistency of the scale is good. （3） Validity analysis results. Content validity：During the development stage of the scale，the item pool，dimensions，and structure of the scale are designed reasonably， and the content is complete. The evaluation of content validity shows that the item-level content validity index （I-CVI） ranges from 0.83 to 1.00， and the scale-level content validity index for universal agreement （S-CVI/UA） is 0.92，indicating good content validity of the scale. Construct validity extracts 22 common factors based on an eigenvalue of 1，with a contribution rate of 62.333% to the overall system. The number of common factors in the five subscales is 4，5，4，5，and 4，respectively，with contribution rates of 52.64%，53.376%，51.445%，51.359%，and 50.714%，respectively，indicating the required structure for physical fitness measurement in elderly people. ConclusionThe scale constructed in this study has high reliability and validity，and it is suitable for evaluating the physical condition of elderly people in TCM.

Objective To observe the effects and safety of semaglutide and saxagliptin combined with metformin in the treatment of type 2 diabetes mellitus(T2DM)with abdominal obesity(AO).Methods The data of patients with T2DM and AO were retrospectively analyzed.Patients with T2DM and AO were divided into semaglutide group and saxagliptin group according to the cohort method.Both groups were given metformin orally,0.5 g a time,tid.On this basis,the semaglutide group was injected with semaglutide,0.25 mg a time,2 weeks later,the dose was adjusted to 0.5 mg a time,qw.The saxagliptin group was given oral administration of saxagliptin on the basis of metformin,5 mg a time,qd.All patients received 3 months of treatment.Glucose metabolism indexes,pancreatic islet function indexes,adipokines and adverse drug reactions were compared between the groups.Results There were 48 cases in semaglutide group and 49 cases in saxagliptin group.After treatment,the levels of fasting plasma glucose(FPG)in the semaglutide group and the saxagliptin group were(7.45±1.22)and(7.98±1.30)mmol·L-1;the levels of 2 h plasma glucose(2 h PG)were(9.78±1.64)and(10.55±1.82)mmol·L-1;the levels of hemoglobin A1c(HbA1c)were(5.66±0.94)and(6.25±0.87)％;the levels of fasting insulin(FINS)were(29.12±2.46)and(34.34±7.15)pmol·L-1;the levels of fasting C-peptide(FC-P)were(292.66±67.53)and(319.03±77.92)pmol·L-1;homeostatic model assessment-insulin resistance(HOMA-IR)were 2.51±0.78 and 2.94±0.89;homeostatic model assessment-β(HOMA-β)were 51.74±15.31 and 43.72±14.56;levels of Irisin were(4.56±0.32)and(4.17±0.54)ng·L-1;the levels of spexin(SPX)were(0.71±0.15)and(0.64±0.17)ng·mL-1;the levels of asprosin(ASP)were(1.22±0.16)and(1.34±0.25)μg·L-1.The above indexes were significantly different between semaglutide group and saxagliptin group(all P＜0.05).The total incidence rates of adverse drug reactions in semaglutide group and saxagliptin group were 10.42％(5 cases/48 cases)and 2.04％(1 case/49 cases),without statistically significant difference(P＞0.05).Conclusion The combination of semaglutide and metformin can lower blood glucose and in patients with T2DM and AO more significantly,and improve pancreatic function and adipokines,with good safety.

Objective To explore the protective mechanism of icariin on neuronal oxidative damage,providing a basic pharmacological basis for the treatment of cognitive impairment.Methods Glutamate was used to induce oxidative stress injury in HT22 cells.HT22 cells were divided into control group(normal cultured cells),model group(glutamate injury model)and experimental-L,-M,-H groups(5,10 and 20 μmol·L-1 icariin pretreatment for modeling,respectively).Cell proliferation was detected by cell counting kit-8(CCK-8)method;cytotoxicity was detected by lactate dehydrogenase(LDH)method;reactive oxygen species(ROS)levels were detected by flow cytometry;superoxide dismutase(SOD)levels were detected by biochemical kits;the expression levels of Kelch-like epichlorohydrin-related protein-1(Keap1),nuclear factor E2-related factor 2(Nrf2)were detected by Western blotting;the corresponding mRNA expression was detected by real-time fluorescence quantification polymerose chain reaction.Results The cell viability of control group,model group and experimental-L,-M,-H groups were(100.00±1.31)％,(66.38±2.44)％,(72.07±4.95)％,(82.41±3.57)％and(87.97±4.98)％;LDH release were(0.48±0.52)％,(18.82±2.09)％,(15.32±1.17)％,(10.37±1.39)％and(6.51±0.87)％;ROS level were(14.23±1.13)％,(41.74±1.60)％,(35.69±1.08)％,(33.28±1.69)％and(30.32±2.03)％;SOD levels were(54.84±1.17),(37.95±1.13),(48.02±1.28),(50.56±1.34)and(52.55±1.04)U·mg-1;Keap1 protein levels were 0.36±0.01,0.52±0.03,0.46±0.04,0.39±0.09 and 0.35±0.12;Nrf2 protein levels were 0.29±0.02,0.13±0.08,0.18±0.03,0.21±0.11 and 0.26±0.04;catalase(CAT)mRNA levels were 1.01±0.08,0.81±0.06,0.90±0.04,1.05±0.15 and 1.33±0.26;SOD mRNA levels were 1.09±0.12,0.83±0.03,0.86±0.08,0.94±0.08 and 1.09±0.16.Among the above indicators,the differences between the model group and the control group were statistically significant(all P＜0.01);the differences between the experimental-M,-H groups and the model group were statistically significant(P＜0.01,P＜0.05).Conclusion Icariin may activate the Keap1/Nrf2/antioxidant response element(ARE)signaling pathway,regulate the expression of related proteins,and reduce the level of ROS to effectively alleviate oxidative stress injury in neuronal cells.

OBJECTIVE To investigate the relationship between metformin and sarcopenia-related traits. METHODS Based on the data from publicly genome-wide association study-related databases， using single nucleotide polymorphisms strongly associated with metformin as instrumental variables， the two-sample Mendelian randomization （MR） analysis methods [inverse variance weighting （IVW） method， MR-Egger regression method and weighted median estimator method] were employed to investigate the relationship between metformin and three sarcopenia-related traits （low grip strength， muscle mass and walking speed）. Cochran’s Q test was used to assess heterogeneity， MR-Egger intercept test was used to detect horizontal pleiotropy， and leave-one-out analysis was performed for sensitivity analysis. RESULTS The results of IVW method showed that metformin use was significantly associated with an increased risk of low grip strength （β＝1.550， 95%CI was 0.389-2.711， P＝0.009） and reduced limb muscle mass （right leg lean body mass： β＝－0.665， 95%CI was －1.018-－0.312， P＜0.001； left leg lean body mass： β＝－0.710， 95%CI was －1.049-－0.371，P＜0.001； right arm lean body mass： β＝－0.471， 95%CI was －0.890-－0.053， P＝0.027； left arm lean body mass： β＝－0.463， 95%CI was －0.865-－0.061， P＝0.024），but was not associated with walking speed. The results or causal effects of the other two methods are consistent with it. The Cochran’s Q test indicated some degree of heterogeneity in the result of this study. No horizontal pleiotropy was detected by the MR-Egger intercept test. The sensitivity analysis suggested that the results of this study were stable. CONCLUSIONS Metformin may increase the risk of sarcopenia.

Objective:To discuss the protective effect of ginsenoside Rh1(G-Rh1)on kidney injury in the diabetic mellitus(DM)mice,and to clarify its mechanism.Methods:The diabetic kidney disease(DKD)model was prepared by using the high-fat,high-sugar diet combined with intraperitoneal injection of streptozotocin(STZ).A total of 48 C57/BL6 model mice were randomly divided into model group,nuclear factor erythroid 2-related factor 2(Nrf2)inhibitor ML385 group(ML385 group)(30 mg·kg-1),G-Rh1 group(30 mg·kg-1),and G-Rh1+ML385 group(30 mg·kg-1 G-Rh1+30 mg·kg-1 ML385),and there were 12 mice in each group.Additionally,12 C57/BL6 mice were selected as control group.After treated for 8 weeks,automatic analyzer was used to detect the levels of fasting blood glucose(FBG),blood urea nitrogen(BUN),and serum creatinine(Scr)in serum of the mice in various groups,as well as 24 h urinary protein(24 h UP)levels in urine,and the kidney index was calculated;kits were used to detect the activities of superoxide dismutase(SOD)and lactate dehydrogenase(LDH),and the levels of malondialdehyde(MDA)in kidney tissue of the mice in various groups;Western blotting method was used to detect the expression levels of Nrf2 and heme oxygenase-1(HO-1)proteins in kidney tissue of the mice in various groups.Results:Compared with control group,the levels of FBG and kidney indexes in serum of the mice in model group,ML385 group,and G-Rh1+ML385 group were significantly increased(P<0.01),and the level of FBG in serum of the mice in G-Rh1 group was significantly increased(P<0.01);compared with model group,the kidney index of the mice in ML385 group was significantly increased(P<0.05),while the levels of FBG and kidney index of the mice in G-Rh1 group were significantly decreased(P<0.05 or P<0.01);compared with G-Rh1 group,the level of FBG and kidney index of the mice in G-Rh1+ML385 group were significantly increased(P<0.01).Compared with control group,the levels of BUN and Scr in serum,and 24 h UP in urine of the mice in model group,ML385 group,G-Rh1 group,and G-Rh1+ML385 group were significantly increased(P<0.01);compared with model group,the level of BUN in serum and 24 h UP in urine of the mice in ML385 group were significantly increased(P<0.05),while the levels of BUN and Scr in serum,and 24 h UP in urine of the mice in G-Rh1 group were significantly decreased(P<0.01);compared with G-Rh1 group,the levels of BUN and Scr in serum,and 24 h UP in urine of the mice in G-Rh1+ML385 group were significantly increased(P<0.01).Compared with control group,the activities of SOD in kidney tissue of the mice in model group,ML385 group,G-Rh1 group,and G-Rh1+ML385 group were significantly decreased(P<0.01),while the levels of MDA and LDH activities were significantly increased(P<0.01);compared with model group,the activity of SOD in kidney tissue of the mice in ML385 group was significantly decreased(P<0.05),and the level of MDA was significantly increased(P<0.05);the activity of SOD in kidney tissue of the mice in of G-Rh1 group was significantly increased(P<0.01),and the level of MDA and activity of LDH were significantly decreased(P<0.01);compared with G-Rh1 group,the activity of SOD in kidney tissue of the mice in G-Rh1+ML385 group was significantly decreased(P<0.01),and the level of MDA and activity of LDH were significantly increased(P<0.01).Compared with control group,the expression levels of Nrf2 and HO-1 proteins in kidney tissue of the mice in model group,ML385 group,G-Rh1 group,and G-Rh1+ML385 group were significantly decreased(P<0.05 or P<0.01);compared with model group,the expression levels of Nrf2 and HO-1 proteins in kidney tissue of the mice in ML385 group and G-Rh1+ML385 group were significantly decreased(P<0.05),while the expression levels of Nrf2 and HO-1 proteins in kidney tissue of the mice in G-Rh1 group were significantly increased(P<0.01);compared with G-Rh1 group,the expression levels of Nrf2 and HO-1 proteins in kidney tissue of the mice in G-Rh1+ML385 group were significantly decreased(P<0.01).Conclusion:Ginsenoside Rh1 reduces the oxidative stress and improves the kidney function,providing protective effects on kidney injury in the DM mice,and its mechanism may be related to the activation of the Nrf2/HO-1 signaling pathway.

Objective:To make clear the duties of the clinical research coordinators (CRC) and evaluate any inadequacies in their management and training in the industry, ideas for ameliorating the construction of the CRC team and the promotion of clinical trial quality should be suggested.Methods:Drawing from the author′s experience in CRC management and a literature review, this paper assessed the current state of CRC work and management, and provides advice on how to improve CRC management.Results:In China, the CRC domain lacked a unified standard and access mechanism, leading to inconsistent levels of basic quality and business ability among CRC offerings within the sector.In order to maintain a steady CRC personnel team and promote the quality of clinical trials, it was essential to improve the training of CRC professionals, determine their career development paths, arrange different levels and fields of CRC training, adjust wages and appraisals, and take other suitable measures.Conclusions:It is proposed that the top medical organizations in China collaborate with sponsors and site management organizations to create a standardized and unified CRC occupational admission system and assessment criteria, in order to enhance the capacity and standard of CRC and addressing China′s increasing demand for clinical trials.