Triggering receptor expressed on myeloid cells 2 (TREM2)-mediated microglial phagocytosis is an energy-intensive process that plays a crucial role in amyloid beta (Aβ) clearance in Alzheimer's disease (AD). Energy metabolic reprogramming (EMR) in microglia induced by TREM2 presents therapeutic targets for cognitive impairment in AD. Jiawei Xionggui Decoction (JWXG) has demonstrated effectiveness in enhancing energy supply, protecting microglia, and mitigating cognitive impairment in APP/PS1 mice. However, the mechanism by which JWXG enhances Aβ phagocytosis through TREM2-mediated EMR in microglia remains unclear. This study investigates how JWXG facilitates microglial phagocytosis and alleviates cognitive deficits in AD through TREM2-mediated EMR. Microglial phagocytosis was evaluated through immunofluorescence staining in vitro and in vivo. The EMR level of microglia was assessed using high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA) kits. The TREM2/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway was analyzed using Western blotting in BV₂ cells. TREM2^-/- BV₂ cells were utilized for reverse validation experiments. The Aβ burden, neuropathological features, and cognitive ability in APP/PS1 mice were evaluated using ELISA kits, immunohistochemistry (IHC), and the Morris water maze (MWM) test. JWXG enhanced both the phagocytosis of EMR disorder-BV₂ cells (EMRD-BV₂) and increased EMR levels. Notably, these effects were significantly reversed in TREM2^-/- BV₂ cells. JWXG elevated TREM2 expression, adenosine triphosphate (ATP) levels, and microglial phagocytosis in APP/PS1 mice. Additionally, JWXG reduced Aβ-burden, neuropathological lesions, and cognitive deficits in APP/PS1 mice. In conclusion, JWXG promoted TREM2-induced EMR and enhanced microglial phagocytosis, thereby reducing Aβ deposition, improving neuropathological lesions, and alleviating cognitive deficits.
Drugs, Chinese Herbal/pharmacology* ; Microglia/drug effects* ; Phagocytosis ; Cognitive Dysfunction/drug therapy* ; Metabolic Reprogramming ; Animals ; Mice ; Cell Line ; Receptors, Immunologic/metabolism* ; Membrane Glycoproteins/metabolism* ; Signal Transduction ; Amyloid beta-Peptides/metabolism* ; Energy Metabolism

ObjectiveTo investigate the association between albumin （Alb） and recompensation by comparing recompensation rate between hepatitis B/C virus-related decompensated liver cirrhosis patients with different Alb levels， and to provide guidance for the identification and management of high-risk patients in clinical practice. MethodsRelated clinical data were collected from 734 patients with hepatitis B/C virus-related decompensated liver cirrhosis who attended The Third People’s Hospital of Kunming from January 1， 2016 to December 31， 2022， and they were divided into three groups based on the level of Alb. The linear regression analysis and chi-square test were used for trend tests. The Kaplan-Meier curve was plotted for the cumulative incidence rate of recompensation in the three groups， and the log-rank test was used for comparison between groups. A Cox proportional-hazards regression model analysis was used to investigate the association between Alb and recompensation in patients with hepatitis B/C virus-related decompensated liver cirrhosis. ResultsAmong the 734 patients with hepatitis B/C virus-related decompensated liver cirrhosis， 270 achieved recompensation， with a recompensation rate of 36.8%. All patients had a median Alb level of 29.90 （25.90 — 34.80） g/L on admission， and according to the level of Alb， they were divided into <25.9 g/L group with 177 patients， 25.9 — 34.8 g/L group with 377 patients， and >34.8 g/L group with 180 patients； 36 patients （20.3%） in the <25.9 g/L group， 138 （36.6%） in the 25.9 — 34.8 g/L group， and 96 （53.3%） in the >34.8 g/L group achieved recompensation， and the recompensation rate increased with the increase in Alb level （χ²=41.730， P<0.001）. After adjustment for all confounding factors， compared with the <25.9 g/L group， there was a significant increase in the incidence rate of recompensation in the 25.9 — 34.8 g/L group （hazard ratio ［HR］=1.842， 95% confidence interval ［CI］： 1.274 — 2.663） and the >34.8 g/L group （HR=2.336， 95% CI： 1.575 — 3.463）. The Kaplan-Meier survival analysis showed that there was a significant difference in the cumulative incidence rate of recompensation between the three groups （χ²=41.632， P<0.001）. ConclusionAlb level is an influencing factor for recompensation in patients with hepatitis B/C virus-related decompensated liver cirrhosis， and the recompensation rate increases with the increase in Alb level.

Objective To analyze the risk factors for moderate-to-severe coronary artery stenosis in the population of Tacheng,Xinjiang Uygur Autonomous Region,and to construct and verify a nomogram prediction model for the degree of coronary artery ste-nosis.Methods We retrospectively selected 629 patients who were hospitalized in the Cardiovascular Department of Tacheng Peo-ple's Hospital from January 2021 to June 2023.Using R language software,the sociodemographic data,disease-related data,and va-rious laboratory indicators of the 629 patients were included in the initial screening of risk factors for use in the LASSO regression analysis using a random number table method.The 629 patients were divided into a training group(n=440)and a validation group(n=189)in a 7:3 ratio.Data from the training group were used for model construction,with the degree of coronary artery stenosis as the dependent variable,and the variables selected by LASSO regression as independent variables in the logistic regression model.The validation group was used for model validation.Based on the results of the logistic regression analysis,a visual nomogram for predicting the degree of co-ronary artery stenosis was constructed using R language software.The discriminability,calibration,and clinical utility of the model were evaluated using the area under the receiver operating characteristic curve(AUC),a calibration curve,and decision curve analysis(DCA).Results Age,non-Han ethnicity,hypertension,hyperlipidemia,and a history of cerebrovascular disease were risk factors for mode-rate-to-severe coronary artery stenosis and were included in the risk prediction model.The AUC of the training group and the validation group were 0.905(95％CI:0.790-0.863)and 0.864(95％CI:0.744-0.861),respectively.The predicted values of the calibration curve were consistent with the actual values(Brier scores of the training and validation group:0.03 and 0.14,respectively).The predictive per-formance of the model was good,and the DC A results indicated that the model had net clinical benefits.Conclusion The risk prediction model for coronary artery stenosis in the population of the Tacheng area constructed in this study has good predictive performance and can provide a simple,feasible,economical,and easy-to-promote evaluation tool for medical personnel to screen patients with moderate-to-se-vere coronary artery stenosis.

This research aimed to comprehensively understand the prevalence of mutation in drug-resistant molecular markers of imported Plasmodium vivax in Chongqing,the Pvmdr1,Pvdhps,Pvdhfr,Pvcrt-o and Pvk12 genes of Plasmodium vivax were systematically analyzed.Blood samples were collected from imported Plasmodium vivax-infected patients in Chongqing between 2011 and 2022.The Pvmdr1,Pvdhps,Pvdhfr,Pvcrt-o,and Pvk12 genes were amplified and then sequenced to precisely evaluate gene mutations.Bioinformatics methods were employed to conduct in depth analysis of the mutation prevalence.Regarding the Pvdhfr gene,mutations at codons 50,57,58,61,99,117,and 199 were detected in 2.9%,23.5%,76.4%,23.53%,2.9%,82.3%,and 5.88%of the samples,respectively.The double-mutant haplotype S58R/S117N was the most prevalent,accounting for 50%,followed by the quadruple-mutant haplotype F57L/S58R/T61M/S117T,which accounted for 11.76%.Among the four types of tandem-repeat variations of Pvdhfr,the wild-type was the most common,and the insertion type was a novel discovery in this study.For the Pvdhps gene,the prevalence among mutation genotypes was relatively low.The single-mutant genotype was dominant,constituting 27.03%.The prevalence of Pvmdr1 mutations at codons 958 and 1076 was 100%and 89.19%,respectively.Among the 37 successfully sequenced samples,K10 insertion was detected in only 8 cases(22.22%).Notably,no non-synonymous mutations of Pvk12 were identified in this study.The cases in this study were imported from various countries of origin.Novel tandem-repeat variation tyres of Pvdhfr and new mutation sites of Pvdhps were identifide,thus enriching the mutation information of imported Plasmodium vivax resistance molecular markers in China.

Objective To analyze the risk factors for moderate-to-severe coronary artery stenosis in the population of Tacheng,Xinjiang Uygur Autonomous Region,and to construct and verify a nomogram prediction model for the degree of coronary artery ste-nosis.Methods We retrospectively selected 629 patients who were hospitalized in the Cardiovascular Department of Tacheng Peo-ple's Hospital from January 2021 to June 2023.Using R language software,the sociodemographic data,disease-related data,and va-rious laboratory indicators of the 629 patients were included in the initial screening of risk factors for use in the LASSO regression analysis using a random number table method.The 629 patients were divided into a training group(n=440)and a validation group(n=189)in a 7:3 ratio.Data from the training group were used for model construction,with the degree of coronary artery stenosis as the dependent variable,and the variables selected by LASSO regression as independent variables in the logistic regression model.The validation group was used for model validation.Based on the results of the logistic regression analysis,a visual nomogram for predicting the degree of co-ronary artery stenosis was constructed using R language software.The discriminability,calibration,and clinical utility of the model were evaluated using the area under the receiver operating characteristic curve(AUC),a calibration curve,and decision curve analysis(DCA).Results Age,non-Han ethnicity,hypertension,hyperlipidemia,and a history of cerebrovascular disease were risk factors for mode-rate-to-severe coronary artery stenosis and were included in the risk prediction model.The AUC of the training group and the validation group were 0.905(95％CI:0.790-0.863)and 0.864(95％CI:0.744-0.861),respectively.The predicted values of the calibration curve were consistent with the actual values(Brier scores of the training and validation group:0.03 and 0.14,respectively).The predictive per-formance of the model was good,and the DC A results indicated that the model had net clinical benefits.Conclusion The risk prediction model for coronary artery stenosis in the population of the Tacheng area constructed in this study has good predictive performance and can provide a simple,feasible,economical,and easy-to-promote evaluation tool for medical personnel to screen patients with moderate-to-se-vere coronary artery stenosis.

This research aimed to comprehensively understand the prevalence of mutation in drug-resistant molecular markers of imported Plasmodium vivax in Chongqing,the Pvmdr1,Pvdhps,Pvdhfr,Pvcrt-o and Pvk12 genes of Plasmodium vivax were systematically analyzed.Blood samples were collected from imported Plasmodium vivax-infected patients in Chongqing between 2011 and 2022.The Pvmdr1,Pvdhps,Pvdhfr,Pvcrt-o,and Pvk12 genes were amplified and then sequenced to precisely evaluate gene mutations.Bioinformatics methods were employed to conduct in depth analysis of the mutation prevalence.Regarding the Pvdhfr gene,mutations at codons 50,57,58,61,99,117,and 199 were detected in 2.9%,23.5%,76.4%,23.53%,2.9%,82.3%,and 5.88%of the samples,respectively.The double-mutant haplotype S58R/S117N was the most prevalent,accounting for 50%,followed by the quadruple-mutant haplotype F57L/S58R/T61M/S117T,which accounted for 11.76%.Among the four types of tandem-repeat variations of Pvdhfr,the wild-type was the most common,and the insertion type was a novel discovery in this study.For the Pvdhps gene,the prevalence among mutation genotypes was relatively low.The single-mutant genotype was dominant,constituting 27.03%.The prevalence of Pvmdr1 mutations at codons 958 and 1076 was 100%and 89.19%,respectively.Among the 37 successfully sequenced samples,K10 insertion was detected in only 8 cases(22.22%).Notably,no non-synonymous mutations of Pvk12 were identified in this study.The cases in this study were imported from various countries of origin.Novel tandem-repeat variation tyres of Pvdhfr and new mutation sites of Pvdhps were identifide,thus enriching the mutation information of imported Plasmodium vivax resistance molecular markers in China.

Objective To analyze the risk factors of heart failure in patients with coronary heart disease(CHD),and to construct and verify a nomogram prediction model for the risk of heart failure in patients with CHD.Methods The clinical data of 453 patients with CHD who were hospitalized in the Second Affiliated Hospital of Shenyang Medical College from January to December 2022 were retrospectively analyzed,including 278 patients with CHD combined with heart failure and 175 patients without heart failure.The patients were divided into training group(318 cases)and validation group(135 cases)according to the ratio of 7:3.R software was applied to perform LASSO regression to screen the risk factors,and Logistic regression to establish a prediction model and construct a nomogram.The calibration curve and receiver operating characteristic(ROC)curve were used to evaluate the calibration and discrimination of the model.Results LASSO regression analysis ultimately screened five risk factors from 22 variables,and Logistic regression results showed that age,smoking,history of myocardial infarction,New York Heart Association(NYHA)cardiac function class Ⅳ,and left ventricular ejection fraction(LVEF)were all independent risk factors for heart failure in CHD patients(P＜0.05).The model formula was Z=-2.927+0.045 × age+0.886 × smoking+0.808 × history of myocardial infarction-2.829 × NYHA cardiac function class Ⅳ+0.037×LVFF.Internal validation of the model showed that area under the curve was 0.727(95％CI:0.588-0.752),the sensitivity was 40.4％,the specificity was 84.3％,and the Youden index was 0.247.According to the calibration curve,the predicted value of the calibration curve was highly consistent with the actual value,and the Brier score was 0.106.Conclusion The risk prediction model for heart failure in patients with CHD based on LASSO regression has good discrimination and prediction efficiency,which can be used as an evaluation tool for medical staff to predict the risk of patients.

Objective:To explore the application and effect of flipped classroom in community clinical pharmacist training.Methods:Seventeen pharmacists trained in 2017-2018 were used as the control group and received traditional teaching mode. Fourteen pharmacists trained in 2019-2020 were used as the experimental group and received the flipped classroom teaching mode. Finally, the teaching effect was evaluated through the trainees' graduation examination results and satisfaction degree. The SPSS 25.0 was used to conduct the t test and chi-square test. Results:The task performance, prescription audit scores, clinical practice scores, and total scores in the experimental group were significantly higher than those in the control group ( P<0.05). However, there was no significant difference in usual performance between the two groups ( P>0.05). For satisfaction survey, the total score of Likert scale in the experimental group was (20.1±3.4), which was significantly higher than that in the control group (16.9±3.4). However, there was no significant difference in the satisfaction of clinical practice and teachers' level between the two groups ( P>0.05). Conclusion:Flipped classroom can improve the enthusiasm of community clinical pharmacist trainees to participate in learning, increase the level of the trainees' theoretical knowledge and professional practice, and is conducive to the cultivation of high-quality community clinical pharmacists.

Objective To investigate the cognition of colorectal cancer-related knowledge and influencing factors of patients with middle- and advanced-stage colorectal cancer in ethnic minority areas of Inner Mongolia. Methods According to the national population and the prevalence of colorectal cancer, 277 patients with colorectal cancer were selected by stratified and random sampling in Inner Mongolia. The patients were surveyed in Baotou, Chifeng, Bayannaoer, and other hospitals. The questionnaire included patients' basic information, cognition of colorectal cancer risk factors and screening knowledge, screening information, etc. Results Before suffering from the disease, the patients' knowledge of colorectal cancer (risk factors, early screening knowledge, treatment methods) was low. About 54.9% of patients were unaware of high risk factors for colorectal cancer, 75.8% of patients did not understand the knowledge of early screening of colorectal cancer, and 37.5% of patients did not underst and the treatment of colorectal cancer. The main influencing factors of colorectal cancer cognition were education level and occupation. Patients who work in institutions and enterprises and with higher education level had better cognition. Conclusion Patients with middle- and advanced-stage colorectal cancer in Inner Mongolia have poor knowledge and awareness of risk factors and screening of colorectal cancer before diagnosis. Education level and occupation are factors influencing colorectal cancer cognition, therefore, people with low knowledge rate of colorectal cancer and low education level as well as unemployed laid-off people should be given priority intervention.

Objective:To determine lysophosphatidic acid receptor 6 (LPAR6) expression in patients with mycosis fungoides (MF) , a variant of cutaneous T-cell lymphoma (CTCL) , and to investigate its role and mechanism of action in the development and prognosis of CTCL.Methods:A total of 110 patients with confirmed MF were collected from Department of Dermatology, Peking University First Hospital from 2011 to 2020, including 24 with large-cell transformation (LCT) and 25 with non-large cell transformation (NLCT) in the discovery cohort, and 24 with LCT and 37 with NLCT in the validation cohort. RNA sequencing and RT-PCR were conducted to determine the LPAR6 expression in patients in the discovery cohort and validation cohort respectively. LPAR6 expression was compared between patients with LCT and those with NLCT, and its effect on the prognosis of patients was evaluated. Two LPAR6-overexpressing CTCL cell lines MyLa and Sz4 were constructed to evaluate the effect of LPAR6 overexpression on proliferative activity of MyLa and Sz4 cells, with the cells normally expressing LPAR6 as the control group; after the treatment with LPAR6-related ligand lysophosphatidic acid (LPA) , 2S-OMPT, adenosine triphosphate (ATP) or adenosine (ADO) , the effects of LPAR6 activation on the proliferative activity and apoptosis of LPAR6-overexpressing MyLa and Sz4 cells were evaluated by the MTS method and flow cytometry respectively. Log-rank test was used for prognostic analysis, and t test or Mann-Whitney U test was used for comparisons between two groups. Results:As RNA sequencing showed, LPAR6 was one of the significantly underexpressed genes in the LCT group in the discovery cohort; in the validation cohort, LPAR6 expression (median[ Q1, Q3]) was significantly lower in the LCT group (204.90[81.90, 512.70]) than in the NLCT group (809.40[417.50, 1 829.20], U= 242.00, P= 0.002) ; in the two cohorts, the underexpression of LPAR6 was significantly associated with increased risk of poor prognosis (both P < 0.01) . Cell proliferation assay showed no significant difference in the proliferative activity of MyLa or Sz4 cells between the LPAR6 overexpression group and control group at 0, 24, 48 and 72 hours during the experiment (all P > 0.05) ; 48 hours after activation of LPAR6 by LPA, 2S-OMPT, ATP and ADO in MyLa cells, the LPAR6 overexpression group showed significantly decreased cellular proliferative activity (1.38 ± 0.01, 1.04 ± 0.01, 1.09 ± 0.03, 1.23 ± 0.01, respectively) compared the control group (1.73 ± 0.04, 1.23 ± 0.01, 1.24 ± 0.01, 1.42 ± 0.03, t= 30.33, 18.38, 4.78, 5.75, respectively, all P < 0.05) , but significantly increased cell apoptosis rate (17.93% ± 0.88%, 17.75% ± 0.35%, 23.97% ± 0.57%, 31.44% ± 0.34%, respectively) compared the control group (3.98% ± 0.03%, 7.81% ± 0.59%, 11.95% ± 0.85%, 12.02% ± 0.48%, t= 15.93, 14.49, 11.74, 33.01, respectively, all P < 0.05) ; 48 hours after activation of LPAR6 by 2S-OMPT and ADO in Sz4 cells, compared with the control group, the LPAR6 overexpression group also showed significantly decreased cellular proliferative activity (2S-OMPT: 1.29 ± 0.04 vs. 1.48 ± 0.01; ADO: 1.27 ± 0.01 vs. 1.51 ± 0.02; both P < 0.05) , but significantly increased cell apoptosis rate (2S-OMPT: 41.70% ± 0.70% vs. 29.35% ± 0.55%; ADO: 37.05% ± 0.15% vs. 24.60% ± 1.00%; both P < 0.05) . Conclusions:LPAR6 was underexpressed in the patients with LCT, and its underexpression was significantly associated with increased risk of poor prognosis. In vitro activation of LPAR6 could inhibit the proliferation of CTCL cells and promote their apoptosis, suggesting that the decrease of LPAR6 expression may be one of the important mechanisms underlying disease progression in patients with LCT.