ObjectiveTo investigate the mechanism of action of modified Chaihu Shugan Powder in the treatment of abnormal gallbladder relaxation in gallbladder cholesterol stone （CS） with liver depression syndrome， and to provide a basis for clinical medication. MethodsMice were given a high-fat lithogenic diet combined with chronic unpredictable mild stress （CUMS） to establish a model of CS. A total of 45 male C57BL/6 mice were randomly divided into blank group （6 mice fed a normal diet） and CS group （39 mice fed a high-fat lithogenic diet）. After CS modeling， the CS group was further randomly divided into four subgroups of CS group， CS liver depression group， traditional Chinese medicine group （treated with modified Chaihu Shugan Powder）， and Western medicine group （treated with ursodeoxycholic acid）， with 9 mice in each group. All subgroups were fed with the high-fat lithogenic diet， and all mice except those in the CS group were given 21 days of CUMS for modeling. Samples were collected after intervention. The serum levels of cholecystokinin （CCK）， liver function parameters， and blood lipid profiles were measured； HE staining was performed for liver and gallbladder tissue； qPCR and Western blot were used to measure the mRNA and protein expression levels of G protein-coupled bile acid receptor 1 （TGR5） and glucagon-likepeptide-1/2 （GLP-1/2） in the intestine and TGR5 and glucagon-like peptide-2 receptor （GLP-2R） in gallbladder； metabolomics methods were used to determine bile acid composition in intestinal contents. The independent-samples t-test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test or the Games-Howell method was used for further comparison between two groups. ResultsCompared with the blank group， the CS group showed significant gallstone formation， bile turbidity， hepatic steatosis， abnormal gallbladder wall structure， and significant increases in anxiety- and depression-like behaviors based on behavioral tests； significant increases in the level of total cholesterol in bile and the serum levels of alanine aminotransferase， aspartate aminotransferase， and low-density lipoprotein and significant reductions in the level of total bile acid （TBA） in bile and the serum levels of CCK and high-density lipoprotein （HDL） （all P<0.05）； significant increases in the mRNA expression levels of GLP-1/2 and TGR5 in the intestine and the protein expression levels of GLP-2R and TGR5 in the gallbladder and significant reductions in the mRNA expression levels of GLP-2R and TGR5 in the gallbladder （all P<0.05）； significant changes in multiple bile acid components in intestinal contents （all P<0.05）. Compared with the CS group， the CS liver depression group had further aggravation of pathological and behavioral manifestations， changes in bile acid composition， significant increases in the protein and mRNA expression levels of TGR5 and GLP-1/2 in the intestine， and significant increases in the protein and mRNA expression levels of TGR5 and GLP-2R in the gallbladder （all P<0.01）. Compared with the CS liver depression group， both treatment groups had an improvement in gallbladder morphology， alleviation of stones and liver injury， and recovery of liver function and blood lipid levels， as well as significant reductions in the protein and mRNA expression levels of TGR5 and GLP-1/2 in the intestine and TGR5 and GLP-2R in the gallbladder （all P<0.05）； the traditional Chinese medicine group showed significant increases in glycodeoxycholic acid （GDCA）， tauro-α-muricholic acid （T-α-MCA）， and taurochenodeoxycholic acid （TCDCA） （all P<0.05）， while the Western medicine group showed significant increases in taurohyodeoxycholic acid， T-α-MCA， TCDCA， GDCA， and glycoursodeoxycholic acid （all P<0.05）. Compared with the Western medicine group， the traditional Chinese medicine group had significantly greater behavioral improvements， significantly higher levels of TBA in bile and serum HDL （both P<0.01）， significant reductions in the protein expression levels of TGR5 and GLP-1/2 in the intestine and TGR5 and GLP-2R in the gallbladder， and a significant reduction in the mRNA expression level of TGR5 in the intestine （all P<0.01）， as well as a significant increase in tauroursodeoxycholic acid and significant reductions in glycoursodeoxycholic acid， taurohyodeoxycholic acid， TCDCA， and taurolithocholic acid （all P<0.05）. ConclusionModified Chaihu Shugan Powder can improve liver function and abnormal gallbladder relaxation in CS with liver depression syndrome by regulating the bile acid-TGR5 axis， thereby exerting the therapeutic effect of soothing the liver， resolving depression， moving Qi， and promoting bile flow.

Objective:To explore the relationship between life events, anxiety, depression, and behavior problems in adolescents.Methods:From September to October 2022, the cluster sampling method was used to select 5 341 adolescents from 4 middle schools in Xinxiang urban area.The subjects and their parents were investigated by the adolescent self-rating life events check list (ASLEC), generalized anxiety disorder scale (GAD-7), patient health questionnaire (PHQ-9), and child behavior checklist (CBCL). SPSS 27.0 software was used for Spearman correlation analysis, and AMOS 28.0 software was used to construct the structural equation model.Results:The scores of anxiety, depression, and behavioral problems were 1 (0, 4), 1 (0, 4), and 3 (0, 10). The total score of life events was 5 (1, 13), and the dimensions scored as follows: interpersonal conflict 1 (0, 4), academic pressure 2 (0, 5), punishment 0 (0, 2), loss 0 (0, 0), health and adaptation problem 0 (0, 1), and others 0 (0, 2). There were positive correlations between life events and its dimensions, depression, anxiety and behavioral problems ( r=0.28-0.69, all P<0.01). In the overall population, anxiety and depression played parallel mediating roles in the impact of life events on behavior problems. Life events could positively predict anxiety ( β=0.68, P<0.01), and anxiety could positively predict behavior problems ( β=0.04, P=0.02). Life events could positively predict depression ( β=0.77, P<0.01), and depression could positively predict behavior problems ( β=0.18, P<0.01). The standardized total effect size of the impact of life events on behavioral problems was 0.622 (95% CI=0.564-0.675). The standardized direct effect size and indirect effect size were 0.460 (95% CI=0.374-0.539) and 0.162 (95% CI=0.108-0.218), accounting for 74.0% and 26.0%of the total effect, respectively. After stratification by gender, the results for male adolescents were consistent with the overall population, while the mediating effect of anxiety was not significant in the female adolescents. Conclusion:Life events can lead to anxiety and depression in adolescents, thereby increasing the risk of behavior problems.

Objective:To explore the relationship between life events, anxiety, depression, and behavior problems in adolescents.Methods:From September to October 2022, the cluster sampling method was used to select 5 341 adolescents from 4 middle schools in Xinxiang urban area.The subjects and their parents were investigated by the adolescent self-rating life events check list (ASLEC), generalized anxiety disorder scale (GAD-7), patient health questionnaire (PHQ-9), and child behavior checklist (CBCL). SPSS 27.0 software was used for Spearman correlation analysis, and AMOS 28.0 software was used to construct the structural equation model.Results:The scores of anxiety, depression, and behavioral problems were 1 (0, 4), 1 (0, 4), and 3 (0, 10). The total score of life events was 5 (1, 13), and the dimensions scored as follows: interpersonal conflict 1 (0, 4), academic pressure 2 (0, 5), punishment 0 (0, 2), loss 0 (0, 0), health and adaptation problem 0 (0, 1), and others 0 (0, 2). There were positive correlations between life events and its dimensions, depression, anxiety and behavioral problems ( r=0.28-0.69, all P<0.01). In the overall population, anxiety and depression played parallel mediating roles in the impact of life events on behavior problems. Life events could positively predict anxiety ( β=0.68, P<0.01), and anxiety could positively predict behavior problems ( β=0.04, P=0.02). Life events could positively predict depression ( β=0.77, P<0.01), and depression could positively predict behavior problems ( β=0.18, P<0.01). The standardized total effect size of the impact of life events on behavioral problems was 0.622 (95% CI=0.564-0.675). The standardized direct effect size and indirect effect size were 0.460 (95% CI=0.374-0.539) and 0.162 (95% CI=0.108-0.218), accounting for 74.0% and 26.0%of the total effect, respectively. After stratification by gender, the results for male adolescents were consistent with the overall population, while the mediating effect of anxiety was not significant in the female adolescents. Conclusion:Life events can lead to anxiety and depression in adolescents, thereby increasing the risk of behavior problems.

BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION ClinicalTrials.gov (NCT02763566).
Humans ; Female ; Fulvestrant/therapeutic use* ; Breast Neoplasms/metabolism* ; Aminopyridines/therapeutic use* ; Benzimidazoles/therapeutic use* ; Middle Aged ; Aromatase Inhibitors/therapeutic use* ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Letrozole/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anastrozole/therapeutic use*

Objective:To develop and externally validate a nomogram prediction model for assessing the risk of treatment dropout in allergic rhinitis (AR) patients undergoing sublingual immunotherapy (SLIT).Methods:Between February 2016 and December 2019, data from 358 and 259 AR patients undergoing SLIT were collected from Guizhou Provincial People′s Hospital and Huangshi Central Hospital, respectively. The data included general patient information, dust mite sIgE levels, allergen types, and 22 other clinical variables. Data from Guizhou Provincial People′s Hospital were used as the training set, while data from Huangshi Central Hospital were served as the external validation set. A multivariable Cox regression model was used to identify independent factors associated with SLIT dropout and to develop a nomogram prediction model.Results:Multivariate Cox regression analysis identified several significant factors influencing SLIT dropout, including dust mite sIgE levels (Grade Ⅱ-Ⅳ; HR=1.48, 95% CI: 1.16-1.88), presence of other allergic diseases ( HR=0.47, 95% CI: 0.37-0.61), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score ( HR=0.98, 95% CI: 0.97-1.00), WeChat management ( HR=0.77, 95% CI: 0.60-0.98), treatment efficacy ( HR=0.72, 95% CI: 0.56-0.92), age (5-17 years, HR=0.50, 95% CI: 0.36-0.71;≥60 years, HR=1.42, 95% CI: 1.08-1.87), household income (<5 000 CNY, HR=1.44, 95% CI: 1.09-1.90;>20 000 CNY, HR=0.66, 95% CI: 0.44-0.99), allergen types (single dust mite, HR=0.70, 95% CI: 0.49-0.93; and combined pollen or mold, HR=1.45, 95% CI: 1.02-2.04), and time to efficacy <3 months ( HR=0.73, 95% CI: 0.56-0.94), all P<0.05. At the third-year follow-up, the area under curve (AUC) for the nomogram model was 0.913 (95% CI: 0.881-0.943) in the training group and 0.886 (95% CI: 0.838-0.933) in the validation group. Calibration and decision curve analyses demonstrated the model′s consistency with actual dropout rates and clinical benefit in both groups. Additionally, a Brier score of 0.29 further confirmed the model′s predictive accuracy. Conclusion:We successfully develop a nomogram-based prediction model for SLIT dropout in AR patients, which could assist healthcare professionals in effectively identifying high-risk patients and facilitate the development of more personalized and timely treatment plans aimed at enhancing patient compliance.

Objective:To develop and externally validate a nomogram prediction model for assessing the risk of treatment dropout in allergic rhinitis (AR) patients undergoing sublingual immunotherapy (SLIT).Methods:Between February 2016 and December 2019, data from 358 and 259 AR patients undergoing SLIT were collected from Guizhou Provincial People′s Hospital and Huangshi Central Hospital, respectively. The data included general patient information, dust mite sIgE levels, allergen types, and 22 other clinical variables. Data from Guizhou Provincial People′s Hospital were used as the training set, while data from Huangshi Central Hospital were served as the external validation set. A multivariable Cox regression model was used to identify independent factors associated with SLIT dropout and to develop a nomogram prediction model.Results:Multivariate Cox regression analysis identified several significant factors influencing SLIT dropout, including dust mite sIgE levels (Grade Ⅱ-Ⅳ; HR=1.48, 95% CI: 1.16-1.88), presence of other allergic diseases ( HR=0.47, 95% CI: 0.37-0.61), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score ( HR=0.98, 95% CI: 0.97-1.00), WeChat management ( HR=0.77, 95% CI: 0.60-0.98), treatment efficacy ( HR=0.72, 95% CI: 0.56-0.92), age (5-17 years, HR=0.50, 95% CI: 0.36-0.71;≥60 years, HR=1.42, 95% CI: 1.08-1.87), household income (<5 000 CNY, HR=1.44, 95% CI: 1.09-1.90;>20 000 CNY, HR=0.66, 95% CI: 0.44-0.99), allergen types (single dust mite, HR=0.70, 95% CI: 0.49-0.93; and combined pollen or mold, HR=1.45, 95% CI: 1.02-2.04), and time to efficacy <3 months ( HR=0.73, 95% CI: 0.56-0.94), all P<0.05. At the third-year follow-up, the area under curve (AUC) for the nomogram model was 0.913 (95% CI: 0.881-0.943) in the training group and 0.886 (95% CI: 0.838-0.933) in the validation group. Calibration and decision curve analyses demonstrated the model′s consistency with actual dropout rates and clinical benefit in both groups. Additionally, a Brier score of 0.29 further confirmed the model′s predictive accuracy. Conclusion:We successfully develop a nomogram-based prediction model for SLIT dropout in AR patients, which could assist healthcare professionals in effectively identifying high-risk patients and facilitate the development of more personalized and timely treatment plans aimed at enhancing patient compliance.

Objective: To examine the mediating effects of blood pressure, glucose, lipids, and serum uric acid on the association between childhood overweight/obesity and left ventricular hypertrophy (LVH), and to provide scientific evidence for the prevention and control of cardiovascular diseases during childhood. Methods: One public school in Huantai County, Zibo City was selected to conduct the baseline survey from November 2017 to January 2018 using a convenient cluster sampling method. A total of 1 400 children aged 6 to 11 were included in the study. According to the classification criteria based on body mass index (BMI), participants were divided into the non overweight/obese group ( n =787) and the overweight/obese group ( n =613). The mediating effects of metabolic variables on the association between childhood overweight/obesity and left ventricular hypertrophy (LVH) were analyzed using the "mediation" package in R software. Results: Children who were overweight/obese had higher levels of BMI- Z score (2.0±0.8), systolic blood pressure (SBP) (109.1±8.9 mmHg), diastolic blood pressure (DBP) (65.4±6.8 mmHg), fasting plasma glucose (FPG) (4.8±0.5 mmol/L), insulin (INS) (11.3±7.6 μU/mL), apolipoprotein B (ApoB) (0.7±0.2 g/L), lowdensity lipoprotein cholesterol (LDL-C) (2.4±0.7 mmol/L), total cholesterol (TC) (4.2±0.9 mmol/L), triglycerides (TG) (0.9±0.4 mmol/L), and serum uric acid (SUA) (321.2±91.4 μmol/L) compared to those who were non-overweight/obese [the corresponding values were (-0.2±0.7),(104.3±8.8) mmHg, (62.2±6.2) mmHg, (4.7±0.6) mmol/L, (6.1±4.2) μU/mL, (0.6±0.2) g/L, (2.2±0.6) mmol/L, (4.1±0.7) mmol/L, (0.7±0.2) mmol/L, and (278.6±74.7) μmol/L, respectively], whereas the levels of high density lipoprotein cholesterol (HDL-C) were lower in overweight/obese children (1.5±0.3 mmol/L) than in non-overweight/obese children (1.7±0.4 mmol/L). All differences were statistically significant ( t =53.66, 9.88, 9.19, 3.60, 16.32, 7.36, 5.11, 2.55, 11.08, 9.58, -10.31, P <0.05). After adjusting for potential covariates, overweight/obese children had 8.72 times increased risk of developing LVH compared to the non-overweight/obese children ( OR=8.72, 95%CI =5.45-14.66， P <0.01). Mediation analysis showed that INS, HDL-C, LDL-C, TG, ApoB, and SUA partially mediated the association between childhood overweight/obesity and LVH, and among these, INS and TG had relatively strong mediating effects, accounting for 28.05% and 13.71% of the total effects, respectively. Conclusions INS, HDL-C, LDL-C, TG, ApoB, and SUA are intermediate risk factors on the association between childhood overweight/obesity and LVH. Keeping metabolic indicators (especially INS and TG) at healthy levels is particularly important for reducing the burden of cardiovascular diseases in overweight/obese children.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective Investigating the impact of miR-15a-5p on autophagy in trophoblast cells of pre-eclamptic placenta.Methods Collect 20 cases of normal placental tissue and 20 cases of preeclamptic placental tissue from December 2020 to December 2022.Use fluorescence quantitative PCR to detect the expression of miR-15a-5p in placental tissue and trophoblast cells,and study its correlation with patient blood pressure.The HTR8-S/Vneo cells are divided into normal group(control)and hypoxia group,and the effect of hypoxia on the expression of miR-15a-5p is observed.Additionally,mimic-NC group,mimic-NC+hypoxia group,miR-15a-5p mimic group,miR-15a-5p mimic+hypoxia group,inhibitor-NC group,inhibitor-NC+hypoxia group,miR-15a-5p inhibitor group,and miR-15a-5p inhibitor+hypoxia groups are set up to observe the effect of miR-15a-5p on hypoxia-induced autophagy-related proteins LC3B and p62 protein in trophoblast cells.Western blot is used to detect the expression levels of autophagy-related proteins LC3B and p62 protein in each group;TargetScan website predicts the target genes of miR-15a-5p,and detects their expression levels in placental tissue and trophoblast cells.Results Compared with the control group,the expression levels of miR-15a-5p were significantly increased in the placentas and hypoxic trophoblasts of preeclampsia,and they were positively correlated with the blood pressure of the patients.Under hypoxic conditions,the overexpressed miR-15a-5p promoted the protein expression of LC3BII/I,while the relative expression of P62 was decreased.But after interference with miR-15a-5p,LC3BII/I expression was down-regulated and P62 expression was up-regulated.The results of quantitative PCR and Western blot showed that the expression levels of YAP1 in the preeclampsia placental tissues and hypoxic trophoblasts were significantly reduced.Conclusion The upregulation of miR-15a-5p in trophoblast cells of the placenta in individuals with preeclampsia could enhance autophagy in preeclampsia by forming a complex with YAP1.

Goniotomy (GT) is a safe and effective type of minimally invasive glaucoma surgery (MIGS) extensively utilized in China.It is particularly suited for treating primary open-angle glaucoma and advanced primary angle-closure glaucoma.Although GT is generally safe, hyphema and postoperative intraocular pressure (IOP) spikes remain common complications after GT.Currently, there is no standardized protocol for managing these issues, which can impact clinicians' assessment of surgical outcomes and potentially affect the prognosis.Therefore, it is crucial to establish comprehensive and detailed management protocols for perioperative hyphema and IOP spike following GT.This will guide clinical practitioners in managing complications appropriately and systematically, thereby promoting the further development and refinement of MIGS.To address these concerns, several domestic glaucoma treatment experts along with members of the Glaucoma Society of Ophthalmology, Guangdong Medical Association reviewed existing literature and held recommendation meetings to develop a guideline for managing perioperative hyphema and IOP spikes following GT.It includes defining perioperative hyphema in GT, discussing its high-risk factors and outcomes, exploring methods for prevention prior to surgery and techniques to reduce bleeding during the procedure, and managing postoperative hemorrhage.Additionally, it covers defining IOP spikes after GT, investigates their causes and contributing factors, and outlines management strategies and anticipated outcomes to provide a valuable resource for clinicians.