Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, characterized by poor prognosis due to its high proliferative and invasive potential. Tumor metabolic reprogramming, particularly involving glucose metabolism, is essential for tumor survival. This study investigates the role of the Hippo pathway effector transcriptional co-activator with PDZ-binding motif (TAZ) in regulating gluconeogenesis and promoting tumorigenesis in HCC. Methods: TAZ expression in HCC was analyzed using The Cancer Genome Atlas data and validated in clinical samples and cell lines. TAZ was overexpressed or silenced in HCC cell lines to evaluate its effects on cell proliferation, apoptosis, migration, and invasion. The expression and prognostic relevance of the gluconeogenesis-related genes phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6-phosphatase (G6PC) were examined, along with their correlation with TAZ expression. Tumor growth was assessed in nude mice. Interactions between TAZ and the glucocorticoid receptor (GR) were investigated using co-immunoprecipitation, immunofluorescence, and chromatin immunoprecipitation assays. Results: TAZ was significantly upregulated in HCC tissues and cell lines. TAZ overexpression enhanced proliferation, reduced apoptosis, and promoted migration and invasion. In contrast, PCK1 and G6PC were downregulated in HCC and showed a negative correlation with TAZ expression. Conclusion TAZ modulates gluconeogenesis and accelerates tumor growth, whereas its knockdown attenuates tumor progression. TAZ interacts with GR, suppressing its transcriptional activity on gluconeogenic gene promoters.

Sarcopenia is a systemic disease characterized by accelerated loss of skeletal muscle mass and function,leading to an increased incidence of adverse outcomes such as falls and fractures.Sarcopenia is classified into primary and secondary types,with primary sarcopenia being closely related to aging and posing a serious threat to a healthy life among the elderly.Sarcopenia has an insidious onset and is often overlooked in terms of its clinical treatment.Its pathogenesis is complex,involving functional changes and pathological alterations in multiple systems,and presenting major research challenges.Cell models can effectively be used to simulate the pathological changes of diseases under controllable conditions,thus facilitating the investigation of the etiology and factors influencing sarcopenia,and providing an important approach for in-depth studies of its mechanism;however,there is currently no standardized cell model in the field of sarcopenia research.Commonly used cell models currently include models involving protein metabolism interventions,oxidative stress,and inflammatory response interventions.This review considers the commonly used skeletal muscle cell types and modeling method of sarcopenia,to provide a solid foundation and important method ological reference for further simulation of the pathological process of sarcopenia in subsequent experimental studies.

Objective:To screen bile acid-related characteristic genes in IgA nephropathy (IgAN) based on the feature gene selection algorithm in the machine learning method, aiming to exploring the molecular biological mechanisms and biomarkers of IgAN.Methods:The gene expression data and sample grouping information of GSE93798, GSE116626 and GSE35487 were downloaded from the Gene Expression Omnibus (GEO). Bile acid-related gene sequences were obtained from the Molecular Signatures Database (MSigDB). R language was used to identify differentially expressed genes between IgAN samples and healthy control samples. Candidate genes were obtained by intersecting differentially expressed genes and bile acid-related genes. The least absolute shrinkage and selection operator (LASSO) algorithm in machine learning was used to screen the feature genes in the candidate genes as biomarkers, and the feature genes in the training set and validation set were analyzed by the rate of change index. Receiver operating characteristic curve (ROC) method was used to evaluate the diagnostic value of identified bile acid related characteristic genes for IgAN. Gene set enrichment analysis (GSEA) was used to analyze the Spearman correlation between the characteristic genes and all other genes and their related metabolic pathways. The expression of disease-characteristic genes in the kidney tissues of IgAN rats was validated by real-time PCR.Results:Gene expression information from kidney tissue samples of 20 IgAN cases and 22 healthy controls were obtained from GEO database. A total of 204 bile acid-related genes including 24 pathways were obtained from MSigDB. The results of gene differential expression analysis showed that 333 genes in the kidney tissues of IgAN patients were differentially expressed compared with those of healthy controls, including 102 up-regulated genes and 231 down-regulated genes, among which 12 differentially expressed genes were related to bile acid genes, as follows: NR1H4,SLC23A1, ALDH8A1, FABP1, ALB, SLC27A2, DIO1, CYP8B1, BBOX1, PIPOX, AKR1C1 and SLC10A2. Five characteristic genes ( NR1H4, SLC23A1, FABP1, ALB and AKR1C1) were screened by LASSO regression algorithm.ROC analysis results showed that in GSE93798 cohort genes, the AUC of NR1H4, SLC23A1, FABP1 and ALB genes with differential expression was >0.95 respectively in diagnosing IgAN, and that of AKR1C1 genes with differential expression was >0.85 in diagnosing IgAN. The gene expression data of SLC23A1 in GSE35487 cohort was missing. ROC analysis results of other four genes showed that the AUC of differential expression of ALB gene for IgAN was >0.95 respectively, that of NR1H4 gene was >0.70, and that of both FABP1 and AKR1C1 gene was >0.60. In the GSE116626 cohort genes, the AUC of five disease characteristic genes ( NR1H4, SLC23A1, FABP1, ALB, AKR1C1) for diagnosing IgAN was >0.60, respectively. These results suggested that 5 characteristic genes have certain distinguishing ability between IgAN group and control group. GSEA results were displayed that the characteristic genes were related to butyric acid metabolism, propionic acid metabolism, arginine and proline metabolism, valine leucine and isoleucine degradation, fatty acid metabolism, etc. These results suggested that five characteristic genes might be related to IgAN through the above metabolic mechanisms. The verification results of five bile acid characteristic genes in the rat model of IgAN in the kidney tissue showed that the expressions of four genes, NR1H4, SLC23A1, FABP1 and ALB, were higher than those of the control group, and there was no statistical significance in the expression of AKR1C1 gene between the two groups. Conclusions:The expression of bile acid-related characteristic genes is abnormal in the kidney tissue of IgAN patients. Four bile acid-related differentially expressed genes, NR1H4, SLC23A1, FABP1 and ALB, are expected to be biomarkers for non-invasive diagnosis and therapeutic targets .

Clinical pharmacist training is an important way to strengthen the clinical pharmacist team's construction and improve their pharmaceutical service capabilities and levels.The Pharmacy Administration and Pharmacy Practice in Healthcare Institutions-Part 4-8-1:Pharmacy Administration-Pharmacy Training Management-Clinical Pharmacist Training was based on the relevant requirements of the current clinical pharmacist training system of the Chinese Hospital Association,and formulated by sor-ting out relevant materials,such as standards,policies and regulations,technical specifications,literature,the current situation of clinical pharmacist training in China,and expert opinions.A total of 15 key elements of clinical pharmacist training were selected and divided into three aspects(base management,training process and assessment,and the quality management,evaluation and improvement).This article mainly introduced the construction method and content of the clinical pharmacist training standard,to deepen the understanding of the standard for relevant units and to promote the implementation of the standard.

Objective:To investigate the association between estimated glomerular filtration rate (eGFR) and the onset and progression of type 2 diabetic retinopathy (DR).Methods:Observational studies on the relationship between eGFR and the progression of DR were searched in the databases of PubMed, Web of Science, Foreign Medical Literature Retrieval Service (FMRS), China National Knowledge Infrastructure and Wanfang data. The search period was from the inception of the databases to January 20, 2024. Meta-analysis of the association between eGFR and the onset and progression of DR with the research data was conducted by using Review Manager 5.3 and Stata 15.0, the weighted mean difference (WMD) and 95% confidence interval (CI) were calculated. Sensitivity analysis and Egger′s test were performed to assess the result stability and publication bias.Results:A total of 30 studies involving 119 142 patients with type 2 diabetes were included in the analysis. The eGFR in the DR group was significantly lower than that in the non-DR group (WMD=8.11, 95% CI: 5.97-10.25, P<0.001). Subgroup analysis by DR type revealed that patients with diabetic macular edema (WMD=7.61, 95% CI: 3.82-11.40) and proliferative DR (WMD=17.40, 95% CI: 10.13-24.66) had significantly lower eGFR when compared to that in non-DR group (both P<0.001). The subgroup analysis results according to different DR diagnostic criteria showed that both the 2003 International DR Grading Standard Group (WMD=8.55, 95% CI: 5.29-11.81) and the 2002 International Clinical DR Severity Grading Standard Group (WMD=10.70, 95% CI: 7.99-13.41) indicated the statistically significant differences in eGFR in relation to the occurrence and progression of DR. Conclusion:The decrease of eGFR is closely related to the occurrence and progression of DR.

Objective:To investigate the adjunctive diagnostic value of retinal imaging structural parameters combined with apolipoprotein E (ApoE) gene polymorphisms for Alzheimer′s disease (AD).Methods:It was a case-control study, 71 confirmed AD patients who attended the Department of Neurology in Sichuan Provincial People′s Hospital from May 2023 to June 2024 and 156 healthy medical checkups who participated in medical checkups in the Health Management Center were continuously with convenience sampling method; the subjects were included as the AD case group and healthy control group, respectively. Optical coherence tomography (OCT) was used to measure the structural parameters of retinal imaging such as the thickness of the retinal nerve fiber layer (RNFL) and the retinal nerve fiber layer-inner plexiform layer (RNFL-IPL) in the study subjects. Information on demographic characteristics and disease history of the study participants were collected through a questionnaire, and venous blood was collected to test for ApoE gene polymorphisms. The retinal imaging structural parameters, ApoE gene polymorphisms and other related indicators were included in a multifactorial logistic regression model to analyze the main factors affecting the risk of AD. Based on the results of the multifactorial analysis, the receiver operating characteristic (ROC) curves were plotted and the areas under the curve (AUC) were calculated to evaluate the efficacy of different models in the adjunctive diagnosis of AD.Results:Of the 227 study subjects included in the analysis, 153 were females and 74 were males; there were 71 cases in the AD case group with a mean age of (66.73±8.83) years, and there were 156 subjects in the healthy control group with an average age of (61.95±8.21) years. Educational attainment of elementary school and below ( OR=4.683, 95% CI: 2.133-10.282), living visual acuity<0.5 ( OR=2.716, 95% CI: 1.12-6.583), and carrying ≥1 ApoE ε4 genes ( OR=5.331, 95% CI: 2.309-11.891) were positively correlated with the risk of AD. RNFL thickening ( OR=0.923, 95% CI: 0.854-0.998) was negatively associated with the risk of AD (all P<0.05). The AD risk assessment model (Model 4), which included fundus imaging features and ApoE gene polymorphisms, had the highest predictive efficacy (AUC=0.857, P<0.001). Conclusion:Retinal imaging structural parameters differ significantly between AD patients and healthy examinees, and a risk assessment model combining retinal imaging structural parameters and ApoE gene polymorphisms has high predictive value and is expected to serve as an auxiliary diagnostic tool for AD.

The surgical treatment of esophageal cancer is moving towards minimally invasiveness and individualization. Thoracoscopic-laparoscopic esophagectomy has become the mainstream due to its superior short-term outcomes and potential survival benefits. Robotic surgery demonstrates advantages in precise lymph node dissection, particularly in the protection of the recurrent laryngeal nerve. Transcervical mediastinoscopic esophagectomy provides a new option for patients unable to tolerate transthoracic surgery.For adenocarcinoma of esophagogastric junction, the choice between transthoracic and transabdominal approaches should be individualized based on factors such as the extent of esophageal invasion. In the treatment of cervical esophageal cancer, larynx-preserving surgery is increasingly prominent. Additionally, active surveillance (organ-preser-vation strategy) after neoadjuvant therapy, as well as conversion and salvage surgeries, offer more curative opportunities for specific patients. The authors review the latest advances in the surgical treatment of esophageal cancer, provide an outlook on future directions, with the aim of offering references for clinical practice.

Purpose To explore the expression level of let-7b-5p in glioma and its effects and potential mecha-nisms on U251 cell growth.Methods The expression of let-7b-5p in glioma was detected using qRT-PCR.Data from the CGGA database were analyzed to examine the relationship between the let-7b-5p expression levels,WHO grade and overall survival rates of glioma patients.Transient transfection was used to downregulate the expression of let-7b-5p and IGF1R in U251 cells.The role and potential mechanism of let-7b-5p in the U251 cell were evaluated using qRT-PCR,CCK8 assays,clone formation assays,Western blotting,and double luciferase reporter assays.Results The expres-sion of let-7b-5p in glioma cells(A172:3.64±0.64,V251:4.56±0.52,U87-MG:3.31±0.50)and tissues(2.18±0.22)was significantly higher than that in astrocytes(HMC3:1.00±0.21,P＜0.05 or P＜0.01)and nor-mal brain tissues(1.01±0.19,P＜0.05).Let-7b-5p expression was negatively correlated with WHO grades but pos-itively correlated with survival rates in primary and recurrent glioma patients(P＜0.000 1 and P=0.028,respective-ly).Knockdown of let-7b-5p in U251 cells significantly promoted the growth of glioma cells(CCK8:knockdown group 126.00±12.09 vs miR-NC group 90.93±5.13,P＜0.05)and activated PI3K/AKT signal pathway.Suppressing IGF1R expression in U251 cells reversed the effects of let-7b-5p knockdown on glioma cell growth[CCK8:let-7b-5p knockdown+IGF1R knockdown group(92.08±6.14)vs let-7b-5p knockdown+sh-NC group(116.67.08±8.50)]and PI3K/AKT signal pathway activation.Conclusion Let-7b-5p functions as a tumor suppressor gene in glioma.It may regulate glioma cell growth by targeting IGF1R and modulating PI3K/AKT signal pathway.

Schizophrenia is a chronic and debilitating mental disorder.Around 20%to 40%of patients do not respond well to normal antipsychotic medication,and are ultimately diagnosed with treatment-resistant schizophrenia(TRS),representing the most severe and challenging form of schizophrenia.Currently,clozapine is the standard treatment for TRS.Early identification and standardized treatment can be beneficial to patients with TRS by controlling acute-phase symptoms as soon as possible,reducing suicidal rate and improving their quality of life.Under the guidance of the Steering Committee,this consensus was formed after multiple discussions by 30 psychiatric experts and anonymous Delphi surveys including 17 consensus opinions on treatment-resistant schizophrenia,which cover risk factors and prevention,diagnosis and evaluation,standardized clozapine treatment and management of adverse reactions,treatment regimens for clozapine resistance and intolerance,and psychosocial intervention,etc.The consensus-making process also incorporated evidence-based medicine to help standardize and guide diagnosis and treatment for adults with TRS in China.

Astrocytes and microglia engage in extensive and complex communication and mutual effect, which referrs to microglia-astrocyte crosstalk. Recent studies have highlighted that this crosstalk plays a pivotal role in neurodegenerative diseases, exerting either protective or detrimental effects. This review briefly introduces the molecular mechanism of microglia-astrocyte crosstalk and its research progress in Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Parkinson's disease, aiming to provide new research directions and therapeutic targets for clinical improvement of neurodegenerative diseases from perspective of microglia-astrocyte crosstalk.