OBJECTIVES: To investigate the mechanism through which salidroside inhibits proliferation of gastric cancer (GC) cells focusing on glucose metabolic reprogramming pathways. METHODS: High-throughput sequencing combined with bioinformatics analysis was employed to identify the potential targets of salidroside in human GC MGC-803 cells. Liposome-mediated transfection experiments were carried out to validate the functional and mechanistic roles of these targets. CCK-8 and colony formation assays were used to assess the effects of salidroside on GC cell viability and clonogenic ability. qRT-PCR, Western blotting, and biochemical assay kits were used to analyze the regulatory effects of salidroside on the miR-1343-3p-OGDHL/PDHB enzyme complex-pyruvate metabolic pathway in GC cells. RESULTS: Bioinformatics analysis suggested that the tumor-suppressive factor miR-1343-3p negatively regulated the key glycolytic enzyme gene oxoglutarate dehydrogenase-like (OGDHL) in GC cells, and OGDHL and pyruvate dehydrogenase E1 subunit beta (PDHB) were both significantly upregulated in GC tissues, which was close by correlated with reduced survival rates of GC patients. In MGC-803 cells, salidroside treatment significantly enhanced the expression level of miR-1343-3p and downregulated OGDHL expression, resulting in disruption of the stability of PDHB, reduced pyruvate oxidative decarboxylation, and consequently decreased production of acetyl-CoA and ATP. CONCLUSIONS Salidroside inhibits GC cell proliferation possibly by regulating the miR-1343-3p-OGDHL/PDHB enzyme complex-pyruvate metabolic pathway, which provides new insights into its anti-tumor mechanisms and suggests new strategies for targeted therapy for GC.
Humans ; Stomach Neoplasms/pathology* ; MicroRNAs/genetics* ; Cell Proliferation/drug effects* ; Glucosides/pharmacology* ; Phenols/pharmacology* ; Cell Line, Tumor ; Glucose/metabolism* ; Pyruvate Dehydrogenase (Lipoamide)/metabolism*

Objective To investigate the molecular mechanism by which salidroside inhibits the proliferation of gastric cancer(GC)cells through upregulation of miR-1343-3p.Methods RNA databases were used to screen for mRNAs associated with tumor proliferation and with miR-1343-3p,and exhibiting significant changes in their expression levels after salidroside treatment of human GC cells.Gene matching and immunoprecipitation of RNA-binding proteins were conducted to analyze the association between miR-1343-3p and SOX18.Immunocytochemistry was performed to determine the localization of SOX18 protein.The effect of salidroside on the proliferation of human GC cells(MGC-803 and AGS)was determined by CCK-8 assay.Human GC cells were divided into a blank control group and low-and high-dose salidroside groups.The expression of miR-1343-3p and SOX18 mRNA was measured by real-time quantitative fluorescence PCR(qPCR).The protein expression of SOX18 was measured by Western blot.GC cells were co-transfected with miR-1343-3p mimic and miR-1343-3p inhibitor,respectively,via LipofectamineTM 2000 liposomes.The expression of miR-1343-3p and SOX18 mRNA was measured by qPCR,and the protein expression of SOX18 was measured by Western blot.Results Through bioinformatic analysis,SOX18 was identified as a downstream target of miR-1343-3p.Gene alignment confirmed the presence of specific binding sites between the two genes,and immunoprecipitation of RNA-binding proteins validated the targeting relationship between them(P<0.05).Immunocytochemistry demonstrated the nuclear localization of SOX18 protein.CCK-8 assay findings demonstrated that salidroside significantly inhibited the proliferation of GC cells in a time-and dose-dependent manner.Compared with the blank control group,salidroside-treated GC cells showed decreased expression of both SOX18 mRNA and protein(P<0.05)and an increased miR-1343-3p expression(P<0.05).Compared with the control group,GC cells in the miR-1343-3p mimic group exhibited increased expression of miR-1343-3p and decreased expression of SOX18 mRNA and protein.In contrast,GC cells in the miR-1343-3p inhibitor group showed decreased expression of miR-1343-3p and increased expression of SOX18 mRNA and protein(all P<0.05).Conclusion Salidroside may inhibit the proliferation of GC cells by regulating the miR-1343-3p/SOX18 signaling axis and these regulators may present new potential therapeutic targets or biomarkers for gastric cancer.

OBJECTIVE To develop a standard of hierarchical management for patients with chronic obstructive pulmonary disease （COPD） from the perspective of pharmacists. METHODS The triangle hierarchical management model was used as the framework. Through literature research， the indicators of the hierarchical management standard for COPD patients were preliminarily compiled. A questionnaire was designed and administered to 18 experts， and Delphi method was conducted in two rounds to determine the contents of the standard. RESULTS The response rates for both rounds of expert consultation were 100%， with both authority coefficients of experts of 0.903 and Kendall coordination coefficiens of 0.279 and 0.189 for each indicator. The final established standard of hierarchical management for COPD patients included 25 stratified indicators and 17 pharmaceutical hierarchical management indicators. There were 9， 8 and 8 indicators in the high-risk， medium-risk， and stable layers， respectively， considering three aspects： disease， medication， and self-management level. The corresponding first-level， second- level， and third-level pharmaceutical management included 6， 6 and 5 indicators， respectively， including inhalation technical guidance， medication adherence guidance， treatment monitoring， and follow-up， etc. CONCLUSIONS The standard of hierarchical management for COPD patients established by Delphi method is scientific and reliable， which can provide a reference for pharmacists to carry out hierarchical management of COPD patients in China.

Objective To retrospective analyze the use of inpatients taking sacubitril/valsartan in Nanjing Drum Tower Hospital,and to provide references for rational clinical application.Methods The relevant data of inpatients taking sacubitril/valsartan in our hospital were systematically collected from July 2019 to September 2021,and the rationality of drug use was eval-uated.Results A total of 2 682 cases were collected,and 868 cases(32.36%)of them involved 918 times of irrational drug use.The specific situations of irrational drug use included off-label use(182 times),irrational usage and dosage(389 times),irrational conversation of drugs(251 times),and irrational drug use for special populations(96 times).Conclusion The use of sacubitril/valsartan exists in unreasonable situations in our hospital.Clinical pharmacists should participate in medication man-agement to a certain extent,strengthen the pharmaceutical care of patients,and improve the rational rate of drug use.

Objective:To assess the efficacy of neoadjuvant treatment with PD-1 (programmed cell death protein 1) inhibitors combined with paclitaxel (albumin-conjugated) and cisplatin (TP regimen) for locally advanced hypopharyngeal squamous cell carcinoma and laryngeal organ function preservation.Methods:Data of 53 patients, including 51 males and 2 females, aged 38-70 years old, who were diagnosed with locally advanced hypopharyngeal squamous carcinoma confirmed by histology and enhanced CT at the Cancer Prevention and Control Center of Sun Yat-sen University during the initial treatment from January 1, 2019 to January 15, 2023, were retrospectively analyzed. All patients received neoadjuvant therapy with PD-1 inhibitors combined with albumin-bound paclitaxel (260 mg/m 2) and cisplatin (60 mg/m 2) for 3 to 4 cycles. The main outcome measures were larynx dysfunction-free survival (LDFS), overall survival (OS), and progression-free survival (PFS). Survival curves were plotted using the Kaplan-Meier method, and Cox multifactorial analysis was further performed if Cox univariate analysis was statistically significant. Results:The overall efficiency was 90.6% (48/53). The 1-year and 2-year LDFS rates were 83.8% (95% CI: 74.0% to 94.8%) and 50.3% (95% CI: 22.1% to 91.6%), the 1-year and 2-year OS rates were 95.2% (95% CI: 88.9% to 100.0%) and 58.2% (95% CI: 25.6% to 81.8%), and the 1-year and 2-year PFS rates were 83.9% (95% CI: 74.2% to 94.9%) and 53.5% (95% CI: 32.1% to 89.1%). Adverse events associated with the neoadjuvant therapy were mainly myelosuppression (45.3%), gastrointestinal reactions (37.7%) and hypothyroidism (20.8%). Conclusion:The neoadjuvant treatment of locally advanced hypopharyngeal squamous cell carcinoma using PD-1 inhibitors combined with paclitaxel and cisplatin can provide with a higher survival rate with a improved laryngeal organ function preservation rate.

Schizophrenia is a serious mental disorder that is often associated with profound impairment in patients′ daily functioning, and its etiology and pathophysiology are still to be fully elucidated. There is a pathological correlation between inflammation, brain injuries, and the pathogenesis of schizophrenia, with microglia actively participating in these processes. This review provides a comprehensive overview of the impact of microglial cells on neurodevelopment and neuroplasticity, and microglia abnormalities mediating the onset of schizophrenia by contributing to damage in different brain regions.

Schizophrenia is a serious mental disorder that is often associated with profound impairment in patients′ daily functioning, and its etiology and pathophysiology are still to be fully elucidated. There is a pathological correlation between inflammation, brain injuries, and the pathogenesis of schizophrenia, with microglia actively participating in these processes. This review provides a comprehensive overview of the impact of microglial cells on neurodevelopment and neuroplasticity, and microglia abnormalities mediating the onset of schizophrenia by contributing to damage in different brain regions.

OBJECTIVE To analyze the research status and development trends of the use of sacubitril/valsartan. METHODS Related literature about the use of sacubitril/valsartan were retrieved from CNKI and the core database of Web of Science. CiteSpace 5.8.R3 software was used to analyze authors， countries/areas， institutions and keywords. RESULTS & CONCLUSIONS Totally 1 193 Chinese literature and 1 060 English literature were included. The number of literature increased， with numerous literature covering the United States （429）， the United Kingdom （185） and China （184）. ZHANG Jing （5） and Solomon S D （118） published the highest number of Chinese and English articles. The authors of Chinese literature had less cooperation while the authors of English literature were in close contact. Dept. of Cardiology in the First Affiliated Hospital of Zhengzhou University （9）， Dept. of Cardiology in the Affiliated Hospital of Xuzhou Medical University （9） and Novartis AG （134） had the highest quantity of publications of Chinese and English literature. The institutions of Chinese literature had a small number of overall publications and less cooperation while the institutions of English literature were closely connected. The clinical efficacy of sacubitril/valsartan for heart failure， hypertension and their complications were research hotspots in Chinese and English literature. Chinese scholars and research teams need to strengthen cooperation and communication in the future， as well as conduct research from the perspectives of sacubitril/valsartan in the treatment of heart failure， hypertension and related complication， the improvement of oxidative stress， and the evaluation of the efficacy of combination therapy with dapagliflozin.

OBJECTIVE: To explore the genetic basis for a child with congenital heart disease (CHD) and global developmental delay (GDD). METHODS: A child who was hospitalized at the Department of Cardiac Surgery of Fujian Children's Hospital on April 27, 2022 was selected as the study subject. Clinical data of the child was collected. Umbilical cord blood sample of the child and peripheral blood samples of his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 3-year-and-3-month-old boy, had manifested cardiac abnormalities and developmental delay. WES revealed that he had harbored a nonsense variant of c.457C>T (p.Arg153*) in the NONO gene. Sanger sequencing showed that neither of his parents has carried the same variant. The variant has been recorded by the OMIM, ClinVar and HGMD databases, but not in the normal population databases of 1000 Genomes, dbSNP and gnomAD. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was rated as a pathogenic variant. CONCLUSION The c.457C>T (p.Arg153*) variant of the NONO gene probably underlay the CHD and GDD in this child. Above finding has expanded the phenotypic spectrum of the NONO gene and provided a reference for the clinical diagnosis and genetic counseling for this family.
Humans ; Male ; Computational Biology ; DNA-Binding Proteins ; Genetic Counseling ; Genomics ; Heart Defects, Congenital/genetics* ; Mutation ; Parents ; RNA-Binding Proteins ; Child, Preschool ; Developmental Disabilities/genetics*

Objective To observe the regulatory effect of roxadustat on lipid metabolism while correcting anemia in hemodialysis patients.Methods Sixty patients with chronic kidney disease(CKD)receiving hemodialysis treatment at Nanjing Drum Tower Hospital and combined with concurrent renal anemia were selected.These included 30 patients receiving erythropoietin(EPO)therapy at a dose of 10 000 U per week,and 30 patients receiving roxadustat treatment at a dose based on body weight.The patients'hemoglobin levels were measured,and data on lipid and iron metabolism-related indicators were collected for statistical analysis.Results After 6 months of treatment,the mean hemoglobin levels of both groups of patients were significantly higher than the baseline levels.The mean hemoglobin level in the roxadustat group was higher than that in the EPO group(114.1±7.88 vs.122.23±10.33,P<0.05),but there was no significant difference in the achievement rate between the two groups(77%vs.93%,P>0.05).The total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and triglycerides(TG)in the roxadustat group decreased significantly(P<0.05),while there was no significant change in the EPO group.Compared with the EPO group,roxadustat showed an improvement in iron metabolism indicators.Conclusion Roxadustat has been shown to improve lipid metabolism while correcting anemia.