OBJECTIVE To explore the main factors influencing the blood concentration of duloxetine， and provide a scientific basis for the individualized use of duloxetine. METHODS Retrospective analysis was conducted on 434 inpatients with depressive disorders at the First Hospital of Hebei Medical University， who were treated with duloxetine and underwent blood concentration monitoring between January 2022 and April 2024. The study examined the impact of various factors， including gender， age， body mass index （BMI）， gene phenotypes， combined medication， drug type （original/generic）， and genotyping results of gene single nucleotide polymorphism loci， on blood concentration and the concentration-to-dose （C/D） after dose adjustment. RESULTS The blood concentration of duloxetine was 76.65 （45.57， 130.31） ng/mL， and C/D was 0.96 （0.63， 1.60） ng·d/（mL·mg）. The blood concentration of duloxetine was positively correlated with the daily dose of administration （R2＝0.253 7， P＜0.001）. Blood concentration of duloxetine in 38.94% of patients exceeded the recommended range specified in the guidelines. Gender， age， BMI， combined use of CYP2D6 enzyme inhibitors， and CYP2D6 and CYP1A2 phenotypes had significant effects on C/D of duloxetine （P＜0.05）. CONCLUSIONS The patient’s age， gender， BMI， combined medication， and genetic phenotypes are closely related to the blood concentration of duloxetine.

Objective To investigate the reliability and validity of the assessment tools of Brief ICF Core Sets for Arthroplasty of Knee Osteoarthritis in Perioperative Period(ICSAKOPP). Methods From May,2022 to April,2023,320 patients undergoing knee arthroplasty were selected in Peking University Third Hospital,China-Japan Friendship Hospital,Peking University First Hospital and Chinese PLA General Hospital.Trained assessors used Brief ICSAKOPP to evaluate all enrolled patients before arthroplasty,three days(±one day)after arthroplasty,three weeks(±one week)after arthroplasty,and three months(±one month)after ar-throplasty.Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)scores were recorded at the same time.Five professionals were asked to score all the items of Brief ICSAKOPP,and the content validity index(CVI)was caculated. Results A total of 64 cases were dropped down.CVI of all the items of the Brief ICSAKOPP were above 0.8,with a av-erage CVI of the scale of 0.938.The Cronbach's α coefficient of the Brief ICSAKOPP was 0.813.There was a moderate correlation(r=0.681,P<0.001)between the overall Brief ICSAKOPP and WOMAC scores,as well as body functional dimension score(r=0.668,P<0.001)and activities and participation dimension score(r=0.657,P<0.001). Conclusion Brief ICSAKOPP is good in content validity,internal consistency reliability and criterion validity.

Objective:To explore the efficacy and safety of neoadjuvant chemoimmunotherapy combined with surgery for stage ⅢA NSCLC patients.Methods:Six patients with NSCLC who were diagnosed as ⅢA and received two cycles of neoadjuvant chemoimmunotherapy and surgery between September 2019 and January 2020 were described in this study.Results:Five of them experienced AEs during neoadjuvant therapy. All of them received surgery and achieved an MPR of 50%. No viable tumor cells were found in the tissues of one patient. One patient with a small bronchopleural fistula after lobectomy.Conclusion:Neoadjuvant chemoimmunotherapy combined with surgery for stage ⅢA NSCLC patients is safe and efficient. Long-term outcomes of neoadjuvant chemoimmunotherapy combined with surgery should be further validated.

Glioma is one of the most common primary intracranial tumors, accounting for 80% of malignant brain tumors. The conventional treatment of glioma is surgical resection followed by temozolomide chemotherapy, but the drug resistance will gradually appear that results in a poor prognosis of the patient. Berberine is an alkaloid extracted from Coptis Rhizoma, which has a wide range of pharmacological activities. It exerts its pharmacological effects on glioma such as inhibiting tumor growth through controlling different molecular and cellular pathways. In this article, the application of berberine in the treatment of glioma and the research progress of specific molecular mechanism are reviewed.

OBJECTIVES: To study the gene expression of adipose tissue CD14 METHODS: The data of GSE54350 were obtained from the public database of gene expression profiling. The data were pre-processed by Network Analyst, String 11.0, Cytoscape 3.7.1, and other analytical software. The differentially expressed genes were analyzed by gene ontology biological function and kyoto encycopedia of genes and genomes (KEGG) signaling pathway to establish differential gene protein interaction network, transcription factor-gene regulatory network, microRNA-gene regulatory network, environmental factors-gene regulatory network, and other interaction systems. RESULTS: The gene expression pattern of CD14 CONCLUSIONS The gene expression of adipose tissue CD14
Adipose Tissue ; Computational Biology ; DNA-Binding Proteins ; Diabetes Mellitus, Type 2/genetics* ; Gene Expression ; Gene Expression Profiling ; Gene Regulatory Networks ; Humans ; MicroRNAs/genetics* ; Muscle Proteins

The application of biological technology and the deepening of tumor research have effectively improved the level of tumor diagnosis, treatment and clinical outcome prediction. However, the specific mechanisms of tumorigenesis and development are still unclear, and tumor drug resistance has also become an urgent problem that needs to be solved to improve the clinical outcome of patients. Considerable studies have shown that the extrachromosomal DNA (ecDNA) can promote tumorigenesis, development and drug resistance. EcDNA is a looser, rounded form of DNA with unique genetic properties that carry specific genes and regulatory elements. This paper will discuss the biological characteristics, tumor-promoting mechanisms and drug resistance-facilitating of ecDNA.

Objective:To prepare a dual targeting nanobubble both for HER2 target and cancer cell target, and compare the targeting ability with single targeting nanobubble either with HER2 targeting or cancer cell targeting ability in vitro.Methods:Nanobubbles(NBs) were prepared using the modified thin film hydration method and then connected with IR783 directly (NBs-IR783), HER2 antibody Affibody by avidin-biotin method (NBs-Affibody), or both of them (IR783-NBs-Affibody). The size distribution, stability, and biosafety of these contrast agents were observed. Flow cytometry and immunofluorescence were applied to compare the binding rate of these NBs against HER2 positive breast cancer cell in vitro.Results:The average size of NBs-Affibody, NBs-IR783 and IR783-NBs-Affibody was (538.4±95.8)nm, (551.8±114.8)nm, and (482.7±54.3)nm, respectively. The binding rate for HER2 positive cell was 26.6%, 97.6%, 84.5%, while for HER2 negative cell was 5.4%, 99.9% and 99.3%, respectively. The results of dual-labeled flow cytometry showed that the binding rate of IR783-NBs-Affibody mediated by IR783 to HER2 positive breast cancer cells were 79.5% and Affibody mediated HER2 targeting binding rate were 19.4%. However, NBs-IR783 only showed IR783-mediated tumor targeted binding without HER2 targeting ability with binding rate of 2.3%.Conclusions:The prepared IR783-NBs-Affibody has the dual targeting ability for HER2 positive breast cancer cell, which is superior to the single targeting NBs (NBs-Affibody and NBs-IR783). IR783-NBs-Affibody is optimal to meet the imaging requirements of tumor heterogeneity.

Glioma is one of the most common and invasive malignant tumors in the central nervous system. The Wnt-β-catenin signaling pathway is a classical Wnt pathway, which is involved in the occurrence and development of glioma and other tumors. Long non-coding RNA (LncRNA) is a functional RNA molecule without protein coding function, which plays a regulatory role in the occurrence and development of various tumors. Recent studies have shown that LncRNA and Wnt-β-catenin signaling pathways are jointly involved in glioma growth, invasion, migration and other processes, but the complex mechanism has not been thoroughly elaborated. In this paper, the influence of Wnt-β-catenin signaling pathway and its related LncRNA on glioma was reviewed, and the pathogenesis of glioma was deeply understood, so as to find a better way for the diagnosis and treatment of glioma.

Objective:To explore the clinical characteristics and establish a corresponding prognostic scoring model in patients with early-stage clinical features of hepatitis B-induced acute-on-chronic liver failure (HBV-ACLF).Methods:Clinical characteristics of 725 cases with hepatitis B-related acute-on-chronic hepatic dysfunction (HBV-ACHD) were retrospectively analyzed using Chinese group on the study of severe hepatitis B (COSSH). The independent risk factors associated with 90-day prognosis to establish a prognostic scoring model was analyzed by multivariate Cox regression, and was validated by 500 internal and 390 external HBV-ACHD patients.Results:Among 725 cases with HBV-ACHD, 76.8% were male, 96.8% had cirrhosis base,66.5% had complications of ascites, 4.1% had coagulation failure in respect to organ failure, and 9.2% had 90-day mortality rate. Multivariate Cox regression analysis showed that TBil, WBC and ALP were the best predictors of 90-day mortality rate in HBV-ACHD patients. The established scoring model was COSS-HACHADs = 0.75 × ln(WBC) + 0.57 × ln(TBil)-0.94 × ln(ALP) +10. The area under the receiver operating characteristic curve (AUROC) of subjects was significantly higher than MELD, MELD-Na, CTP and CLIF-C ADs( P < 0.05). An analysis of 500 and 390 cases of internal random selection group and external group had similar verified results. Conclusion:HBV-ACHD patients are a group of people with decompensated cirrhosis combined with small number of organ failure, and the 90-day mortality rate is 9.2%. COSSH-ACHDs have a higher predictive effect on HBV-ACHD patients' 90-day prognosis, and thus provide evidence-based medicine for early clinical diagnosis and treatment.

Background: Disruption of tight junctions between intestinal epithelial cells followed by loss of barrier function is crucial for the pathogenesis and progression of a variety of gastrointestinal disorders.Aims: To investigate the protective effect of ulinastatin on hydrogen peroxide (H2O2)-induced intestinal epithelial barrier disruption.Methods: Model of intestinal epithelial monolayer barrier was established with Caco-2 cells in vitro,and then divided into four groups: blank control group (without any intervention),H2O2 group (500 μmol/L H2O2),low-dose (500 U/mL) and high-dose (3 000 U/mL) ulinastatin groups (ulinastatin + H2O2).Level of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) were detected;transepithelial electrical resistance (TEER) and flux of sodium fluorescein were measured to assess the barrier function;expression and localization of two tight junction proteins,ZO-1 and occludin were evaluated by Western blotting and immunofluorescence;ultrastructure of tight junctions was observed by transmission electron microscopy (TEM).Results: Compared with the blank control group,treatment of Caco-2 cell monolayers with H2O2 resulted in increase in level of MDA,flux of sodium fluorescein and decrease in activity of SOD,TEER and expressions of ZO-1 and occludin (P all ＜0.05).TEM and immunofluorescence showed that the brusher border of Caco-2 cells in H2O2 group was destroyed,the cell-cell junction was vague and the localization of ZO-1 and occludin was discontinuous and the fluorescence intensity was extremely low.While in ulinastatin groups,especially the high-dose group,all the indices above-mentioned were significantly improved (P all ＜0.05).Conclusions: Ulinastatin protects intestinal epithelial monolayer barrier against H2O2-induced disruption at least partially by its antioxidant activity and modulating expression and localization of tight junction proteins.