Objective To investigate the correlation between insulin resistance and interleukin-6 (IL-6), chemerin, total cholesterol (TC)/high density lipoprotein cholesterol (HDL-C) ratio, triglyceride (TG)/HDL-C ratio, low density lipoprotein cholesterol (LDL-C)/HDL-C ratio and insulin resistance in obese patients with type 2 diabetes mellitus (T2DM), and to provide scientific basis for T2DM prevention and control. Methods A total of 355 obese T2DM patients in Songjiang Hospital Affiliated to Shanghai Jiaotong University School of Medicine were selected from January 2021 to December 2023. IL-6, chemerin and lipids were detected, and the assessment of insulin resistance was conducted through the homeostasis model assessment of insulin resistance (HOMA-IR). Results Among the 355 obese T2DM patients, there were 280 cases of insulin resistance, with the incidence rate of 78.87%. The BMI, IL-6, chemerin, TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C in the insulin resistance group were higher than those in the non-insulin resistance group (P<0.05). The above insulin resistant patients were divided into 4 subgroups by means of insulin resistance, and there were significant differences in BMI, IL-6, chemerin, and TG/HDL-C among the subgroups (P<0.05). IL-6, chemerin, and TG/HDL-C were positively correlated with HOMA-IR in obese T2DM patients (P<0.05), while TC/HDL-C and LDL-C/HDL-C had no significant correlation with HOMA-IR (P>0.05). BMI, IL-6, chemerin, and TG/HDL-C were all influencing factors of insulin resistance in obese T2DM patients (P<0.05). Conclusion IL-6, chemerin and TG/HDL-C are correlated with insulin resistance in obese patients with T2DM and are influencing factors for the occurrence of insulin resistance.

Objective To investigate the role of cytochrome P450 2E1 (CYP2E1) in trichloroethylene (TCE)-induced skin sensitization and liver damage in guinea pigs, using diallyl sulfide (DAS), a CYP2E1 inhibitor, as an intervention. Methods Specific pathogen-free female guinea pigs were randomly divided into blank control group, solvent control group, positive control (2,4-dinitrochlorobenzene) group, TCE-exposure group, and DAS-intervention group. Skin sensitization experiments were conducted using the guinea pig TCE maximal dose-skin sensitization test. Urinary trichloroacetic acid levels were determined following TCE induction and challenge. At 48 hours after the final challenge, serum liver function markers and inflammatory cytokines levels were detected. Histopathological examination on skin and liver tissues was performed, and hepatic CYP2E1 protein expression and oxidative stress indicators were assessed. Results The sensitization rates of guinea pigs were 100.0%, 75.0%, and 33.3% in the positive control, TCE-exposure, and DAS-intervention groups, respectively, while the blank control and solvent control groups were both 0.0%. Compared with the guinea pigs in TCE-exposure group, those in the DAS-intervention group had lower urinary trichloroacetic acid levels at intradermal induction, local induction, first challenge, and 24 hours after the final challenge time point (all P<0.05). Histopathology of guinea pigs showed dermal inflammatory infiltration and basal keratinocyte necrosis in the TCE-exposure group, whereas only mild dermal inflammation was observed in the DAS-intervention group. The guinea pigs in TCE-exposure group exhibited diffuse hepatocellular necrosis, while hepatic damage in the DAS-intervention group was alleviated, characterized by only mild hepatocellular steatosis and hepatocyte swelling around the central vein. The skin sensitization rate of guinea pigs in the TCE-exposure group increased (all P<0.01), the serum alanine aminotransferase (ALT )activity, the levels of interleukin (IL)-2, IL-17, and tumor necrosis factor-α (TNF- α) increased (all P<0.05), the relative expression of CYP2E1 protein, the activity of superoxide dismutase (SOD), and the level of malondialdehyde in liver tissue increased (all P<0.05), while the activity of catalase decreased (P<0.05), compared with the blank control and solvent control groups. The serum ALT activity and the levels of IL-2, IL-17, and TNF-α of guinea pigs in DAS-intervention group reduced (all P<0.05), as well as CYP2E1 protein expression, SOD activity, and malondialdehyde level in liver tissue reduced (all P<0.05), compared with the TCE-exposure group. Conclusion TCE can induce hepatic CYP2E1 expression, thereby promoting oxidative stress and inflammatory responses, which contributes to skin sensitization and liver damage. DAS alleviates TCE-induced toxic effects on skin and liver by inhibiting CYP2E1 expression.

OBJECTIVE To investigate the current situation of pharmaceutical clinic service in medical institutions in China and provide experience and suggestions for promoting the development of pharmaceutical clinics. METHODS Questionnaire survey was used to investigate the development of pharmaceutical clinics in medical institutions of 31 provinces （autonomous regions and municipalities directly under the central government） in March to April 2023， and the descriptive analysis was conducted. The regression analysis was carried out for the influential factors of pharmaceutical clinic service. RESULTS A total of 1 368 questionnaires were distributed in this survey and 1 304 valid questionnaires were collected with the effective response rate of 95.32%. A total of 463 medical institutions carried out pharmaceutical clinic service， the rate of which was 35.51% （463/1 304）； the rates of pharmaceutical clinics in tertiary， secondary， primary and other medical institutions were 52.80%， 17.18% and 5.88%， respectively. The frequency of opening pharmaceutical clinics was 3.17 days per week on average， with an average of 5.99 visiting pharmacists in each medical institution. Among the visiting pharmacists， clinical pharmacists accounted for the vast majority （88.68%， 2 459/2 773）. There were various categories of pharmaceutical clinics， including joint clinics and pharmacist-independent clinics； among pharmacist-independent clinics， pharmaceutical specialty/specialty disease clinics were the main ones， accounting for 89.72% of the total number of pharmaceutical clinics. The value of pharmacists in pharmaceutical clinics was manifested in various forms， among which the proportion of medical institutions charging pharmaceutical clinics was 10.80%. The main experiences in developing pharmaceutical clinics were to attach importance to discipline construction and personnel training. The main difficulties in developing pharmaceutical clinics were low compensation levels and a shortage of talent.The number of clinical pharmacists， the number of visiting pharmacists in pharmaceutical clinics and additional compensation were positively correlated with the amount of pharmaceutical clinic services（P＜0.05）. CONCLUSIONS In recent years， pharmaceutical clinics have made significant progress； in the future， it is still necessary to further strengthen discipline construction and talent cultivation， pay attention to the value embodiment of pharmacists， to promote the healthy development of pharmaceutical clinics.

Objective:To study the effects and potential mechanisms of the combination of dihydroartemisinin and carfilzomib on the activity, proliferation, and apoptosis of multiple myeloma ARD cell lines.Methods:In vitro cultivation of multiple myeloma ARD cells involved treating the cells with dihydroartemisinin at concentrations of 0, 5, 10, 20, 40, and 80 μg/ml, and with carfilzomib at concentrations of 0, 5, 10, 20, 40, and 80 nmol/L. The ARD cells were divided into a control group (no treatment) , a dihydroartemisinin group (2 μg/ml) , a carfizomib group (8 nmol/L) , and a combination group (dihydroartemisinin 2 μg/ml + carfizomib 8 nmol/L) . Cell activity and proliferation were assessed by MTT assay and EdU-488 assay; cell apoptosis was evaluated using live cell/dead cell dual staining and flow cytometry. The expression levels of apoptosis-related proteins were examined using Western blotting analysis. Results:The cell survival rates of ARD cells treated with 0, 5, 10, 20, 40, and 80 μg/ml dihydroartemisinin were (100.00±2.18) %, (50.22±3.09) %, (37.39±2.34) %, (30.42±1.79) %, (23.80±1.12) %, and (18.04±0.79) %, respectively, and there was a statistically significant difference ( F=653.30, P<0.001) . With the increase of drug concentration, ARD cell activity decreased gradually (all P<0.05) . The cell survival rates of ARD cells treated with 0, 5, 10, 20, 40, and 80 nmol/L carfilzomib were (100.00±1.12) %, (83.98±2.95) %, (67.27±2.10) %, (58.24±2.02) %, (46.34±1.14) %, and (37.47±1.36) %, respectively, and there was a statistically significant difference ( F=227.40, P<0.001) . With the increase of drug concentration, ARD cell activity decreased gradually (all P<0.05) . The cell survival rates for the control group, dihydroartemisinin group, carfilzomib group, and combination group were (100.00±2.67) %, (67.23±0.57) %, (76.23±2.83) %, and (27.06±1.09) %, respectively, and there was a statistically significant difference ( F=655.60, P<0.001) . There were statistically significant differences in the dihydroartemisinin group, carfilzomib group, and combination group compared with control group (all P<0.001) . There were statistically significant differences in the dihydroartemisinin group and carfilzomib group compared with combined group (both P<0.001) . The EdU-488 experiment showed that the EdU-positive rates of ARD cells in the control group, dihydroartemisinin group, carfilzomib group, and combination group were (100.00±8.17) %, (68.07±6.14) %, (85.04±2.78) %, and (19.62±3.83) %, respectively, and there was a statistically significant difference ( F=115.20, P<0.001) . There were statistically significant differences in the dihydroartemisinin group, carfilzomib group, and combination group compared with control group ( P<0.001; P=0.047; P<0.001) . There were statistically significant differences in the dihydroartemisinin group and carfilzomib group compared with combined group (both P<0.001) . The live cell/dead cell dual staining experiment showed, under bright-field observation, the cell morphology was intact in the control group. In all the drug groups, the cell morphology became irregular, reduced in size with condensed cytoplasmic, and apoptotic vesicles with irregular morphology were seen around the cells, among which the most obvious changes were seen in the combination group. Under fluorescence observation, the cells in the control group only displayed green fluorescence. In all drug-treated groups, cells with red fluorescence were observed, with the combination group having the highest percentage of cells with red fluorescence among the total cell population. The apoptosis rates for the control group, dihydroartemisinin group, carfilzomib group, and combination group were (9.06±2.95) %, (29.50±1.34) %, (20.77±3.00) %, and (58.23±5.13) %, respectively, and there was a statistically significant difference ( F=115.80, P<0.001) . There were statistically significant differences in the dihydroartemisinin group, carfilzomib group, and combination group compared with control group ( P<0.001; P=0.012; P<0.001) . There were statistically significant differences in the dihydroartemisinin group and carfilzomib group compared with combined group (both P<0.001) . There were statistically significant differences in the relative expression levels of P53, Cleaved-Caspase-3, Bcl-2, and Bax proteins among the control group, dihydroartemisinin group, carfilzomib group, and combination group ( F=21.76, P<0.001; F=42.87, P<0.001; F=44.27, P<0.001; F=163.50, P<0.001) . There were statistically significant differences in the dihydroartemisinin group, carfilzomib group, and combination group compared with control group (all P<0.05) . There were statistically significant differences in the dihydroartemisinin group and carfilzomib group compared with combined group (both P<0.05) . Conclusion:The combination of dihydroartemisinin and carfilzomib can synergistically inhibit the activity and proliferation of multiple myeloma ARD cells, and promote apoptosis, and the underlying mechanism may be associated with the mitochondrial apoptosis pathway.

Objective:To compare the differences of actual absorbed doses of liver malignant tumors after 90Y-selective internal radiation therapy (SIRT) evaluated by 90Y PET/CT and 90Y bremsstrahlung (BRS) SPECT/CT imaging, and to compare the image quality of the 2 imaging methods. Methods:Twenty-one patients (15 males and 6 females; age: (52.4±15.4) years) with liver malignant tumors (15 cases of primary liver cancer, 6 cases of liver metastases; 39 lesions) between September 2021 and August 2022 were retrospectively analyzed. All patients underwent both 90Y PET/CT imaging and 90Y BRS SPECT/CT imaging in the Department of Nuclear Medicine, Hainan Cancer Hospital. The ratios of the actual absorbed doses based on 90Y PET/CT imaging and 90Y BRS SPECT/CT imaging to the lowest standard absorbed dose(100 Gy) for tumor response were calculated. The image contrast and distinguishability of the two imaging methods were scored. Wilcoxon signed rank test and Wilcoxon rank sum test were used for data analysis. Results:The tumor absorbed doses evaluated by 90Y PET/CT and 90Y BRS SPECT/CT were 143.94(55.91, 233.48) Gy and 107.82(53.59, 157.53) Gy respectively. The doses evaluated by 90Y PET/CT were higher than the standard threshold in 24 lesions, while 19 lesions showed higher evaluated doses by 90Y BRS SPECT/CT than the standard threshold. Compared with 90Y PET/CT, 90Y BRS SPECT/CT underestimated the tumor absorbed dose of -24.25%(-32.32%, -12.14%). The ratio of dose evaluated by 90Y PET/CT to the lowest standard threshold was 1.33(0.56, 1.91), which was higher than that of dose evaluated by 90Y BRS SPECT/CT to the lowest standard threshold (0.97(0.47, 1.25); z=0.04, P<0.001). PET/CT image contrast was scored 0, 1, 2, 3 in 2, 2, 12, 23 lesions respectively, and SPECT/CT image contrast was scored 0, 1, 2, 3 in 2, 3, 16, 18 lesions respectively ( z=-1.29, P=0.199). The distinguishability scores of 0, 1, 2 based on PET/CT images were found in 3, 15, 21 lesions, while those based on SPECT/CT images were found in 4, 32, 3 lesions respectively ( z=-2.79, P=0.005). Conclusion:90Y PET/CT imaging is superior to 90Y BRS SPECT/CT imaging in radiation dose evaluation and tumor focus differentiation in patients with liver malignant tumors after 90Y-SIRT.

Objective To systematically evaluate qualitative studies on the experience of transition from adolescent to adult medical care for patients with congenital heart disease(CHD),and to provide a reference for exploring CHD transition management options and developing intervention strategies.Methods A computerized search of PubMed,Embase,Web of Science,Cochrane Library,EBSCO,CINAHL,China Knowledge Network,Wanfang database,Vipshop database,and China Biomedical Literature Database for qualitative studies on the transition experience of CHD patients from adolescence to adult medical care was conducted for the period from the establishment of the database to April 2023.The quality of the literature was evaluated using the Joanna Briggs Institute(JBI)Australian Centre for Evidence-Based Health Care Quality Assessment Criteria for Qualitative Research(2016),and the results were integrated using meta-integration methods.Results A total of 9 studies were included,and 49 research results were extracted,and 11 categories were summarized.The final synthesis included 4 integrated results:①Complex attitudes towards healthcare transition,with both attachment and expectation:attachment to paediatric healthcare providers,expectation of transition to adult healthcare providers.(2)Facing multiple healthcare transition challenges:lack of adequate preparation for healthcare transition,parents withdrawing from the role of disease manager,large differences in services between paediatric and adult healthcare providers.③Expect to receive multiple supports:expect to receive comprehensive health education from healthcare personnel,expect healthcare institutions to set up healthcare transition counselling clinics and achieve handover of illness,expect to receive companionship and support from parents,expect to receive understanding and help from peers.④ Per-ceived benefits of medical transition:increased ability to manage illness,role change and personal growth.Conclusion Adolescents with CHD have a complex experience of transitioning to adult healthcare,and healthcare professionals should be attentive to their feelings,encourage them to deal with challenges positively,and provide adequate information and joint parental and peer support to facilitate a smooth transition to adult healthcare for adolescents.

Objective:To analyze the differentially expressed genes (DEGs) in visceral adipose tissue of patients with type 2 diabetes mellitus (T2DM) based on bioinformatics.Methods:The microarray dataset GSE78721 was downloaded from the Gene Expression Omnibus (GEO) database, including visceral fat samples data from 19 T2DM patients and 16 non-diabetic subjects. The analysis of transcriptomic profiling results from tissue samples was conducted, and a comparison between different groups of samples based on gender was performed. The online Xintao Academic Database was utilized for the analysis, employing the "limma" package in R language to filter DEGs. Subsequently, the DEGs were visualized, and Gene Ontology (GO) functional annotation along with Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were carried out and visualized. Based on the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, a protein-protein interaction network (PPI) of DEGs was constructed and key differentially expressed genes were identified and visualized using Cytoscape software.Results:Analysis of visceral adipose tissue gene expression profiles revealed 168 DEGs (|log 2FC|≥1, P<0.05). In females, 42 mRNAs were up-regulated, 3 were down-regulated; in males, 105 were up-regulated, 37 were down-regulated, 19 genes were shared by the two groups. GO analysis linked DEGs to insulin-like growth factor receptor signaling and regulation, nutrient response, and leukocyte migration. KEGG analysis implicated extracellular matrix receptor interactions and leukocyte transendothelial migration. The PPI network unveiled 10 key genes, including COL1A1, COL1A2, TGFB3, PCOLCE, TIMP1, COL6A2, COMP, COL14A1, VCAM1 and THY1. Conclusion:Bioinformatics technology can effectively analyze and screen DEGs in visceral adipose tissue of T2DM patients, providing useful clues for further exploring its molecular mechanism and finding therapeutic targets.

Objective To investigate the effect of trehalose(Tre)H9C2 cardiomyocytes under oxy-gen-glucose deprivation/reoxygenation(OGD/R)injury and its mechanism of action with the cel-lular model simulating the process of myocardial ischemia/reperfusion injury.Methods H9C2 cells were divided control group,OGD/R group,Tre group(OGD/R+Tre),and combination group(OGD/R+Tre+ML385).MTT assay was used to observe cell proliferation,and lactate de-hydrogenase(LDH)release and Hoechst/propidium iodide staining were employed to evaluate cell membrane damage.Western blot analysis was utilized to detect the expression of nuclear fac-tor erythroid 2-related factor 2(Nrf2)and its downstream related proteins.The generation of re-active oxygen species(ROS)and mitochondrial membrane potential(MMP)were measured to quantify the level of oxidative stress.The expression of apoptosis-related proteins was determined by Western blot analysis.Results In comparison to the control group,the OGD/R group exhibi-ted a significantly reduced cell viability.When compared with the OGD/R group,the intervention of varying concentrations of Tre obviously improved cell viability in a dose-dependent manner(P＜0.01),increased MMP,and up-regulated the expression of glutathione(GSH),Nrf2,hemeo-xygenase 1,and nicotinamide adenine dinucleotide phosphate quinone oxidoreductase 1(NQO1),Bcl-2,and cysteinyl aspartate specific proteinase 3(Caspase-3)(P＜0.05,P＜0.01),and decreased the production of ROS and MDA and the expression of responding element binding protein 1,Bax,Bax/Bcl-2,and cleaved Caspase-3(P＜0.05,P＜0.01).What's more,the combined group ex-hibited significantly higher production of ROS,MDA,increased mRNA levels of TNF-α,IL-1β,and IL-6,and reduced MMP and GSH levels(P＜0.05,P＜0.01),as well as,enhanced expression of Bax,Bax/Bcl-2,and cleaved Caspase-3(1.77±0.08 vs 1.20±0.20,3.41±1.45 vs 0.99±0.15,4.10±1.05 vs 1.79±0.52,P＜0.01),and decreased expression of Bcl-2 and Caspase-3(0.58±0.21 vs 1.23±0.25,0.87±0.25 vs 1.45±0.31,P＜0.01)in comparison with the Tre group.Conclusion Tre can be regarded as an Nrf2 activator that inhibits oxidative stress and apoptosis by activating Nrf2,and thereby ameliorates OGD/R-induced cardiomyocyte injury.

OBJECTIVE To identify the chemical constituents of the modified Yupingfengsan formula. METHODS UPLC-Q- Exactive Orbitrap-MS technology was adopted. The separation was performed on Waters BEH C18 column with acetonitrile （A）-0.1% formic acid solution （B） as mobile phase for gradient elution. The heating electrospray ionization was used for positive and negative ion mode scanning. The scanning range was m/z 50-1 500， and the spray voltage was 2 kV （positive ion mode） and 1.5 kV （negative ion mode）. The information of chemical constituents of modified Yupingfengsan formula was collected through literature review to establish a database； the structure of the constituent was identified based on the above database， relevant literature， and chromatography and mass spectrometry information of reference standards. RESULTS & CONCLUSIONS Totally 114 chemical constituents were identified from modified Yupingfengsan formula， including 31 flavonoids， 39 phenylpropanoids， 5 saponins， 8 terpenoids， 3 chromones， 3 curcuminoids， etc. Based on the comparison of reference standards， 8 constituents were ultimately determined， including magnoflorine， calycosin， calycosin glycoside， cimifugin， 5-O-methylvisammioside， sec-O- glucosylhamaudol， luteolin and mangiferin. These constituents mainly involved glycosylation cleavage， retro Diels-Alder fragmentation， glycosylation loss， neutral molecule loss and other fragmentation pathways.

OBJECTIVE: To explore the toxicological mechanism of drug-induced liver injury(DILI) in rats induced by cantharidin(CTD). METHODS: SD rats were exposed to different doses of CTD(0.061 4, 0.092 1, 0.184 1 mg·kg−1) by oral gavage for 28 d. Liver index and serum liver function indictors were detected. HE staining was used to evaluate the pathological changes of liver. Then the proteins in endoplasmic reticulum stress(ERS), autophagy, and apoptosis-pathway were detected by Western blotting. RESULTS: The liver index was increased in CTD groups. The ALT, AST, LDH, ALP and T-Bil were increased by CTD with a dose-dependent manner. Disrupted hepatic architecture and dilatation of central vein were observed after CTD intervention. The protein expression levels of GRP78, CHOP, ATF4, Beclin-1, LC3, Caspase-3, Caspase-8, and Bax/Bcl-2 were increased after CTD intervention. Molecular docking results revealed that GRP78, ATF4, and Beclin-1 could directly interconnect with CTD. CONCLUSION CTD can activate ERS, autophagy and synergistically inducing downstream apoptosis in rat, providing a novel insight into the mechanism of CTD-induced DILI.