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 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.

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 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.

To investigate the genomic features and perform cluster analysis of Carbapenem-resistant Klebsiella pneumoniae (CRKP) to provide an experimental basis for guiding the prevention and treatment of CRKP infections.A retrospective case-cohort study was conducted on 19 non-redundant CRKP strains isolated from the Tenth Affiliated Hospital of Southern Medical University between January and June 2023. Whole genome sequencing (WGS) and multilocus sequence typing (MLST) were performed to compare genomic features and analyze the resistance genes and homology of the strains.The results showed that the 19 CRKP strains were isolated from 8 different clinical departments, mainly from respiratory specimens. The whole genome sequencing revealed that the genomic lengths of CRKP ranged from 4.90 to 5.85 Mbp, with contigs N50 values>20 kb for each genome. The median overall GC content was 57.0% (50.4%-57.1%). Comparative genomic analysis identified three regions with high genomic variability. WGS detected 32 resistance genes across 11 categories. All 19 strains carried carbapenem resistance genes ( blaKPC-2 and blaOXA-48), blaTEM-1B extended-spectrum β-lactamase resistance genes, qnrS1 quinolone resistance gene, and fosA fosfomycin resistance gene, with each strain carrying only one carbapenemase gene. The detection rate of blaKPC-2 was 94.7% (18/19). MLST identified three sequence types: ST11, ST437 and ST147, with ST11 being predominant (89.5%, 17/19). Clustering analysis based on acquired resistance genes revealed three clonal transmission patterns among strains 72 and 90, and strains 88, 84, 66 and 79.In conclusion, CRKP strains carry multiple resistance genes, and clustering analysis indicating that nosocomial clonal transmission is closely related to acquired resistance genes. The ST11- blaKPC-2 type strain is the predominant clone. Strengthened surveillance and effective control strategies are necessary to reduce nosocomial transmission of CRKP.

To investigate the genomic features and perform cluster analysis of Carbapenem-resistant Klebsiella pneumoniae (CRKP) to provide an experimental basis for guiding the prevention and treatment of CRKP infections.A retrospective case-cohort study was conducted on 19 non-redundant CRKP strains isolated from the Tenth Affiliated Hospital of Southern Medical University between January and June 2023. Whole genome sequencing (WGS) and multilocus sequence typing (MLST) were performed to compare genomic features and analyze the resistance genes and homology of the strains.The results showed that the 19 CRKP strains were isolated from 8 different clinical departments, mainly from respiratory specimens. The whole genome sequencing revealed that the genomic lengths of CRKP ranged from 4.90 to 5.85 Mbp, with contigs N50 values>20 kb for each genome. The median overall GC content was 57.0% (50.4%-57.1%). Comparative genomic analysis identified three regions with high genomic variability. WGS detected 32 resistance genes across 11 categories. All 19 strains carried carbapenem resistance genes ( blaKPC-2 and blaOXA-48), blaTEM-1B extended-spectrum β-lactamase resistance genes, qnrS1 quinolone resistance gene, and fosA fosfomycin resistance gene, with each strain carrying only one carbapenemase gene. The detection rate of blaKPC-2 was 94.7% (18/19). MLST identified three sequence types: ST11, ST437 and ST147, with ST11 being predominant (89.5%, 17/19). Clustering analysis based on acquired resistance genes revealed three clonal transmission patterns among strains 72 and 90, and strains 88, 84, 66 and 79.In conclusion, CRKP strains carry multiple resistance genes, and clustering analysis indicating that nosocomial clonal transmission is closely related to acquired resistance genes. The ST11- blaKPC-2 type strain is the predominant clone. Strengthened surveillance and effective control strategies are necessary to reduce nosocomial transmission of CRKP.

Since the 1970s, the laboratory animal industry in Suzhou has gone through five stages: its inception, emergence, growth, transformation, and scaling up. It began with the manufacturing of caging equipment for laboratory animals, initially by imitation and later through independent innovation. The industry evolved from sporadic factories to clustered enterprises, gradually growing and opening up the export market for caging equipment. In the 21st century, with industrial upgrading and transformation, purification systems and related products began to develop, and industry organizations emerged. As China has modernized, the rise of automation and intelligent production has led to technological innovation in enterprises and the emergence of various outsourcing services in the laboratory animal industry, driving the large-scale development of the industrial chain. After nearly half a century of growth, the laboratory animal industry in Suzhou has formed a complete industrial chain, including the production of laboratory animals, caging equipment, feed and bedding materials, design and construction of laboratory animal facilities, quality testing of laboratory animals and environments, and animal experimentation services. Laboratory animal breeding equipment, the core of the industry, has reached the level of developed countries, and the industry's scale and influence are unmatched in China. Since the 21st century, biopharmaceuticals have become the "No.1 industry" in the development of Suzhou. With government support, the guidance of the local economy, and the assistance from universities and research institutes, the animal experiment outsourcing industry has begun to cluster in Suzhou. The continuous influx of CROs has driven the construction of large-scale laboratory animal facilities, and key research projects have been initiated, significantly enhancing the industry's R&D capabilities. The Suzhou laboratory animal industry has quickly expanded alongside the "No. 1 industry," creating a unique "Suzhou Path" for laboratory animals. Over nearly fifty years, the laboratory animal industry in Suzhou has been essential to the rapid development of the biopharmaceutical industry in Suzhou and China.

The gastric fundus fornix and upper part of the gastric body pose challenges for endoscopic submucosal dissection (ESD), resulting in unsatisfactory resection outcomes for lesions in these areas,because of the difficulty in the endoscope reaching the lesion site. Drawing inspiration from the formation of α loop during flexible colonoscopy and double-channel multibending gastroscope, a single-channel treatment gastroscope was utilized to create a multibending state (referred to as single-channel endoscope multibending method, SCMB). This method was employed to treat 6 patients with lesions in the stomach at Digestive Endoscopy Center of Affiliated Hospital of Nanjing University of Chinese Medicine from June 2021 to December 2021. There were 3 cases in the gastric fundus fornix, 2 cases in the greater curvature on the upper part of the gastric body, and 1 case in the posterior wall of gastric fundus and subcardia. After 2-3 attempts during surgery, SCMB was successfully performed in all cases within 60-120 seconds. All 6 cases completed successful endoscopic resection within 20-80 minutes without significant complications, including 4 cases of ESD and 2 cases of endoscopic full-thickness resection (EFR). Preliminary results indicate that SCMB method during ESD and its derivative technologies are both safe and effective for lesions in challenging areas where gastric ESD is difficult to perform. During surgery, this approach facilitates the front end of endoscope access to the lesion, providing a clear visual field and a stable dissection plane.