Objective To investigate the reproductive and developmental effects of Clothianidin in rats. Methods Clothianidin was administrated by diet to both parental and first filial (F 1) generations of rats at the dosages of 0, 30.51, 110.84 and 304.26 mg/(kg·d) in females, and 0, 26.45, 92.69 and 279.42 mg/(kg·d) in males. Clothianidin was administered through diet to male and female rats for 8 weeks before mating. Clothianidin was administered to female rats in the parental and F1 generations during mating, gestation and lactation periods. During the test, toxicity performance was observed, reproduction index was calculated, and pathological examination was carried out. Results The body weights of rats in the parent and F1 generations in the high-dose group were lower than those in the control group during pre-mating exposure and at various time points during pregnancy and lactation (P<0.05). The pregnancy rates of parental and F1 generations in the high-dose group were lower than those of the control group (48.57% vs 71.43%, 45.71% vs 80.00%, P＜0. 05). Sperm concentration and sperm motility of the parental generation were lower than those of the control group [(42.55±12.87) vs (53.84±7.65) ×106/ml, (58.94±10.59) vs (65.59±6.03), （P＜0.05）]. Sperm concentration and sperm motility of the F1 generation were lower than those of the control group [(41.64±12.42) vs (53.09±9.48), (55.13±9.19) vs (64.53±6.31), (P＜0.05). Conclusion Exposure to clothianidin has reproductive toxicity to Wistar rats, and the no-observed adverse effect level (NOAEL) in the two-generation reproductive toxicity test is 92.69 mg/kg·BW for males and 110.84 mg/kg·BW for females in Wistar rats.

Objective To investigate the reproductive and developmental effects of Clothianidin in rats. Methods Clothianidin was administrated by diet to both parental and first filial (F 1) generations of rats at the dosages of 0, 30.51, 110.84 and 304.26 mg/(kg·d) in females, and 0, 26.45, 92.69 and 279.42 mg/(kg·d) in males. Clothianidin was administered through diet to male and female rats for 8 weeks before mating. Clothianidin was administered to female rats in the parental and F1 generations during mating, gestation and lactation periods. During the test, toxicity performance was observed, reproduction index was calculated, and pathological examination was carried out. Results The body weights of rats in the parent and F1 generations in the high-dose group were lower than those in the control group during pre-mating exposure and at various time points during pregnancy and lactation (P<0.05). The pregnancy rates of parental and F1 generations in the high-dose group were lower than those of the control group (48.57% vs 71.43%, 45.71% vs 80.00%, P＜0. 05). Sperm concentration and sperm motility of the parental generation were lower than those of the control group [(42.55±12.87) vs (53.84±7.65) ×106/ml, (58.94±10.59) vs (65.59±6.03), （P＜0.05）]. Sperm concentration and sperm motility of the F1 generation were lower than those of the control group [(41.64±12.42) vs (53.09±9.48), (55.13±9.19) vs (64.53±6.31), (P＜0.05). Conclusion Exposure to clothianidin has reproductive toxicity to Wistar rats, and the no-observed adverse effect level (NOAEL) in the two-generation reproductive toxicity test is 92.69 mg/kg·BW for males and 110.84 mg/kg·BW for females in Wistar rats.

Aim To express and purify recombinant hCGH-CTP fusion protein in high-density suspension culture of Chinese hamster ovary cells (CHO-S), and to verify the lipid accumulation effect of rhCGH-CTP on 3T3-L1 mature adipocytes. Methods The recombinant protein expression vector (pcDNA3. 1-rhCGH-CTP) was constructed, achieved by fusing the human glycoprotein hormone beta 5/alpha 2 cDNA with CTP Linker. The expression plasmid was transiently transfected into the suspended CHO-S to express rhCGH-CTP protein and then purified, and the protein biological activity was verified. Intervention with 3T3-L1 mature adipocyte cells for 24 h was performed to detect the changes of intracellular triglyceride (TG) level. Results Western blot results showed that rhCGH-CTP protein was successfully expressed in CHO-S cells, and the yield was up to 715. 4 mg • L~ . The secreted protein was purified by AKTA pure system with higher purity that was up to 90% as identified by SDS-PAGE. In addition, the intracellular cAMP content of mature adipocytes with high expression of TSHR gene significantly increased after intervention with different concentrations of rhCGH-CTP protein by ELISA kit, indicating that rhCGH-CTP protein had biological activity. Oil red 0 staining showed that compared with the control group, the lipid content of mature adipocytes in the intervention groups with different concentrations of rhCGH-CTP protein significantly decreased (P < 0. 05) . Conclusions The rhCGH-CTP protein has been successfully expressed and purified with biological activity, and effectively reduce TG. This research provides an important theoretical basis for further revealing the physiological role of CGH protein and its potential application in clinical practice.

ObjectiveTo provide technical support for the molecular surveillance of pathogenic bacteria strains carrying mobile colistin resistance-1 （mcr⁃1） gene isolate from inlet of wastewater treatment plants （WWTP）. MethodsThe Enterobacteriaceae strains carrying mcr⁃1 resistance gene isolate from inlet of WWTP during April 1 to June 30， 2023 in Shanghai were cultured on blood-rich and SS culture medium and were identified using a mass spectrometry analyzer. The mcr⁃1 gene and copy number were detected by real-time fluorescence quantitative PCR. Drug susceptibility test was performed by microbroth dilution method. The copy numbers of Escherichia coli carrying mcr⁃1 gene isolated from wastewater and human fecel were statistically analyzed by SPSS 25.0. ResultsA total of 14 strains carrying the mcr⁃1 gene were isolated from 49 WWTP samples， and the positive isolation rate was 28.6%， including 12 non-diarrheal E. coli strains and 2 Klebsiella pneumoniae strains. The drug susceptibility results showed that all 14 strains were multi-drug resistant bacteria. They were all sensitive to imipenem and tigecycline， but were ampicillin- and cefazolin-resistant. There was no significant difference in the copy number between human-sourced diarrheal E. coli and wastewater-sourced non-diarrheal E. coli （t=0.647， P>0.05）. ConclusionThe isolation and identification of strains carrying the mcr⁃1 gene from inlet of WWTP samples were firstly established in Shanghai. The multi-drug resistance among the isolated strains is severe. To effectively prevent and control the spread of colistin-resistant bacteria， more attention should be paid to the surveillance of mcr⁃1 gene.

Objective To investigate the relationship between perioperative nutritional risk and venous thromboembolism(VTE)in patients with hip fracture.Methods A total of 379 patients with unilateral hip fracture due to fall or sprain who underwent elective surgery were selected and divided into the non-VTE group(246 cases)and the VTE group(133 cases)according to whether or not VTE occurred during perioperative period.Basic information,surgical and anesthesia records,nutritional risk related indicators,inflammatory indicators and outcome indicators of patients were collected.Multiple Logistic regression was used to analyze the independent influencing factors of perioperative VTE.Receiver operating characteristics(ROC)curves were used to assess the ability to discriminate independent factors,and DeLong test was used to compare area under the curve(AUC).Results Compared with the non-VTE group,the proportion of patients in the VTE group was older,complicated with hypertension,the time to visit hospital more than 2 days,received(hollow/intramedullary nail)internal fixation,perioperative blood transfusion,ASA gradeⅢtoⅣ,and higher nutritional risk screening Table(NRS)-2002 scores on admission and higher postoperative neutrophil/lymphocyte ratio(NLR).Nutritional prognosis index(PNI),hemoglobin(Hb)and prealbumin(PA)at admission and after operation were lower in the VTE group than those in the non-VTE group(P＜0.01).Multivariate Logistic regression analysis showed that PNI was decreased,NRS-2002 scores and PA were increased,and the time of visit hospital was>2 days after internal fixation.American College of Anesthesiologists(ASA)gradesⅢ-Ⅳwere independent risk factors for perioperative VTE of hip fracture(P＜0.05).ROC curve analysis showed that the AUC(95%CI)of NRS-2002 at admission was 0.739(0.692-0.783),and that of PNI at admission was 0.720(0.672-0.765),both of which were better than other influencing factors(P＜0.01).Conclusion NRS-2002 and PNI are good predictors of perioperative VTE in patients with hip fracture.

Pharmaceutical excipients, as an indispensable part of drug preparation, play crucial roles as drug carriers, improving drug release, ensuring drug stability, and enhancing patient compliance. Traditional Chinese Medicine (TCM) boasts a rich developmental history. With the modernization of technology, the deep integration of pharmacy, chemistry, and materials science has provided broader opportunities for innovative research in TCM. Simultaneously, the demand for high-quality excipients has become increasingly critical.This paper aims to review current research and applications of excipients in TCM preparations, including pre-mixed and co-processed excipients, modified excipients, and the unification of drugs and excipients, such as flavoring agents, fillers, penetration enhancers, and delivery systems. A meticulous synthesis and analysis of existing research aims to provide a reference for selecting excipients in TCM preparations, stimulate innovation in excipient development for TCM, and advocate for the development of personalized excipients.

italic>Artemisia argyi is a traditional Chinese medicine in China, which is used as medicine with its leaves. The leaves of A. argyi mainly contain flavonoids, phenolic acids, volatile oils and other compounds, and have a variety of pharmacological activities. AP2/ERF transcription factors are abundant in plants and are mainly involved in plant growth and development, abiotic stress response and secondary metabolite biosynthesis regulation. However, there are few reports on the AP2/ERF gene family and its functions in A. argyi. In this study, we systematically identified the AP2/ERF gene family in A. argyi genome, and analyzed its phylogenetic tree, protein physicochemical properties, subcellular localization, conserved motifs, promoter elements, and expression patterns. The results showed that a total of 204 AP2/ERF transcription factors were identified in A. argyi genome, encoding proteins consisting of 88-483 amino acids with a relative molecular mass of 10-52.94 kDa and a theoretical isoelectric point of 4.62-9.88. Subcellular prediction showed that the majority of AP2/ERFs were located in the nucleus, cytoplasm, and the minority of them is located in the membrane and chloroplasts. According to the Arabidopsis AP2/ERF family classification, A. argyi AP2/ERF proteins were divided into four subfamilies: Soloist, AP2, ERF (B3, B4, B5, B6), and DREB (A1, A2, A4, A5, A6), among which DREB family accounted for the largest proportion, and the same subfamily had similar conserved motifs. cis-Acting element analysis showed that AP2/ERF promoters have a large number of elements responding to light and abiotic stress. Expression pattern analysis showed that most of the genes of the AP2/ERF family were dominantly expressed mainly in roots and stems, of which 19 were dominantly expressed in leaves, 77 would be induced to be expressed by methyl jasmonate, of which 16 genes were both dominantly expressed in leaves and induced to be expressed by methyl jasmonate, and these AP2/ERF genes may be the key regulatory genes for the synthesis of active ingredients in A. argyi leaves.This study lays the foundation for the functional study of AP2/ERF family genes and their regulating roles in the active components biosynthesis in A. argyi leaves.

Objective With the widespread of transcatheter aortic valve replacement(TAVR)in patients with severe symptomatic aortic stenosis(AS),the life-cycle management has become a major determinant of prognosis.Methods A total of 408 AS patients who underwent successfully TAVR from June 2021 to August 2023 were consecutively enrolled in Hospital Valve Intervention Center.Patients were assigned to the Usual Care(UC)group between June 2021 and October 2022,while patients were assigned to the Heart Multi-parameter Monitoring(HMM)group between November 2022 and August 2023.The primary endpoint was defined as composite endpoint within 6 months post-TAVR,including all-cause death,cardiovascular death,stroke/transient ischemic attack,conduction block,myocardial infarction,heart failure rehospitalization,and major bleeding events.Secondary endpoints were the time interval(in hours)from event occurrence to medical consultation or advice and patient satisfaction.Statistical analysis was performed using Kaplan-Meier and multivariable Cox proportional hazards models.Results The incidence of primary endpoint in HMM group was significantly lower than that in UC group(8.9％vs.17.7％,P=0.016),the driving event was the rate of diagnosis and recognition of conduction block.The average time intervals from event occurrence to receiving medical advice were 3.02 h in HHM group vs.97.09 h in UC group(P＜0.001).Using cardiac monitoring devices and smart healthcare platforms provided significant improving in patients long-term management(HR 0.439,95％CI 0.244-0.790,P=0.006).Conclusions The utilization of cardiac monitoring devices and smart healthcare platforms effectively alerted clinical events and improved postoperative quality of life during long-term management post TAVR.

Purpose/Significance To solve the problem that regional clinical research data are difficult to integrate efficiently,and to promote"Chinese evidence"and"Chinese protocol"in the global clinical research community.Method/Process Based on the standard-ization theory,the data standardization system is proposed,and the construction and application methods of the regional clinical research data platform are explored with the integration of multi-center clinical research data as the starting point.Result/Conclusion The theo-retical framework of the regional clinical research data platform has been preliminarily established,and the clinical research capabilities of tertiary hospitals in Shanghai have been significantly improved.

Objective To investigate the antitumor effects of ethoxydihydrosanguinarine(ESG)on colorectal cancer cells and its possible mechanisms.Methods Colorectal cancer cell lines RKO and HRT-18 were used.The cells were divided into blank control group and drug treatment groups(1.0,1.5,2.0 μmol/L ESG).CCK-8 assay,real time cellular analysis(RTCA)and colo-ny formation assay were used to detect the effect of ESG on cell proliferation and survival.Flow cytometry,DAPI staining,JC-1 mitochondrial membrane potential assay,and reactive oxygen species detection were performed to detect the effect of ESG on cell apoptosis.High-content analysis and Transwell invasion assay were used to detect the effect of ESG on cell invasion and mi-gration.Western blot was used to detect the expression of apoptosis,invasion and migration-related proteins,and the expression and phosphorylation of epidermal growth factor receptor(EGFR)and Akt/ERK signaling pathway proteins.The roles of EGFR in ESG-induced apoptosis,proliferation,invasion,and migration inhibition in colorectal cancer cells were detect through overex-pression and knockdown of EGFR.The direct binding between ESG and EGFR was detected by molecular docking and drug af-finity responsive target stability assay.Results The result showed that the proliferation and colony formation ability of colorec-tal cancer cells were significantly inhibited by ESG.Apoptosis through mitochondrial pathway was induced by ESG.The inva-sion and migration ability of colorectal cancer cells were inhibited by ESG.Moreover,ESG directly bound to EGFR and down-regulated the phosphorylation levels of Akt and ERK.Conclusion ESG targets and inhibits EGFR,thereby inhibiting the malig-nant progression of colorectal cancer cells and inducing mitochondrial apoptosis through its downstream Akt/ERK signaling pathway.This study provides new targeted drugs for targeting EGFR in the treatment of colorectal cancer.