Objective Objective To explore the effects of Propofol on neuronal autophagy,memory function,and the classical protein kinase Cγ(cPKCγ)-related pathway in the offspring of rats during the second trimester of pregnancy.Methods Thirty-six SD rats at 14 d of gestation were randomly divided into the control group,the Propofol group and the Propofol+cPKCγ inhibitor group,with 12 rats in each group.Ten pregnant mice were randomly selected from each group.The pregnancy continued until the offspring mice were born.The Morris water maze test was performed on the offspring mice at 30-34 d after birth.Western blotting was used to detect microtubule-associated protein light chain 3Ⅱ/Ⅰ(LC3 Ⅱ/LC3 Ⅰ),Beclin-1,cPKCγ and growth-associated protein-43(GAP-43)expression levels in hippocampal tissue,and immunofluorescence was used to determine the expression of autophagy-related protein ATG7 in hippocampal tissue.Results Compared with the control group,the Propofol group and the propofol+cPKCγ inhibitor group showed increased escape latency at 31,32,33 and 34 d after birth(P<0.05),while there was significantly decreased escape latency in the Propofol+cPKCγ inhibitor group,compared with the Propofol group(P<0.05).Compared with the control group,the Propofol group and the Propofol+cPKCγ inhibitor group had significantly decreased number of platform crossings(P<0.05),while there was significantly increased number of platform crossings in the Propofol+cPKCγ inhibitor group,compared with the Propofol group(P<0.05).Compared with the control group,the Propofol group and the Propofol+cPKCγ inhibitor group had increased time spent in quadrant I and decreased time spent in quadrant Ⅱ(P<0.05),while there was decreased time spent in quadrant Ⅰ and increased time spent in quadrant Ⅱ in the Propofol+cPKCγ inhibitor group,compared with the Propofol group(P<0.05).Compared with the control group,the LC3 Ⅱ/LC3 Ⅰratio,and the expression of Beclin-1,cPKCγ,and GAP-43 protein in the hippocampal tissue of offspring rats in the Propofol group and the Propofol+cPKCγ inhibitor group were significantly increased(P<0.05).Compared with the Propofol group,the LC3Ⅱ/LC3Ⅰ ratio,and the expression of Beclin-1,cPKCγ,and GAP-43 protein in the hippocampal tissue of offspring rats in the Propofol+cPKCγ inhibitor group was significantly decreased(P<0.05).Compared with the control group,the expression of ATG7 in the hippocampal tissue of offspring rats in both the Propofol group and the Propofol+cPKCγ inhibitor group was significantly increased(P<0.05).Compared with the propofol group,the expression of ATG7 in the hippocampal tissue of offspring rats in the Propofol+cPKCγ inhibitor group was significantly decreased(P<0.05).Conclusion Propofol can cause cognitive impairment in the offspring of rats during the second trimester of pregnancy,promote neuronal autophagy,and inhibit activation of the cPKCγ/GAP-43 pathway in the hippocampus,which may improve cognitive impairment in the offspring rats.

Objective Objective To explore the effects of Propofol on neuronal autophagy,memory function,and the classical protein kinase Cγ(cPKCγ)-related pathway in the offspring of rats during the second trimester of pregnancy.Methods Thirty-six SD rats at 14 d of gestation were randomly divided into the control group,the Propofol group and the Propofol+cPKCγ inhibitor group,with 12 rats in each group.Ten pregnant mice were randomly selected from each group.The pregnancy continued until the offspring mice were born.The Morris water maze test was performed on the offspring mice at 30-34 d after birth.Western blotting was used to detect microtubule-associated protein light chain 3Ⅱ/Ⅰ(LC3 Ⅱ/LC3 Ⅰ),Beclin-1,cPKCγ and growth-associated protein-43(GAP-43)expression levels in hippocampal tissue,and immunofluorescence was used to determine the expression of autophagy-related protein ATG7 in hippocampal tissue.Results Compared with the control group,the Propofol group and the propofol+cPKCγ inhibitor group showed increased escape latency at 31,32,33 and 34 d after birth(P<0.05),while there was significantly decreased escape latency in the Propofol+cPKCγ inhibitor group,compared with the Propofol group(P<0.05).Compared with the control group,the Propofol group and the Propofol+cPKCγ inhibitor group had significantly decreased number of platform crossings(P<0.05),while there was significantly increased number of platform crossings in the Propofol+cPKCγ inhibitor group,compared with the Propofol group(P<0.05).Compared with the control group,the Propofol group and the Propofol+cPKCγ inhibitor group had increased time spent in quadrant I and decreased time spent in quadrant Ⅱ(P<0.05),while there was decreased time spent in quadrant Ⅰ and increased time spent in quadrant Ⅱ in the Propofol+cPKCγ inhibitor group,compared with the Propofol group(P<0.05).Compared with the control group,the LC3 Ⅱ/LC3 Ⅰratio,and the expression of Beclin-1,cPKCγ,and GAP-43 protein in the hippocampal tissue of offspring rats in the Propofol group and the Propofol+cPKCγ inhibitor group were significantly increased(P<0.05).Compared with the Propofol group,the LC3Ⅱ/LC3Ⅰ ratio,and the expression of Beclin-1,cPKCγ,and GAP-43 protein in the hippocampal tissue of offspring rats in the Propofol+cPKCγ inhibitor group was significantly decreased(P<0.05).Compared with the control group,the expression of ATG7 in the hippocampal tissue of offspring rats in both the Propofol group and the Propofol+cPKCγ inhibitor group was significantly increased(P<0.05).Compared with the propofol group,the expression of ATG7 in the hippocampal tissue of offspring rats in the Propofol+cPKCγ inhibitor group was significantly decreased(P<0.05).Conclusion Propofol can cause cognitive impairment in the offspring of rats during the second trimester of pregnancy,promote neuronal autophagy,and inhibit activation of the cPKCγ/GAP-43 pathway in the hippocampus,which may improve cognitive impairment in the offspring rats.

Objective To develop an innovative minimally invasive rotary-cutting surgical system for axillary osmidrosis,and conduct clinical validation.Methods The design concept,technical principles and system composition of the innovative minimally invasive rotary-cutting surgical system for axillary osmidrosis were introduced.A total of 73 patients(146 axillae)with axillary osmidrosis were enrolled as subjects,and underwent surgery using the newly developed surgical system.Clinical validation of the system was performed by evaluating postoperative scarring,odor elimination rate,postoperative complication incidence,and patient satisfaction.Results The study demonstrated favorable clinical outcomes in the following aspects:postoperative scarring,odor elimination rate,postoperative complication incidence,and patient satisfaction.Conclusion The minimally invasive rotary-cutting surgical system for axillary osmidrosis is rationally designed.The rotary-cutting puncture device is safe,effective,minimally invasive,and convenient for axillary osmidrosis surgery,warranting further clinical validation and widespread application.

Objective To develop an innovative minimally invasive rotary-cutting surgical system for axillary osmidrosis,and conduct clinical validation.Methods The design concept,technical principles and system composition of the innovative minimally invasive rotary-cutting surgical system for axillary osmidrosis were introduced.A total of 73 patients(146 axillae)with axillary osmidrosis were enrolled as subjects,and underwent surgery using the newly developed surgical system.Clinical validation of the system was performed by evaluating postoperative scarring,odor elimination rate,postoperative complication incidence,and patient satisfaction.Results The study demonstrated favorable clinical outcomes in the following aspects:postoperative scarring,odor elimination rate,postoperative complication incidence,and patient satisfaction.Conclusion The minimally invasive rotary-cutting surgical system for axillary osmidrosis is rationally designed.The rotary-cutting puncture device is safe,effective,minimally invasive,and convenient for axillary osmidrosis surgery,warranting further clinical validation and widespread application.

Objective:To evaluate the morphological characteristics of the fetal heart and the contractile function of the left and right ventricles in fetuses with pulmonary stenosis (PS) and pulmonary atresia (PA) using fetal heart quantitative analysis technology (fetal HQ), and to assess the impact of different degrees of right ventricular outflow tract obstruction (RVOTO) on the contractile function of the fetal left and right ventricles. To accumulate early data and explore parameters for constructing a predictive model and clinical decision-making tool for the progression of fetal PS and PA.Methods:A retrospective analysis was conducted on 42 cases of mild to moderate PS and 23 cases of severe PS or PA detected through fetal echocardiography in the Department of Ultrasound, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, from July 2020 to December 2021. A control group of 195 normal fetal cases matching gestational weeks was selected. The fetal HQ technique was employed to measure the global sphericity index (GSI), left ventricular ejection fraction (EF), left/right ventricular area change percentage (LVFAC, RVFAC), and left/right ventricular longitudinal strain (LVGLS, RVGLS). Additionally, 24-segment sphericity index (SI) and fractional shortening (FS) for both left and right ventricles were measured. Comparative analyses were performed between the case and control groups, as well as within the case group.Results:In comparison with the control group, the case group exhibited significantly decreased GSI, LVGLS, LVEF, LVFAC, RVGLS, and RVFAC.The differences were statistically significant in the mild to moderate PS group (all P<0.05) and highly significant in the severe PS/PA group (all P<0.01). In the mild to moderate PS group, the left ventricle′s 2nd segment, right ventricle′s 24th segment SI, and the left ventricle′s 1st-13th segments, right ventricle′s 1st-16th and 20th-24th segments FS showed statistically significant differences compared to the control group (all P<0.05). In the severe PS/PA group, the right ventricle′s 1st-22nd segment SI, and the left ventricle′s 6th-13th, 21st-24th segments, and the right ventricle′s 1st-14th segments FS were reduced, showing statistically significant differences compared to the control group (all P<0.05). The severe PS/PA group showed lower RVGLS, RVFAC, and SI for the right ventricle′s 1st to 17th segments when compared to the mild to moderate PS group, with statistically significant differences (all P<0.05). Conclusions:Quantitative indices derived by fetal HQ is capable of evaluating the cardiac morphology and function of fetuses with PS/PA, which may provide for reference information for comprehensive understanding of cardiac morphological and functional changes in such fetuses.

ObjectiveTo explore the function of DANCR during the differentiation of human embryonic stem cells （hESC） toward definitive endoderm （DE）. MethodsThe in vitro DE differentiation system was established and its efficiency was verified. The correlation between the expression level of DANCR and DE differentiation process was detected. Using lentivirus system， we stably knocked down DANCR in hESC. The shDANCR hESC line was applied to DE differentiation， using qPCR and Western blot to detect the expression of DE marker genes SOX17 and FOXA2， and that of primitive streak marker genes Brachyury （T）， EOMES， MIXL1 and GSC. Dual luciferase reporter assay and qPCR were used to confirm the interaction between DANCR and the WNT pathway during DE differentiation. ResultsThe in vitro differentiation system mimicked DE differentiation efficiently. And the expression of DANCR was gradually downregulated during differentiation. DANCR was efficiently knocked down in the shDANCR hESC line （P < 0.001）. Compared with those in the control group， the expression levels of primitive markers Brachyury （T）， EOMES， MIXL1 and GSC， as well as DE markers SOX17 and FOXA2， were significantly decreased in shDANCR groups （P < 0.05）. Furthermore， the transcriptional activity of the WNT pathway in shDANCR groups was lower than that in the control group （P < 0.05）. And RNA levels of downstream genes of the WNT pathway， FZD5， FZD8， SFRP1， FRZB and ANKRD6， were significantly decreased in shDANCR groups （P < 0.05）. However， differences in protein levels of the TGFβ pathway effectors SMAD2/3 and p-SMAD2 were statistically insignificant in shDANCR and control groups （P > 0.05）. Forced activation of β-CATENIN rescued DANCR knock down-induced deficiency in DE differentiation. ConclusionsThe expression of DANCR decreases during DE differentiation. DANCR may promote DE differentiation through modulating the activity of the WNT pathway.

Strengthening Party building in public hospitals is a crucial guarantee politically and organizationally for the high-quality development.This study aims at promoting high-quality development in public hospitals.It employs literature analy-sis,research interviews,and questionnaires to access the new situations and requirements of such development.It examines the status of promoting the high-quality development of hospitals through Party building,identifies problems and breakthrough points in work,and explores the four strategic points of focus for Party building in public hospitals.This paper proposes four implemen-tation pathways centered around the keywords"closed-loop Party responsibility system","duties and tasks of the General Party Branch","medical humanities",and"co-construction in Party building".These pathways are intended to provide a fresh and sustainable impetus for the high-quality Party building that drives the high-quality development of public hospitals.

Blood deficiency syndrome (BDS) refers to a pathological state with blood dysfunction and organ dystrophy in traditional Chinese medicine. Danggui Wuji granules (DWG) was developed from a formula containing Angelicae Sinensis Radix and Musculus et Os Galli Domestici. Herein, we investigated the mechanism of DWG in treating BDS by modulating gut microbiota. We found that DWG protected mice from BDS by elevating the levels of red blood cell count, hemoglobin, and hematocrit in peripheral blood and increasing the erythrocyte membrane Na⁺-K⁺-ATPase activity. Danggui Wuji granules changed the composition and metabolites of colonic flora. Notably, Lactobacillus, Muribaculaceae, and Alistipes were the main genera showing changes after DWG treatment. Our findings revealed that DWG presented a positive therapeutic effect on BDS in mice by regulating the gut microbiota and metabolites. The protective mechanism of DWG was associated with pathways such as metabolic pathways, biosynthesis of secondary metabolites, ABC transporters, ribosome, thyroid hormone synthesis, lysine degradation, galactose metabolism, tyrosine metabolism, etc.

Pulmonary fibrosis (PF) is a pathological change caused by repeated injuries and repair dysfunction of the alveolar epithelium. Our previous study revealed that the residues Asn3 and Asn4 of peptide DR8 (DHNNPQIR-NH₂) could be modified to improve stability and antifibrotic activity, and the unnatural hydrophobic amino acids α-(4-pentenyl)-Ala and d-Ala were considered in this study. DR3penA (DHα-(4-pentenyl)-ANPQIR-NH₂) was verified to have a longer half-life in serum and to significantly inhibit oxidative damage, epithelial-mesenchymal transition (EMT) and fibrogenesis in vitro and in vivo. Moreover, DR3penA has a dosage advantage over pirfenidone through the conversion of drug bioavailability under different routes of administration. A mechanistic study revealed that DR3penA increased the expression of aquaporin 5 (AQP5) by inhibiting the upregulation of miR-23b-5p and the mitogen-activated protein kinase (MAPK) pathway, indicating that DR3penA may alleviate PF by regulating MAPK/miR-23b-5p/AQP5. Safety evaluation showed that DR3penA is a peptide drug without obvious toxicity or acute side effects and has significantly improved safety compared to DR8. Thus, our findings suggest that DR3penA, as a novel and low-toxic peptide, has the potential to be a leading compound for PF therapy, which provides a foundation for the development of peptide drugs for fibrosis-related diseases.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*