ObjectiveTo investigate the effect and molecular mechanism of exosomes derived from bone marrow mesenchymal stem cells（BMSC-exos） modified with Bushen Yisui capsule（BSYS）-containing serum on promoting the differentiation and maturation of OLN-93 oligodendrocytes by regulating miR-15b/Wnt signaling pathway. MethodsOLN-93 cells were divided into 5 groups， including the normal（NC） group， BMSC-exos group， BSYS-BMSC-exos group， BSYS-BMSC+LV-miR-15b-5p inhibitor-exos group， and BSYS-BMSC+LV-miR-15b-5p NC-exos group. DiR staining was used to observe the uptake of Exos by OLN-93 cells. The effective dosage of BSYS-BMSC-exos on OLN-93 cells was assessed by cell proliferation and activity assay（CCK-8）. Stable BMSCs lentiviral transfection strains were established to inhibit miR-15b-5p expression in both BMSCs and their exos， and transfection efficiency was verified by real-time fluorescent quantitative polymerase chain reaction（Real-time PCR） detection of miR-15b-5p. The expressions of 2′，3′-cyclic nucleotide 3′-phosphodiesterase（CNPase） and myelin proteolipid protein（PLP） in OLN-93 cells were detected by immunocytochemistry（ICC） and Western blot. The mRNA expressions of miR-15b-5p and Wnt3a in OLN-93 cells were detected by Real-time PCR， and the protein expression of Wnt3a was measured by Western blot. The expression levels of key molecules in the Wnt/β-catenin signaling pathway of OLN-93 cells， including glycogen synthase kinase（GSK）-3β， β-catenin， and T-cell specific transcription factor 4/transcription factor 7-like 2（TCF4/TCF7L2）， were measured by Real-time PCR and Western blot. ResultsDiR-labeled Exos were efficiently taken up by OLN-93 cells. The CCK-8 assay results indicated that 20 mg·L^-1 of BSYS-BMSC-exos exhibited the most significant effect in enhancing OLN-93 cell viability（P<0.01） and this dosage was selected for subsequent experiments. Following lentiviral transfection of BMSCs， Real-time PCR results revealed that miR-15b-5p was significantly suppressed in BMSCs（P<0.01）， and miR-15b-5p was also notably inhibited in BSYS-BMSC-exos（P<0.01）. ICC analysis further revealed an increase in the number of differentiated， mature CNPase and PLP-positive cells following BSYS-BMSC-exos treatment（P<0.01）. Western blot results demonstrated that the protein expression of CNPase and PLP was significantly enhanced with BSYS-BMSC-exos treatment（P<0.01）. Additionally， BSYS-BMSC-exos also increased the expression levels of miR-15b-5p and p-β-catenin proteins in OLN-93 cells， while decreased the mRNA and protein expressions of Wnt3a， as well as the mRNA expressions of β-catenin and TCF4/TCF7L2， and the protein expression level of p-GSK-3β（Ser9） was significantly reduced（P<0.05， P<0.01）. After the transfection of miR-15b-5p inhibitor into BSYS-BMSC-exos， the above effects were significantly diminished（P<0.05， P<0.01）. ConclusionBSYS-BMSC-exos facilitate the differentiation and maturation of OLN-93 cells， and its mechanism is related to the upregulation of miR-15b-5p in OLN-93 cells， which inhibits the expression of Wnt3a and thereby suppresses the Wnt signaling pathway.

ObjectiveTo investigate the intervention effects and mechanisms of the flavonoid hyperoside （Hyp） on lipopolysaccharide （LPS）-induced inflammation in the zebrafish model. MethodsZebrafish larvae were either microinjected with 0.5 g·L^-1 LPS or immersed in 1 g·L^-1 LPS for the modeling of inflammation. The larvae were then treated with Hyp at 25， 50， and 100 mg·L^-1 through immersion for four consecutive days. The inflammatory phenotypes were assessed by analyzing the mortality rate， malformation rate， body length， and yolk sac area ratio. Behavioral tests were conducted to evaluate the inflammatory stress responses， and macrophage migration was observed by fluorescence microscopy. Additionally， the mRNA levels of inflammation-related genes， including interleukin-1β （IL-1β）， interleukin-6 （IL-6）， chemokine C-C motif ligand 2 （CCL2）， chemokine C-X3-C motif receptor 1 （CX3CR1）， chemokine C-C motif receptor 2 （CCR2）， and genes associated with the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-kappa B （NF-κB） signaling pathway， were measured by Real-time quantitative polymerase chain reaction（Real-time PCR）. ResultsCompared with the pure water injection group， the model group exhibited increased mortality， malformation rates and yolk sac area ratio （P0.01）， reduced body length （P0.01）， increased total swimming distance and high-speed swimming duration （P0.01）， and up-regulated mRNA levels of TLR4， MyD88， NF-κB， IL-1β， IL-6， CCL2， CX3CR1， and CCR2 （P0.01）. Hyp at low， medium and high doses， as well as aspirin， reduced the mortality and malformation rates （P0.05，P0.01）， increased the body length （P0.05，P0.01）， decreased the yolk sac area ratio （P0.01）， reduced the high-speed swimming duration （P0.01）， and down-regulated the mRNA levels of TLR4， MyD88， NF-κB， IL-1β， IL-6， CCL2， CX3CR1， and CCR2 （P0.05，P0.01） compared with the model group. ConclusionHyp may modulate the TLR4/MyD88/NF-κB pathway to ameliorate inflammatory phenotypes and alleviate stress conditions in zebrafish， thereby exerting the anti-inflammatory effect.

Porcine epidemic diarrhea virus (PEDV) is an intestinal coronavirus that can cause porcine epidemic diarrhea, leading to diarrhea, vomiting, weight loss, and even death in piglets. Due to the diversity of PEDV strains, traditional vaccines are difficult to sustainably and effectively prevent and control PEDV. This article reviews the strategies and mechanisms of active substances in regulating intracellular signaling pathways, viral proteins, and microbial metabolites to enhance the host immune function against PEDV. It emphasizes the prevention of PEDV resistance and the potential harm of PEDV breaking through interspecies barriers to the human society, aiming to provide reliable theoretical support for the development of new antiviral drugs or vaccines.
Porcine epidemic diarrhea virus/immunology* ; Animals ; Swine ; Swine Diseases/prevention & control* ; Antiviral Agents/pharmacology* ; Coronavirus Infections/virology* ; Viral Vaccines/immunology* ; Humans ; Signal Transduction

Objective:To investigate the effects of external application of Sanying Plaster on the size of thyroid nodules and the states of depression and anxiety in patients with benign thyroid nodules.Methods:A randomized controlled trial was conducted. A total of 120 patients with benign thyroid nodules from the outpatient clinic of the Department of Thyroid Diseases at Shanghai Traditional Chinese Medicine Hospital from June to December 2022 were selected as the subjects of the study. They were divided into two groups using the random number table method, with 60 patients in each group. The control group received lifestyle intervention treatment, while the treatment group received Sanying Ointment in addition to the treatment of the control group. Both groups were treated for 3 months. TCM syndrome scores were measured before and after treatment; the maximum diameter of thyroid nodules was measured using a color Doppler ultrasound transverse section; the quality of life was assessed using the short form 36 (SF-36); the degree of anxiety and depression was evaluated using the self-rating anxiety scale (SAS) and the self-rating depression scale (SDS); adverse reactions during the treatment period were recorded, and the clinical efficacy was evaluated.Results:During the treatment period, 4 cases in the treatment group and 3 cases in the control group did not complete the treatment. Finally, 56 cases in the treatment group and 57 cases in the control group entered the efficacy evaluation. The total effective rate of the treatment group was 71.4% (40/56), and that of the control group was 14.0% (8/57), with a statistically significant difference between the two groups ( χ2=26.82, P<0.001). After treatment, the TCM syndrome score of the treatment group (10.02±3.65 vs. 16.65±3.44, t=-10.24) was lower than that of the control group ( P<0.001); the maximum diameter of thyroid nodules [11.00 (4.65, 19.93) mm vs. 15.00 (7.15, 28.50) mm, Z=-2.43] was lower than that of the control group ( P<0.05); the SF-36 score [121.83 (117.00, 130.00) vs. 114.42 (104.25, 127.50), Z=-2.62] was higher than that of the control group ( P<0.01); the SDS (46.72±4.59 vs. 57.02±5.99, t=14.80) and SAS (42.25±5.72 vs. 50.60±7.12, t=10.04) scores were lower than those in the control group ( P<0.001). The incidence of adverse reactions during the treatment period in the treatment group was 3.5% (2/57), and no adverse reactions occurred in the control group. Conclusion:The external application of Sanying Ointment helps to reduce the size of thyroid nodules in patients with benign thyroid nodules, improve the quality of life and anxiety and depression, and increase clinical efficacy with good safety.

Objectives:To investigate the efficacy and safety of anlotinib combined with niraparib in treating patients with platinum-resistant ovarian cancer.Methods:Thirty-five patients with pathological confirmed platinum-resistant ovarian cancer who experienced progression after receiving at least two lines of standard treatment were eligible. All of them were treated with anlotinib combined with niraparib between September 2019 and October 2021. The primary endpoint was progression-free survival (PFS). The second endpoints included overall survival, objective response rate (ORR), disease control rate (DCR) and safety. Survival analysis was performed using the Kaplan-Meier method and Log-rank test, and influence factor analysis was performed using Cox proportional risk regression models.Results:The best overall response showed that partial response was observed in 14 patients, stable disease was noted within 13 patients, and progressive disease was found in 8 patients. Therefore, the ORR and DCR of these 35 patients were 40.0% (95% CI:22.9%-57.1%) and 77.1% (95% CI:62.9%-91.4%), respectively. The median follow-up duration was 18.9 months (6.9-32.2). The median PFS was 6.5 months (95% CI:5.35-7.66). Multivariate Cox regression analysis for PFS indicated that age, Eastern Cooperative Oncology Group performance status (ECOG PS) score, International Federation of Gynecology and Obstetrics (FIGO) stage, and BRCA mutation status were independent factors influencing PFS ( P＜0.05). Additionally, the PFS in patients with BRCA mutation who have never received PARP inhibitor treatment was significantly longer than that in patients without BRCA mutation who have been exposed to prior PARPi treatment (15.0 vs 6.0 month, P=0.029). The most common treatment-related adverse reactions were fatigue (85.7%), hematologic toxic (85.7%) and hypertension (74.3%). There were no treatment-related deaths. Conclusion:Anlotinib combined with niraparib shows a promising efficacy and tolerable safety in platinum-resistant ROC patients.

Objective To investigate the relationship between insomnia,gastrointestinal symptoms,and glycosylated hemoglobin(HbA1c)levels in individuals diagnosed with type 2 diabetes mellitus(T2DM),as well as the related influencing factors.Methods A total of 910 T2DM patients treated in our multicenter from January 2022 to December 2022 were enrolled in this study.General information(gender,age,smoking and drinking history,exercise,course of disease,treatment and complications),HbA1c,Athens Insomnia Scale(AIS)scores and Gastrointestinal Symptoms Rating Scale(GSRS)scores of patients were collected.The differences of sleep and gastrointestinal symptoms between groups were analyzed,and the correlation between the differences and HbA1c was analyzed.Furthermore,the risk factors for non-standard HbA1c were analyzed.Results The AIS score and GSRS score in the HbA1c control group were less than those in the non-standard group(P＜0.01).Insomnia was reported by 37.0％of T2DM patients,and the HbA1c level in the insomnia group was significantly higher than that in the non-insomnia group(10.00％±2.38％vs.8.26％±1.73％,P＜0.01).Gastrointestinal symptoms were present in 57.5％of T2DM patients,and the HbA1c levels in the group with gastrointestinal symptoms were significantly higher than those in the group without gastrointestinal symptoms(9.26％±2.23％vs.8.43％±1.98％,P＜0.01).Furthermore,26.3％of T2DM patients experienced both insomnia and gastrointestinal symptoms.Remarkably,the HbA1c levels in the group with both insomnia and gastrointestinal symptoms were significantly higher than those in the group without either condition(10.18％±2.44％vs.8.45％±1.86％,P＜0.01).Correlation analysis demonstrated a significant association between sleep quality,gastrointestinal function,and HbA1c levels(P＜0.01).The logistic regression analysis result revealed that age,GSRS score,AIS score,and the presence of insomnia combined with gastrointestinal symptoms were independent risk factors for predicting HbA1c≥6.5％(P＜0.01).Having both insomnia and gastrointestinal symptoms concurrently was the strongest risk factor for substandard HbA1c control,and the risk of blood sugar control may increase about 5 times when both appear together.Conclusion Insomnia and gastrointestinal symptoms are common comorbidities in T2DM patients,showing a cross-interfering relationship,and they appear together with poor blood sugar control,interact causally,and amplify each other.

Tumor microenvironment(TME)is a complex cellular environment where tumor cells reside,along with various types of cells and extracellular components surrounding the tumor cells.Immune cells are key components of TME,including tumor-associated macrophages(TAMs),myeloid-derived suppressor cells(MDSCs),lymphocytes,regulatory T cells(Tregs),natural killer cells(NK cells),dendritic cells(DCs),and many others.It is worth noting that drug resistance is currently a major factor limiting the efficacy of cancer treatment methods such as chemotherapy,radiotherapy,targeted therapy,and immunotherapy,and a leading cause of treatment failure.Research has found that the development of drug resistance in tumor cells is the result of interactions between tumor cells and TME.Consequently,overcoming drug resistance in tumors caused by TME is considered a significant challenge in cancer treatment.In recent years,with in-depth research into immune cells within TME,significant progress has been made in understanding the specific mechanisms by which immune cells regulate drug resistance in tumor cells.Furthermore,therapeutic strategies that target these immune cells,signaling pathways,or cytokines have been shown to effectively combat tumor drug resistance and enhance the therapeutic outcomes of cancer treatment.This article reviews the research advancements regarding the roles of TAMs,MDSCs,Tregs,and NK cells in tumor drug resistance within TME and discusses the development of targeting strategies to overcome this resistance.Additionally,we explore the relationship of tumor-associated neutrophils(TANs)and B regulatory cells(Bregs)with tumor drug resistance.It is hoped that this review will offer insights and serve as reference for reducing tumor drug resistance and improving the efficacy of anti-tumor therapies.

To create flexible and high-quality pediatric continuing education opportunities, the Children's Hospital of Zhejiang University School of Medicine has developed an online teaching system based on the medical consortium information system, mobile application, and website, which includes "5G+" digital classroom for case teaching, hierarchical diagnosis and treatment tracking, mobile courses, and live interactive lectures about difficult medical cases as support extensions of offline training. From 2020 to 2023, over 9 000 people participated in online activities. The results of questionnaire survey, theoretical examination, and semi-structured interview showed that the members of the medical consortium were satisfied with the training content and effect of the online medical continuing education model; medical personnel's theoretical levels were improved after training; the interviewees believed that online training was flexible and convenient with regard to time, location, and space, with positive impact for improving clinical ability and personal development. However, the online form cannot yet replace the traditional refresher training completely. In the future, we will establish a unified evaluation and assessment mechanism, form a standardized management system, and introduce advanced technologies, so as to encourage enthusiastic and effective participation, and promote the rational and efficient use of medical education resources.

Objective To investigate the value of iterative decomposition of water and fat with echo asymmetry and least-squares(IDEAL-IQ)sequence in evaluating the correlation between renal ectopic fat deposition and early diabetic kidney disease(DKD)in patients with diabetes mellitus(DM).Methods A total of 51 patients with T1DM or T2DM were enrolled in this study from the Endocrinology and Metabolism Department in Affiliated Jinhua Hospital,Zhejiang University School of Medicine during January 2022 to July 2023.All the patients were divided into two groups according to the results of urine albumin creatinine ratio(UACR):normal or slightly increased urinary micro albumin group(NAU,UACR<30 mg/g,n=27)and diabetic kidney disease group(DKD,UACR 30～300 mg/g,n=24).Meanwhile,55 healthy subjects in health examination were selected as control group(NC).Pearson correlation analysis was used to analyze the correlation between renal FF and other indicators.Logistic regression analysis was used to analyze the influencing factors of early DKD,and the diagnostic efficiency of renal FF for early DKD was analyzed by the ROC curve.Results Serum creatinine(Scr)and renal fat fraction(FF)value were higher in DKD group than in NC and NAU groups(P<0.05).Pearson correlation analysis showed that kidney FF were positively correlated with UACR and Hcy(P<0.05).Logistic regression analysis showed that after adjusting for confounding factors,renal FF was a contributing factor to early DKD.The ROC curve revealed that model 2 had the highest diagnostic efficiency,with AUC=0.801,sensitivity of 66.7%,specificity of 85.2%,accuracy of 80.0%,and a renal FF cut-off value was 2.46%.Conclusion IDEAL-IQ could non-invasively measure the renal fat content in DM patients,and the renal FF were significantly associated with DKD in early stage.

Objective To systematically evaluate the risk factors of contrast medium extravasation(CME).Methods The rele-vant literature on the risk factors of CME were searched from CNKI,WanFang,VIP,CBM,Cochrane Library,ProQuest,PubMed,Ovid,Web of Science,and Embase via computer.Meta-analysis was performed via RevMan5.4.Results A total of 10 articles were included,involving 17 risk factors.The results of the Meta-analysis showed that contrast medium(CM)concentration[odds ratio(OR)=2.02],age(OR=2.22),combined tumor(OR=2.87),puncture site(OR=2.73),nursing experience(OR=2.78),osmotic pressure(OR=3.29),combined circulatory disease(OR=4.56)were the statistically significant factors.Conclusion The independ-ent risk factors of CME include CM concentration,age,combined tumor,puncture site,nursing experience,osmotic pressure,and combined circulatory disease.