BACKGROUND:The extracellular-regulated protein kinase 5(ERK5)signaling protein is essential for the survival of organisms,and resveratrol can promote osteoblast proliferation through various pathways.However,whether resveratrol can regulate osteoblast function through the ERK5 signaling protein needs further verification. OBJECTIVE:To explore the regulatory effect of ERK5 on the proliferation of MC3T3-E1 cells and related secreted proteins,and to further verify whether resveratrol can complete the above process by activating ERK5. METHODS:Mouse MC3T3-E1 preosteoblasts were treated with complete culture medium,XMD8-92(an ERK5 inhibitor),epidermal growth factor(an ERK5 activator),resveratrol alone,XMD8-92+EGF,and resveratrol+XMD8-92,respectively.Western blot assay was used to detect the expression of ERK5 and p-ERK5 proteins,proliferation-related proteins Cyclin D1,CDK4 and PCNA,and osteoblast-secreted proteins osteoprotegerin and receptor activator of nuclear factor-κB ligand in MC3T3-E1 cells of each group.The fluorescence intensity of ERK5,osteoprotegerin and receptor activator of nuclear factor-κB ligand in each group was detected by cell immunofluorescence staining,and cell proliferation was detected by EdU staining,respectively.The appropriate concentration and time of resveratrol intervention in MC3T3-E1 cells were determined by cell morphology observation and cell counting kit-8 assay. RESULTS AND CONCLUSION:The activation of ERK5 signaling protein could effectively promote the proliferation of MC3T3-E1 cells,up-regulate the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio.The appropriate concentration and time for resveratrol intervention in MC3T3-E1 cells was 5 μmol/L and 24 hours,respectively.Resveratrol could activate ERK5 signaling protein,thereby promoting osteoblast proliferation and up-regulating the osteoprotegerin/RANKL ratio.All these results indicate that resveratrol can promote the proliferation of MC3T3-E1 cells and up-regulate the osteoprotegerin/RANKL ratio by activating the ERK5 signaling protein.

Objective To analyze the characteristics of adverse drug reactions （ADR） reported in Sixth People’s Hospital South Campus, Shanghai Jiaotong University from 2021 to 2023, to provide reference for promoting rational clinical drug use. Methods ADR data reported in our hospital were collected retrospectively, including patients’ basic information, drugs causing adverse reactions, types of adverse reactions and outcomes. Descriptive analysis methods were used to summarize and analyze the data. Results A total of 979 cases of ADR were reported in our hospital from 2021 to 2023. The highest proportion of patients with ADR occurred in the age range of 31 to 50, and more male patients （63.5%）. The top five drugs involved with adverse reactions were antibiotics （48.8%）, Chinese medicine injections（19.2%）, vitamins（7.5%）, Chinese traditional medicine（7.2%）, equine tetanus immunoglobulin（6.3%）. Among antibiotics, cefuroxime, ceftazidime and cefotiam were the majority. The organs/systems involved in all ADR were mainly skin and accessories damage （55.4%）. The clinical manifestations were rash, itching, and maculopapular rash. Conclusion From 2021 to 2023, the most common drugs causing adverse drug reactions in our hospital were mainly antibacterial drugs, and the rational clinical use of antibacterial drugs still needs to be concerned.

ObjectiveTo understand the awareness of knowledge about chronic obstructive pulmonary disease （COPD） and influencing factors among residents in Yangpu District， Shanghai. MethodsWe used cluster random sampling method to conduct face-to-face questionnaire surveys on selected household residents in 12 streets of Yangpu District. The survey questions included their understanding of COPD name， lung function test， and COPD related knowledge. Multivariate logistic regression analysis was used to analyze the influencing factors of awareness rate. ResultsA total of 1 440 people were ultimately included in the analysis， and the awareness rates of COPD name， lung function test， and COPD awareness were 19.93%， 18.61%， and 14.95%， respectively. Among the people who knew the name of COPD， awareness rate of shortness of breath or dyspnea was the highest （84.12%） in the three main symptoms of COPD. Among the main risk factors of COPD， second-hand smoke（86.78%）and smoking （85.82%） were the highest. The main ways to obtain knowledge of COPD names were through television （12.60%） and the internet （11.97%）. The results of multivariate logistic regression analysis showed that men were significantly higher than women in the awareness of COPD name， lung function test， and COPD knowledge， with the OR values of （OR=1.39， 95%CI：1.08‒1.79）， （OR=1.47，95%CI：1.12‒1.92） and （OR=1.37，95%CI：1.02‒1.84）， respectively. The awareness rate of COPD names and lung function tests was the highest among people aged ≥ 65 years old， while the awareness rate of COPD knowledge was the highest among people aged 35‒50 years old. The awareness rate of COPD names was the highest among people with college education or above， civil servants， teachers， and medical staff， people with an annual household income of 100 000‒200 000 yuan. ConclusionThe overall awareness rate of COPD names， lung function tests， and COPD related knowledge among residents in Yangpu District is still at a low level. We should intensify the promotion and education of COPD among key groups such as women， young people， and those with low income， in order to improve the overall awareness rate of COPD among the population.

Objective:To explore the association between insulin resistance (IR) and genome-wide DNA methylation based on Shanghai twin study.Methods:Monozygotic twins (MZ) from Shanghai were recruited during 2012-2013, 2017-2018, and 2022-2023. Data were collected by questionnaire survey, physical examination and laboratory tests. Genome-wide DNA methylation was quantified. Generalized linear mixed effect model was applied to analyze the association between methylation level at each site and homeostatic model assessment 2-insulin resistance (HOMA2-IR). Non-paired and paired designs were used to assess the association between DNA methylation and phenotype of IR. Cluster analysis was conducted to identify the clusters of top significant sites. Generalized linear regression was performed to examine the differential methylation patterns from clusters.Results:A total of 100 MZ pairs were included in this study. Hypermethylated cg10535199-2q23.1 ( β=0.74%, P=1.51×10 -7, OR=1.06, 95% CI: 1.03-1.09) and ch.17.49619327- SPOP ( β=0.23%, P=7.54×10 -7, OR=1.17, 95% CI: 1.08-1.28) were identified with suggestive significance. After correcting for multiple testing, no sites reached genome-wide significance. There was no statistical significance in the paired analysis. Two clusters with hypomethylated ( β=-0.39%, P<0.001) and hypermethylated ( β=0.47%, P<0.001) patterns were observed for HOMA2-IR. Conclusions:IR was significantly associated with DNA methylation, and genetic factors might contribute to the association.

Objective To observe the value of propofol combined with etomidate in bariatric surgery based on hemodynamics and stress response.Methods Patients admitted to Shanxi Bethune Hospital who underwent bariatric surgery from January 2020 to January 2021 were retrospectively selected and divided into an experimental group (propofol combined with etomidate) and a control group (propofol) according to the intraoperative anesthesia regimen.The patient's surgical time,awakening time,extubation time,hemodynamic indicators[heart rate (HR),mean arterial pressure (MAP),blood oxygen saturation (SpO2)],stress indicators[adrenocorticotropic hormone (ACTH),adrenaline (ADR),cortisol (COR)],Mini Mental State Examination (MMSE) score,and adverse reactions were recorded.Results A total of 80 patients were included in the study,among which 47 cases were in the experimental group,and 33 cases were in the control group.There was no statistically significant difference in operation time,awakening time and extubation time between the two groups (P>0.05).Immediately after intubation,HR and MAP of the experimental group were lower than those of the control group,and SpO2 was higher than that of the control group (P<0.05).Serum ACTH,ADR and COR levels in the experimental group were higher than those in the control group immediately after intubation and 5 min after extubation (P<0.05).The MMSE score of the experimental group 10 min after awakening was higher than that of the control group (P<0.05).The difference in the incidence of adverse reactions between the two groups was not statistically significant (P>0.05).Conclusion The use of propofol combined with etomidate in weight loss surgery can reduce hemodynamic fluctuations,alleviate cognitive impairment,alleviate stress reactions,and does not significantly increase anesthesia adverse reactions,which is with good safety.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective To investigate the effect of nasal mask on preventing respiratory depression and hypoxia during anesthesia under painless gastroscopy.Methods 246 patients underwent elective painless gastroscopy from September 2022 to March 2023 were selected and divided into nasal catheter oxygen group(group C)and nasal mask oxygen group(group M)according to random number table method.The group C was inhaled oxygen by conventional nasal cannula,and in group M,oxygen was inhaled by a nasal mask.Patients in both groups were given 5 L/min preoxygenation for 3 min.After induction of anesthesia,gastroscopy was performed when modified observer's assessment of alertness/sedation(MOAA/S)score≤1.During anesthesia,hypoxia interventions were performed in group C based on percutaneous arterial oxygen saturation(SpO2)and in group M based on partial pressure of end-tidal carbon dioxide(PetCO2)and SpO2.The incidence of subclinical respiratory depression,hypoxia and severe hypoxia during anesthesia was recorded.The minimum SpO2 value during anesthesia was recorded;Implementation of intervention measures of jaw lifting,mask pressure oxygen and tracheal intubation.Record the number of gastroscope withdrawal cases.Mean arterial pressure(MAP),heart rate(HR),and respiratory rate(RR)were recorded at the time of entry(T0),immediately after induction of anesthesia(T1),at the end of gastroscopy(T2),and 5 minutes after awakening(T3).The occurrence of perioperative adverse events and the satisfaction of anesthesiologists and endoscopists were recorded.Results Compared with group C,the incidence of subclinical respiratory depression,hypoxia and severe hypoxia in group M was significantly decreased(P<0.05).The minimum value of SpO2 during anesthesia in group M was higher than that in group C(P<0.05).The incidence of jaw-lifting and mask ventilation were lower in group M than that in group C(P<0.05).The incidence of gastroscope withdrawal due to airway intervention in group M was lower than that in group C(P<0.05).Compared with T0,MAP,HR and RR of the two groups were significant reduction at T1 and T2(P<0.05).There was no significant difference in the incidence of adverse events between the two groups(P>0.05).The satisfaction of endoscopists in group M was higher than that in group C(P<0.05).Conclusion Compared with nasal catheter oxygen inhalation,anesthesia nasal mask can timely detect hypopnea and respiratory depression during gastroscopy,reduce the occurrence of hypoxia,and improve the airway safety of painless gastroscopy patients.

Objective:To explore the genes related to primary myelofibrosis (PMF) and signaling pathways as well as the possible clinical significance.Methods:A total of 3 mRNA expression datasets of PMF (GSE26049, GSE61629 and GSE53482) were downloaded from Gene Expression Omnibus (GEO) database, including the data of peripheral blood samples from 55 PMF patients and 58 controls. The differentially expressed genes (DEG) between PMF patients and the controls were identified by using online tool GEO2R. Gene ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the common DEG of the 3 datasets, and then protein interaction (PPI) network was constructed. The key nodes of the common DEG in PPI network were calculated by using MCC method and Degree method in cytoHubba program; finally the top 10 hub genes were selected and the hub genes shared by the 2 methods were obtained. Peripheral blood samples of 25 PMF patients and 10 controls (normal hematopoietic stem cell transplant donors or iron deficiency anemia patients) admitted to the Second Hospital of Shanxi Medical University from September 2017 to June 2021 were retrospectively collected. Reverse transcription-fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of 10 screened common hub genes in each sample, and the expressions of all genes at transcriptional level of the two groups were compared.Results:A total of 239 common DEG between PMF patients and the controls were screened out in the 3 datasets, including 153 downregulated DEG and 86 upregulated DEG. The GO enrichment analysis showed that the common downregulated DEG were significantly enriched in negative regulation of transcription, translation and fibroblast proliferation, while the upregulated DEG were mainly enriched in protein ubiquitination and ubiquitin-dependent protein catabolic process. The KEGG pathway analysis indicated that the upregulated common DEG and downregulated common DEG were both enriched in PI3K/Akt signaling pathway, cancer pathways and transcriptional misregulation in cancer. There were 8 common hub genes shared by the 2 methods among the top 10 genes ranked by MCC and Degree methods, including 6 downregulated common DEG (TP53, MYC, ATM, FYN, PTPRC and ATRX) and 2 upregulated common DEG (VEGFA and FOXO3). These above 8 common hub genes were mainly involved in PI3K/Akt signaling pathway, cell cycle and cancer transcriptional regulation signaling pathways. RT-qPCR detection of clinical peripheral blood samples showed that the relative expression levels of mRNA in 6 downregulated common DEG of PMF patients were lower compared with those in controls, while the differences were not statistically significant (all P > 0.05); the relative expression levels of mRNA in 2 upregulated common DEG of PMF patients were higher compared with those in controls, and the differences were statistically significant ( U value was 33.00, 36.00, respectively; P value was 0.021, 0.033, respectively). Conclusions:Bioinformatics and clinical sample verification show that VEGFA and FOXO3 are up-regulated in PMF patients, which are mainly involved in the PI3K/Akt signaling pathway, cell cycle and cancer transcriptional regulation signaling pathway. Both genes may be related to the development of PMF and may become potential therapeutic targets.

Objective:To investigate the effect and mechanism of vitamin D supplementation on Hashimoto′s thyroiditis(HT).Methods:Female SD rats were randomly divided into four groups by random number table method: control group, experimental autoimmune thyroiditis(EAT) control model group(model group), low-dose(VD1 group) and high-dose(VD2 group) active vitamin D intervention groups. The morphology of thyroid cells, thyroid function, thyroid antibodies, various CD4 + T cells, and related cytokine levels among different groups were compared. Results:The levels of thyroid peroxidase antibody(TPOAb) and thyroid globulin antibody(TgAb) in model group were significantly higher than those in control group, while the levels of VD1 and VD2 groups were significantly lower than those in model group( P<0.05). Compared with control group, HE staining in model group showed severe damage of follicular epithelial cells; Compared with model group, the degree of atrophy and destruction of follicular epithelial cells in VD1 and VD2 groups were reduced. The proportion of helper T cell(Th)1 and Th17 cells and related cytokine levels in model group were significantly higher than those in control group, while those in VD1 and VD2 groups were lower than those in model group( P<0.05); The proportion of regulatory T cell(Treg) cells and related cytokine levels in model group were significantly lower than those in control group, while those in VD1 and VD2 groups were higher than those in model group( P<0.05). Conclusions:After supplementing with vitamin D, the levels of TPOAb and TgAb in EAT rats decreased, and the number of various CD4 + T cells and related cytokine levels tended towards normalization. This suggests that vitamin D may improve HT by regulating CD4 + T cell differentiation, providing a theoretical basis for the role of vitamin D supplementation in HT treatment.

Objective:To evaluate the safety and efficacy of enhanced recovery after surgery(ERAS) in the perioperative period of congenital choledochal cysts in children.Methods:This is a multicenter prospective randomized controlled study. The clinical data of 273 pediatric congenital choledochal cysts(CCC) patients who underwent surgery at 14 medical centers with complete follow-up data were collected through the medical data analysis platform. Among them, 123 cases in ERAS group were managed perioperatively in strict accordance with ERAS mode, and 150 cases in conventional group were managed according to traditional mode. The length of hospital stay,time to first farting, time to complete feeding, the incidence of complications, cost and readmission rate within 30 days,stress indexes and liver function were compared between the two groups.Results:Compared with the conventional group, median time to start farting (2.0 d vs. 3.0 d, P<0.001), median time to complete feeding (5.0 d vs. 7.0 d, P<0.001), median postoperative hospitalization time (6.0 d vs. 9.0 d, P<0.001),the median total length of stay(13.0 d vs. 15.0 d, P<0.001) were shorter,the median hospitalization cost (37,000 yuan vs.43,000 yuan P<0.001) was lower, and stress indexes recovered quickly. The incidence of postoperative hospital stay and readimission rate within 30 d were not statistically different between the two groups. Conclusion:It is safe and feasible to implement ERAS for children with CCC in the perioperative period, which can reduce stress response, speed up recovery,and save medical costs.