ObjectiveTo investigate the modulating effect of modified Wumeiwan （MWMW） on the ulcerative colitis （UC）-associated intestinal helper T cell 17 （Th17）/regulatory T cell （Treg） balance and intestinal flora by using a human flora-associated model of UC patients with dampness-heat obstruction syndrome， thus providing a new idea for the UC-related research and therapeutic strategies. MethodsThe 24 male C57BL/6J mice were randomized into normal control， model， and MWMW groups （n=8）. Model and MWMW groups were first treated with an antibiotic cocktail （vancomycin， 0.1 g·kg^-1； neomycin sulfate， 0.2 g·kg^-1； ampicillin， 0.2 g·kg^-1； metronidazole， 0.2 g·kg^-1） for 21 days. At the end of antibiotic treatment， the gavage of fecal microbiota suspension from UC patients with dampness-heat obstruction syndrome was started at a dose of 0.2 mL·d^-1 for 19 consecutive days， by which a human flora-associated model of UC was obtained. The MWMW group was administrated daily with MWMW liquid （12.5 g·kg^-1）， while the normal control and model groups were administrated by gavage with an equal amount of sterile water for 7 consecutive days. The symptoms of dampness-heat obstruction were observed. The colon length and spleen index were measured and calculated， and the proportions of Th17 and Treg cells were detected by flow assay. The intestinal flora was analyzed by 16S rRNA high-throughput sequencing. ResultsCompared with the normal control group， the model group showed shortened colon （P<0.05） and increased spleen index （P<0.01）. Compared with the model group， the MWMW group showed prolonged colon （P<0.01） and decreased spleen index （P<0.05）. After the intervention of MWMW， the Th17 proportion and Th17/Treg ratio in the colon decreased （P<0.01）， and the proportion of Treg cells increased （P<0.05）. The number of species and alpha and beta diversity of intestinal flora in mice were regulated by MWMW （P<0.05）. In terms of intestinal flora composition， MWMW increased the relative abundance of several phyla （Firmicutes， Proteobacteria， Fusobacteriota， Actinobacteriota， and Gemmatimonadota）， the genus Bacteroides， and two species （Bacteroides thetaiotaomicron and B. fragilis） in model mice. Moreover， Spearman's correlation analysis showed that the relative abundance of B. thetaiotaomicron and B. fragilis were negatively correlated with the Th17 level （P<0.05）. In addition， the above changes in intestinal flora caused the changes in microbial genes involved in 14 pathways， such as glycolysis， amino acid degradation， inorganic nutrient metabolism， biosynthesis of pyrimidine deoxyribonucleotides， antibiotic resistance， and degradation of polysaccharides. ConclusionsThe human flora-associated model successfully simulated the changes （marked by a decrease in the abundance of Bacteroides） of intestinal flora in UC patients with dampness-heat obstruction syndrome. MWMW can enrich the abundance of beneficial bacteria such as B. thetaiotaomicron and B. fragilis and promote the synergistic intestinal immune modulation with the metabolic functions centered on glycolysis， amino acid metabolism， and nucleotide synthesis through bacterial polysaccharide utilization sites to reduce the Th17/Treg ratio， thereby exerting a protective effect on UC.

Objective:To treat the Crohn's disease(CD)patients with ustekinumab(UST),to eva-luate their clinical and endoscopic remission,and to evaluate their transmural response(TR)and trans-mural healing(TH)condition using intestinal ultrasonography(IUS).Methods:Retrospective analysis was made on patients diagnosed with CD in Peking University People's Hospital from January 2020 to Au-gust 2022,who were treated with UST for remission induction and maintenance therapy.All the patients were evaluated on both week 8 and week 16/20 after treatment,including clinical,biochemical indica-tors,colonoscopy and IUS examination.Results:A total of 13 patients were enrolled in this study,inclu-ding 11 males and 2 females.The minimum age was 23 years,the maximum age was 73 years and the mean age was 36.92 years.All the patients were in the active stage of disease before treatment,and the average Best Crohn's disease activity index(Best CDAI)score was 270.12±105.55.In week 8,the Best CDAI score of the patients decreased from 270.12±105.55 to 133.16±48.66(t=4.977,P＜0.001).Eight patients achieved clinical remission while 5 patients remained in the active stage.Nine patients underwent colonoscopy evaluation.The average simple endoscopic score for Crohn's disease(SES-CD)score decreased from 10.71±7.14 before treatment to 6.00±7.81(t=2.483,P=0.048)in week 16/20.Four patients achieved endoscopic remission while 5 patients did not.In week 8,5 pa-tients achieved TR,2 patients achieved TH,the other 6 patients did not get TR or TH.In week 16/20,6 patients achieved TR,3 patients achieved TH while the other 4 patients did not get TR or TH.There was no significant statistical difference in the TR effect of UST between small intestine and colon lesions(Fisher test,P＞0.999).The rate of UST transmural response in the patients who had had previous bio-logical agent therapy was lower than those with no previous biological agent therapy,but there was no sig-nificant statistical difference(Fisher test,P=0.491).Conclusion:After treatment of UST,the clinical and endoscopic conditions of the CD patients had been improved,and some patients could achieve clini-cal remission and endoscopic remission.UST had good TR and TH effects on CD.TR might appear in week 8,and the TR effect increased in week 16/20.There was no significant statistical difference in the TR effect between small intestine and colon lesions.TR effect of UST was better in the patients who had no previous biological agent therapy than those who had had other biological agents,but the result had no significant statistical difference.

Objective To investigate the impact of the Shared Medical Appointment (SMA) model on blood glucose levels and self-management behaviors in patients with gestational diabetes mellitus (GDM). Methods A total of 87 pregnant women diagnosed with GDM at the Obstetrics and Gynecology and Endocrinology Outpatient Departments of the Affiliated Suqian Hospital of Xuzhou Medical University from October 2021 to October 2022 were enrolled and divided into treatment group (n=44) and control group (n=43). The treatment group received SMA-based GDM management, while the control group underwent routine outpatient follow-up. Baseline data, flash glucose monitoring (FGM)-related indicators before and after treatment, and self-management behavior scale scores were compared between the two groups. Results No statistically significant differences were observed between the two groups in age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), blood urea nitrogen (BUN), creatinine (Cr), uric acid (UA), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and glycated hemoglobin (HbA1c) (P>0.05). After treatment, the time in range (TIR) of glucose was higher in the treatment group than that in the control group, while mean amplitude of glycemic excursions (MAGE), standard deviation of blood glucose (SDBG), coefficient of variation (CV), and mean blood glucose (MBG) were lower in the treatment group (P < 0.05). Within the treatment group, post-treatment TIR was higher, and MAGE, CV, SDBG, and MBG were lower than pre-treatment levels (P < 0.05). In the control group, post-treatment TIR was higher, and SDBG and MBG were lower than pre-treatment levels (P < 0.05). After treatment, the total score and scores for dietary management, exercise management, medication management, and blood glucose monitoring management in the self-management behavior scale were significantly higher in the treatment group than in the control group (P < 0.05). In the treatment group, post-treatment scores for all self-management behaviors were higher than pre-treatment levels, while post-treatment total scores and scores for medication management and blood glucose monitoring management in the control group were higher than pre-treatment levels (P < 0.05). Conclusion SMA management model can comprehensively improve blood glucose levels and enhance self-management behavior capabilities in GDM patients.

Objective:To explore the abundance, diversity, and structural changes of early postoperative pulmonary bacterial microbiota in lung transplant recipients.Methods:Recruiting 40 recipients who underwent lung transplantation surgery at the First Affiliated Hospital of Guangzhou Medical University from October 2020 to May 2022 for the study.All recipients did not receive antibiotic treatment within 4 weeks prior to surgery, and all recipients received a unified immunosuppressive and anti infection regimen after surgery.The bronchoalveolar lavage fluid(BALF) was collected from the amputated lung in vitro before the transplantation for 16S ribosomal RNA sequencing and flora analysis.BALF was also collected at the scheduled time from the transplanted lung on the 7th, 14th and 30th days post transplantaion for analysis.Results:The study included a total of 40 recipients who did not receive antibiotic treatment within 4 weeks before surgery, including 35 males.Among the study participants, there were 14 cases of primary obstructive pulmonary disease, 19 cases of interstitial lung disease, 3 cases of occupational lung disease, and 4 others.Microbiome in BALF of transplanted and detached autologous lungs at the first week after surgery α( P<0.05) and β diversity is statistically significant( R2=0.08, P=0.001), and the bacterial community in the transplanted lungs α Diversity is lower than that of explant lungs.Starting from the second week after surgery, the richness and species diversity of the transplanted lung microbiota gradually increase.The bacterial structure was also changed with postoperative time, and the relative abundance of the same bacterial species were varied at different time points.The bacterial community in BALF was mainly dominated by Proteobacteria both explant lungs and transplant lungs.The relative abundance of Staphylococcus and Acinetobacter genera at the BALF in transplanted lungs was higher than that in explant lung samples, but their relative abundance decreased over time after surgery. Conclusions:The α diversity of the early postoperative pulmonary microbiota after lung transplantation was lower than that of the amputated autologous lung, and the bacterial richness and species diversity in the microbiota of the transplanted lung gradually increased at the second week after the transplantation.The bacterial microbiota of the transplanted lung is changed complicatedly with time.

Objective To analyze the changes of postoperative pulmonary function in lung transplant recipients. Methods Clinical data of 81 recipients undergoing bilateral lung transplantation and combined heart-lung transplantation were collected, and postoperative status of the recipients was analyzed. Pulmonary ventilation and diffusion function indexes at 1 month, 3 months, every 3 months (3-18 months after lung transplantation) and every 6 months (18-36 months after lung transplantation) were analyzed in the recipients. The characteristics of the optimal pulmonary function in the recipients were assessed. Results Postoperative mechanical ventilation time was 4 (2, 9) d, and the length of postoperative ICU stay was 10 (7, 20) d. Among 81 recipients, 27 recipients developed primary graft dysfunction (PGD) after lung transplantation, with an incidence rate of 33%. Postoperative forced vital capacity (FVC) to predicted value ratio (FVC%pred), forced expiratory volume in one second (FEV₁) to predicted value ratio (FEV₁%pred), FEV₁/FVC to predicted value ratio (FEV₁/FVC%pred) and corrected diffusion lung capacity for CO to predicted value ratio (D_LCOc%pred) were changed over time (all P<0.001). FVC%pred and FEV₁%pred were gradually increased within postoperative 9 months, and D_LCOc%pred was gradually elevated within postoperative 3 months (all P<0.05). Thirty-six recipients had FVC%pred≥80%, FEV₁%pred≥80% in 41 cases, FEV₁/FVC%pred≥92% in 76 cases, FVC%pred≤40% in 1 case and FEV₁%pred≤40% in 1 case, respectively. Sixteen recipients had D_LCOc%pred≥80%, corrected diffusion lung capacity for CO/alveolar volume to predicted value ratio (D_LCOc/V_A%pred) ≥80% in 63 cases, D_LCOc%pred≤40% in 4 cases and D_LCOc/V_A%pred≤40% in 1 case, respectively. Postoperative FVC%pred, FEV₁/FVC%pred and D_LCOc%pred in recipients with a primary disease of obstructive pulmonary disease were significantly higher than those in their counterparts with restrictive pulmonary disease (all P<0.05). Postoperative D_LCOc%pred in recipients with PGD was significantly lower than that in those without PGD (P<0.05). Conclusions Pulmonary ventilation function in lung transplant recipients reaches the optimal state and maintains a steady state at postoperative 9 months, and pulmonary diffusion function reaches a steady state at postoperative 3 months. Primary diseases and the incidence of PGD may affect postoperative pulmonary function.

Objective: To describe the prevalence of overweight and obesity among children and adolescents in Jinan City according the national and international criteria, as well as to compare the Chinese and international standards, so as to provide basic data for relevant intervention strategies. Methods: From September to December 2021, using the height and weight data obtained from the health checkup reports of 746 985 primary and secondary school students in Jinan City in 2021, body mass index(BMI) was calculated to evaluate the current status of the prevalence of overweight and obesity among this sample of children and adolescents aged 6- 18 years old. The consistency of the Chinese standard, U.S. Centers for Disease Control and Prevention (CDC) standard, International Obesity Task Force (IOTF) standard, and World Health Organization (WHO) standard was compared by calculating the weighted Kappa value. Results: Based on the Chinese, U.S. CDC, IOTF and WHO standards, the overweight rates of children and adolescents aged 6-18 years in Jinan were 17.3%, 16.5%, 21.1% and 13.6%, respectively, and the obesity rates were 23.1%, 19.5%, 13.5% and 6.6%, respectively. The overweight and obesity rates of boys were higher than those of girls under the four criteria (China: χ 2=1 418.48, 9 868.51, U.S. CDC: χ 2=145.78, 23 211.41, IOTF: χ 2=1 326.94, 13 615.62, WHO: χ 2=873.13, 46.41, P <0.01).The overweight rate of adolescents in the 13-18 year-old age group was higher than that of children aged 6-12 years (China: χ 2=29.13, U.S. CDC: χ 2=6.43, IOTF: χ 2=15.87, WHO: χ 2=19.48, P <0.01) and the obesity rate of the group aged 6-10 years was significantly higher than that of the group aged 11-18 years (China: χ 2=217.02, U.S. CDC: χ 2=227.54, IOTF: χ 2=171.91, WHO: χ 2=165.91, P <0.01). The rates of overweight and obesity in urban children and adolescents were slightly higher than those in rural children and adolescents (China: χ 2=25.06, 245.12, U.S. CDC: χ 2=56.13, 205.93, IOTF: χ 2= 182.34 , 22.04, WHO: χ 2=200.88, 21.61, P <0.01). The Chinese standard showed good agreement with the IOTF standard and U.S. CDC standard, with weighted Kappa values of 0.72 and 0.83, but poor agreement with the WHO standard, with a weighted Kappa value of 0.33. Conclusion The current prevalence of overweight and obesity among children and adolescents in Jinan is serious. The Chinese standard has good consistency with IOTF standard and American CDC standard, and poor consistency with WHO standard.

Objective:To investigate the effects of various concentrations of recombinant human WISP2 protein(WISP2)on lipid metabolism in HepG2 cells.Methods:HepG2 cells were treated with different concentrations(0, 0.4, 1 and 2 μg/L)of recombinant human WISP2 for 48 hours.Cell viability was detected by Cell-Titer, and enzymatic hydrolysis methods were used to measure intracellular triacylglycerol(TG)and total cholesterol(TC)levels.The mRNA expression was detected by quantitative real-time reverse transcription-PCR(RT-qPCR)and protein expression in HepG2 cells was detected by western blot.Results:Compared with the control group, the WISP2 groups treated with various concentration did not significantly reduce the viability of HepG2 cells.TG and TC in HepG2 cells were significantly increased by recombinant human WISP2 treatment(all P<0.05).The concentrations of TG in the 0.4, 1 and 2 μg/L recombinant human WISP2-treated groups were 1.254±0.039, 1.216±0.028 and 1.174±0.014)times the concentration in the untreated group, respectively( F=6.791, P=0.006).The concentration of TC in the untreated group was 1.264±0.057, 1.394±0.101 and 1.392±0.077), respectively, times the concentration in each of the treated groups( F=7.045, P=0.005).Further experiments found that the mRNA expression of sterol regulatory element binding protein 1(SREBP1), 3-hydroxy-3-methylglutaryl coenzyme A reductase(HMGCR), acetyl-CoA carboxylase(ACC), type 2 diacylglycerol acyltransferase(DGAT2)and the protein expression of SREBP1, ACC and fatty acid synthase(FAS)were significantly increased in the recombinant human WISP2-treated groups, compared with the control group(all P<0.05).However, the expression of lipid transporters such as the low-density lipoprotein receptor(LDLR), ApoB and ApoE and adipose triglyceride lipase(ATGL), a key lipolysis protein, was not significantly affected. Conclusions:Human recombinant WISP2 protein increases lipid levels in hepatocytes and the key underlying mechanisms may be through promoting lipid synthesis.

N ⁶-methyladenosine (m⁶A) modification is critical for mRNA splicing, nuclear export, stability and translation. Fat mass and obesity-associated protein (FTO), the first identified m⁶A demethylase, is critical for cancer progression. Herein, we developed small-molecule inhibitors of FTO by virtual screening, structural optimization, and bioassay. As a result, two FTO inhibitors namely 18077 and 18097 were identified, which can selectively inhibit demethylase activity of FTO. Specifically, 18097 bound to the active site of FTO and then inhibited cell cycle process and migration of cancer cells. In addition, 18097 reprogrammed the epi-transcriptome of breast cancer cells, particularly for genes related to P53 pathway. 18097 increased the abundance of m⁶A modification of suppressor of cytokine signaling 1 (SOCS1) mRNA, which recruited IGF2BP1 to increase mRNA stability of SOCS1 and subsequently activated the P53 signaling pathway. Further, 18097 suppressed cellular lipogenesis via downregulation of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and C/EBPβ. Animal studies confirmed that 18097 can significantly suppress in vivo growth and lung colonization of breast cancer cells. Collectively, we identified that FTO can work as a potential drug target and the small-molecule inhibitor 18097 can serve as a potential agent against breast cancer.

Objective:The article aims to explore the positive promoting effect of the construction of a medical university’s incubation platform on the Industry-University-Institute cooperation and biomedical scientific and technological achievements transformation.Methods:Through literature review, the article studied the existing mode of Industry-University-Institute cooperation in universities, analyzed the main bottlenecks, and summarized the practical exploration experience of ″Shanghai Pharmaceuticals-SJTUSM Innovative Achievements″ incubation platform.Results:The incubation platform effectively promoted the process and system construction of the scientific and technological achievements transformation in the university, and improved the project mining level and platform support function.Conclusions:The practical exploration of the incubation platform lays a foundation for the construction of the biomedical industrial park. Through the in-depth construction of the " Government-Industry-University-Institute-Investment-Inventor" development chain, the platform can help to promote strategic innovation and industrialization of achievements, making the " first-in-class" medicine in China.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a common respiratory disease in clinic, and with a pathological manifestation of pulmonary edema, decreased pulmonary compliance as well as pulmonary epithelial/endothelial cells injury. At present, it was suggested that systemic inflammatory response syndrome (SIRS) caused by various causes which play an important role in the occurrence and development of ALI/ARDS. Widely activated neutrophils can migrate to lung tissue and release plenty of proteases in the procedure of SIRS, including neutrophil serine proteases (NSPs), lysozyme, myeloperoxidase and collagenase, which can induce severe lung injury. Meanwhile, NSPs, such as neutrophil elastase (NE), cathepsin G (CG), proteinase 3 (PR3) and neutrophil serine proteinase 4 (NSP4), are important in the pathogenesis of ALI/ARDS. Therefore, Serpins may protect lung tissue by inhibiting NSPs. However, the specific mechanism of Serpins is not totally clear. In this article, we will discuss the mechanism of action of NSPs in the inflammatory response of ALI/ARDS, the structural overview of Serpins, the primary role of Serpins in ALI/ARDS,such as the inhibition of NSPs activity, other roles of Serpins in ALI/ARDS, such as the inhibition of inflammatory factor release, regulation of apoptosis and protection of vascular endothelial cells and pulmonary surfactant-associated glycoprotein D (SP-D), and the clinical application of exogenous Serpins in ALI/ARDS to explore the role of Serpins in the pathogenesis of ALI/ARDS. The aim is to provide new ideas and strategies for the clinical treatment of ALI/ARDS.