G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

Objective:To assess the clinical features and effectiveness of antiviral therapy in newborns with sensorineural hearing loss (SNHL) caused by congenital congenital cytomegalovirus (cCMV) infection, and to speculate the risk factors for poor hearing outcomes.Methods:A multicenter prospective cohort study wasconducted, enrolling 176 newborns diagnosed with cCMV at four research centers in Zhejiang Province from March 1, 2021, to April 30, 2024. Clinical characteristics at birth were recorded and hearing was followed up. The children were divided into groups based on their condition at birth, specifically into asymptomatic, mild symptom, and moderate to severe symptom groups. Additionally, they were divided into SNHL and normal hearing groups based on the results of air conduction brainstem audiometry at birth. And they were also divided into treatment and untreated groups according to antiviral treatment. Mann Whitney U test, and chi square test were used for inter group comparison to analyze the differences in clinical features between different disease groups, and to analyze the effects of clinical features, antiviral therapy, and other factors on hearing improvement. Logistic regression analysis was employed to identify the risk factors influencing hearing outcomes. Results:Among the cohort of 176 children diagnosed infection with cCMV, 90 cases were male and 86 cases were female. Of these, 79 cases were asymptomatic, 12 cases classified as mild cCMV and 85 cases as moderate to severe cCMV. Fifty cases belonged to SNHL group, with different degrees of severity, including 30 cases of mild, 9 cases of moderate, 5 cases of severe, and 6 cases of extremely severe SNHL. Among the 121 cases in the normal hearing group, 2 cases (1.7%) exhibited late-onset hearing loss despite having normal hearing at birth. Among 81 cases (46.0%) who completed the hearing follow-up, 71 cases (87.7%) had good hearing outcomes and 10 cases (12.3%) had poor hearing outcomes. Among the 81 children, 29 cases (35.8%) had SNHL at birth. During follow-up, the hearing threshold improved in 19 cases (65.5%), remained stable in 7 cases (24.1%) and progressed in 3 cases (10.3%). A total of 26 cases in the treatment group and 55 cases in the untreated group completed the hearing follow-up assessment. The rate of hearing improvement in the treatment group was found to be higher compared to the untreated group (13 cases (50.0%) vs. 6 cases (10.9%), χ2=15.00, P<0.01), with individuals in the treatment group having a 4.58 times greater likelihood of experiencing hearing improvement ( RR=4.58,95% CI 1.96-10.70, P<0.05). However, no statistically significant difference was observed in hearing outcomes between the antiviral treatment group and the untreated group ( RR=0.90, 95% CI 0.57-1.41, P=0.517). Multivariate analysis further confirmed SNHL ( OR=11.58, 95% CI 2.10-63.93, P=0.005) and preterm birth ( OR=4.98, 95% CI 1.06-23.41, P=0.042) as independent risk factors for poor hearing outcomes. Conclusions:SNHL resulting from cCMV infection presents symptoms at birth and can be improved by antiviral therapy. Poor hearing outcomes are associated with SNHL and prematurity.

[Objective]To analyze the value of grey-scale reversed T1-weighted(rT1)MRI in the detection of structur-al lesions of the sacroiliac joint(SIJ)in patients with axial spondyloarthritis(ax-SpA).[Methods]Fifty-two ax-SpA pa-tients who underwent both MRI and CT in our hospital within a week from February 2020 to December 2022 were retrospec-tively included.Both sacral and iliac side of each SIJ on oblique coronal images were divided into anterior,middle and pos-terior portion.Two radiologists reviewed independently three groups of MRI including T1-weighted imaging(T1WI),rT1 and T1WI+rT1 images to evaluate the structural lesions like erosions,sclerosis and joint space changes in each of the 6 re-gions of the SIJ.One of the radiologist did the evaluation again one month later.CT images were scored for lesions by a third radiologist and served as the reference standard.Intra-class correlation coefficients(ICC)were calculated to test the inter-and intra-reader agreement for the assessment of SIJ lesions.A Friedman test was performed to compare the lesion results of MRI and CT image findings.We examined the diagnostic performance[accuracy,sensitivity(SE)and specifici-ty]of different groups of MRI in the detection of lesions by using diagnostic test.A McNemar test was used to compare the differences of three groups of MRI findings.[Results]CT showed erosions in 71 joints,sclerosis in 65 and joint space changes in 53.Good inter-and intra-reader agreements were found in three groups of MRI images for the assessment of le-sions,with the best agreement in T1WI+rT1.There were no difference between T1WI+rT1 and CT for the assessment of all lesions,nor between rT1 and CT for the assessment of erosions and joint space changes(P>0.05).T1WI+rT1 yielded better accuracy and SE than T1WI in detection of all lesions(Accuracy erosions:90.3%vs 76.9%;SE erosions:91.6%vs 76.1%;Accu-racy sclerosis:89.4%vs 80.8%;SE sclerosis:84.6%vs 73.9%;Accuracy joint space changes:86.5%vs 73.1%;SE joint space changes:84.9%vs 60.4%;P<0.05).rT1 yielded better accuracy and SE than T1WI in detection of erosions and joint space changes(Accuracy erosions:87.5%vs 76.9%;SE erosions:88.7%vs 76.1%;Accuracy joint space changes:85.6%vs 73.1%;SE joint space changes:83.0%vs 60.4%;P<0.05).[Conclusions]In the detection of SIJ structural lesions in ax-SpA,rT1 improves the diagnostic perfor-mance and T1WI+rT1 is more superior to others.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective　To assess the willingness of students with latent tuberculosis infection (LTBI) in Jiangsu Province to undergo preventive treatment and identify factors influencing their decision, aiming to provide insights for tuberculosis prevention and control strategies in school. Methods The physical examination information of tuberculosis latent infection cases was collected from screenings of new school enrollment and contacts of tuberculosis patients in 6 cities of Jiangsu Province from December 2022 to December 2023. Data on past medical history and understanding of preventive treatment were gathered through an online questionnaire survey on the website of Juanxing, and the influencing factors related to the willingness to take preventive medication were analyzed by logistic regression analysis model. Results In December 2022 to December 2023, a total of 13 school tuberculosis outbreaks occurred in 6 cities, and 1 661 contacts were screened, among which 162 cases met the criteria for prophylactic medication, 96 cases were included in the study by filling in the questionnaire. A total of 22 600 new students from 56 schools participated in the TB screening upon enrollment, of which 358 tested positive for the tuberculin skin test alone, meeting the criteria for preventive medication, and 251 of them completed the willingness survey. Finally, 347 students who met the criteria for preventive treatment were included in the study, with 164 expressing to accept preventive treatment representing a treatment acceptance rate of 47.3%. The results of multivariate analysis showed that university (OR=17.950, 95%CI: 3.078-104.686, P=0.001) and contact with the source of school tuberculosis epidemic (OR=19.542, 95%CI: 6.289-60.726, P<0.001) were associated with increased willingness to receive preventive treatment, while unclear whether to pay for the drugs themselves (OR=0.349, 95%CI:0.133-0.916, P=0.032) was associated with decreased willingness to receive preventive treatment. Compared with Huai'an City, the willingness to receive preventive treatment was significantly lower among students from Nantong City (OR=0.005, 95%CI:0.000-0.063, P<0.001), Nanjing City (OR=0.022, 95%CI: 0.003-0.703, P<0.001) and Lianyungang City (OR=0.074, 95%CI:0.008-0.703, P=0.023). Conclusions The acceptance rate of preventive treatment among LTBI students in Jiangsu Province is not high and is affected by multiple factors. Health education and medication mobilization for preventive medication are essential.

Objective:Differences between randomized controlled trial (RCT) results and real world study (RWS) results may not represent a true efficacy-effectiveness gap because efficacy-effectiveness gap estimates may be biased when RWS and RCT differ significantly in study design or when there is bias in RWS result estimation. Secondly, when there is an efficacy- effectiveness gap, it should not treat every patient the same way but assess the real-world factors influencing the intervention's effectiveness and identify the subgroup likely to achieve the desired effect.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:Ten articles were included to discuss how to use the RCT research protocol as a template to develop the corresponding RWS research protocol. Moreover, based on correctly estimating the efficacy-effectiveness gap, evaluate the intervention effect in the patient subgroup to confirm the subgroup that can achieve the expected benefit-risk ratio to bridge the efficacy-effectiveness gap.Conclusion:Using real-world data to simulate key features of randomized controlled clinical trial study design can improve the authenticity and effectiveness of study results and bridge the efficacy-effectiveness gap.

Objective:Randomized controlled trials (RCT) usually have strict implementation criteria. The included subjects' characteristics of the conditions for the intervention implementation are quite different from the actual clinical environment, resulting in discrepancies between the risk-benefit of interventions in actual clinical use and the risk-benefit shown in RCT. Therefore, some methods are needed to enhance the extrapolation of RCT results to evaluate the real effects of drugs in real people and clinical practice settings.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:A total of 12 articles were included. Three methods in the included literature focused on: ①improving the design of traditional RCT to increase population representation; ②combining RCT Data with real-world data (RWD) for analysis;③calibrating RCT results according to real-world patient characteristics.Conclusions:Improving the design of RCT to enhance the population representation can improve the extrapolation of the results of RCT. Combining RCT data with RWD can give full play to the advantages of data from different sources; the results of the RCT were calibrated against real-world population characteristics so that the effects of interventions in real-world patient populations can be predicted.

Objective To investigate the effects of bone marrow mesenchymal stem cell-derived exosomes(BMSCs-Exo)on the regulation of epithelia-mesenchymal transition(EMT)in human peritoneal mesothelial cells(HPMCs)treated with glucose-based peritoneal dialysis fluid(PDF).Methods BMSCs-Exo were verified by transmission electron microscopy(TEM),nanoparticle tracking analyzer(NTA)and Western blot.Cultured HPMCs(HMrSV5)were divided into 5 groups;control group,high glucose-based PDF(1.5％,2.5％,and 4.25％)group,siNLRP3 group,siNC group and BMSCs-Exo treated group.Expression of E-cadherin,vimentin,α-smooth muscle actin(α-SMA)and NLRP3 inflammasome-related proteins were detected by Western blot.Real time RT-PCR was used to detected the expression of α-SMA,E-cadherin and TGF-β1 mRNAs in HMrSV5 cells.The concentration of TGF-β1,IL-1 β and IL-18 in the culture supernatant was determined by ELISA.Results The exosomes isolated were spherical and double-membrane vesicles with 40-150 nm in diameter,which expressed CD9,CD81,TSG101 and Alix protein.Our results showed that the level of α-SMA and vimentin were significantly up-regulated and E-cadherin(epithelial marker)was significantly decreased in HMrSV5 cells treated with high glucose PDF com-pared with the normal HMrSV5 cells.The expression of NLRP3,pro-caspase-1 and pro-IL-1β were also significantly up-regulated in HMrSV5 cells treated with high glucose PDF compared with the normal HMrSV5 cells.The level of TGF-β1,IL-1 β and IL-18 in high glucose PDF treated HMrSV5 cells culture supernatant was up-regulated in a dose dependent manner.The protein level of α-SMA was decreased and E-cadherin level was increased by an NLRP3 siRNA to inhibit the activation of NLRP3.Compared with 4.25％PDF treated cells,E-cadherin expression was up-regulated,while the expression of α-SMA and vimentin were down-regulated in BMSCs-Exo treatment cells(P＜0.05).Furthermore,the protein expression of NLRP3,pro-caspase-1 and pro-IL-1β in 4.25％PDF-treated HMrSV5 cells were significantly reduced by BMSCs-Exo.BMSCs-Exo also reduced the level of TGF-β1,IL-1 β and IL-8 in the 4.25％PDF-treated HMrSV5 cells culture supernatants(P＜0.05).Conclusions High glucose PDF-induced EMT in HPMCs might be mediated by NLRP3 inflammatory signaling pathway,which can be inhibited by BMSCs-Exo.

Objective To evaluate the antioxidant function of Chrysanthemum morifolium from different origins and to identify their antioxidant material basis.Methods The HPLC fingerprints of the water extracts of C.morifolium from different origins were established.The antioxidant activities of C.morifolium were assayed by measuring the 2.2-diphenyl-l-picrylhydrazyl(DPPH),hydroxyl radical,ABTS,superoxide anion radical scavenging capacity and ferric ion reducing capacity FRAP.Entropy-weighted TOPSIS was used to calculate the weighting coefficients of the single indexes.Grey relational analysis(GRA)and partial least squares were used for spectrum-effect analysis to identify the antioxidant material basis of C.morifolium.Results A total of 16 common peaks were discovered in the fingerprint of the water extracts of 10 batches of C.morifolium,among which 13 common components were identified.All the C.morifolium samples had good antioxidant capacity,and the results of entropy-weighted TOPSIS analysis showed that the ranking of total antioxidant potency of 10 batches of C.morifolium was follows:S1＞S8＞S3＞S5＞S4＞S10＞S7＞S2＞S9＞S6.The peaks of 1-5,9,10,12,14 were positively correlated with the antioxidant activity and the variable influence on projection(VIP)values were greater than 1.The correlation coefficients of these nine peaks in GRA were all greater than 0.7.Conclusion The entropy-weighted TOPSIS method combined with the spectrum-effect analysis could be used to screen out the antioxidant material basis of C.morifolium and the results provide a basis for establishing quality assessment system for C.morifolium based on Quality-markers thus improving the quality control level.

Objective To investigate the features of autonomic nervous function symptoms in patients with different motor subtypes of Parkinson disease(PD)and the impact of autonomic dysfunction on quality of life in patients with different motor subtypes of PD.Methods Basic information was recorded for all patients enrolled in this study,including the scores of both motor and non-motor symptoms.The patients were divided into different subtypes based on tremor-dominant(TD)and postural instability and gait difficulty(PIGD)scores.Motor and non-motor symptoms,especially autonomic symptoms,were compared between the patients with TD subtype and those with PIGD subtype,and the association between autonomic dysfunction and quality of life was analyzed for patients with different motor subtypes.Results There were 105 patients(57.7%)in the TD group and 63(34.6%)in the PIGD group.There were no significant differences between the TD group and the PIGD group in age,sex,lifestyle,course of disease,levodopa equivalent dose,and disease severity,and there were also no significant differences between the two groups in the scores of anxiety,depression,apathy,cognition,and constipation,the reduction in systolic blood pressure(SBP)in standing and supine positions,and the incidence rate of orthostatic hypotension before and after medication.The PIGD group had a significantly higher total score of autonomic nervous function than the TD group,with a median of 24 and 19,respectively.The median of quality of life score was 66 points in the PIGD group and 46 points in the TD group,suggesting that the PIGD group had a poorer quality of life than the TD group.Quality of life was positively correlated with autonomic nervous function symptoms in the PD patients in both the PIGD group(R2=0.209,P=0.000)and the TD group(R2=0.166,P=0.000).In the TD group,quality of life was correlated with constipation(r=0.313,P=0.002)and the maximum difference in SBP in standing and supine positions before Madopar administration(r=0.252,P=0.009).Conclusion PD patients with PIGD subtype tend to have more severe symptoms of autonomic dysfunction and a lower quality of life than those with TD subtype.PD patients with both TD and PIGD subtypes tend to have a worse quality of life due to severe autonomic dysfunction,and the quality of life of patients with TD subtype is also correlated with constipation and the maximal difference in SBP in standing and supine positions before Madopar administration.