Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

Objective To assess the association between Metformin use and the risk of dementia in patients with type 2 diabetes mellitus(T2DM).Methods The research data came from the big medical data platform of Yinzhou District,and we constructed a cohort of T2DM patients who had initiated treatment of Metformin or sulfonylurea since January 1,2009.The inverse probability of treatment weighting(IPTW)was used to control the baseline confounding factors,and the Cox regression model was used to estimate the HR(95%CI)of the association between Metformin use and dementia risk.Results The incidence rate of dementia in new users of Metformin(41181 persons)and sulfonylureas(38092 persons)was 128.4 per 100000 person years and 142.3 per 100000 person years respectively.Compared with sulfonylureas,the crude analysis with no adjustment for confounding factors showed that there was a negative association between the use of Metformin and the incidence of dementia,with an HR(95%CI)0.930(0.800～1.090).After adjusting for potential confounders with IPTW,Metformin was not significantly associated with the risk of dementia HR(95%CI)1.040(0.890～1.220).The subgroup analysis results for different baseline characteristics were consistent with the primary analysis results,and there were no statistically significant associations between Metformin and dementia incidence risk in all subgroups.Conclusions There is no significant association between the use of Metformin and the risk of dementia in T2DM patients in the Yinzhou District.

The treatment of glioblastoma, the most prevalent malignant tumor in the central nervous system, poses considerable challenges. Glioblastoma multiforme, classified as a grade Ⅳ highly malignant brain glioma by the World Health Organization, is typically managed through a combination of surgery, postoperative chemotherapy, and radiotherapy. The treatment of glioblastoma is complicated by its infiltrative nature, genetic heterogeneity, and presence of the blood-brain barrier. Almost all cases of glioblastoma experience recurrence despite aggressive therapy, exploring the development of updated molecular treatment strategies that can improve overall efficacy. A crucial aspect in modern neurosurgery is the precise delineation of brain regions in terms of their anatomy and function. It serves as the fundamental basis for investigating variations in the distribution of brain gliomas. Hence, this review will elucidate the origin of glioblastomas and analyze the potential factors contributing to the spatially specific distribution of gliomas on the basis of a theoretical framework of brain connectomics research. Molecular characteristics, information pathways, tumor microenvironment landscape, and immunology will inform the analysis. We aim to identify novel biomolecular targets and therapeutic pathways to gain scientific insights for effective glioblastoma treatment.

Objective To investigate the differences and the immunocompatibility of wild-type (WT), four-gene modified (TKO/hCD55) and six-gene modified (TKO/hCD55/hCD46/hTBM) pig erythrocytes with human serum. Methods The blood samples were collected from 20 volunteers with different blood groups. WT, TKO/hCD55, TKO/hCD55/hCD46/hTBM pig erythrocytes, ABO-compatible (ABO-C) and ABO-incompatible (ABO-I) human erythrocytes were exposed to human serum of different blood groups, respectively. The blood agglutination and antigen-antibody binding levels (IgG, IgM) and complement-dependent cytotoxicity were detected. The immunocompatibility of two types of genetically modified pig erythrocytes with human serum was evaluated. Results No significant blood agglutination was observed in the ABO-C group. The blood agglutination levels in the WT and ABO-I groups were higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (all P<0.001). The level of erythrocyte lysis in the WT group was higher than those in the ABO-C, TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups. The level of erythrocyte lysis in the ABO-I group was higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (both P<0.01). The pig erythrocyte binding level with IgM and IgG in the TKO/hCD55 group was lower than those in the WT and ABO-I groups. The pig erythrocyte binding level with IgG and IgM in the TKO/hCD55/hCD46/hTBM group was lower than that in the WT group and pig erythrocyte binding level with IgG was lower than that in the ABO-I group (all P<0.05). Conclusions The immunocompatibility of genetically modified pig erythrocytes is better than that of wild-type pigs and close to that of ABO-C pigs. Humanized pig erythrocytes may be considered as a blood source when blood sources are extremely scarce.

Objective To explore the effects of intravenous thrombolysis combined with Solitaire FR stent thrombectomy on vascular recanalization,neurologic function and prognosis in patients with acute cerebral infarction(ACI)due to large artery occlusion(LAO).Methods A total of 172 patients with ACI-LAO treated in our department between October 2020 and March 2023 were retrospectively enrolled.According to treatment regimens,they were assigned into control group(86 cases,alteplase intravenous thrombolysis)and study group(86 cases,alteplase intravenous thrombolysis combined with Solitaire FR stent thrombectomy).Vascular recanalization,neurolog-ic function,cerebral perfusion and occurrence of adverse events were compared between the two groups.After 90 d of follow-up,their prognosis was evaluated with modified Rankin scale.Results There was no significant difference in success rate of vascular recanalization between the two group(P＞0.05),but complete recanalization rate was statistically higher in the study group than the control group(68.60％vs 50.00％,P＜0.05).The study group had obviously lower NHISS scores at 7 and 14 d after treatment,higher cerebral blood volume and cerebral blood flow,but shorter mean transit time when compared with the control group(P＜0.05,P＜0.01).No notable difference was observed in the total incidence of adverse events between them(P＞0.05).After 90 d of follow-up,the proportion of good prognosis was higher in the study group than the control group(80.23％vs 63.95％,P＜0.05).Conclusion Intravenous thrombolysis combined with Soli-taire FR stent thrombectomy shows better efficacy in ACI-LAO patients,with better vascular re-canalization and great improvements in neurologic function and prognosis.

BACKGROUND:In recent years,with the improvement of living standards,non-alcoholic fatty liver disease has a gradually increasing trend.miRNA-122 is one of the most abundant microRNAs in the liver,which plays an important role in maintaining the environmental stability and differentiation of the liver.Exercise training is a non-drug treatment for non-alcoholic fatty liver disease,which may improve liver lipid metabolism by regulating the expression of miRNA-122. OBJECTIVE:To review the effects of miRNA-122 on the pathological factors related to non-alcoholic fatty liver disease as well as the effects of exercise on the expression of miRNA-122 and the occurrence and development of nonalcoholic fatty liver disease. METHODS:The first author searched the databases of CNKI,WanFang,VIP,PubMed,Geenmedical,EBSCO,Medline,Web of Science,and Elsevier using"non-alcoholic fatty liver disease,microRNA,microRNA-122,lipid metabolism,inflammatory response,insulin resistance,exercise,physical exercise,exercise training"as the English and Chinese search terms for all relevant literature published before June 5,2022.All included documents were screened,summarized,and analyzed.Finally,68 documents were included for review. RESULTS AND CONCLUSION:Compared with the healthy control group,the expression of circulating miRNA-122 is increased in patients with non-alcoholic fatty liver disease.The level of miRNA-122 may show different expression levels at different stages of non-alcoholic fatty liver disease.miRNA-122 can regulate the expression of downstream-related proteins,influence lipid metabolism,inflammatory response,insulin resistance and other pathogenic factors in non-alcoholic fatty liver disease by targeting base complementary pairing sites on mRNA or directly acting as physiological ligands of some RNA receptors.Different exercise modes can improve non-alcoholic fatty liver disease.Therefore,patients with non-alcoholic fatty liver disease need to complete at least 120 minutes of moderate-intensity exercise every week to have a positive effect.For patients who can tolerate various exercises,priority should be given to the combination of aerobic and resistance exercises 4-5 times a week.The exercise intensity should be 50%-70%of the maximum heart rate and the exercise should last for>3 months.For patients with poor tolerance,resistance exercise may be more feasible than aerobic exercise.In addition,patients with non-alcoholic fatty liver disease can also choose proper exercise modes according to their own disease conditions(such as liver enzymes and lipid levels).Exercise can be used as a feasible strategy to prevent non-alcoholic fatty liver disease,reduce liver steatosis,and alleviate liver inflammatory response and insulin resistance.Exercise training can regulate the expression of miRNA-122,but in patients with non-alcoholic fatty liver disease,the effect of exercise on miRNA-122 and its related signal pathways remains to be studied.

Objective To study the correlation between semen quality and bacterial infection in men with abnormal fer-tility,and provide clinical basis for guiding the reproductive health of men with abnormal fertility.Methods 200 male semen samples with abnormal fertility were collected,and then separated and cultured for 48 hours.According to the culture results,they were divided into three groups:the non-pathogenic group,the pathogenic group,and the sterile group.The bacterial resist-ance analysis of the pathogenic group was conducted,and the semen quality between each group was compared.Results After 48 hours of isolation and cultivation,200 semen samples had been tested,non-pathogenic bacteria was detected in 163 semen samples,accounting for 81.5% ;pathogenic bacteria was detected in 33 semen samples,accounting for 16.5% ;and bacteria was not detected in 4 semen samples,accounting for 2.0% .The top three strains of pathogenic bacteria in 33 cases were Escherichia coli,Streptococcus agalactiae,and Enterococcus faecalis,with drug resistance rates of 80.0% ,87.5% ,and 100.0% ,respec-tively.Conclusion The detection rate of bacterial culture in semen of men with abnormal fertility is relatively high,and patho-genic bacteria can affect semen quality.

Background and purpose:Limbs soft tissue sarcoma(STS)is a common malignant tumor,and surgical resection is the main treatment method for it.The concept of barrier made us realize the blocking effect of natural barrier on STS,and we aimed to search for tissues that can act as barrier,and to perform complete resection of surgical margins around the tissue barrier.This study aimed to investigate the feasibility,safety and prognosis of barrier resection in the treatment of limbs STS.Methods:From December 2013 to September 2016,data of 72 patients who underwent barrier resection of STS of extremities in department of oncosurgery,Minhang Branch,Fudan University Shanghai Cancer Center were retrospectively analyzed,and the resection margin was sampled.All 72 patients underwent preoperative magnetic resonance imaging(MRI)or computed tomography(CT)design,and the physiological barrier or at least 3 cm distance was found outward from the anatomical location of the tumor.And en bloc excision was performed outside this barrier or at a distance of 3 cm.The influence of postoperative pathological margin,musculoskeletal tumor society(MSTS)score and postoperative complications on the patients were analyzed.The 1-and 3-year locoregional recurrence-free survival(LRFS)rates and sarcoma-specific survival(SSS)rates were evaluated,and the influencing factors were analyzed.This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center(number:1212117-12&1212117-12-1301).Results:All patients had negative margins.The 1-and 3-year LRFS rates were 98.2%and 93.3%,respectively.The 1-and 3-year SSS rates were 98.4%and 94.2%,respectively.The mean MSTS scores were 28.3 preoperatively and 25.5 postoperatively.Surgical complications were grade 1 to 2 in 20 cases and grade 3 in 1 case,and there were no grade 4 to 5 complications.Conclusion:Based on the combination of clinical,imaging and pathology data,barrier resection,including tumor resection and functional reconstruction,can be applied to the surgical treatment of STS,with good feasibility and safety,reliable margin and satisfactory local control.

Objective:To evaluate the health benefits and intervention efficiency of different strategies of initiating antihypertensive therapy for the primary prevention of cardiovascular diseases in a community-based Chinese population from the Chinese electronic health records research in Yinzhou(CHERRY)study.Methods:A decision-analytic Markov model was used to simulate and compare different antihy-pertensive initiation strategies,including:Strategy 1,initiation of antihypertensive therapy for Chinese adults with systolic blood pressure(SBP)≥140 mmHg(2020 Chinese guideline on the primary preven-tion of cardiovascular diseases);Strategy 2,initiation of antihypertensive therapy for Chinese adults with SBP≥130 mmHg;Strategy 3,initiation of antihypertensive therapy for Chinese adults with SBP ≥140 mmHg,or with SBP between 130 and 140 mmHg and at high risk of cardiovascular diseases(2017 American College of Cardiology/American Heart Association guideline for the prevention,detection,evaluation,and management of high blood pressure in adults);Strategy 4,initiation of antihypertensive therapy for Chinese adults with SBP≥ 160 mmHg,or with SBP between 140 and 160 mmHg and at high risk of car-diovascular diseases(2019 United Kingdom National Institute for Health and Care Excellence guideline for the hypertension in adults:Diagnosis and management).The high 10-year cardiovascular risk was de-fined as the predicted risk over 10％based on the 2019 World Health Organization cardiovascular disease risk charts.Different strategies were simulated by the Markov model for ten years(cycles),with parame-ters mainly from the CHERRY study or published literature.After ten cycles of simulation,the numbers of quality-adjusted life years(QALY),cardiovascular events and all-cause deaths were calculated to evaluate the health benefits of each strategy,and the numbers needed to treat(NNT)for each cardiovas-cular event or all-cause death could be prevented were calculated to assess the intervention efficiency.One-way sensitivity analysis on the uncertainty of incidence rates of cardiovascular disease and probabilis-tic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted.Results:A to-tal of 213 987 Chinese adults aged 35-79 years without cardiovascular diseases were included.Com-pared with strategy 1,the number of cardiovascular events that could be prevented in strategy 2 increased by 666(95％UI:334-975),while the NNT per cardiovascular event prevented increased by 10(95％UI:7-20).In contrast to strategy 1,the number of cardiovascular events that could be prevented in strategy 3 increased by 388(95％UI:194-569),and the NNT per cardiovascular event prevented decreased by 6(95％UI:4-12),suggesting that strategy 3 had better health benefits and intervention efficiency.Compared to strategy 1,although the number of cardiovascular events that could be prevented decreased by 193(95％UI:98-281)in strategy 4,the NNT per cardiovascular event prevented decreased by 18(95％UI:13-37)with better efficiency.The results were consistent in the sensitivity analyses.Conclusion:When initiating antihypertensive therapy in an economically developed area of China,the strategy combined with cardiovascular risk assessment is more efficient than those purely based on the SBP threshold.The cardiovascular risk assessment strategy with different SBP thresholds is suggested to balance health benefits and intervention efficiency in diverse populations.

Head and neck malignant tumor is one of the most heterogeneous diseases.The multi-disciplinary team(MDT)is an essen-tial component for personal precise diagnosis,treatment and integrated care management of oncologic diseases including head and neck malignant tumor.MDT clinical practice is also an important teaching mode for head and neck malignant tumors,but it is limited by time and space in actual teaching.An internet visualization platform was constructed based on the Internet,hospital HIS/PACS/LIS/EMR system,medical visualization screen,oral endoscope,remote consultation platform and other accessible audio and video terminals,and has been applied in MDT clinical teaching of head and neck malignant tumors,allowing medical students to participate in MDT through a networked visualization platform.Medical students will achieve deep learning for the most heterogeneous malignant tumor.MDT sup-ported by the internet visualization platform provides a new pathway for clinical medical education.