ObjectiveTo investigate the associations of multiple glycolipid metabolic indicators and their cumulative abnormality burden with incident colorectal cancer risk in a general population-based prospective cohort, and to examine the mediating role of glycolipid metabolic abnormalities in the relationships between smoking, alcohol consumption, physical activity, and colorectal cancer incidence. MethodsA total of 17 897 eligible participants recruited from the Taizhou Cohort between 2011 and 2014 were included. Cox proportional hazards regression models were used to assess the associations of conventional and derived glycolipid indicators, as well as a glycolipid abnormality index constructed from total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, and insulin, with incident colorectal cancer risk. Restricted cubic spline models were applied to evaluate dose-response relationships for major indicators. Receiver operating characteristic curves were generated to compare predictive performance across indicators. Mediation analyses were conducted to assess the mediating effects of the glycolipid abnormality index on the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence. ResultsDuring a median follow-up of 11.2 years, 102 incident colorectal cancer cases were identified, with an incidence density of 51.2 per 100 000 person-years. After adjustment for potential confounders, Cox proportional hazards regression analyses showed that decreased high-density lipoprotein cholesterol was associated with a 1.74-fold higher risk of colorectal cancer (HR=1.74, 95%CI: 1.03‒2.95), elevated low-density lipoprotein cholesterol was associated with a 1.78-fold higher risk (HR=1.78, 95%CI: 1.05‒3.02), and abnormal fasting plasma glucose was associated with a 1.86-fold higher risk (HR=1.86, 95%CI: 1.15‒3.02). Triglycerides and fasting plasma glucose showed an approximately linear increasing association with colorectal cancer risk in multivariable restricted cubic spline models. The glycolipid abnormality index showed a clear gradient association with colorectal cancer risk; participants with three or more abnormal indicators had a 3.08-fold higher risk than those without abnormalities (HR=3.08, 95%CI: 1.60‒5.92). The area under the curve was 0.795, higher than that of individual glycolipid indicators and other combined indices, and gender-stratified analyses showed generally consistent patterns. Glycolipid metabolic abnormalities partially mediated the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence, with mediation proportions of 8.33%, 9.45%, and 9.04%, respectively. ConclusionGlycolipid metabolic abnormalities are associated with an increased risk of incident colorectal cancer. The glycolipid abnormality index shows an increasing relationship with colorectal cancer risk and demonstrates better discrimination, and it partially mediates the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence in the overall population.

Objective:To apply combined serological diagnostic methods for anti-BP180-type and anti-laminin 332 (Ln332) -type mucous membrane pemphigoid (MMP), and to summarize their clinical and immunoserological characteristics.Methods:A retrospective analysis was conducted on the data from 52 patients clinically suspected of having MMP at the Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2017 to February 2022. Serum samples were collected, and combined serological tests, including indirect immunofluorescence on salt-split skin, enzyme-linked immunosorbent assay, and immunoblotting, were performed to analyze the immunoserological and clinical characteristics of the patients. The Fisher′s exact test was used to compare the lesion occurrence rates between groups.Results:Among the 52 patients clinically suspected of MMP, 32 (61.5%) were diagnosed with anti-BP180-type MMP, 10 (19.2%) with anti-Ln332-type MMP, and 4 (7.7%) with anti-BP180- and anti-Ln332-type MMP due to the presence of both anti-BP180 and anti-Ln332 antibodies; 2 tested positive for IgG on the epidermal side of salt-split skin, but no target antigens were identified by serological tests, and they were diagnosed with MMP (subtype pending) ; 4 tested negative by immunoserological tests. Ocular involvement was observed in 6 out of 10 patients with anti-Ln332-type MMP, whereas only 6 out of 32 anti-BP180-type MMP patients (18.8%) had ocular symptoms, and there was a significant difference in the occurrence rate of ocular involvement between the two groups ( P = 0.02) ; the occurrence rates of nasal involvement and multi-mucosal involvement were significantly higher in the anti-Ln332-type MMP patients (50%[5/10], 90%[9/10], respectively) than in the anti-BP180-type MMP patients (0, 25%[8/32], respectively, both P < 0.001). Scar formation occurred in 6 out of 10 anti-Ln332-type MMP patients, but occurred in only 6 out of 32 anti-BP180-type patients (18.8%, P = 0.02) . Conclusion:The combination of indirect immunofluorescence on salt-split skin, enzyme-linked immunosorbent assay, and immunoblotting could effectively identify anti-BP180 and anti-Ln332 autoantibodies in MMP patients, with BP180 being the most common target antigen; compared with anti-BP180-type MMP, anti-Ln332-type MMP appeared to be more frequently involve the ocular and nasal mucosae, associated with the involvement of multiple mucosal sites, carrying a higher risk of scar formation.

Low-altitude unmanned technology represented by unmanned aerial vehicle (UAV) has shown broad application prospects in the medical field. Since June 2023, Affiliated Hospital of Jiaxing University The First Hospital of Jiaxing, focusing on the demand for medical supplies transport among hospitals, has led the construction and operation practice of a low-altitude transfer system for medical supplies featuring UAV. By establishing a management organizational structure, building a low-altitude digital intelligence platform, constructing UAV take-off and landing platforms, formulating and approving flight routes, and improving the medical supply distribution process, it successfully achieved the transportation of medical blood and biological specimens between Jiaxing Central Blood Station and relevant medical institutions, as well as among different campus and medical alliance units of Affiliated Hospital of Jiaxing University The First Hospital of Jiaxing. As of June 2024, a total of 6 routes have been opened within the Jiaxing municipal area, with a cumulative flight distance exceeding 5 000 km. A total of 64 flights for medical blood, 720 flights for blood specimens, and 5 flights for pathological specimens have been transported. Compared with land transportation methods, UAV transportation effectively shortened transportation time, enhanced the service capabilities and diagnosis and treatment quality of grassroots medical institutions, and also saved costs. It can provide a reference for other medical institutions to carry out low-altitude medical supplies distribution.

Objective:To apply combined serological diagnostic methods for anti-BP180-type and anti-laminin 332 (Ln332) -type mucous membrane pemphigoid (MMP), and to summarize their clinical and immunoserological characteristics.Methods:A retrospective analysis was conducted on the data from 52 patients clinically suspected of having MMP at the Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2017 to February 2022. Serum samples were collected, and combined serological tests, including indirect immunofluorescence on salt-split skin, enzyme-linked immunosorbent assay, and immunoblotting, were performed to analyze the immunoserological and clinical characteristics of the patients. The Fisher′s exact test was used to compare the lesion occurrence rates between groups.Results:Among the 52 patients clinically suspected of MMP, 32 (61.5%) were diagnosed with anti-BP180-type MMP, 10 (19.2%) with anti-Ln332-type MMP, and 4 (7.7%) with anti-BP180- and anti-Ln332-type MMP due to the presence of both anti-BP180 and anti-Ln332 antibodies; 2 tested positive for IgG on the epidermal side of salt-split skin, but no target antigens were identified by serological tests, and they were diagnosed with MMP (subtype pending) ; 4 tested negative by immunoserological tests. Ocular involvement was observed in 6 out of 10 patients with anti-Ln332-type MMP, whereas only 6 out of 32 anti-BP180-type MMP patients (18.8%) had ocular symptoms, and there was a significant difference in the occurrence rate of ocular involvement between the two groups ( P = 0.02) ; the occurrence rates of nasal involvement and multi-mucosal involvement were significantly higher in the anti-Ln332-type MMP patients (50%[5/10], 90%[9/10], respectively) than in the anti-BP180-type MMP patients (0, 25%[8/32], respectively, both P < 0.001). Scar formation occurred in 6 out of 10 anti-Ln332-type MMP patients, but occurred in only 6 out of 32 anti-BP180-type patients (18.8%, P = 0.02) . Conclusion:The combination of indirect immunofluorescence on salt-split skin, enzyme-linked immunosorbent assay, and immunoblotting could effectively identify anti-BP180 and anti-Ln332 autoantibodies in MMP patients, with BP180 being the most common target antigen; compared with anti-BP180-type MMP, anti-Ln332-type MMP appeared to be more frequently involve the ocular and nasal mucosae, associated with the involvement of multiple mucosal sites, carrying a higher risk of scar formation.

Low-altitude unmanned technology represented by unmanned aerial vehicle (UAV) has shown broad application prospects in the medical field. Since June 2023, Affiliated Hospital of Jiaxing University The First Hospital of Jiaxing, focusing on the demand for medical supplies transport among hospitals, has led the construction and operation practice of a low-altitude transfer system for medical supplies featuring UAV. By establishing a management organizational structure, building a low-altitude digital intelligence platform, constructing UAV take-off and landing platforms, formulating and approving flight routes, and improving the medical supply distribution process, it successfully achieved the transportation of medical blood and biological specimens between Jiaxing Central Blood Station and relevant medical institutions, as well as among different campus and medical alliance units of Affiliated Hospital of Jiaxing University The First Hospital of Jiaxing. As of June 2024, a total of 6 routes have been opened within the Jiaxing municipal area, with a cumulative flight distance exceeding 5 000 km. A total of 64 flights for medical blood, 720 flights for blood specimens, and 5 flights for pathological specimens have been transported. Compared with land transportation methods, UAV transportation effectively shortened transportation time, enhanced the service capabilities and diagnosis and treatment quality of grassroots medical institutions, and also saved costs. It can provide a reference for other medical institutions to carry out low-altitude medical supplies distribution.

Objective:To compare the prognostic values of different classification by using transpulmonary pressure gradient (TPG), diastolic pressure gradient (DPG) and pulmonary vascular resistance (PVR) in patients with pulmonary hypertension due to left heart disease (PH-LHD), and investigated hemodynamic and clinical factors associated with mortality in patients with PH-LHD.Methods:This was a single-center prospective cohort study. In-hospital patients diagnosed with PH-LHD via right heart catheterization at the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, from September 2013 to December 2019 were enrolled. Patients were divided according to TPG (cutoff value 12 mmHg; 1 mmHg=0.133 kPa), DPG (cutoff value 7 mmHg), PVR (cutoff value 3 Wood Units), and the combination of TPG and PVR. Baseline characteristic was recorded. All patients were followed up until the occurrence of endpoint event, defined as all-cause death that occurred during the follow-up period, or until April 18, 2022. Receiver operating characteristic curves were used to compare the predictive value of 3 classification methods for all-cause death in PH-LHD patients. The optimal cutoff values were calculated using Jorden index. Survival analysis was performed using Kaplan-Meier analysis, and log-rank test was used to compare the predictive efficacy of classification methods based on optimal cutoff values or guidance-recommended thresholds for the survival of PH-LHD patients. Variables showing statistical significance in the univariate analysis were incorporated into multivariate Cox regression model to analyze the independent risk factors for all-cause mortality.Results:A total of 243 patients were enrolled, aged (54.9±12.7) years old, including 169 (69.5%) males. During a median follow-up of 57 months, there were 101 (41.6%) deaths occurred. Grouping results were as follows: (1) TPG: TPG≤12 mmHg group 115 patients, TPG>12 mmHg group 128 patients; (2) DPG: DPG<7 mmHg group 193 patients, DPG≥7 mmHg group 50 patients; (3) PVR: PVR≤3 Wood Units group 108 patients, PVR>3 Wood Units group 135 patients; (4) TPG and PVR: TPG≤12 mmHg and PVR≤3 Wood Units group 89 patients, TPG>12 mmHg and PVR>3 Wood Units group 109 patients. PVR ( AUC=0. 698,95% CI:0.631-0.766) had better predictive value for all-cause mortality than TPG ( AUC=0.596, 95% CI: 0.523-0.669) and DPG ( AUC=0.526, 95% CI: 0.452-0.601) (all P<0.05). The optimal cutoff values for TPG, DPG, and PVR were13.9 mmHg, 2.8 mmHg, and 3.8 Wood Units, respectively. Kaplan-Meier analysis based on the optimal cutoff values or guidance-recommended thresholds showed that PVR and TPG were the predictors of survival ( P<0.05), while DPG did not showed significance ( P>0.05). Multivariate Cox regression analysis showed that age, PVR and log 2N-terminal pro-B-type natriuretic peptide were independent risk factors for all-cause mortality in PH-LHD patients (all P<0.05). Conclusion:Classification according to PVR was most valuable in predicting all-cause death in PH-LHD patients, while TPG showed moderate predictive ability and DPG had no predictive value.

Objective:To analyze clinical, immunoserological, and therapeutic features of patients with anti-p200 pemphigoid.Methods:Clinical data were collected from patients with confirmed anti-p200 pemphigoid at the Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2015 to February 2024. Their clinical, immunoserological, and therapeutic characteristics were retrospectively analyzed.Results:A total of 35 patients were included, with a male-to-female ratio of 2.5∶1 (25 males and 10 females) and ages of 57.74 ± 17.12 years. Two (5.71%) patients were accompanied by psoriasis. In these patients, anti-p200 pemphigoid exhibited heterogeneous clinical phenotypes, mimicking classic bullous pemphigoid (20 cases, 57.14%), linear IgA bullous dermatosis (8 cases, 22.86%), or eczema (4 cases, 11.43%). The positive rates of direct immunofluorescence (DIF), indirect immunofluorescence on salt-split skin (ss-IIF), Western blot analysis with dermal extracts as substrates, and Western blot analysis with laminin γ1 C-terminal region (Lnγ1C) as substrates were 100% (24/24), 82.86% (29/35), 100% (35/35), and 80.64% (25/31), respectively. Among the 35 patients, treatment and follow-up information was available for analysis in 33. Six patients (18.18%) received non-glucocorticoid systemic therapy and topical glucocorticoid therapy, with a follow-up period ( M [ Q1, Q3]) of 19.50 (6.50, 69.25) months, and 1 withdrew the drugs. Sixteen patients received systemic glucocorticoids combined with traditional anti-inflammatory drugs, with a follow-up period of 13.50 (4.25, 18.00) months, the initial dose of glucocorticoids was equivalent to 0.30 - 0.50 mg·kg -1·d -1 of prednisone, and the time to disease control was 15.31 ± 5.23 days; among the 16 patients, 3 experienced fluctuations in disease condition which were alleviated by adding dapsone, and 1 discontinued glucocorticoids. Five patients (15.15%) received systemic glucocorticoids combined with immunosuppressants, with a follow-up period of 26.00 (14.00, 90.00) months, the initial dose of glucocorticoids was equivalent to 0.50 - 0.75 mg·kg -1·d -1 of prednisone, and the time to disease control was 10.20 ± 3.27 days; among the 5 patients, 2 received maintenance treatment with glucocorticoids (5 - 10 mg/d prednisone), 2 withdrew the drugs, and 1 relapsed after discontinuing glucocorticoids. One patient (3.03%) received systemic glucocorticoids combined with rituximab therapy, with a follow-up period of 53 months, and discontinued glucocorticoids thereafter. One patient (3.03%) received systemic glucocorticoids combined with dupilumab therapy, which proved to be effective. Four patients (12.12%) received systemic glucocorticoids combined with Janus kinase inhibitors, and 3 responded well. Conclusions:Anti-p200 pemphigoid presented a heterogeneous clinical profile in this series of patients, but scarring and milia were rare. Some patients showed negative results in Western blot analysis with Lnγ1C as substrates. The prognosis of anti-p200 pemphigoid was usually favorable, and most patients could achieve complete remission and ultimately discontinue medication.

Objective:To analyze clinical and immunoserological features of patients with epidermolysis bullosa acquisita (EBA) .Methods:Clinical data were collected from patients with confirmed EBA at the Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2017 to January 2022, and their clinical and immunoserological characteristics were retrospectively analyzed.Results:A total of 20 patients were collected, including 7 males and 13 females, and they were aged 41.85 ± 18.43 years. Ten patients presented with the classical phenotype of EBA, 8 with the inflammatory phenotype of EBA, and 2 with the mixed phenotype of EBA. Mucosal involvement occurred in 19 cases, nail involvement occurred in 4, scarring was observed in 9, and milia in 13. Indirect immunofluorescence on salt-split skin showed IgG deposition on the dermal side in 19 cases. Enzyme-linked immunosorbent assay for type Ⅶ collagen revealed positive results in 19 cases, with a diagnostic sensitivity of 95%. Western blot analysis with dermal extracts as substrates revealed a protein band with a relative molecular mass of 290 000 in 16 cases, with a diagnostic sensitivity of 80%, and multiple autoantibodies against different basement membrane zone antigens were identified in 3 cases. Fifteen patients received systemic glucocorticoids, including 2 receiving combined immunosuppressive agents and 13 receiving combined anti-inflammatory agents with dapsone and colchicine as the first and second commonly used anti-inflammatory agents respectively; among 5 patients receiving non-glucocorticoid therapy, 2 with inflammatory EBA were sensitive to dapsone and colchicine, while the other 3 patients were lost to follow-up. Totally, 17 patients were followed up for an average duration of 26.21 months. Among the 17 patients, 1 achieved complete remission off therapy, 2 achieved complete remission on minimal therapy, and the remaining 14 patients achieved partial remission.Conclusions:The treatment of EBA is challenging, and anti-inflammatory agents such as dapsone and colchicine are often used. Immunoserological tests are of great value in the diagnosis of EBA.

Intestinal dysbiosis and disrupted bile acid(BA)homeostasis are associated with obesity,but the precise mechanisms remain insufficiently explored.Hepatic protein phosphatase 1 regulatory subunit 3G(PPP1R3G)plays a pivotal role in regulating glycolipid metabolism;nevertheless,its obesity-combatting potency remains unclear.In this study,a substantial reduction was observed in serum PPP1R3G levels in high-body mass index(BMI)and high-fat diet(HFD)-exposed mice,establishing a positive correlation between PPP1R3G and non-12α-hydroxylated(non-12-OH)BA content.Additionally,hepatocyte-specific overexpression of Ppp1r3g(PPP1R3G HOE)mitigated HFD-induced obesity as evidenced by reduced weight,fat mass,and an improved serum lipid profile;hepatic steatosis alleviation was confirmed by normalized liver enzymes and histology.PPP1R3G HOE considerably impacted systemic BA homeostasis,which notably increased the non-12-OH BAs ratio,particularly lithocholic acid(LCA).16S ribosomal DNA(16S rDNA)sequencing assay indicated that PPP1R3G HOE reversed HFD-induced gut dysbiosis by reducing the Firmicutes/Bacteroidetes ratio and Lactobacillus population,and elevating the relative abundance of Blautia,which exhibited a positive correlation with serum LCA levels.A fecal microbiome transplantation test confirmed that the anti-obesity effect of hepatic PPP1R3G was gut microbiota-dependent.Mechanistically,PPP1R3G HOE markedly suppressed hepatic cholesterol 7α-hydroxylase(CYP7A1)and sterol-12α-hydroxylase(CYP8B1),and concurrently upregulated oxysterol 7-α hydroxylase and Takeda G protein-coupled BA receptor 5(TGR5)expression under HFD conditions.Furthermore,LCA administration significantly mitigated the HFD-induced obesity phenotype and elevated non-12-OH BA levels.These findings emphasize the significance of hepatic PPP1R3G in ameliorating diet-induced adiposity and hepatic steatosis through the gut microbiota-BA axis,which may serve as potential ther-apeutic targets for obesity-related disorders.

Digestive system malignant tumor is one of the common malignant tumors in humans,and its high morbidity and low survival rate at advanced stages bring heavy disease burden to patients,families and society.However,current tumor screening technologies are not suitable for screening in large-scale populations and long-term follow-up because of the invasiveness or complexity.Thus,liquid biopsy,which based on biomarkers such as circulating tumor DNA,circulating tumor cells,exosomes and other new biomarkers,has broad prospects for development in tumor screening.Exosome,secreted by living cells,is a type of extracellular vesicle with the lipid bilayer.Compared to other biomarkers,exosome has the advantages of high stability,wide distribution,and high quantity.The various proteins carried by exosome can reflect the characteristics of the origin cells,and exosome has important research value for the early diagnosis of tumors.This article reviews the studies of exosomal proteins as biomarkers for early diagnosis of digestive system malignant tumors in the past five years,and summarizes the characteristics and limitations of the above studies,so as to provide reference for promoting the clinical transformation of exosomal proteins.