Objective To explore the feasibility and reference value of allogeneic lung transplantation and postoperative monitoring in miniature pigs for lung transplantation research. Methods Two miniature pigs (R1 and R2) underwent left lung allogeneic transplantation. Complement-dependent cytotoxicity tests and blood cross-matching were performed before surgery. The main operative times and partial pressure of arterial oxygen (PaO₂) after opening the pulmonary artery were recorded during surgery. Postoperatively, routine blood tests, biochemical blood indicators and inflammatory factors were detected, and pathological examinations of multiple organs were conducted. Results The complement-dependent cytotoxicity test showed that the survival rate of lymphocytes between donors and recipients was 42.5%-47.3%, and no agglutination reaction occurred in the cross-matching. The first warm ischemia times of D1 and D2 were 17 min and 10 min, respectively, and the cold ischemia times were 246 min and 216 min, respectively. Ultimately, R1 and R2 survived for 1.5 h and 104 h, respectively. Postoperatively, in R1, albumin (ALB) and globulin (GLB) decreased, and alanine aminotransferase increased; in R2, ALB, GLB and aspartate aminotransferase all increased. Urea nitrogen and serum creatinine increased in both recipients. Pathological results showed that in R1, the transplanted lung had partial consolidation with inflammatory cell infiltration, and multiple organs were congested and damaged. In R2, the transplanted lung had severe necrosis with fibrosis, and multiple organs had mild to moderate damage. The expression levels of interleukin-1β and interleukin-6 increased in the transplanted lungs. Conclusions The allogeneic lung transplantation model in miniature pigs may systematically evaluate immunological compatibility, intraoperative function and postoperative organ damage. The data obtained may provide technical references for subsequent lung transplantation research.

Objective:To explore the clinical efficacy of layered thinning superficial circumflex iliac artery perforator (SCIP) flap based on color Doppler ultrasound (CDU) positioning.Methods:The study was a retrospective observational study. From February 2023 to February 2024, 14 patients who met the inclusion criteria were admitted to the Department of Hand Surgery of Beijing Jishuitan Hospital Affiliated to Capital Medical University, including 11 males and 3 females, aged 15 to 60 years. The wound area was from 7 cm×4 cm to 14 cm×11 cm. Before the flap transplantation surgery, CDU was used to accurately locate the deep fascial exit point of the superficial branch of the superficial circumflex iliac artery. During the surgery, the SCIP flap was thinned in layers to repair the hand and forearm wounds of 11 patients and foot wounds of 3 patients. The flap incision area ranged from 8 cm×5 cm to 15 cm×12 cm. The donor area wounds of flaps were sutured directly. During the surgery, the deep fascial exit point of the superficial branch of the superficial circumflex iliac artery in the flap donor area was observed and compared with the result of CDU positioning before the surgery, and the flap thickness was measured. The flap survival and occurrence of adverse reactions were observed after the surgery. During follow-up, the appearance and texture of flaps, and the wound healing in the donor area was observed. At the last follow-up, the function of the wrist and hand in the affected limbs was evaluated according to the trial standards for evaluation of partial function of upper extremity by the Hand Surgery Society of Chinese Medical Association, and the function of the foot and ankle in the affected limbs was evaluated according to the scoring standard of American Orthopaedic Foot and Ankle Society.Results:During the surgery, the deep fascial exit point of the superficial branch of the superficial circumflex iliac artery in the flap donor area was consistent with the result of CDU positioning before the surgery, and the distance between them was less than 10 mm. The flap thickness was 5 to 8 mm with an average of 6.2 mm. All the flaps survived after surgery. During the follow-up of 5 to 12 months, the flaps had good appearance and texture, all the wounds in the donor areas healed with only linear scar left. At the last follow-up, the function of the wrist and hand in the affected limbs was evaluated as excellent in 9 cases, good in one case, and fair in one case; the function of the foot and ankle in the affected limbs was evaluated as excellent in one case and good in two cases.Conclusions:CDU examination can provide precise preoperative perforator positioning for layered thinning of SCIP flap and contribute to the optimization of flap design, so as to avoid the problem of flap necrosis caused by improper preoperative design to some extent and improve the safety of surgery. In addition, the layered thinning SCIP flap results in less damage to the donor area and is beneficial for the recovery of the affected limb function, which is worthy of clinical promotion.

OBJECTIVE: To establish and validate a novel diabetic retinopathy (DR) risk-prediction model using a whole-exome sequencing (WES)-based machine learning (ML) method. METHODS: WES was performed to identify potential single nucleotide polymorphism (SNP) or mutation sites in a DR pedigree comprising 10 members. A prediction model was established and validated in a cohort of 420 type 2 diabetic patients based on both genetic and demographic features. The contribution of each feature was assessed using Shapley Additive explanation analysis. The efficacies of the models with and without SNP were compared. RESULTS: WES revealed that seven SNPs/mutations ( rs116911833 in TRIM7, 1997T>C in LRBA, 1643T>C in PRMT10, rs117858678 in C9orf152, rs201922794 in CLDN25, rs146694895 in SH3GLB2, and rs201407189 in FANCC) were associated with DR. Notably, the model including rs146694895 and rs201407189 achieved better performance in predicting DR (accuracy: 80.2%; sensitivity: 83.3%; specificity: 76.7%; area under the receiver operating characteristic curve [AUC]: 80.0%) than the model without these SNPs (accuracy: 79.4%; sensitivity: 80.3%; specificity: 78.3%; AUC: 79.3%). CONCLUSION Novel SNP sites associated with DR were identified in the DR pedigree. Inclusion of rs146694895 and rs201407189 significantly enhanced the performance of the ML-based DR prediction model.
Diabetic Retinopathy/diagnosis* ; Humans ; Machine Learning ; Male ; Female ; Polymorphism, Single Nucleotide ; Middle Aged ; Exome Sequencing ; Aged ; Adult ; Pedigree ; Diabetes Mellitus, Type 2/complications* ; Genetic Predisposition to Disease ; Mutation

Objective:To investigate the relationship between nonalcoholic fatty liver disease (NAFLD) and the long-term prognosis in patients with acute myocardial infarction (AMI).Methods:It was a retrospective cohort study. A total of 712 patients diagnosed with AMI who were admitted to the People′s Hospital of Xinjiang Uygur Autonomous Region from January 2018 to December 2019 were continuously included as subjects. The fatty liver index (FLI) was used to evaluate the degree of hepatic steatosis. Subjects were divided into No NAFLD group (FLI?30), grade 1 NAFLD group (30≤FLI?60), and grade 2 NAFLD group (FLI≥60). The endpoint event was defined as the occurrence of major cardiovascular adverse events (MACEs). The Cox proportional risk model was used to assess the risk of MACEs. The Kaplan-Meier curve was used to analyze the survival differences between the groups, and subgroup analysis was performed for age, gender, and complicity with hypertension, diabetes, dyslipidemia, and abdominal obesity.Results:During the follow-up period, the incidence of MACEs was 10.92% (26/238) in the No NAFLD group, it was 18.01% (47/261) in the grade 1 NAFLD group, and 24.41% (52/213) in the grade 2 NAFLD group, there was significant difference in the incidence of adverse events among the groups ( χ2=9.136, P?0.05). After adjusting for confounding factors, compared with the No NAFLD group, the risk of MACEs in grade 1 NAFLD group was increased by 69.0%( HR=1.690, 95% CI: 1.026-2.783, P=0.039) and 131.2%( HR=2.312, 95% CI: 1.415-3.773, P=0.001), respectively. Kaplan-Meier curve analysis indicated that the cumulative incidence of MACEs was significantly increased and the prognosis was worse in grade 2 NAFLD group (Log-rank test χ2=13.500, P=0.001). The results of subgroup analysis suggested that grade 2 NAFLD could significantly increase the risk of MACEs in all age groups, women, dyslipidemia, normal body type, and people with or without hypertension or diabetes. In particular, it had higher predictive value in women and normal-size people (interaction P?0.05). Conclusion:The degree of NAFLD is closely related to the long-term prognosis of AMI patients, the more severe the NAFLD, the higher the risk of adverse events in AMI patients.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To investigate and compare the epidemiological characteristics of common respiratory viruses among influenza-like illness(ILI)and severe acute respiratory infection(SARI)cases in Huzhou,Zhejiang Province before and after the COVID-19 pandemic,so as to provide a basis for formulating and adjusting the prevention and control strategies for viral respiratory infectious diseases.Methods ILI and SARI cases at two influenza surveillance sentinel hospitals in Huzhou and had throat swab samples collected during Nov 2017 to Feb 2020(pre-COVID-19 pandemic period)and Dec 2022 to Apr 2024(post-COVID-19 mitigation phase)were selected as the participants.Seven common viral respiratory pathogens were tested,including influenza A virus(H1N1 and H3N2 subtypes),influenza B virus(Victoria lineage,FluB),respiratory syncytial virus(RSV),rhinovirus(HRV),adenovirus(ADV),and severe acute respiratory syndrome coronavirus-2(SARS-CoV-2).The positive rates of respiratory pathogens before and after the COVID-19 pandemic were compared across different age groups and different time.Results A total of 7 948 ILI samples and 2 294 SARI samples were included.The overall positive rate of ILI samples increased from 33.6%to 47.1%,primarily due to the increase in influenza and COVID-19 infections;the overall positive rate of SARI samples decreased from 31.4%to 24.8%,mainly due to the reduction in HRV and ADV infections.During the post-COVID-19 mitigation phase,SARS-CoV-2(22.1%),H3N2(12.7%),and FluB(6.0%)were the primary pathogens in ILI samples,while RSV(7.1%),H3N2(5.3%),and HRV(4.5%)dominated in SARI samples.During the post-COVID-19 mitigation phase,the influenza virus circulation period was shortened.Before the COVID-19 pandemic,RSV was mainly detected in autumn and winter,while during the post-COVID-19 mitigation phase,out-of-season RSV epidemics were observed in spring and summer.Co-infection rate in ILI cases increased significantly in the post-COVID-19 mitigation phase,predominantly consisting of co-infections of COVID-19 and influenza A virus,while co-infection rate in SARI cases showed a decline.Conclusion We found important epidemiological changes in respiratory viruses in Huzhou during the post-COVID-19 mitigation phase compared to pre-COVID-19 period,including increased positive rates of influenza and COVID-19,and disruptions to the seasonal patterns of influenza and RSV.The prevention and control strategies should be adjusted in a timely manner based on the monitoring data.

Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson's disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K⁺ channels, or Ca²⁺-activated K⁺ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
Animals ; Histamine/metabolism* ; Male ; Oxidopamine/toxicity* ; Rats ; Ventral Thalamic Nuclei/physiopathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Parkinson Disease/metabolism* ; Neurons/physiology* ; Humans ; Optogenetics

Objective:To explore the diagnostic value of total bilirubin to albumin ratio(B/A ratio)combined with alpha-fetoprotein(AFP)and abnormal prothrombin induced by vitamin K absence-Ⅱ(PIVKA-Ⅱ)for hepatocellular carcinoma(HCC).Methods:35 HCC patients(HCC group),35 cirrhosis patients(cirrhosis group),35 HCC patients post-transcatheter arterial chemoembolization(TACE)(TACE postoperative group),and 35 healthy volunteers(healthy control group)were selected in our hospital from October 2023 to October 2024.The serum B/A ratio,AFP,and PIVKA-Ⅱ levles were measured and compared across the groups.The correlations between serum B/A ratio,AFP,and PIVKA-Ⅱ in the HCC group were analyzed.The B/A ratio,AFP,PIVKA-Ⅱ were compared across different clinical and pathological features in HCC patients.The serum B/A ratio,AFP,and PIVKA-Ⅱ levels were compared pre and post operation in the HCC group.The diagnostic value of B/A ratio,AFP,PIVKA-Ⅱ alone and in combination for HCC were analyzed by receiver operating characteristic(ROC)curves.Results:The serum B/A ratio,AFP,and PIVKA-Ⅱ levels in HCC group and TACE postoperative group were significantly higher than those in the cirrhosis group and healthy control group,and the HCC group was higher than that in the TACE postoperative group(P＜0.05).Pearson correlation analysis results showed that,B/A ratio in the HCC group was positively correlated with AFP(r=0.352,P=0.001),B/A ratio was positively correlated with PIVKA-Ⅱ(r=0.327,P=0.003),and AFP was positively correlated with PIVKA-Ⅱ(r=0.285,P=0.008).Higher TNM stage,larger tumor diameter,presence of vascular invasion,and lower differentiation degree of HCC patients,who had higher B/A ratio,AFP,and PIVKA-Ⅱ levels(P＜0.05).Serum B/A ratio,AFP,and PIVKA-Ⅱ levels in the HCC group post operation were significantly lower than those in pre operation(P＜0.05).ROC curve analysis results showed that,when B/A ratio,AFP,and PIVKA-Ⅱ were detected separately,the area under the curve(AUC)was 0.785,0.756,and 0.802,respectively.The AUC for joint detection was 0.925.The AUC in combination was greater than that of individual detection of each indicator.Conclusion:The combination of B/A ratio,AFP,and PIVKA-Ⅱ testing significantly improves the diagnostic efficiency for HCC,which is worthy of clinical application.