To address the current issue of low performance in predicting the binding affinity between antigenic peptides and specific MHC class II molecules, which fails to meet clinical requirements, we proposed T5MHCII, a deep learning-based prediction model for the affinity of MHC II class molecules to peptides. The model employed the knowledge previously acquired from the protein language model ProtT5 to extract the amino acid sequences via a transfer learning approach, thereby generating high-quality characterizations. This knowledge was then integrated with the robust learning abilities of deep learning to develop a novel model with enhanced predictive capabilities. The results of the five-fold cross-validation demonstrated that the model exhibited superior performance compared to NetMHCIIpan-3.2, PUFFIN, DeepMHCII, and RPEMH, with an AUC of 0.893±0.003 and a PCC of 0.780±0.006. The leave-one-out cross-validation (LOOCV) further demonstrated that the model exhibited enhanced generalization capabilities. This study proposes a novel approach to enhance the precision of peptide-MHCII prediction in the context of limited data affinity through the application of deep learning techniques.

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

OBJECTIVES: To evaluate the causal association between circulating levels of zinc, magnesium, and other minerals and autism spectrum disorder (ASD). METHODS: A two-sample Mendelian randomization (MR) analysis was performed using summary statistics from large-scale genome-wide association studies of European populations, including 18 382 ASD cases and 27 969 controls. Genetic data for iron, calcium, and magnesium were obtained from the UK Biobank, and data for zinc and selenium were sourced from an Australian-British cohort. A total of 351 genetic instrumental variables were selected. Causal inference was performed using inverse-variance weighting as the primary analysis method. Sensitivity analyses were performed by Cochran's Q test and MR-PRESSO global test to assess the robustness of the findings. RESULTS: No statistically significant causal effect was observed for circulating zinc, magnesium, calcium, selenium, or iron levels on ASD risk (all P>0.05). The odds ratios and 95% confidence intervals from the inverse-variance weighting analysis were 0.934 (0.869-1.003) for zinc, 1.315 (0.971-1.850) for magnesium, 1.055 (0.960-1.159) for calcium, 1.015 (0.953-1.080) for selenium, and 0.946 (0.687-1.303) for iron. Sensitivity analysis revealed significant heterogeneity in the causal association between circulating calcium and ASD (P=0.006), while the effect estimate remained stable after MR-PRESSO correction (P=0.487). The causal effect estimates for the remaining minerals demonstrated good robustness. CONCLUSIONS This study did not find significant evidence supporting a causal association between circulating zinc, magnesium, calcium, selenium, or iron levels and ASD risk, providing important clues for the etiology of ASD and precision nutritional interventions.
Humans ; Mendelian Randomization Analysis ; Autism Spectrum Disorder/genetics* ; Magnesium/blood* ; Zinc/blood* ; Minerals/blood* ; Genome-Wide Association Study ; Selenium/blood*

Transcatheter arterial embolization (TAE) is the mainstay for treating advanced hepatocellular carcinoma (HCC), and the performance of the embolization material is crucial in TAE. With the development of medical imaging and the birth of "X-ray-free" technologies, we designed a new dual-mode imaging material of dimethoxy tetraphenyl ethylene (DMTPE) via emulsification by mixing poly(N-isopropylacrylamide-co-acrylic acid) (PNA) with lipiodol and fluorocarbons, which was evaluated for temperature sensitivity, stability, and dual-mode visualization in vitro. Additionally, blood vessel casting embolization and renal artery imaging were assessed in healthy rabbits. In a rabbit model with a VX2 tumor, the effectiveness of TAE for treating HCC was examined, with an emphasis on evaluating long-term outcomes of embolization and its effects on tumor growth, necrosis, and proliferation through imaging techniques. In vitro experiments confirmed that the temperature-sensitive dual-oil-phase Pickering emulsion had good flow, stable contrast, and embolism when the oil-to-oil ratio and water-to-oil ratio were both 7:3 ( v/v) and stabilized with 8% PNA. Similarly, in vivo, arterial embolization confirmed the excellent properties of DMTPE prepared at the abovementioned ratios. It was observed that DMTPE not only has an antitumor effect but can also achieve dual imaging using X-rays and ultrasound, making it a promising excellent vascular embolization material for TAE in tumor treatment.

Objective:To investigate the sedative effect of remimazolam on ICU elderly patients undergoing mechanical ventilation and its influence on circulatory system.Methods:Using a prospective research approach, 189 ICU elderly patients undergoing mechanical ventilation in Hebei Petro China Central Hospital from October 2021 to June 2023 were selected. The patients were divided into remimazolam group, dexmedetomidine group and propofol group by random number table method with 63 cases in each group. The patients in remimazolam group, dexmedetomidine group and propofol group were sedated with remimazolam, dexmedetomidine and propofol, respectively. The sedation standard time, sedation standard rate, sedation maintenance time and recovery time after drug withdrawal were compared among the three groups. The heart rate, mean arterial pressure (MAP), respiratory rate and pulse oxygen saturation (SpO 2) before medication (T 0) and medication for 15 min (T 1), 30 min (T 2), 1 h (T 3), 6 h (T 4), 12 h (T 5) were recorded. The incidences of bradycardia, hypotension, respiratory depression, body movement and delirium during sedation were recorded. Results:The sedation standard time and recovery time after drug withdrawal in remimazolam group were significantly shorter than those in dexmedetomidine group and propofol group: (22.27 ± 5.31) min vs. (29.45 ± 6.24) and (30.12 ± 5.87) min, (28.66 ± 7.06) min vs. (32.22 ± 6.85) and (34.34 ± 7.24) min, and there were statistical differences ( P<0.05); there were no statistical difference between dexmedetomidine group and propofol group ( P>0.05). The sedation standard rate in remimazolam group and dexmedetomidine group was significantly higher than that in propofol group: 87.43% (661/756) and 83.60% (632/756) vs. 72.49% (548/756), and there was statistical difference ( P<0.016 7); there was no statistical difference between remimazolam group and dexmedetomidine group ( P>0.016 7). There was no statistical difference in sedation maintenance time among the three groups ( P>0.05). There were no statistical difference in T 0 heart rate, MAP, respiratory rate and SpO 2 among the three groups ( P>0.05). The T 1 to T 5 heart rate and MAP in remimazolam group were significantly higher than those in dexmedetomidine group and propofol group, the T 2 to T 5 heart rate and MAP in dexmedetomidine group were significantly lower than those in propofol group, and there were statistical differences ( P<0.05). The T 2 to T 5 respiratory rate in remimazolam group was significantly lower than that in dexmedetomidine group, the T 1 to T 5 respiratory rate in remimazolam group and dexmedetomidine group was significantly higher than that in propofol group, and there were statistical differences ( P<0.05). The T 2 to T 5 SpO 2 in remimazolam group and dexmedetomidine group was significantly higher than that in propofol group, and there was statistical difference ( P<0.05). The incidence of bradycardia in remimazolam group was significantly lower than that in dexmedetomidine group: 7.94% (5/63) vs. 25.40% (16/63), the incidence of hypotension was significantly lower than that in propofol group: 6.35% (4/63) vs. 23.81% (15/63), and there were statistical differences ( P<0.016 7). The incidence of respiratory depression in remimazolam group and dexmedetomidine group was significantly lower than that in propofol group: 4.76% (3/63) and 1.59% (1/63) vs. 22.22% (14/63), and there was statistical difference ( P<0.016 7). There was statistical difference in incidence of delirium among the three groups ( P<0.05), but there was no statistically significant difference in pairwise comparison ( P>0.016 7). There was no statistical difference in the incidence of body movement among the three groups ( P>0.05). Conclusions:The effect of remimazolam sedation in ICU elderly patients undergoing mechanical ventilation is satisfactory, with little influence on circulation and respiratory system and few adverse reactions.

A boy,aged 14 years,was admitted due to recurrent cough and expectoration for more than 1 month,with aggravation and fever for 2 days. After admission,he presented with tachypnea and a significant reduction in transcutaneous oxygen saturation,and emergency chest CT examination showed large patchy exudation and consolidation of both lungs. The boy was given tracheal intubation and invasive mechanical ventilation immediately,and his condition was improved after active symptomatic treatment. On the 10th day of hospitalization,the boy experienced fever again,and the laboratory tests showed positive results for Epstein-Barr virus and Mycoplasma antibody IgM,along with pancytopenia,elevated triglycerides,decreased fibrinogen,and increased levels of ferritin and soluble CD25. The boy was diagnosed with hemophagocytic lymphohistiocytosis. Bone marrow biopsy showed the presence of atypical lymphocytes,and aggressive natural killer cell leukemia was considered according to clinical manifestations and flow cytometry immunophenotype. Therefore,the possibility of hemophagocytic lymphohistiocytosis should be suspected in case of severe infection with pancytopenia and rapid disease progression,and hematological malignancies should also be ruled out. Bone marrow biopsy should be performed as early as possible to make a confirmed diagnosis and perform timely treatment.

Objective To investigate the role of microRNA(miR)-567 in the proliferation,migration and cell cycle of non-small cell lung cancer(NSCLC)through regulation of cyclin dependent kinase 8(CDK8)and its clinical relevance.Methods Tumor tissues and adjacent tissues of 40 NSCLC patients were collected,and the expressions of miR-567 and CDK8 were detected by real-time quantitative fluorescent PCR(qRT-PCR).miR-NC mimic,miR-567 mimic,oe-NC,and oe-CDK8 were transfected into A549 and H1975 cells.The ex-pressions of miR-567 and CDK8 were detected using qRT-PCR.Cell proliferation was detected by CCK-8 method,and cell migration was detected by Transwell assay.Cell cycle changes were detected by flow cytome-try.The targeting of miR-567 and CDK8 was detected by luciferase reporter gene assay.Results In the tumor tissues of NSCLC patients,the expression of miR-567 was decreased,while the expression of CDK8 was in-creased,and the two were negatively correlated(P＜0.05).In A549 and H1975 cells,miR-567 mimic group was compared with miR-NC mimic group,the expression of miR-567 was increased,the expression of CDK8 was decreased,the proliferation and migration levels of cells were decreased,the proportion of G1 phase was increased,and the proportion of S phase was decreased.The fluorescence intensity of miR-567 mimic group was lower than that of miR-NC mimic group in normal CDK8.miR-567 mimic+oe-CDK8 group was compared with miR-567 mimic+oe-NC group,the expression of CDK8 was increased,the proliferation and migration levels of cells were increased,the proportion of cells in G1 phase was decreased,and the proportion of cells in S phase was increased.Conclusion miR-567 can inhibit NSCLC proliferation and migration by targeting CDK8 expression and controlling tumor cell arrest in the S phase.

Objective To analyze the epidemiological characteristics of new elderly malignant tumor cases in Tongren City from 2018 to 2022, so as to provide a theoretical basis for the prevention and control of elderly malignant tumor in this area. Methods A retrospective analysis of the epidemiological characteristics of cases aged 60 and above who were first diagnosed with malignant tumors by pathology in our hospital from 2018 to 2022 was conducted based on the International Classification of Diseases (ICD-10). Results The incidence rate of elderly malignant tumors in Tongren City increased from 123.83/100 000 in 2018 to 126.14/100 000 in 2022, and the incidence rate showed a trend of first rising and then declining. The top five tumors in incidence rate are lung cancer, rectal cancer, liver cancer, stomach cancer and cervical cancer. The tumor order has changed over the years except lung cancer, which was the first. Lung cancer was the main high incidence tumor among the elderly of all ages. With the increase of age, the number of bladder cancer patients increases significantly, and the number of colon cancer patients also shows an upward trend. The prevalence rate of lung cancer（χ²=16.032，P=0.014) , liver cancer（χ²=8.099，P=0.030) , bladder cancer（χ²=11.274 , P=0.018) , and gastric cancer（χ²=19.387 , P=0.011) in elderly people of different sexes was generally higher in men than in women, and the difference was statistically significant (P<0.05). Conclusion Lung cancer , rectal cancer and liver cancer, as the malignant tumors with high case composition and rapid increase in the elderly, can be the focus of early screening and prevention of malignant tumors in the elderly in Tongren City, and men should pay more attention.

BACKGROUND:Early identification of patients requiring ventilator support will be beneficial for the outcomes of botulism.The present study aimed to establish a new scoring system to predict mechanical ventilation(MV)for botulism patients. METHODS:A single-center retrospective study was conducted to identify risk factors associated with MV in botulism patients from 2007 to 2022.Univariate analysis and multivariate logistic regression analysis were used to screen out risk factors for constructing a prognostic scoring system.The area under the receiver operating characteristic(ROC)curve was calculated. RESULTS:A total of 153 patients with botulism(66 males and 87 females,with an average age of 43 years)were included.Of these,49 patients(32.0%)required MV,including 21(13.7%)with invasive ventilation and 28(18.3%)with non-invasive ventilation.Multivariate analysis revealed that botulinum toxin type,pneumonia,incubation period,degree of hypoxia,and severity of muscle involvement were independent risk factors for MV.These risk factors were incorporated into a multivariate logistic regression analysis to establish a prognostic scoring system.Each risk factor was scored by allocating a weight based on its regression coefficient and rounded to whole numbers for practical utilization([botulinum toxin type A:1],[pneumonia:2],[incubation period≤1 day:2],[hypoxia<90%:2],[severity of muscle involvement:grade II,3;grade III,7;grade IV,11]).The scoring system achieved an area under the ROC curve of 0.82(95%CI 0.75-0.89,P<0.001).At the optimal threshold of 9,the scoring system achieved a sensitivity of 83.7%and a specificity of 70.2%. CONCLUSION:Our study identified botulinum toxin type,pneumonia,incubation period,degree of hypoxia,and severity of muscle involvement as independent risk factors for MV in botulism patients.A score≥9 in our scoring system is associated with a higher likelihood of requiring MV in botulism patients.This scoring system needs to be validated externally before it can be applied in clinical settings.

Objective To screen the differentially expressed proteins in glomeruli during the treatment of lupus nephritis(LN)with hydroxychloroquine sulfate(HCQ).Methods Sixty female NZB/WF1 mice were used.At the age of 28 weeks,40 mice with proteinuria of 3+to 4+were divided into HCQ and control groups.After feeding for 36 weeks,the glomerular proteins were extracted by magnetic beads and analyzed by two-dimensional fluorescence difference gel electrophoresis(2D-DIGE)and matrix-assisted laser desorption/ioniza-tion time-of-flight mass spectrometry(MALDI-TOF-MS).The expression of the candidate proteins in the glomeruli of the LN mice was exa-mined by immunohistochemistry.Results A total of 31 differentially expressed proteins were identified between the two groups,including 24 upregulated and seven downregulated proteins.Conclusion The expression of proteins like RI and ENOA in the glomeruli of LN mice was significantly different during HCQ treatment.These proteins may be involved in the pathogenesis of LN and are therefore potential targets of HCQ in the treatment of LN.