Hemophilia, which includes different types such as hemophilia A and hemophilia B, is a hemorrhagic disorder with inherited blood clotting abnormalities. The main clinical manifestations are spontaneous bleeding of joints, muscles and deep tissues or repeated bleeding after trauma. It often starts at an early age and affects the whole life. The treatment of hemophilia patients is still dominated by alternative therapy, supplementing the corresponding clotting factors. In addition, non-factor drug therapy is adopted such as bispecific monoclonal antibodies and gene therapy. In recent years, the research on the pathogenesis of hemophilia A has made great progress, which is no longer limited to the mutation of the coding sequence of coagulation factor gene as the only cause of hemophilia. Many studies have found that abnormal expression of non-coding RNA (ncRNA) is involved in the regulation of coagulation factor Ⅷ (FⅧ) mRNA and protein, which not only explains why patients with normal FⅧ genotypes still present with hemophilia A, but also provides new directions for understanding the pathogenesis of other types of hemophilia. This paper reviews the research progress on the regulatory mechanism of ncRNA in hemophilia A.

Autophagy is an essential cellular metabolic process that involves clearance of damaged organelles and protein aggregates in cells through lysosomes, providing energy for cells, and maintaining cellular tissue homeostasis. Impaired autophagy is closely related to the pathophysiology of a variety of diseases. In the pathogenesis of atherosclerosis (AS), the dysfunction of autophagy of vascular cells plays a crucial role in the formation and progression of AS. The functional status, survival or death of vascular cells, including endothelial cells, vascular smooth muscle cells and macrophages, can influence the formation and stability of plaques, thereby affecting the progression of AS. This review summarizes the relationship between autophagy and AS, and details the impact of autophagy dysfunction on vascular cell function in the process of AS, as well as the role of mitophagy and inflammasome in the development of AS, aiming to provide novel insights for the prevention and treatment of AS.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease characterized by excess fat accumulation within liver cells. The main causes include obesity, diabetes, and hyperlipidemia. In recent years, NAFLD and other metabolic diseases have become global public health issues. Although some progress has been made in the drug treatment of NAFLD, the efficacy is limited and there are many adverse effects. As a treatment method with high safety and few adverse effects, exercise therapy has good application prospects in the treatment of NAFLD and other metabolic diseases. However, challenges remain in overcoming patients' low exercise compliance and in finding safe and effective exercise therapy drug targets. This article explores the mechanisms and application prospects of exercise therapy in the treatment of NAFLD and other metabolic diseases, summarizes the energy consumption, metabolic pathways, and inter-organ communication induced by exercise, aiming to provide useful references for clinical practitioners.

Tumor neoantigens are antigens encoded by tumor-specific mutated genes, characterized by high specificity, significant exogenous origin, mutation randomness, clonal distribution and correlation with gene mutation. Because these antigens are not negatively screened by the thymus and recognized by T cells as "heterogeneous". They are less easily affected by the immune tolerance mechanism and exhibit strong immunogenicity, making them excellent targets for immunotherapy. Tumor neoantigens can be used to develop therapeutic vaccines, induce and cultivate T cells with stronger targeting capabilities, and are promising for predicting tumor survival prognosis and responses to immune checkpoint blockade therapies. This review summarizes the recent advances in clinical application of tumor neoantigen-based immunotherapy, and prospects for future research directions.

Objective To evaluate the methodological and reporting quality of published guidelines/consensus for childhood autism (CA), providing a basis for formulating domestic CA guidelines. Methods We searched databases including CNKI, Wanfang Data, SinoMed, Medlive, PubMed, national institute of health and clinical excellence (NICE), national guideline clearinghouse (NGC), and Scottish intercollegiate guidelines network (SIGN) for Chinese and foreign guideline/consensus on childhood autism published before February 1, 2024. Two researchers independently evaluated the methodology and reporting quality of the guideline/consensus using the Appraisal of Guidelines Research and Evaluation Ⅱ (AGREE Ⅱ) and Reporting Items for Practice Guidelines in Healthcare (RIGHT) tools. Results After literature screening, 19 CA guidelines/consensus were included, comprising 11 guidelines, 7 consensus, and 1 expert recommendation, with 9 domestic and 10 foreign articles. The AGREE Ⅱ evaluation scores for the six domains were as follows: scope and purpose (91.1%±4.5%), stakeholder involvement (86.8%±6.7%), rigour of development (83.0%±10.2%), clarity of presentation (84.3%±6.2%), applicability (82.7%±13.3%), and editorial independence (65.4%±21.8%). The RIGHT checklist reported rates for the seven domains were: basic information (87.6%±11.0%), background (87.6%±13.8%), evidence (81.1%±22.6%), recommendation (71.1%±38.4%), review and quality assurance (83.5%±16.7%), funding and declaration and management of interests (48.7%±29.4%), and other information (64.4%±11.8%). The domain with the lowest score for methodological quality was "editorial independence" and for reporting quality, it was "funding and declaration and management of interests". The reporting rate of domestic articles (26.2%±1.5%) was significantly lower than that of foreign articles (52.6%±2.2%), with a statistically significant difference (P<0.05). Conclusion The overall quality of current childhood autism guidelines/consensus requires improvement. During the formulation and reporting of guidelines/consensus, strictly adhering to AGREE Ⅱ and RIGHT is imperative, and it is essential to clearly report funding sources and conflicts of interest.

Objective To investigate the relationship between single nucleotide polymorphisms (SNPs) in the eNOS gene and genetic susceptibility to systemic lupus erythematosus (SLE) in Hainan. Methods Blood samples were collected from SLE patients (SLE group, n=214) and healthy controls (control group, n=214) from January 2020 to December 2022 at the First Affiliated Hospital of Hainan Medical College and Hainan Provincial People's Hospital. The bases of eNOS gene rs3918188, rs1799983 and rs1007311 loci in each group were detected by SNaPshot sequencing technology. Logistic regression was used to analyze the correlation between genotypes, alleles and gene models (dominant model, recessive model, and overdominant model) of the above 3 target loci of the eNOS gene and genetic susceptibility to SLE. Haplotype analysis was conducted using HaploView 4.2 software to investigate the relationship between haploid and genetic susceptibility to SLE at each site. Results The results of logistic regression analysis revealed that the CC genotype and the C allele at rs3918188 locus were risk factors for genetic susceptibility to SLE (CC vs. AA: OR=2.449, P<0.05; C vs. A: OR=2.133, P<0.001). In recessive model at rs3918188 locus, CC genotype carriers had an increased risk of SLE development compared with AA+AC genotype carriers (OR=2.774, P<0.001). In contrast, in overdominant model at this locus, AC genotype carriers had a decreased risk of SLE occurrence compared with AA+CC genotype carriers (OR=0.385, P<0.001). In addition, polymorphisms of rs1799983 and rs1007311 were not associated with susceptibility to SLE in genotype, allele type and the 3 genetic models (P>0.05). Haplotype analysis revealed a strong linkage disequilibrium between the rs1007311 and rs1799983 loci of the eNOS gene, but no significant correlation was found between haplotype and genetic susceptibility to SLE (P>0.05). Conclusion The CC genotype and C allele at rs3918188 locus of eNOS gene may be risk factors for SLE in Hainan, while the risk of SLE occurrence is reduced in carriers of AC genotype under the overdominant model.

Objective To summarize and analyze the surgical evolution and clinical efficacy of benign prostatic hyperplasia (BPH) surgery. Methods A retrospective cohort study was used to analyze the clinical data of 2050 patients who underwent surgery for BPH in the Department of Urology, the First Medical Center of PLA General Hospital from January 2012 to August 2022. These patients were divided into 3 groups in chronological order: the early group (n=683), the middle group (n=683) and the late group (n=684). The cumulative time of patients in each group was from January 2012 to February 2017, March 2017 to September 2020 and October 2020 to August 2022. The indicators, such as age, hypertension, diabetes, serum cholesterol, serum triacylglycerol, serum high-density lipoprotein cholesterol, body mass index (BMI), preoperative prostate volume, prostate specific antigen (PSA), free prostate specific antigen (fPSA), operation time, preoperative hospital stay, postoperative hospital stay, postoperative bladder flushing time, postoperative indwelling time, cystostomy situation, intraoperative and postoperative blood transfusion, postoperative readmission rate, and postoperative pathology were collected and compared between 3 groups, and the annual trend of changes in the number of BPH surgeries and surgical methods was analyzed. Results Transurethral resection of prostate (TURP) and TURP+laser resection decreased year by year, while transurethral laser resection of prostate increased and became the mainstream prostate resection method in recent two years, accounting for more than 90%. The patients in the early, middle and late groups were (69.7±7.9) years old, (68.7±7.4) years old and (69.8±8.5) years old (P=0.027); the operation time was 108.0(80.0, 130.0) min, 80.0(60.0, 110.0) min and 75.0 (60.0, 100.0) min (P<0.001); the postoperative indwelling time was 4.1(2.7, 5.9) d, 3.9(2.9, 4.9) d and 2.7(0.9, 3.9) d (P<0.001); the rates of cystostomy were 68.8%, 66.6% and 5.0% (P<0.001); the intraoperative and postoperative blood transfusion rates were 4.5%, 3.1% and 0.9% (P<0.001); the preoperative hospitalization time was 5.6(3.8, 7.1) d, 4.7(3.5, 5.9) d, and 4.7(3.1, 6.7) d (P<0.001); the postoperative hospital stays were 5.7(4.8, 7.0) d, 4.7(3.0, 5.9) d and 2.8(1.0, 4.0) d (P<0.001), with statistically significant differences. Thirty-seven cases (1.8%) of BPH patients who underwent surgery in our center for 10 years were re-admitted after surgery, and 64 cases had postoperative pathological abnormalities or were diagnosed with prostate cancer, with a total detection rate of 3.1%. Conclusions Laser enucleation of prostate has become the mainstream surgical treatment of BPH in our center, and perioperative indexes such as operation time, hospital stay, postoperative catheter indwelling time, cystostomy rate, and surgical blood transfusion rate have shown a significant improvement trend.

Objective To investigate the correlation between the level of N-terminal pro-Brain natriuretic peptide (NT-proBNP) and cardiorespiratory fitness following acute exposure to high altitude. Methods Forty-six subjects were recruited from the Second Affiliated Hospital of Army Medical University in June 2022, including 19 males and 27 females. After completing cardiopulmonary exercise test (CPET), serological detection of myocardial cell-related markers, and multiple metabolites at a plain altitude (300 meters above sea level), all subjects flew to a high-altitude location (3900 meters above sea level). Biomarker testing and CPET were repeated on the second and third days after arrival at high altitude. Changes in serum biomarker and key CPET indicators before and after rapid ascent to high altitude were compared, and the correlation between serum levels of various myocardial cell-related markers and metabolites and high altitude cardiorespiratory fitness was analyzed. Results Compared with the plain altitude, there was a significant decrease in maximal oxygen uptake after rapid ascent to high altitude [(25.41±6.20) ml/(kg.min) vs. (30.17±5.01) ml/(kg.min), P<0.001]. Serum levels of NT-proBNP, Epinephrine (E), plasma renin activity (PRA), angiotensin Ⅱ (Ang Ⅱ), angiotensin-converting enzyme 2 (ACE2) and leptin (LEP) significantly increased, with all differences being statistically significant(P<0.05) after acute high altitude exposure. In contrast, no statistically significant differences were observed for creatine kinase MB (CK-MB), cardiac troponin I (cTnI), myoglobin (Myo) and norepinephrine (NE) (P>0.05). Correlation analysis showed a significant negative correlation between NT-proBNP at plain altitude (r=-0.768, P<0.001) and at high altitude (r=-0.791, P<0.001) with maximal oxygen uptake at high altitude. Multivariate linear regression analysis indicated that maximal oxygen uptake at plain altitude (t=2.069, P=0.045), NT-proBNP at plain altitude (t=-2.436, P=0.020) and at high altitude (t=-3.578, P=0.001) were independent influencing factors of cardiorespiratory fitness at high altitude. Conclusion Cardiorespiratory fitness significantly decreases after rapid ascent to high altitude, and the baseline NT-proBNP level at plain altitude is closely related to cardiorespiratory fitness at high altitude, making it a potential predictor indicator for high altitude cardiorespiratory fitness.

Objective To analyze the clinical characteristics of high energy metabolism in lung cancer patients and its correlation with body composition, nutritional status, and quality of life, and to develop a corresponding risk prediction model. Methods Retrospectively analyzed 132 primary lung cancer patients admitted to the First Hospital of Shanxi Medical University from January 2022 to May 2023, and categorized into high (n=94) and low energy metabolism group (n=38) based on their metabolic status. Differences in clinical data, body composition, Patient Generated Subjective Global Assessment (PG-SGA) scores, and European Organization for Research and treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) scores were compared between the two groups. Logistic regression was used to identify the risk factors for high energy metabolism in lung cancer patients, and a risk prediction model was established accordingly; the Hosmer-Lemeshow test was used to assess the model fit, and the ROC curve was used to test the predictive efficacy of the model. Results Of the 132 patients with primary lung cancer, 94 (71.2%) exhibited high energy metabolism. Compared with low energy metabolism group, patients in high-energy metabolism group had a smoking index of 400 or higher, advanced disease staging of stage Ⅲ or Ⅳ, and higher levels of IL-6 level, low adiposity index, low skeletal muscle index, and malnutrition (P<0.05), and lower levels of total protein, albumin, hemoglobin level, and prognostic nutritional index (PNI) (P<0.05). There was no significant difference in age, gender, height, weight, BMI and disease type between the two groups (P>0.05). Logistic regression analysis showed that smoking index ≥400, advanced disease stage, IL-6 ≥3.775 ng/L, and PNI <46.43 were independent risk factors for high energy metabolism in lung cancer patients. The AUC of the ROC curve for the established prediction model of high energy metabolism in lung cancer patients was 0.834(95%CI 0.763-0.904). Conclusion The high energy metabolic risk prediction model of lung cancer patients established in this study has good fit and prediction efficiency.

Objective To report the clinical characteristics, diagnosis, and treatment process of two infants with infantile epileptic spasms syndrome (IESS) caused by DYNC1H1 mutation, and to review the relevant literature. Methods A retrospective analysis was conducted on the clinical data of two IESS patients with DYNC1H1 mutations who were treated at the First Medical Center of Chinese PLA General Hospital. Databases such as PubMed, Online Mendelian Inheritance in Man (OMIM), China National Knowledge Infrastructure (CNKI), and Wanfang Data Knowledge Service Platform were searched to obtain relevant literature, aiming to summarize the clinical characteristics of IESS patients with DYNC1H1 mutations, and to explore the relationship between treatment and phenotype-genotype. Results Two IESS patients with DYNC1H1 mutations were identified (case 1: c.874C>T, p.Arg292Trp; case 2: c.5884C>T, p.Arg1962Cys). Both patients presented with the onset of spastic seizures in infancy, which were poorly controlled with various medications. They exhibited severe developmental delay, and cranial magnetic resonance imaging in case 1 revealed pachygyria. A search of multiple databases and manual screening yielded a total of 7 English articles and 2 Chinese articles. Fifteen cases of DYNC1H1-related IESS were identified, of which 12 cases progressed to drug-resistant epilepsy and 12 cases had significant congenital structural abnormalities of the cranium. Nine different mutation sites were distributed in 3 structural domains, including 4 cases in the tail domain, 3 cases in the motor with ATPase subunit domain, and 2 cases in the stalk or microtubule-binding domain. Conclusions DYNC1H1 gene variations can cause IESS, often accompanied by brain developmental abnormalities and developmental delay/intellectual disability. The poor prognosis may be attributed to the combined effects of gene dysfunction and brain developmental abnormalities.