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 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.

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 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.

Post-stroke cognitive impairment (PSCI) is a prevalent functional impairments following stroke that seriously affects patients' quality of life and daily activities. Studies indicate a close relationship between intestinal microflora dysbiosis and central nervous system diseases. Intestinal microflora profoundly impacts on human physiological health, contributing to the stability of nervous, metabolic and immune systems through regulation of the gut-brain axis. An increasing number of studies confirmed the important role of the gut microbiome-gut-brain axis in the occurrence and development of stroke and its associated PSCI, and regulation of microbiome-gut-brain could be potential target to treatment of PSCI. This review summarizes research progress on gut microbiome-gut-brain axis and PSCI to provide a reference for exploration of related mechanisms and clinical prevention and treatment strategies.

Objective To investigate the effect of dexmedetomidine (Dex) on the rat model of perioperative stroke and its mechanism. Methods One hundred male rats were randomly divided into sham group , middle cerebral artery occlusion (MCAO) group, low dose Dex [Dex-L, 0.5 μg/(kg·h)] group, medium dose Dex [Dex-M, 2 μg/(kg·h)] group, high dose Dex [Dex-H, 10 μg/(kg·h)] group, 20 rats in each group. A rat model of perioperative stroke was established by middle cerebral artery occlusion. Dex was injected intravenously at different doses during ischemia. After 24 h, the neurological function of the rats was evaluated. Then, the rats were sacrificed and the peripheral blood and whole brain tissue were collected, ischemic core area tissue was separated from some brain tissues and the cerebral infarction area was observed by TTC staining. The inflammatory cytokine contents in serum and ischemic core area were measured by ELISA. In addition, the expressions of formyl peptide receptor 1 (FPR1), transmembrane protein 119 (TMEM119), CD31 and VE-cadherin proteins were assayed by immunofluorescence, and the expressions of FPR1, nuclear factor-κB (NF-κB) and NLRP3 proteins by Western blotting in the ischemic core area. Results Compared with sham group, the proportion of cerebral infarction area and neurological scores in the MCAO group were significantly increased, and the contents of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α in the serum and the ischemic core area were significantly increased, the expressions of FPR1, TMEM119, p-NF-κB, NLRP3, CD31 and VE-cadherin in the ischemic core were significantly increased(P<0.001), and there was obvious co-expression of FPR1 and TMEM119. Compared with MCAO group, the proportion of cerebral infarction area and neurological scores in the Dex-M and Dex-H groups were significantly decreased, and the contents of IL-1β, IL-6 and TNF-α in serum and brain ischemic core area were significantly decreased, the expressions of FPR1, TMEM119, p-NF-κB, NLRP3, CD31 and VE-cadherin in the ischemic core were significantly decreased (P<0.001). Conclusions Dex can significantly alleviate perioperative stroke injury. The mechanism may be due to inhibiting the expression of FPR1 protein, activation of microglia cells and cerebral collateral circulation angiogenesis.

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.

Interleukin-1 receptor associated kinase 4 (IRAK4) plays a crucial role in signal transduction and regulation in the TLRs/IL-1R signaling pathway, coordinating multiple inflammatory pathways involving immune system activation, cytokine production, and cell proliferation and differentiation. IRAK4 is associated with the pathogenesis and progression of hematological malignancies, including myelodysplastic syndrome, acute myeloid leukemia, chronic lymphocytic leukemia, and lymphoma. Therefore, IRAK4 may serve as an effective therapeutic target for hematologic malignancies. This review summarizes the research advances in the structure and function of IRAK4, as well as its mechanism of action and therapeutic implications in hematological malignancies, aiming to provide insights into pathogenesis of related diseases and targeted therapy research.

With the in-depth study of molecular biology, non-small cell lung cancer (NSCLC) has opened the era of precision medicine based on mutation-based molecular targeting therapy. Epidermal growth factor receptor (EGFR) driver mutations are closely related to the progression of NSCLC, and EGFR-tyrosine kinase inhibitors (TKIs) developed based on this have achieved significant therapeutic effects, but acquired drug resistance is still one of the major factors limiting their long-term use. As resistance mechanisms are further investigated, in addition to secondary EGFR mutation, MET amplification, HER2 amplification, histologic transformation, etc., receptor tyrosine kinase (RTK) fusion mutation have been shown to be a targetable mechanism of acquired resistance. Among the acquired RTK fusion mutations, rearranged during transfection (RET) fusion mutations are the accessible targets of our concern. As the RET molecule continues to be explored, drugs targeting RET fusions have been approved and marketed. There are different clinical strategies to deal with acquired RET fusion mutation mediating resistance to EGFR-TKIs treatment. In this review, the structure and function of RET, its relationship with EGFR-TKIs resistance, and treatment strategies are reviewed to further improve patient survival outcomes.

Objective To explore the application value of pathogen-targeted next-generation sequencing (tNGS) technology in patients with suspected pulmonary infections. Methods A retrospective analysis was conducted on the clinical data of 80 patients with suspected pulmonary infections admitted to the Department of Respiratory and Critical Care Medicine at the Third People's Hospital of Hubei Province from January 2021 to July 2023. All patients underwent bronchoalveolar lavage fluid (BALF) tNGS and conventional pathogen detection. Demographic characteristics of the patients were analyzed, and the distribution of pathogens detected by tNGS and conventional methods were compared. The clinical data of patients diagnosed with single pulmonary infections and those with mixed infections were also compared. Results Among the 80 patients, 74 were diagnosed with infections. Most of the infected patients had underlying conditions, mainly chronic heart disease (42.5%), chronic respiratory disease (35%), and diabetes (20%). The tNGS test results led to changes in treatment strategy for 35 patients (43.8%). A total of 45 types of pathogens were detected, with 169 strains identified by tNGS and 63 strains by conventional methods. Within pathogens detected by both methods, bacteria were detected the most. The order of pathogen types detected by tNGS was bacteria > viruses > fungi > atypical pathogens > Mycobacterium tuberculosis. The order of pathogen types detected by conventional methods was fungi > viruses > bacteria > atypical pathogens > Mycobacterium tuberculosis. The consistency between the two pathogen detection methods was poor (kappa value 0.172, P=0.020). The number of positive cases and the positive detection rates for bacteria, viruses, and atypical pathogens detected by tNGS were significantly higher than those of conventional methods (P<0.05), but there was no statistically significant difference in the positive detection rates for fungi and Mycobacterium tuberculosis between the two methods (P>0.05). Using clinical diagnosis as the gold standard, the sensitivity of tNGS detection was significantly higher than that of conventional methods (P=0.026), while there was no statistically significant difference in specificity between the two methods (P>0.05). Among the 74 confirmed pulmonary infection cases, 6 had no clear pathogen, 23 had single infections, and 45 had mixed infections. Among the mixed infections, the most common combination was bacterial-viral mixed infections (12/45, 26.7%). The mortality rate and hospitalization duration of patients with mixed infections were significantly higher than those with single infections (P<0.05); there were no statistically significant differences in gender, age, underlying conditions, white blood cell count, and neutrophil percentage between the two groups (P>0.05). Conclusions tNGS technology has higher pathogen detection sensitivity compared to conventional methods, especially for bacteria, viruses, atypical pathogens, and rare pathogens. This technology is beneficial for identifying mixed infections and can serve as a supplement to conventional pathogen detection methods in clinical practice.