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 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.

Objective To investigate the effect of Mex3c gene knockout on embryonic neural tube development and its possible mechanisms. Methods The NCBI database was used to analyze the expression of Mex3c gene in various tissues of mice. Fluorescence in situ hybridization (FISH) was employed to detect the expression of Mex3c in neural tubes of Mex3c^+/+ mice at different developmental stages (E12.5 d, E14.5 d). Sexual mature mice were mated at a ratio of Mex3c^+/- male to female (1:1) in the same cage. Embryos were collected and genotyped using PCR. They were divided into 3 groups based on their genotype: wild-type group (Mex3c^+/+, WT group), homozygous knockout group (Mex3c^-/-, KO group), and heterozygous knockout group (Mex3c^+/-). HE staining was employed to observe the development of neural tubes in the 3 groups of embryos. Immunofluorescence staining and Western blotting were performed to detect the proliferation and apoptosis of embryonic neural stem cells in the WT and KO groups. Transmission electron microscopy was used to observe the ultrastructure of the neural tubes and mitochondria in the WT and KO groups. RNA was extracted from the neural tubes of WT and KO groups for RNA-seq sequencing. The R.3.6.3 software was used to perform KEGG signaling pathway enrichment analysis on differentially expressed genes. RT-qPCR was used to validate the sequencing results. Results The NCBI database analysis and FISH detection results showed that the Mex3c gene was mainly expressed in the central nervous system of embryos. HE staining results showed that there was no significant difference in the development of embryonic neural tubes between KO group, WT group, and heterozygous knockout group at E12.5 d and E13.5 d. However, at E14.5 d, the embryonic neural tube development in KO group was delayed and the phenotype was significantly abnormal compared with those in WT group. Therefore, the embryonic neural tube tissues of KO group and WT group at E14.5 d were selected for subsequent experiments. The immunofluorescence staining results showed that the PCNA positive cell rate in KO group was significantly lower than that in WT group (P<0.001). The Western blotting results showed that the Bax/Bcl-2 ratio in KO group was higher than that in WT group (P<0.01). Transmission electron microscopy observation showed that compared with WT group, the synaptic gap in KO group disappeared, the mitochondrial of the embryonic neural tube in KO group were swollen, the mitochondrial cristae were disrupted, and the structure was significantly abnormal. The results of RNA-seq analysis showed that a total of 377 differentially expressed genes were obtained, including 101 up-regulated genes and 276 down-regulated genes. KEGG signaling pathway enrichment analysis revealed that the main signaling pathways of differentially expressed genes were enriched in the neuroactive ligand receptor interaction signaling pathways. The RT-qPCR validation results showed that the mRNA expression levels of Avpr1a, Drd1, Htr7, Sstr1, Oxtr and Gabra5 in this signaling pathway were down-regulated (P<0.05 or P<0.01), which was consistent with the RNA-seq results. Conclusion Mex3c plays an important role in the development of neural tubes in mouse embryos, which may participate in regulating the proliferation and apoptosis of neural stem cells through neural active ligand receptor interaction signaling pathways, thereby affecting the development of neural tubes.

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.

Endoplasmic reticulum is an important organelle in eukaryotic cells, which is responsible for the folding, processing and transportation of secretory proteins. A variety of stimuli inside and outside cells can lead to the accumulation of misfolded or unfolded proteins in the endoplasmic reticulum, resulting in abnormal structure and function of the endoplasmic reticulum, which is called endoplasmic reticulum stress (ERS). Endoplasmic reticulum autophagy is an important endogenous mechanism to alleviate ERS. It is often considered as a cell protective procedure, which participates in many important physiological processes, such as metabolism, immune response, inflammatory response and cell proliferation. Endoplasmic reticulum autophagy is an important endogenous protective mechanism to alleviate endoplasmic reticulum stress and restore the endoplasmic reticulum homeostasis, through eliminating redundant and disabled endoplasmic reticulum membrane and macromolecular protein complexes, which is critical to cell function and fate. This paper reviews the types of endoplasmic reticulum autophagy, related specific receptors, main regulatory mechanisms, and its role and significance in the related diseases.

Lipids, including fats (triglycerides) and lipoids (phospholipids and sterols), not only serve as an energy source for the body but also play a pivotal role throughout the reproductive process, particularly in the establishment and maintenance of early pregnancy. This encompasses the regulate of early embryonic development and uterine tolerance, and the facilitation of embryo implantation. Given the diversity of lipids, this review focuses on extensively studied lipid mediators such as polyunsaturated fatty acids, endocannabinoids, prostaglandins, lysophosphatidic acid, sphingolipids and steroid hormones. It systematically elaborates on the regulatory effects of fatty acid, phospholipid, and cholesterol metabolism on the formation of endometrial receptivity and embryo implantation, as well as the potential underlying mechanisms. The review aims to provide new insights and feasible intervention approaches for predicting and improving the outcomes of natural pregnancy and/or assisted reproductive technology.

Objective To analyze the clinical efficacy of total laparoscopic proximal gastrectomy and esophagogastric anastomosis to provide a new surgical method for the treatment of early proximal gastric cancer. Methods The clinical data of 80 patients with early gastric cancer who underwent proximal gastrectomy in the Department of General Surgery, the First Medical Center of Chinese PLA General Hospital from January 2019 to June 2021 were retrospectively analyzed. According to different surgical methods, the patients were divided into two groups: a total laparoscopic proximal gastrectomy group (n=36) and a laparoscopic-assisted proximal gastrectomy group (n=44). The perioperative conditions, long-term complications, and survival status were compared between the two groups. Results The length of surgical incision [(59.9±4.7) mm vs. (119.7±8.3) mm, P<0.001], first exhaust time [(58.2±15.3) h vs. (66.8±16.4) h, P=0.019] and postoperative hospital stay [(7.6±1.1) d vs. (9.2±1.3) d, P<0.001] of total laparoscopic proximal gastrectomy group were significantly shorter than those of laparoscope-assisted proximal gastrectomy group. The duration of operation [(186.9±16.4) min vs. (154.0±17.2) min, P<0.001] of total laparoscopic proximal gastrectomy group was significantly longer than that of laparoscopic-assisted proximal gastrectomy group. There were no significant differences in intra-operative hemorrhage, number of lymph nodedissection and first liquid diet feeding time between the two groups (P>0.05), and no early complications requiring surgical intervention occurred. The incidence of reflux esophagitis in the total laparoscopic proximal gastrectomy group was less than that in laparoscope-assisted proximal gastrectomy group [16.7%(6/36) vs. 38.6%(17/44), P=0.031]. There was no significant difference in gastric motility, residual gastritis, anastomosis stenosis and anastomotic ulcer between the two groups (P>0.05). Conclusion Total laparoscopic proximal gastrectomy and esophagogastric anastomosis have the characteristics of good safety, rapid postoperative recovery and anti-reflux, being worthy of clinical popularization.

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 analyze the effects and mechanisms of a disintegrin and metalloproteinase with thrombospondin motifs 14 (ADAMTS14) gene in gastric cancer associated with Helicobacter pylori (Hp) infection and explore the potential of ADAMTS14 as a novel target for biological therapy of gastric cancer. Methods The Caner Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized to analyze differentially expressed genes in gastric cancer tissues and Hp-positive gastric mucosa, and to screen potential targets. For the selected target ADAMTS14, its expression pattern in gastric cancer and Hp-positive gastric mucosa was analyzed. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed on the genes co-expressed with ADAMTS14 in gastric cancer. Kaplan-Meier Plotter database was used to analyze the correlation between high- and low-ADAMTS14 expression and prognosis of gastric cancer patients. The expression of ADAMTS14 and its relationship with clinicopathological features in 30 patients with gastric cancer were analyzed using real-time fluorescent quantitative PCR (RT-qPCR) and immunohistochemistry. The relationship between Hp infection and ADAMTS14 expression was analyzed using GEO database, and confirmed by cell line infection experiment. ADAMTS14 expression in gastric cancer cell line NCI-N87 was silenced by small interfering RNA to analyze its effect on the function of gastric cancer cells; The effect of ADAMTS14 knockdown on downstream target genes of Hippo signaling pathway was analyzed by RT-qPCR and Western blotting. Results A total of 16 genes closely related to Hp infection and gastric cancer were identified by analyzing the TCGA and GEO databases. According to TCGA database, the ADAMTS14 expression in gastric cancer tissues was higher than that in healthy gastric mucosa (P<0.0001). RT-qPCR and immunohistochemistry results also showed higher ADAMTS14 expression in gastric cancer tissues compared to adjacent tissues (P<0.01). Survival analysis demonstrated poor prognosis in patients with high ADAMTS14 expression (P<0.001). Data from GSE60427 showed that ADAMTS14 expression was upregulated in Hp-infected gastric mucosa and cell lines (P<0.001). After Hp P12 infection, the ADAMTS14 expression in NCI-N87 cells was higher than that in uninfected group. ADAMTS14 knockdown significantly inhibited the proliferation and migration of NCI-N87 cells (P<0.05), and it also significantly inhibited the expression of Hippo signaling pathway target genes, including BMP7, BMPR2, FZD4, PARD3 and SAV1 (P<0.05). Conclusion ADAMTS14 is highly expressed in Hp-positive gastric mucosa and gastric cancer tissues, which may accelerate gastric cancer progression by regulating Hippo signaling pathway, and holds potential as a new marker and therapeutic target for Hp infective gastric cancer.