最新刊期

    49 9 2024

      Guideline and Consensus

    • 最新研究评估了儿童孤独症诊疗指南的质量和报告情况,发现存在改进空间,建议明确资金来源和利益冲突。
      Deng Hui, Wang Meng-Qi, Meng Xiang-Ran, Long Zheng-Li, Cao Xue, Liu Jia
      Vol. 49, Issue 9, Pages: 977-985(2024) DOI: 10.11855/j.issn.0577-7402.0030.2024.0607
      Quality evaluation of childhood autism guidelines/consensus based on AGREE Ⅱ and RIGHT
      摘要:ObjectiveTo evaluate the methodological and reporting quality of published guidelines/consensus for childhood autism (CA), providing a basis for formulating domestic CA guidelines.MethodsWe 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.ResultsAfter 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).ConclusionThe 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.  
      关键词:childhood autism;guideline;consensus;quality evaluation   
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      Clinical Research

    • 海南地区研究发现,eNOS基因rs3918188位点CC基因型和C等位基因可能是系统性红斑狼疮的危险因素。
      Zhang Xuan, Wu Hui-Tao, Zhang Qi, Lin Gui-Ling, Yin Xi-Yu, Xu Wen-Lu, Wang Zhe, He Zi-Man, Liu Ying, Mi Long, Zhuang Yan-Ping, Gong Ai-Min
      Vol. 49, Issue 9, Pages: 986-991(2024) DOI: 10.11855/j.issn.0577-7402.0985.2024.0506
      Correlation analysis between <italic style="font-style: italic">eNOS</italic> gene single nucleotide polymorphism and systemic lupus erythematosus in Hainan
      摘要:ObjectiveTo investigate the relationship between single nucleotide polymorphisms (SNPs) in the eNOS gene and genetic susceptibility to systemic lupus erythematosus (SLE) in Hainan.MethodsBlood 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 above3 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.ResultsThe 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).ConclusionThe 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.  
      关键词:systemic lupus erythematosus;endothelial nitric oxide synthase;single nucleotide polymorphism   
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    • 在前列腺增生治疗领域,解放军总医院泌尿外科通过分析2050例手术患者资料,发现前列腺激光剜除术成为主流术式,手术及住院时间、尿管留置时间、膀胱造瘘率等指标显著改善。
      Yang Guo-Rong, Lyu Chao, Lyu Kai-Kai, Wu Yang-Yang, Song Tao, Yuan Qing
      Vol. 49, Issue 9, Pages: 992-997(2024) DOI: 10.11855/j.issn.0577-7402.0864.2023.1130
      Data analysis of perioperative period in 2050 cases of benign prostatic hyperplasia surgery in a single center over 10 years
      摘要:ObjectiveTo summarize and analyze the surgical evolution and clinical efficacy of benign prostatic hyperplasia (BPH) surgery.MethodsA 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.ResultsTransurethral 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%.ConclusionsLaser 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.  
      关键词:benign prostatic hyperplasia;surgical treatment;surgical method;perioperative period   
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    • 在陆军军医大学第二附属医院,46名受试者从低海拔急进高原后,心肺适能明显降低,低海拔基线NT-proBNP水平与急进高原后心肺适能密切相关,是高原心肺适能的潜在预测指标。
      Li Ping-Ping, Ye Xiao-Wei, Yang Jie, Qin Zhe-Xue, Bian Shi-Zhu, Zhang Ji-Hang, Gao Xu-Bin, Sun Meng-Jia, Liu Zhen, Lyu Hai-Lin, Jia Qian-Yu, Yang Yuan-Qi, Yang Bing-Jie, Huang Lan
      Vol. 49, Issue 9, Pages: 998-1003(2024) DOI: 10.11855/j.issn.0577-7402.1273.2024.0717
      Correlation between the level of NT-proBNP and cardiorespiratory fitness of individuals following acute high altitude exposure
      摘要:ObjectiveTo investigate the correlation between the level of N-terminal pro-Brain natriuretic peptide (NT-proBNP) and cardiorespiratory fitness following acute exposure to high altitude.MethodsForty-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.ResultsCompared 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. ConclusionCardiorespiratory 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.  
      关键词:cardiorespiratory fitness;high altitude;N-terminal pro-Brain natriuretic peptide;cardiopulmonary exercise test   
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    • 山西医科大学第一医院研究团队分析肺癌患者高能量代谢特征,建立风险预测模型,为临床治疗提供参考。
      Ren Jiang-Shan, Jia Jun-Mei, Sun Ping, Ping Mei, Zhang Qiong-Qiong, Liu Yan-Yan, Zhao He-Ping, Chen Yan, Rong Dong-Wen, Wang Kang, Qiu Hai-Le, Liu Chen-An, Fan Yu-Yu, Yu De-Gang
      Vol. 49, Issue 9, Pages: 1004-1010(2024) DOI: 10.11855/j.issn.0577-7402.1574.2024.0327
      Clinical characterization and prediction modeling of lung cancer patients with high energy metabolism
      摘要:ObjectiveTo 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.MethodsRetrospectively 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.ResultsOf 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).ConclusionThe high energy metabolic risk prediction model of lung cancer patients established in this study has good fit and prediction efficiency.  
      关键词:lung cancer;high energy metabolism;risk prediction model;body composition;quality of life   
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    • 在婴儿癫痫性痉挛综合征研究领域,解放军总医院第一医学中心专家报道了2例DYNC1H1基因异常患儿的临床特点和诊治过程,为该病的诊疗提供了新见解。
      Zhang Shan, Zhang Jing, Yang Guang
      Vol. 49, Issue 9, Pages: 1011-1017(2024) DOI: 10.11855/j.issn.0577-7402.0561.2024.0418
      <italic style="font-style: italic">DYNC1H1</italic>-related infantile epileptic spasms syndrome: two cases report and literature review
      摘要:ObjectiveTo 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.MethodsA 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.ResultsTwo 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.ConclusionsDYNC1H1 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.  
      关键词:Infantile epileptic spasms syndrome;gene, DYNC1H1;malformations of cortical development   
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    • Clinical efficacy of total laparoscopic proximal gastrectomy for cancer AI导读

      最新研究显示,完全腹腔镜近端胃切除术治疗早期胃癌疗效显著,具有安全性好、术后恢复快、抗反流等特点,值得推广。
      Liu Bo-Yan, Yan Yang, Chen Yu-Hui, Hu Shi-Dong, Li Song-Yan
      Vol. 49, Issue 9, Pages: 1018-1021(2024) DOI: 10.11855/j.issn.0577-7402.0384.2023.1229
      Clinical efficacy of total laparoscopic proximal gastrectomy for cancer
      摘要:ObjectiveTo 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.MethodsThe 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.ResultsThe 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).ConclusionTotal laparoscopic proximal gastrectomy and esophagogastric anastomosis have the characteristics of good safety, rapid postoperative recovery and anti-reflux, being worthy of clinical popularization.  
      关键词:gastroesophageal junction carcinoma;surgical treatment;total laparoscopy;clinical efficacy   
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    • 在肺部感染诊断领域,湖北省第三人民医院专家通过回顾性分析,验证了病原体靶向测序技术在提高病原体检测敏感度、识别混合感染方面的优势,为临床病原学检测提供了新方法。
      Zhang Cai-Xia, Ye Li-Wen, Huang Chun-Yan
      Vol. 49, Issue 9, Pages: 1022-1028(2024) DOI: 10.11855/j.issn.0577-7402.1543.2024.0428
      Application value of pathogen targeted next generation sequencing technology in patients with suspected pulmonary infection
      摘要:ObjectiveTo explore the application value of pathogen-targeted next-generation sequencing (tNGS) technology in patients with suspected pulmonary infections.MethodsA 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.ResultsAmong 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).ConclusionstNGS 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.  
      关键词:pathogen targeted next generation sequencing technology;routine pathogen detection;pulmonary infection;bronchoalveolar lavage fluid;application value   
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      Basic Research

    • 最新研究发现,Mex3c基因在小鼠胚胎神经管发育中起关键作用,可能通过调控神经干细胞的增殖和凋亡过程,影响神经管发育。
      Lu Zhi-Guo, Wu Xiao-Ting, Wang Kai, Zhang Bo, Wang Yong, Du Yong
      Vol. 49, Issue 9, Pages: 1029-1037(2024) DOI: 10.11855/j.issn.0577-7402.1012.2024.0124
      Effect and mechanism of <italic style="font-style: italic">Mex3c</italic> gene knockout on embryonic neural tube development
      摘要:ObjectiveTo investigate the effect of Mex3c gene knockout on embryonic neural tube development and its possible mechanisms.MethodsThe 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.ResultsThe 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.ConclusionMex3c 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.  
      关键词:gene, Mex3c;neural tube;dysplasia;gene knockout   
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    • 最新研究发现,烟草烟雾和机动车尾气暴露均可建立大鼠慢性阻塞性肺疾病模型,但烟草烟雾暴露能更好地模拟COPD急性加重期特征。
      Li De-Fu, Ye Yuan-Yuan, Zhang Hong-Ping, Hou Run-Hua, He Yao-Jun, Zhang Chun-Yun, Hu Jie-Ying, Chen Rui
      Vol. 49, Issue 9, Pages: 1038-1044(2024) DOI: 10.11855/j.issn.0577-7402.0025.2024.0605
      A comparative study of chronic obstructive pulmonary disease models in rats established by exposure to cigarette smoke and motor vehicle exhaust
      摘要:ObjectiveTo compare the fidelity of chronic obstructive pulmonary disease (COPD) models established using two methods: exposure to cigarette smoke (CS) and exposure to motor vehicle exhaust (MVE) in rats.MethodsTwenty-four male SD rats were randomly divided into control, CS-exposed (CS), and MVE-exposed (MVE) groups, with 8 rats per group. Rats in CS and MVE groups were exposed to CS or MVE, respectively, to induce COPD models. After COPD model established, lung function of each group was assessed. Bronchoalveolar lavage fluid (BALF) was collected to measure inflammatory cell counts, levels of inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor (TNF)‑α, and expression levels of mucin 5AC (MUC5AC). Lung tissue sections were stained with hematoxylin and eosin (HE) to observe pulmonary tissue and airway pathological changes. Periodic acid-Schiff (PAS) staining was used to detect goblet cell hyperplasia in airways.ResultsCompared with control group, rats in CS and MVE groups showed significantly increased inspiratory resistance (RI), total lung capacity (TLC), and lung static compliance (Cchord) (P<0.05), while expiratory flow parameters FEV50/FVC were significantly decreased (P<0.05). Compared with MVE group, rats in CS group had significantly higher RI, TLC, and Cchord (P<0.05), and lower FEV50/FVC (P<0.05). HE staining of lung tissues showed that mean linear intercept (MLI) was significantly higher in both CS and MVE groups compared with control group (P<0.05), with CS group having higher MLI than MVE group (P<0.05). BALF analysis revealed that white blood cells, neutrophils, macrophages, lymphocytes, IL-6, and TNF-α levels were significantly higher in both CS and MVE groups compared with control group (P<0.05), and inflammatory cell counts, IL-6, and TNF-α levels were higher in CS group compared with MVE group(P<0.05). PAS staining of lung tissues indicated that goblet cells in large airways were significantly increased in both CS and MVE groups compared with control group (P<0.05), with CS group showing higher goblet cell counts than MVE group (P<0.05). Expression levels of MUC5AC in BALF were significantly higher in both CS and MVE groups compared with control group (P<0.05), with CS group having significantly higher MUC5AC levels than MVE group (P<0.05). ConclusionsExposure to CS or MVE can establish a rat model of COPD, with CS exposure better mimicking characteristics of acute exacerbation of COPD compared to MVE exposure.  
      关键词:chronic obstructive pulmonary disease;cigarette smoke;motor vehicle exhaust;animal model   
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    • 最新研究发现,ADAMTS14基因在幽门螺杆菌感染相关胃癌中高表达,可能通过调控Hippo信号通路促进胃癌进展,有望成为胃癌治疗新靶点。
      Zhang Bo, Mi Yang, Liu Bin, Lu Yan-Wen, Zheng Peng-Yuan
      Vol. 49, Issue 9, Pages: 1045-1054(2024) DOI: 10.11855/j.issn.0577-7402.0934.2024.0527
      Effects of <italic style="font-style: italic">Helicobacter pylori</italic> on gastric cancer progression by upregulating <italic style="font-style: italic">ADAMTS14</italic> and activating Hippo signaling pathway and its underlying mechanisms
      摘要:ObjectiveTo 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.MethodsThe 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.ResultsA 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).ConclusionADAMTS14 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.  
      关键词:gastric cancer;Helicobacter pylori;ADAMTS14;hippo signaling pathway   
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    • 在围手术期脑卒中治疗领域,研究者发现右美托咪定能减轻脑损伤,其机制可能与降低FPR1蛋白表达,发挥抗小胶质细胞活化、抑制侧支循环血管新生相关。
      Li Pei-Pei, Ma Gang, Qu Bao-Fu, Zhang Cai-Xia
      Vol. 49, Issue 9, Pages: 1055-1061(2024) DOI: 10.11855/j.issn.0577-7402.0848.2023.1227
      Therapeutic effect and its mechanism of dexmedetomidine on the rat model of perioperative stroke
      摘要:ObjectiveTo investigate the effect of dexmedetomidine (Dex) on the rat model of perioperative stroke and its mechanism.MethodsOne 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.ResultsCompared 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). ConclusionsDex 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.  
      关键词:formyl peptide receptor 1;dexmedetomidine;ischemic stroke;microglia;angiogenesis   
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      Review

    • 最新研究发现,内质网自噬在缓解内质网应激、维持细胞稳态中发挥关键作用,为相关疾病治疗提供新思路。
      Tong Sen, Dong Ning, Zhu Xiao-Mei, Yao Yong-Ming
      Vol. 49, Issue 9, Pages: 1062-1072(2024) DOI: 10.11855/j.issn.0577-7402.0217.2023.0719
      Research advances in endoplasmic reticulum autophagy and its roles in associated diseases
      摘要: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.  
      关键词:endoplasmic reticulum stress;autophagy;reasearch progress   
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    • 最新研究揭示肠道微生物-肠-脑轴与卒中后认知障碍的密切关系,为治疗提供新思路。
      Lyu Zhuan, Wang Ya-Min, Liu Rui-Dong, Su Kai-Qi, Wu Ming-Li, Zhang Ming, Gao Jing, Feng Xiao-Dong
      Vol. 49, Issue 9, Pages: 1073-1079(2024) DOI: 10.11855/j.issn.0577-7402.0992.2024.0130
      Research progress on the relation between gut microbiome-gut-brain axis and post-stroke cognitive impairment
      摘要: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.  
      关键词:post-stroke cognitive impairment;gut microbiome-gut-brain axis;blood brain barrier;neuroinflammation   
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    • 在非小细胞肺癌治疗领域,RET融合突变成为新的研究热点,为克服EGFR-TKIs耐药提供新思路。
      Wang An, Li Tao, Lu Di, Mao Yun-Ye, Qin Jia-Pei, Zhou Xin, Fan Hao, Hu Yi
      Vol. 49, Issue 9, Pages: 1080-1087(2024) DOI: 10.11855/j.issn.0577-7402.0627.2023.1129
      Research progress on acquired RET fusion induces secondary resistance to EGFR therapy in advanced EGFR-mutated non-small cell lung cancer
      摘要: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.  
      关键词:non-small cell lung cancer;targeted therapy;EGFR-TKIs resistance;rearranged during transfection   
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    • 最新研究揭示脂质代谢在生殖过程中的关键作用,为预测和改善妊娠结局提供新思路。
      Ma Li-Na, Qin Ying, Wang Ke-Hua, Pang Cong-Hui, Lu Li-Ge, Yuan Wen-Xian, Zhang Duo-Jia, Wu Xiao-Ke
      Vol. 49, Issue 9, Pages: 1088-1093(2024) DOI: 10.11855/j.issn.0577-7402.1066.2024.0514
      摘要: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.  
      关键词:lipid metabolism;endometrial receptivity;embryo implantation;prostaglandins;endocannabinoids   
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    • 在血液系统恶性肿瘤治疗领域,IRAK4作为关键信号转导分子,为疾病发生机制和靶向治疗研究提供新思路。
      Shang Ying, Li Li-Juan, Zhang Lian-Sheng
      Vol. 49, Issue 9, Pages: 1094-1098(2024) DOI: 10.11855/j.issn.0577-7402.1579.2024.0418
      摘要: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.  
      关键词:Interleukin-1 receptor associated kinase 4;hematological malignancies;pathogenesis;targeted therapy   
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