Objective:To investigate the clinical phenotype and genetic characteristics of patients with Fabry disease caused by a GLA variant, IVS4+919G>A.Methods:It was a prospective study. Fabry disease screening was conducted among high-risk population in Ninghai from October 2021 to August 2023. Those children with decreased α-galactosidase enzyme activity<2.40 μmol/(L·h) or elavated Lyso-GL-3 level>1.10 μg/L in dried blood spot (DBS) method underwent GLA genetic testing for diagnosis confirmation. Meanwhile, family screening was carried out. A proband and his family members diagnosed with Fabry disease were research subjects. The clinical and genetic characteristics of patients with Fabry disease caused by the GLA variant (IVS4+919G>A) were analyzed.Results:The female proband aged 9.8 years with pain in both lower limbs as the initial symptom was found to have a heterozygous GLA variant IVS4+919G>A among 102 patients. In family screening, there were 4 family members (proband's father, elder sister, elder male cousin and elder female cousin) with Fabry disease and a family member (proband's fifth aunt) with a GLA variant. Among these 4 diagnosed family members, the elder male cousin of the proband, a boy aged 13.2 years had a heterozygous GLA variant, IVS4+919G>A with intermittent pain in both lower limbs as the initial symptom. The proband′s father had knee joint pain. The proband′s elder sister had decreased vision and his elder female cousin had no obvious symptoms. The proband′s fifth aunt with a GLA variant had decreased vision.Conclusions:High-risk screening in children and family screening are helpful for early diagnosis and treatment of Fabry disease. Neuropathic pain may be a early symptom in children with Fabry disease caused by the GLA variant, IVS4+919G>A.

Objective:To systematically evaluate the dose-response relationships of resistance exercise intensity in frail elderly.Methods:A comprehensive search of randomized controlled trials on the dose-response relationships of resistance exercise for frail elderly in PubMed, Embase, The Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Database. The documents that met the conditions were screened out, and after the data were extracted and the quality of the documents were evaluated, the RevMan 5.3 software was used for Meta analysis.Results:A total of 10 eligible randomized controlled trials were included in this study. The subjects of the study were 454 cases of frail and pre-frail elderly. After Meta analysis, there was a dose-response relationships between the training intensity of resistance exercise and the muscle strength, muscle endurance, and physical function of frail elderly. Both low-intensity and high-intensity resistance exercises can significantly increase the leg muscle strength of frail elderly people ( MD=4.58, 95% CI 3.34-5.82, P<0.05) and muscle endurance ( MD=12.27, 95% CI 6.54-17.99, P<0.05). Compared with low-intensity resistance exercise, high-intensity resistance exercise increased leg muscle strength of frail elderly people ( MD=7.97, 95% CI 0.85-15.09, P<0.05) and muscle endurance ( MD=6.94, 95% CI 5.21-8.66, P<0.05) showed more obvious advantages. The analysis of the results of the chair sitting test and the stairs climbing test shows that low-intensity resistance exercise has no obvious advantage in improving the physical function of frail elderly people, while high-intensity resistance exercise can significantly improve the physical function of frail elderly people ( MD=-5.8, 95% CI -7.3--4.29, P<0.05; MD=-1.20, 95% CI-2.17--0.23, P<0.05). Conclusions:Resistance exercise can significantly improve the muscle strength, muscle endurance and physical function of the frail elderly. High-intensity resistance exercise is more effective than low-intensity resistance exercise.

Objective: To understand the epidemiologic features of the rabies in Xishuang banna prefecture of Yunnan province, China in 2008-2017 and the viral molecular-evolution characteristics. Methods: The data of rabies case questionnaire were collected. The brain tissue samples from mad dogs, suspicious sick dogs and human brain tissue, saliva and cerebrospinal fluid samples from rabies patients were collected in Xishuangbanna. Coding region of nucleoprotein and glycoprotein genes were amplified by RT-PCR and sequenced. Homology and phylogenetic analysis were performed using the relevant bioinformatics software. Results: A total of 62 cases of human rabies were occurred in 28 districts of the 3 counties, Xishuangbanna prefecture in 2008-2017. Of them, 37 cases in Jinghong county, 15 in Menghai county and 10 in Mengla county. In which 48 cases were bitten by domestic dogs (77.42%), 11 cases were bitten by wild dogs (17.74%). Rabies case was occurred every year in the past decade. The seasonal incidence was not obvious. The majority of patients were aged from 30 to 59 years-old, with the youngest 1 year-old and the eldest 91 year-old. The male to female ratio was 1.70∶1, most cases were farmers. The nucleotide sequences of nucleoprotein gene of 9 virus strains (7 from Jinghong, 1 from Menghai and 1 from Mengla) were obtained from the samples of dogs and patients. Homology and phylogenetic analyses indicated that the 5 strains belonged to clade China-Ⅰ, 3 clade China-Ⅱ and 1 clade China-Ⅵ. The nucleotide sequences of glycoprotein gene of 5 virus strains (3 from Jinghong, 1 from Menghai and 1 from Mengla) were obtained from these positive samples, and all were clade China-Ⅰ, it is same with nucleoprotein genes analysis result from these 5 virus strains. These China-Ⅰ and China-Ⅱ strains from Xishuangbanna have a closer genetic relationship with same clade strains isolated from Pu’er and other prefectures of Yunnan province as well as Sichuan, Guizhou and Guangxi. The China-Ⅵ strain from Xishuangbanna share high homology and genetic relationship with China-Ⅵ strains isolated from southwestern Yunnan and neighbouring countries such as Myanmar, Laos and Vietnam in recent years. Conclusions In Xishuangbanna, rabies mainly occurred in rural area and domestic dog was the main source of transmission. These RABV clades China-Ⅰ, China-Ⅱ and China-Ⅵ were found in this region and the China-Ⅰ was principal clade. The transmission source of China-Ⅰ and China-Ⅱ were from adjacent areas in the province and China-Ⅵ was from Myanmar and Laos.

BACKGROUND: Oscillatory positive expiratory pressure (OPEP) training is a kind of breathing exercise with Acapella. The clinical value of OPEP has been widely discussed in chronic obstructive pulmonary disease, bronchiectasis as well as pulmonary cyst. However, few studies have explored the application of OPEP in surgery lung cancer patients underwent lobectomy. Thus, the aim of this study is to explore the impact of the application of OPEP device (acapella) in lung cancer patients undergoing video-assisted thorascopic surgery (VATS). METHODS: Sixty-nine patients receiving VATS lobectomy in Department of Thoracic Surgery, West China Hospital, Sichuan University from September 15, 2017 to January 15, 2018 were randomly divided into the acapella group (AG) or the control group (CG). The patients in the AG received oscillating positive expiratory pressure training and the CG underwent standard perioperative treatment. The differences of morbidity, pulmonary function, quality of life were compared between the two groups. RESULTS: Thirty-five patients were assigned to the AG and thirty-four patients were assigned to the CG. The incidences of postoperative pulmonary complications (PPCs) and atelectasis (2.9%, 0.0%) in the AG were significantly lower than that in the CG (20.6%, 14.7%)(P=0.03, P=0.03). The duration of total hospital stay and postoperative hospital stay in the AG (10.86±5.64, 5.09±4.55) d were significantly shorter than that in the CG (10.86±5.64, 5.09±4.55) d (P=0.01, P=0.01). The drug cost in the AG (4,413.60±1,772.35) ¥ were significantly lower than that in the CG (6,490.35±3,367.66) ¥ (P=0.01). The patients in the AG had better forced expiratory volume in the first second and peak expiratory flow [(1.50±0.32) L,(252.06±75.27) L/min] compared with the CG [(1.34±0.19) L, (216.94±49.72) L/min] (P=0.03, P=0.03) at discharge. CONCLUSIONS The application of OPEP device during the perioperative period was valuable in decreasing PPCs and enhancing recovery for lung cancer patients receiving VATS lobectomy.
Adult ; Aged ; Female ; Forced Expiratory Volume ; Humans ; Lung ; physiopathology ; surgery ; Lung Neoplasms ; physiopathology ; surgery ; Male ; Middle Aged ; Perioperative Period ; Pneumonectomy ; Quality of Life ; Thoracic Surgery, Video-Assisted

Background and objective Postoperative pulmonary complications (PPCs),especially postoperative pneumonia (POP),directly affect the rapid recovery of lung cancer patients after surgery.Peak expiratory flow (PEF) can reflect airway patency and cough efficiency.Moreover,cough impairment may lead to accumulation of pulmonary secretions which can increase the risk of PPCs.The aim of this study is to investigate the effect of preoperative PEF on PPCs in patients with lung cancer.Methods Retrospective research was conducted on 433 lung cancer patients who underwent lobectomy at the West China Hospital of Sichuan University from January 2014 to December 2015.The associations between preoperative PEF and PPCs were analyzed based on patients' basic characteristics and clinical data in hospital.Results Preoperative PEF value in PPCs group (280.93±88.99) L/min was significantly lower than that in non-PPCs group (358.38±93.69) L/min (P＜0.001).According to the binary logistics regression analysis,PEF and operative time were independent risk factors for PPCs.Further,ROC curve showed that PEF=320 L/min was the cut-off value for predicting the occurrence of PPCs (AUC=0.706,95％CI:0.661-0.749).The incidence of PPCs in PEF≤320 L/min group (26.6％) was significantly higher than that in PEF＞320 L/min group (9.4％)(P＜0.001).Conclusion Preoperative PEF and PPCs are correlated,and PEF maybe used as a predictor of PPCs.

Background and objective hTere are incresing lung cancer patients detected and diagnosed at the in-termediate stage when the pre-malignant or early lesions are amenable to resection and cure, owing to the progress of medical technology, the renewal of detection methods, the popularity of medical screening and the improvement of social health con-sciousness. hTe aim of this study is to investigate the risk factors of the occurrence of postoperative cardio-pulmonary compli-cations in stage I non-small cell lung cancer (NSCLC) patients, based on routine laboratory tests, basic characteristics, and in-traoperative variables in hospital.Methods hTe 421 patients atfer lobectomy in patients with stage I NSCLC at the West China Hospital of Sichuan University from January 2012 to December 2013 were included into the study and stratiifed into complica-tion group and non-complication group, according to whether to occur postoperative cardio-pulmonary complications atfer lobectomy in 30 days.Results Of them, 64 (15.2%) patients were ifnally identiifed and selected into the complication group, compared with 357 (84.8%) in non-complication group: pneumonia (8.8%, 37/421) was the primary complication, and other main complications included atelectasis (5.9%, 25/421), pleural effusion (≥middle) (5.0%, 21/421), persistent air leak (3.6%, 15/421); hTe operation time (P=0.007), amount of blood loss (P=0.034), preoperative chronic obstructive pulmonary disease (COPD) (P=0.027), white blood cell (WBC) count (P<0.001), neutrophil-lymphocyte ratio (NLR) (P<0.001) were signiif-cantly different between the two groups. According to the binary logistics regression analysis, preoperative COPD (OR=0.031, 95%CI: 0.012-0.078,P<0.001) and WBC count (OR=1.451, 95%CI: 1.212-1.736,P<0.001) were independent risk factors for postoperative cardio-pulmonary complications.Conclusion Among an array of clinical variables in hospital, operation time, preoperative white blood cell count, preoperative COPD, may be the independent risk factors of the occurrence of postopera-tive cardio-pulmonary complications.

Objective To investigate the clinical effect of vagus nerve preserving pericardial devascularization plus subtotal splenectomy in treating portal hypertension with a history of variceal bleeding.Methods The clinical data of 33 cases of portal hypertension with variceal hemorrhage treated with vagus nerve preserving selective pericardial devascularization plus subtotal splenectomy from April 2004 to December 2013 (study group) were compared with that of 34 cases treated with pericardial devascularization plus splenectomy (control group).Results There was no mortality in two groups.The postoperative gastric drainage during the first 72 h were(1 525 ±30) ml in the study group and (2 130 ±40) ml in control group(P ＜0.05).Portal vein thrombosis developed in one case in the study group and 15 cases in the control group(P ＜ 0.05).Postoperative 3-year recurrent gastroesophageal varices hemorrhage was 15％ in the study group and 25％ in the control group (P ＜ 0.05).Postoperative 5-year variceal hemorrhage recurrence rate were 28％ in the study group and 30％ in the control group (P ＞ 0.05).Conclusions Maitaining vagus nerve selective pericardial devascularization plus subtotal splenectomy is of less postoperative complication and lower portal vein thrombosis rate and better patients' survival compared with pericardial devascularizatim plus total splenectomy.

The monoamine oxidase mutant A-1 (F210V/L213C) from Aspergillus niger showed some catalytic activity on mexiletine. To futher improve its activity, the mutant was subjected to directed evolution with MegaWHOP PCR (Megaprimer PCR of Whole Plasmid) and selection employing a high-throughput agar plate-based colorimetric screen. This approach led to the identification of a mutant ep-1, which specific activity was 189% of that for A-1. The ep-1 also showed significantly improved enantioselectivity, with the E value increased from 101 to 282; its kinetic k(cat)/K(m) value increased from 0.001 51 mmol/(L x s) to 0.002 89 mmol/(L x s), suggesting that catalytic efficiency of ep-1 had been improved. The mutant showed obviously higher specific activities on 7 of all tested 11 amines substrates, and the others were comparable. Sequence analysis revealed that there was a new mutation T162A on ep-1. The molecular dynamics simulation indicated that T162A may affect the secondary structure of the substrate channel and expand the binding pocket.
Aspergillus niger ; enzymology ; Catalysis ; Kinetics ; Monoamine Oxidase ; genetics ; metabolism ; Mutation ; Polymerase Chain Reaction ; Protein Engineering ; Protein Structure, Secondary ; Substrate Specificity

Objective The current study aimed to evaluate whether the induction of macrophage inflammatory cytokines by Ox-LDL is related to the expression of ABCA1 pathway. Methods After THP1/PMA macrophages were transfected with ABCA1 antisense oligonucleotides (100nmol/L) followed by treatment with Ox-LDL (30mg/L), the expressions of ABCA1, ICAM-1 and MCP-1 mRNA and protein were determined by real-time fluorescent quantitative RT-PCR, Western blot or ELISA. Results Ox-LDL induced expressions of ABCA1, ICAM-1, and MCP-1 at both mRNA and protein levels from THP1/PMA macrophages. Transfection with ABCA1 antisense oligonucleotides reduced ABCA1 mRNA levels after 3 and 6 hours and protein levels after 12 and 24 hours. The expression of ICAM-1 and MCP-1 induced by Ox-LDL was also decreased after inhibition of ABCA1 protein expression by ABCA1 antisense oligonucleotide decreased. Conclusion The induction of macrophage inflammatory cytokines by Ox-LDL is partially dependent on expression of ABCA1. Our studies disclose new functions of ABCA1 in macrophages.

Human arrest defective 1 (hARD1) is an acetyltransferase; its physiological significance remains unclear. To explore the relationship between ARD1 protein and tumors, we detected the hARD1 protein in tumor tissues in vivo. We cloned hARD1 gene from Hela cell and construct recombinant plasmid pET28b-hARD1. The recombinant plasmid was transformed into E. coli BL21 (DE3)plysS. hARD1 protein was expressed by inducing with IPTG(1 mmol/L) and purified up to 95% through Ni2+ chelation affinity chromatography. We used the purified hARD1 protein as antigen immunized the Balb/c mice and obtained the hARD1 specific polyclonal antiserum. Through immunohistochemical analysis of different tumor tissues in vivo, we found that hARD1 expressed at high frequency in breast cancer, prostate cancer and lung cancer, especially, hARD1 expression frequency in breast cancer was up to 70%, which is higher than in the other tumors. These results indicate that the high expression level of hARD1 could be an indicator of the breast cancer. This new finding would be a foundation to further explore the relationship between breast tumor and hARD1.
Acetyltransferases ; analysis ; genetics ; immunology ; Amino Acid Sequence ; Animals ; Antibodies ; blood ; immunology ; Base Sequence ; Biomarkers, Tumor ; Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cloning, Molecular ; Escherichia coli ; genetics ; metabolism ; Female ; Humans ; Immune Sera ; biosynthesis ; Immunization ; Immunohistochemistry ; Lung Neoplasms ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; N-Terminal Acetyltransferase A ; N-Terminal Acetyltransferase E ; Prostatic Neoplasms ; metabolism ; pathology ; Recombinant Proteins ; biosynthesis ; genetics ; immunology