Objective:To investigate the effect of nicotinamide nucleotide adenylyltransferase 1(NMNAT1) liver-specific knockout on nicotinamide adenine dinucleotide(NAD + ) and overall metabolism in obese mice. Methods:NMNAT1 fl/fl mice were injected with AAV8-TBG-CRE through the tail vein to produce NMNAT1 liver-specific knockout mice, which were fed with either chow diet or high-fat diet, and the body weight of the mice was measured weekly, followed by glucose tolerance test, insulin tolerance test, body composition analysis, metabolic cage test and related assays, and finally the mouse liver was taken for liquid chromatography-mass spectrometry to detect the changes of metabolites. The related metabolic pathways were analyzed by metabolic database enrichment. Results:There was no difference in body weight between NMNAT1 LKO mice and control mice, and the body composition measurement of mice by EchoMRI also showed no difference in fat mass and lean mass. Metabolic cage experiments showed that NMNAT1 LKO had no effect on oxygen consumption, carbon dioxide production, respiration exchange ratio, energy expenditure and other indexes in mice. The glucose tolerance test and insulin tolerance test showed that NMNAT1 LKO did not affect glucose tolerance and insulin sensitivity in mice. NMNAT1 LKO does not affect the content of triglycerides in the liver of obese mice. NAD + detection confirmed that NMNAT1 LKO reduced hepatic NAD + content of obese mice by approximately 50%, resulting in the increase and accumulation of the NMNAT1 substrates, i. e. nicotinamide mononucleotide(NMN) and nicotinic acid mononucleotide(NaMN). Conclusion:Liver-specific knockout of NMNAT1 significantly reduced the NAD + content and changed the NAD + metabolism in the liver of obese mice, but without altering the glucose, lipid or energy metabolism.

Objective:To investigate the effect of nicotinamide nucleotide adenylyltransferase 1(NMNAT1) liver-specific knockout on nicotinamide adenine dinucleotide(NAD + ) and overall metabolism in obese mice. Methods:NMNAT1 fl/fl mice were injected with AAV8-TBG-CRE through the tail vein to produce NMNAT1 liver-specific knockout mice, which were fed with either chow diet or high-fat diet, and the body weight of the mice was measured weekly, followed by glucose tolerance test, insulin tolerance test, body composition analysis, metabolic cage test and related assays, and finally the mouse liver was taken for liquid chromatography-mass spectrometry to detect the changes of metabolites. The related metabolic pathways were analyzed by metabolic database enrichment. Results:There was no difference in body weight between NMNAT1 LKO mice and control mice, and the body composition measurement of mice by EchoMRI also showed no difference in fat mass and lean mass. Metabolic cage experiments showed that NMNAT1 LKO had no effect on oxygen consumption, carbon dioxide production, respiration exchange ratio, energy expenditure and other indexes in mice. The glucose tolerance test and insulin tolerance test showed that NMNAT1 LKO did not affect glucose tolerance and insulin sensitivity in mice. NMNAT1 LKO does not affect the content of triglycerides in the liver of obese mice. NAD + detection confirmed that NMNAT1 LKO reduced hepatic NAD + content of obese mice by approximately 50%, resulting in the increase and accumulation of the NMNAT1 substrates, i. e. nicotinamide mononucleotide(NMN) and nicotinic acid mononucleotide(NaMN). Conclusion:Liver-specific knockout of NMNAT1 significantly reduced the NAD + content and changed the NAD + metabolism in the liver of obese mice, but without altering the glucose, lipid or energy metabolism.

Objective:To compare the results of invasive prenatal diagnosis and preimplantation genetic testing (PGT) and explore the underlying mechanism.Methods:Clinical data of pregnant women undergoing PGT and invasive prenatal diagnosis at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2022 were collected. The results of PGT and invasive prenatal diagnosis were compared, and the outcomes of pregnancies were followed up. This study has been approved by the Medical Ethics Committee of the the Sixth Affiliated Hospital of Sun Yat-sen University (No. 2022SLYEC-491).Results:A total of 172 couples were included in this study, and 26 non-targeted variants were discovered upon prenatal diagnosis, including 10 cases (38.5%) by chromosomal karyotyping, 15 (57.7%) by chromosomal microarray analysis (CMA), and 1 (3.8%) by whole exome sequencing. The 10 karyotypic anomalies had included 6 chromosomal polymorphisms, 2 chromosomal mosaicisms, 1 paternally derived translocation, and 1 missed maternal chromosomal inversion. CMA has identified 15 copy number variations (CNVs), which included 11 microdeletions and microduplications, 3 loss of heterozygosity, and 1 low-level mosaicism of paternal uniparental disomy. One CNV was classified as pathogenic, and another one was likely pathogenic, whilst the remaining 13 were classified as variants of uncertain significance. Therefore, 8.7% of CNVs was detected by invasive prenatal diagnosis after PGT. 92.3% (24/26) of the non-targeted variants have been due to technological limitations of next-generation sequencing (NGS).Conclusion:Invasive prenatal diagnosis after PGT can detect non-targeted variants, which may further reduce the incidence of birth defects.

Objective:To explore the risk factors associated with a three-month prognosis in patients with aortic acute cerebral infarction.Methods:A prospective study was conducted on 191 patients with aorthropathic acute cerebral infarction included in the Department of Neurology from June 2018 to December 2019, and the patients were divided into good prognosis group (153 cases) and poor prognosis group (38 cases) according to the MRS score of the patient's 3-month prognosis, and the general data, past medical history and blood pressure variability evaluation index (BPV) between the two groups were correlated analysis. The t-test was used to compare the measurement data with normal distribution, the χ 2 test was used to compare the counting data, and the Logistic regression analysis was used to analyze the risk factors. Results:The proportion of patients with diabetes history in the poor prognosis group (20.3% (31/153)), admission NIHSS score ((3.03±2.01) points), standard deviation (SD) ((12.06±4.46) mmHg) and coefficient of variation (CV) ((8.61±3.08)%) of systolic blood pressure at 24 h were lower than those in the good prognosis group (47.4% (18/38), (5.61±3.84) points, (14.75±3.46) mmHg, (10.41±2.18)%), the differences were statistically significant (the statistical values were χ 2=11.73, t=4.01, t=3.46, t=3.38; P values were 0.001, <0.001, 0.001, and 0.001, respectively). Because 24 h systolic blood pressure SD and 24 h systolic blood pressure CV had obvious collinearity, they were respectively included in the Logistic regression model. Taking diabetes history, NIHSS score and 24 h systolic blood pressure SD into the variables, the multivariate Logistic regression results of adverse prognostic risk factors in patients with acute cerebral infarction showed that the history of diabetes mellitus ( OR=3.649, 95% CI: 1.545-8.648, P=0.003), NIHSS score ( OR=1.472, 95% CI: 1.247-1.725, P<0.001) and 24 h systolic blood pressure SD ( OR=1.201, 95% CI: 1.085-1.336, P<0.001). Taking diabetes history, NIHSS score and 24 h systolic blood pressure CV into consideration, multivariate Logistic regression results of adverse prognostic risk factors in patients with acute cerebral infarction showed that the history of diabetes mellitus ( OR=4.695, 95% CI: 1.873-11.766, P=0.001), admission NIHSS score ( OR=1.922, 95% CI: 1.513-2.441, P<0.001) and 24 h systolic blood pressure CV ( OR=1.220, 95% CI: 1.045-1.425, P=0.012). All are independent risk factors influencing the prognosis of patients. Conclusion:The effect of 24 h systolic blood pressure SD and 24 h systolic blood pressure CV on patient prognosis was more valuable in clinical prediction, and the prognosis value of controlling blood glucose levels in patients with diabetes was higher in patients with cerebral infarction.

Objective: To investigate the effect of holistic nursing on the rehabilitation of patients with occupational pneumoconiosis complicated with acute exacerbation of chronic obstructive pulmonary disease (COPD) . Methods: In October 2018, from September 2016 to September 2018, 120 pneumoconiosis patients with copd admitted to the occupational disease department of Laigang Hospital attached to Affilated to Shandong First Medical University were selected, according to random number table method is divided into experimental group (60 cases) and control group (60 cases) in the control group given conventional nursing, the experimental group to implement the holistic nursing, before and after the intervention were compared of two groups of patients with disease recognition grade self-management behavior of related parameters of blood gas analysis and lung function changes. Results: Comparison of disease recognition score between the two groups, the experimental group was higher than the control group (P<0.05) . Comparison of scores of self-management behaviors such as diseases medical management, daily life management. Emotion management and so on between the two groups showed that the experimental group was higher than the control group (P<0.05) . Comparison of blood gas analysis indicators between the two groups showed that PaO₂ in the experimental group was higher than that in the control group (P<0.05) . Comparison of pulmonary function indicators between the two groups showed that FEV₁ and FEV₁/FVC in the experimental group were higher than that in the control group (P<0.05) . Conclusion Holistic nursing can effectively improve the cognition of pneumoconiosis patients with copd in the acute exacerbation stage, regulate their self-management behavior, improve arterial oxygen content, improve pulmonary ventilation function. and promote the recovery of the disease.

Objective To establish a test of autoantibody-panel for the diagnosis of autoimmune cerebellitis (AC) and determine the prevalence of AC in patients with cerebellar ataxia of unknown etiology.Methods Autoantibody screening tests with indirect immunofluorescence were performed in serum and cerebrospinal fluid (CSF) samples of 400 previously'idiopathic'Chinese patients with cerebral ataxia (inpatients and outpatients in Peking Union Medical College Hospital or referred from hospitals of Beijing Encephalitis Group from 2016 to 2018).Immunotherapy was given to autoantibody positive patients and the effectiveness of immunotherapy was assessed.Detailed AC autoantibodies panel included anti-glutamate decarboxylase 65 (GAD65) antibody,anti-Tr (delta notch-like epidermal growth factor-related receptor (DNER)) antibody,anti-zinc finger protein 4 (ZIC4) antibody,anti-inositol 1,4,5-trisphosphate receptor 1 (ITPR1) antibody,anti-homer protein homolog 3 (Homer 3) antibody,anti-neurochondrin (NCDN) antibody,anti-carbonic anhydrase-related protein (CARP) antibody and anti-Purkinje cell antibody 2 (PCA2) antibody.Results Eight out of 400 (2％) ataxia patients were positive for this AC panel tests,of whom two were positive for anti-GAD65 antibody,two for anti-Tr antibody,one for anti-PCA2 antibody,one for anti-Homer 3 antibody and two were positive for serum anti-NCDN antibody.Autoantibodies against ZIC4,ITPR1 and CARP were not detected in this cohort.Two of the eight ataxia patients also presented with limbic encephalitis,and only one anti-GAD antibody patient was screened with underlying small cell lung carcinoma (SCLC).All the eight patients received immunotherapy and four experienced partial response.Conclusions Autoimmune cerebellitis is the cause of acquired cerebellar ataxia.Tests of autoantibodies associated with AC have diagnostic value for paraneoplastic and non-paraneoplastic cerebellar ataxia.Immunotherapy may yield partial response in patients with AC.

BACKGROUND:Acel ular dermal matrix has good biocompatibility and absorbability and exhibits superiority in the guided bone regeneration. OBJECTIVE:To compare the histological changes and osteogenic effects in bone defects after guided bone regeneration with acel ular dermal matrix and Bio-Gide membrane. METHODS:Mandibular second, third and fourth premolars and the first molars bilateral y were extracted from 12 beagle dogs. Three months later, four three-wal bone defect models in the mandible of each dog were made, and randomized into acel ular dermal matrix plus bone graft group (acel ular dermal matrix group), Bio-Gide plus bone graft group (Bio-Gide group), bone graft group, and blank control group (no treatment). In the former two groups, acel ular dermal matrix and Bio-Gide were used to cover the bone grafts, respectively. RESULTS AND CONCLUSION:After surgery, al the beagle dogs recovered wel . Al the groups except the control group showed dramatical improvement in histological changes and percentage of new bone area, and this improvement was more significant in the Bio-Gide and acel ular dermal matrix groups. Moreover, there was no significant difference between the Bio-Gide and acel ular dermal matrix groups. Therefore, the acel ular dermal matrix can be a candidate for bone repair instead of Bio-Gide membrane in the clinical practice.

Objective To observe the changes of pulmonary function parameters in healthy middle-aged and elderly people in Shanghai.Methods A total of 298 subjects aged 45 years and over with normal pulmonary function and no smoking history were selected among subjects who underwent routine physical examination from Jun 2009 to Sep 2011.The subjects were divided into three groups:45-59 years,60-69 years,and ≥70 years.The tested pulmonary function included 13 parameters:vital capacity (VC),residual volume (RV),functional residual capacity (FRC),total lung capacity (TLC),RV/TLC,forced vital capacity (FVC),forced expiratory volume in one second (FEV1),FEV1/FVC,peak expiratory flow (PEF),forced expiratory flow at 25 ％ of FVC exhaled (FEF25),forced expiratory flow at 50％ of FVC exhaled (FEF50),diffusion capacity of the lung for carbon monoxide (DLCO),and specific diffusion capacity of CO (KCO).Results Compared with the young adults,7 pulmonary function parameters including VC,FVC,FEV1,PEF,TLC,DLCO and KCO were declined significantly in healthy middle aged and elderly people Compared with the young adults,pulmonary function parameters including RV and RV/TLC were increased [male (1.9 ±0.4)Lvs.(1.6±0.3)L,(34.7±4.9)％ vs.(26.4±4.3)％,P＜0.01;female (1.5±0.3)L vs.(1.3±0.3)L,(36.1±5.3)％ vs.(30.3±5.5)％,P＜0.01].Although RVincreased with aging in middle-aged and elderly people,but there was no statistical significance (P＞0.05).FRC didn't change obviously.FEV1/FVC was lower in old people than in young people[male (80.7±4.3)％ vs.(84.2±5.6)％,P ＜0.01;female (82.5± 5.5) ％ vs.(86.4±4.8)％,P＜0.01],but the difference between 3 groups of middle-aged and the elderly was not significant.The FEV1/FVC of men and women aged 70 and more were (80.2±4.5)％ and (81.8±5.6)％,respectively.Conclusions Both ventilation function and diffusion function of healthy elderly people are decreased with ageing,RV is increased and FRC is steady,and the declining tendency of FEV1/FVC obviously slows down with aging in middle aged and elderly people.

Objective To study the changes of intestinal epithelial barrier function in rats with aging.Methods SD rats were divided into 3 groups:3-month-old group (group A),12-month-old group (group B) and 24-month-old group (group C,established by D-galactose injection with the dose of 0.125 g· kg-1 · d-1subcultaneously for 6 weeks) (n=10,each).The terminal ileum was obtained to make microtome section,and the morphology of small intestine mucous membrane,trophonema altitude and thickness were observed under light microscope.Occludin and ZO-1 protein expressions in terminal ileum mucous membrane were detected by immunohistochemistry.The expressions of Occludin and ZO 1 mRNA were determined by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).Results The small intestinal mucosa thickness and villus height were lower in group C and B than in group A [thickness:(87.6± 6.32) μm,(131.8± 5.22) μm vs.(162.9±7.28) μm; villus height:(56.4±5.38) μm,(76.7±5.40) μm vs.(108.1±6.42) μm;both P＜0.05].The small intestinal mucosa thickness and villus height was lower in group C than in group B (both P＜0.05).Occludin and ZO-1 protein expressions in small intestine tissue were reduced in group C and B as compared with group A [Occludin protein:(2.23±0.60)％,(4.21±0.61)％ vs.(12.31±0.94)％; ZO-1 protein:(2.03±0.54)％,(4.02±0.65) ％ vs.(12.21±0.81)％ ; both P＜0.05],and Occludin and ZO-1 protein expressions were less in group C than in group B (both P＜0.05).The levels of Occludin and ZO-1 mRNA in small intestine tissue were reduced in group C and B as compared with group A [Occludin:(0.20±0.03),(0.38±0.02) vs.(0.66±0.03) ; ZO-1:(0.18±0.03),(0.37±0.02) vs.(0.63±0.03); both P＜0.05],and Occludin and ZO-1 mRNA expressions were less in group C than in group B (both P ＜ 0.05).Conclusions The small intestinal mucosa thickness and villus height are reduced,the levels of Occludin and ZO-1 expressions are significantly decreased in small intestinal mucosa,and the intestinal barrier function is impaired with rat aging.

OBJECTIVETo investigate the effects of lactulose on intestinal bacterial overgrowth (IBO), bacterial translocation (BT), intestinal transit and permeability in cirrhotic rats.

METHODSBT in all animals was assessed by bacterial culture of mesenteric lymph node (MLN), liver and spleen, and IBO was assessed by a jejunal bacterial count of the specific organism. Intestinal permeability was determined by the 24-hour urinary (99m)Tc-diethylenetriamine pentaacetatic acid ((99m)Tc-DTPA) excretion, and intestinal transit was determined by measuring the distribution of (51)Cr in the intestine.

RESULTSBT and IBO were found in 48% and 80% of the cirrhotic rats, respectively, while not in the control rats. Cirrhotic rats with IBO had significantly higher levels of intestinal endotoxin higher rates of bacterial translocation, shorter intestinal transit time and higher intestinal permeability than those without IBO. It was also found that BT were closely associated with IBO and injury of the intestinal barrier. Compared with the placebo group, lactulose-treated rats had lower rates of BT and IBO, which were closely associated with increased intestinal transit and improved intestinal permeability by lactulose.

CONCLUSIONSOur study indicate that endotoxin and bacterial translocation in cirrhotic rats may attribute to IBO and increased intestinal permeability. Lactulose that accelerates intestinal transit and improves intestinal permeability might be helpful in preventing intestinal bacterial and endotoxin translocation.

Animals ; Bacterial Translocation ; drug effects ; Endotoxins ; analysis ; Gastrointestinal Agents ; pharmacology ; Intestines ; metabolism ; microbiology ; Lactulose ; pharmacology ; Liver Cirrhosis, Experimental ; metabolism ; microbiology ; Male ; Rats ; Rats, Sprague-Dawley