Objective: To investigate the functional changes of key gut microbiota (GM) that produce lipopolysaccharide (LPS) in atrial fibrillation (AF) patients and to explore their potential role in the pathogenesis of AF. Methods: This was a prospective cross-sectional study. Patients with AF admitted to Beijing Chaoyang Hospital of Capital Medical University were enrolled from March 2016 to December 2018. Subjects with matched genetic backgrounds undergoing physical examination during the same period were selected as controls. Clinical baseline data and fecal samples were collected. Bacterial DNA was extracted and metagenomic sequencing was performed by using Illumina Novaseq. Based on metagenomic data, the relative abundances of KEGG Orthology (KO), enzymatic genes and species that harbored enzymatic genes were acquired. The key features were selected via the least absolute shrinkage and selection operator (LASSO) analysis. The role of GM-derived LPS biosynthetic feature in the development of AF was assessed by receiver operating characteristic (ROC) curve, partial least squares structural equation modeling (PLS-SEM) and logistic regression analysis. Results: Fifty nonvalvular AF patients (mean age: 66.0 (57.0, 71.3), 32 males(64%)) were enrolled as AF group. Fifty individuals (mean age 55.0 (50.5, 57.5), 41 males(82%)) were recruited as controls. Compared with the controls, AF patients showed a marked difference in the GM genes underlying LPS-biosynthesis, including 20 potential LPS-synthesis KO, 7 LPS-biosynthesis enzymatic genes and 89 species that were assigned as taxa harbored nine LPS-enzymatic genes. LASSO regression analysis showed that 5 KO, 3 enzymatic genes and 9 species could be selected to construct the KO, enzyme and species scoring system. Genes enriched in AF group included 2 KO (K02851 and K00972), 3 enzymatic genes (LpxH, LpxC and LpxK) and 7 species (Intestinibacter bartlettii、Ruminococcus sp. JC304、Coprococcus catus、uncultured Eubacterium sp.、Eubacterium sp. CAG:251、Anaerostipes hadrus、Dorea longicatena). ROC curve analysis revealed the predictive capacity of differential GM-derived LPS signatures to distinguish AF patients in terms of above KO, enzymatic and species scores: area under curve (AUC)=0.957, 95%CI: 0.918-0.995, AUC=0.940, 95%CI 0.889-0.991, AUC=0.972, 95%CI 0.948-0.997. PLS-SEM showed that changes in lipopolysaccharide-producing bacteria could be involved in the pathogenesis of AF. The key KO mediated 35.17% of the total effect of key bacteria on AF. After incorporating the clinical factors of AF, the KO score was positively associated with the significantly increased risk of AF (OR<0.001, 95%CI:<0.001-0.021, P<0.001). Conclusion: Microbes involved in LPS synthesis are enriched in the gut of AF patients, accompanied with up-regulated LPS synthesis function by encoding the LPS-enzymatic biosynthesis gene.
Aged ; Atrial Fibrillation/complications* ; Cross-Sectional Studies ; Gastrointestinal Microbiome ; Humans ; Lipopolysaccharides ; Male ; Middle Aged ; Prospective Studies

Objective: To analyze the dynamic changes and influencing factors of HIV-1 DNA load in HIV-1 infected individuals under antiretroviral therapy (ART) in Dehong Dai and Jingpo autonomous prefecture, Yunnan province, and provide information support for the clinical use of HIV-1 DNA quantitative detection. Methods: The HIV infection cases in recent infection cohort from Dehong Center for Disease Control and Prevention during 2009-2018 were selected as study subjects. The dynamic curve of HIV-1 DNA load varrying with time was generated and logistic regression analysis was conducted to identify the risk factors for HIV-1 load in the recent follow up after ART and statistical analysis was performed by using SPSS 17.0. Results: Among the 113 HIV infection cases detected from the recent infection cohort, the recent HIV infection rate were 49.6%(56/113) males, sexual transmission cases and drug injection transmission cases accounted for 53.1% (60/113), 80.5% (91/113) and 19.5% (22/113), respectively. The dynamic changes curve showed that HIV-1 DNA load was relatively high (>800 copies /10⁶ PBMCs) before ART, and droped rapidly (<400 copies /10⁶ PBMCs) after ART for 1 year. However, HIV-1 DNA load decreased insignificantly from the second year of ART, and remained to be 269 copies/10⁶ PBMCs after ART for 6 years. Univariable logistic regression analysis indicated that OR (95%CI) of CD8, CD4/CD8 and HIV-1 DNA load were 1.00 (1.00-1.00), 0.30 (0.09-1.05) and 1.01 (1.00-1.01), respectively. Multivariable logistic regression analysis showed that OR value of HIV-1 DNA load base was 1.00 (1.00-1.01). Conclusions: HIV-1 DNA load decreased significantly in the first year of ART, then remained stable for years. HIV-1 DNA load base was the key factor associated with the decrease of HIV-1 DNA load, the lower the HIV-1 DNA load base, the lower HIV-1 DNA load. Therefore, earlier ART can contribute to the decrease of HIV-1 DNA load.
China/epidemiology* ; DNA/therapeutic use* ; HIV Infections/drug therapy* ; HIV Seropositivity ; HIV-1/genetics* ; Humans ; Male ; Viral Load

ObjectiveThe aim of this study is to investigate the proportion of DN2 cell and the correlation between the expression of calcium ion release activated calcium ion channel（ Ca²⁺ release-activated Ca²⁺， CRAC） protein in DN2 cells and the clinical activity of lupus nephritis （LN）. MethodsFlow cytometry was used to detect the proportion of DN2 cells in healthy controls （HC， n=15）， LN （HC， n=30）， rheumatoid arthritis （RA， n=15） and primary Sjogren syndrome （pSS， n=15） patients and the expression of SOCE protein Orai1 in DN2 cells. One-way ANOVA was used to analyze the differences among the four groups. The correlation between Orai1 expression and LN disease activity was analyzed by Pearson correlation analysis. ResultsThere was a statistically significant difference in the proportion of DN2 cells in peripheral blood among the four groups （F= 9.315， P＜0.000 1）. The proportion of DN2 cells in the peripheral blood of patients with LN was significantly higher than that of HC， RA and pSS ［（2.60±2.20）% vs.（0.68±0.56）% vs.（0.69±0.45）% vs.（1.04±0.72）%］ and was correlated with 24-hour urinary protein excretion （r=0.599 9， P=0.000 5）. There was a statistically significant difference in the Orai1 expression in DN2 cells among the four groups （F= 7.935， P＜0.000 1）. The Orai1 expression in DN2 cells of LN was significantly higher than that of HC， RA and pSS （2.30±1.50 vs. 0.86±0.39 vs. 1.34±0.57 vs. 1.13±0.64）. Orai1 expression in DN2 cells was positively correlated with SLEDAI （r=0.56， P＜0.005）， blood anti-dsDNA antibody level （r=0.43， P＜0.05） and 24-hour urinary protein excretion （r=0.44， P＜0.05）， and negatively correlated with complement C3 （r=-0.39， P＜0.05）. ConclusionsThe proportion of DN2 cells and the expression of Orai1 increases in patients with LN and is correlated with disease activity. SOCE of DN2 cells may be a potential therapeutic target for LN.

Objective To understand the prevalence and epidemiological characteristics of hepatitis C virus (HCV) co-infection among newly reported HIV-infected patients from 2016 to 2017 in Dehong Prefecture of Yunnan Province. Methods A cross-sectional survey was conducted to detect HCV antibodies in 2 196 newly reported HIV-infected persons in Dehong Prefecture, Yunnan Province, from 2016 to 2017. Results A total of 694 cases(31.6%) were detected antibodies against HCV during HIV-infected persents. The prevalence of HCV co-infection among newly reported HIV-infected patients in Chinese and Burmese was 14.4% (112/780) and 41.1% (582/1 416), respectively. Moreover, the prevalence of HCV co-infection was higher in male, ethnic minorities such as Dai and Jingpo minority, primary school and below and farmers in both Chinese and Burmese. Multivariate Logistic regression model showed that HCV infection was associated with male, Dai minority, HIV infection by injecting drug and famers among Chinese and Burmese reported HIV-infected patients. Conclusions The prevalence of HCV co-infection was high among newly reported in Dehong Prefecture of Yunnan Province. Meanwhile, the epidemiological characteristics of HIV/HCV co-infections in Chinese and Burmese are different, thus different prevention and control measures are needed for patients of different nationalities.

To make clear of the absorbed components of Tianzhusan (TZS) and its possible mechanism in preventing vascular dementia (VD), the rats' models of VD were prepared by a permanent ligation of the bilateral common carotid arteries. After 60 days, rats were administrated with TZS for 0.1 g x kg(-1), and the volume is 0.02 mL x g(-1). After 3 days, the medicated serum was prepared and detected by UPLC, and then we predicted the possible chemical structure of the absorbed components of TZS. According to the absorbed components, the potential targets of TZS were found by ligand profiling of Discovery Studio 3.5. All of these target genes were submitted to DAVID onine for gene set enrichment analysis (GSEA). The 5 absorbed components of TZS have been predicted, and four of them have been identified as parishin B, parishin C, parishin, pennogenin-3-O-alpha-L-rhamnopyranosy-(1-->2)-beta-D-glucoside. Through reverse finding targets, we got 861 pharmacophore models and 9 pathways from KEGG, BIOCARTA after document verification. These results showed that the efficacy mechanism of TZS on VD perhaps were be related with these absorbed components and pathways. If the traditional herbs could be proved effective by efficacy tests, the serum pharmacochemistry, computer-aided drug design, system biology and other technologies can be used in the next experiments, which will be beneficial to fast discovery of material basis and mechanisms of traditional medicine coming form ethnic minorities.
Animals ; Dementia, Vascular ; prevention & control ; Drug Discovery ; Drugs, Chinese Herbal ; therapeutic use ; Gastrodia ; chemistry ; Male ; Medicine, Chinese Traditional ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Electrospray Ionization ; Trillium ; chemistry

BACKGROUNDLocal failure of nasopharyngeal carcinoma (NPC) after radiotherapy (RT) remains one of the major treatment failures. This study aimed to evaluate the clinical efficacy and complications of fractionated stereotactic radiotherapy (FSRT) with vagina carotica protection technique for local residual of NPC patients after the primary RT.

METHODSFrom August 2006 to August 2010, FSRT with vagina carotica protection technique was applied to 36 patients in our department, the patients aged between 13 and 76 years with a median of 41.3 years, 25 of them were male and 11 were female. According to 2002 Union for International Cancer Control (UICC) Staging System, the stages before primary radiotherapy were: IIa 2, IIb 5, III 18, IVa 7, IVb 4. In the first course of radiotherapy, 9 patients received conventional RT, 27 patients received intensity modulated radiotherapy (IMRT) and 20 out of the 36 patients received concurrent chemoradiotherapy. The total dose in the first course of RT was 69.96 - 76.90 Gy (median, 72.58 Gy). The intervals between the primary RT and FSRT ranged from 12 to 147 days (median, 39.8 days). Target volumes ranged from 1.46 to 32.98 cm(3) (median, 14.94 cm(3)). The total FSRT doses were 10.0 - 24.0 Gy (median, 16.5 Gy) with 2.0 - 5.0 Gy per fraction. The most common regimen was 15 Gy in 5 fractions of 3 Gy, the irradiation dose to vagina carotica was less than 2 Gy per fraction.

RESULTSThe median follow-up time was 34 months (range, 12 - 59 months). The 3-year local control rate was 100%; the 3-year overall survival rate was 94.4%; the 3-year disease-free survival rate was 77.8%. In this study, we had one case of cranial nerve injury, two cases of temporal lobe necrosis, and no nasopharyngeal massive hemorrhage was observed.

CONCLUSIONFSRT with vagina carotica protection technique is an effective and safe RT regimen for local residual of NPC with reduction of radiation-related neurovascular lesions.

Adolescent ; Adult ; Aged ; Carcinoma ; Dose Fractionation ; Female ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; radiotherapy ; Neoplasm Recurrence, Local ; prevention & control ; Radiotherapy Dosage ; Young Adult