Adult ; Chlorides ; toxicity ; Female ; Humans ; Inhalation Exposure ; Lung ; diagnostic imaging ; Lung Injury ; diagnostic imaging ; Male ; Middle Aged ; Phosphorus Compounds ; toxicity ; Radiography ; Young Adult

Adult ; Bone and Bones ; diagnostic imaging ; Chronic Disease ; Humans ; Male ; Mandible ; diagnostic imaging ; Middle Aged ; Occupational Exposure ; Phosphorus ; poisoning ; Radiography

Transketolase (TK), a thiamine diphosphate (ThDP)-dependent enzyme, catalyzes several key reactions of non-oxidative branch of pentose phosphate pathway. TK is a homodimer with two active sites that locate at the interface between the contacting monomers. Both ThDP and bivalent cations are strictly needed for TK activation, just like that for all ThDP-dependent enzymes. TK exists in all organisms that have been investigated. Up to now, one TK gene (TKT) and two transketolase-like genes (TKTL1 and TKTL2) have been identified in human genome. TKTL1 is reported to play a pivotal role in carcinogenesis and may have important implications in the nutrition and future treatment of patients with cancer. Researchers have found TK variants and reduced activities of TK enzyme in patients with neurodegenerative diseases, diabetes, and cancer. Recent studies indicated TK as a novel role in the prevention and therapy of these diseases.
Animals ; Humans ; Models, Molecular ; Neurodegenerative Diseases ; enzymology ; Research ; trends ; Transketolase ; chemistry ; genetics ; metabolism

Objective To investigate the influence of thiamine deficiency(TD)at early pre- pathological lesion stage on cognitive function and the correlation between cognitive dysfunction and hippocampal neurogenesis.Methods TD mouse model was prepared by feeding a thiamine-depleted diet. Learning and memory functions of TD mice were tested with Y-maze.Hippoeampal neurogenesis was studied with bromodeoxyuridine(BrdU),proliferative cell nuclear antigen(PCNA),and Doublecortin(Dcx) immunohistochemical staining on the 7th(TD7),9th,14th and TD25th day.Results TD9 mice without pathological impairment and cholinergic nerve degeneration needed more times of training(22.3?2.2)in the learning test of Y maze compared with the controls(13.5?3.5).Correspondingly,the numbers of BrdU-positive ceils and the immunoreactivity of Dcx decreased significantly in the TD9 mice(19.8?0.4, 1537.2?50.2 vs 23.9?0.3,2688.9?127.9 pixels/mm~2).Thiamine re-administration reversed the declined hippocampal neurogenesis:the number of BrdU-positive cells was 23.6?1.9 and Dcx immunoreactivity was 2052.3?269.6 pixels/mm~2:the impaired learning ability was simultaneously restored,with the number of total training trial being 16.8?0.5.Conclusion The decreased hippocampal neurogenesis contributes to retarded learning ability at early pre-pathological lesion stage of TD.

Objective To explore a better method for treatment atrophic rhinitis.Methods 56 patients with atrophic rhinitis(96 lateral)were treated by nasal submucou pediculated bone-suberiosteal muscle flap extracted from anterior wall of sinus maxillaries.Results All patients were followed 2 to 10 years,total effective rate was 100 %, with 49 cases(87.5 %)showing prominent effect.Conclusion The grafted flap cannot be assimilated,felled off and necrosis,because the flap has rich blood supply.This methods has obvious short-term effective and stable long-term effective.No complications were found.

Aim To evaluate the effect of ZST93 on the proliferation in human chronic myeloid leukemia(CML)cells(K562)and explore the possible mechanism.Methods MTT assay, cell growth curve and inverted microscope were used to investigate the effect of ZST93 on proliferation of K562 cells.Cell transfection and Western blot were performed to detect the autophagy, while PI staining, Annexin V-FITC/PI and flow cytometry were conducted to determine cell apoptosis and its anticancer mechanism.Results ZST93 could significantly inhibit the proliferation of K562(IC50=2.59 μmol·L-1)and induce cell cycle arrest at G1-phase in a dose- and time-dependent manner.Also, through leading to accumulation of GFP-LC3, transition into LC3- II from LC3- 1 , and decrease of p62 expression, ZST93 induced autophagy initiation and autophagic flux.Furthermore, ZST93 induced extrinsic apoptotic pathway by activating caspase-8, and further promoted the cleavage of apoptosis related proteins including caspase-9, caspase-3 and PAR P.Moreover, Z-DEYD-FMK, the specific inhibitor of caspase-3 , could dramatically reduce the apoptosis induced by ZST93.Taken together, ZST93 could effec tively inhibit CML cells, arrest eell cycle at G,-phase, induce cell apoptosis anrl initiate autophagy.Conclusions The potential mechanism may he related to the regulation of autophagy intiation/caspase-8/caspase-3 signaling pathway, which provides a new idea and theoretical basis for the treatment of CML.

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications

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

Background: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. Methods: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital, Wuhan, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. Results: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8–99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6–87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. Conclusion: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
Adult ; Aged ; Betacoronavirus ; genetics ; isolation & purification ; Coronavirus Infections ; diagnostic imaging ; therapy ; virology ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnostic imaging ; therapy ; virology ; Tomography, X-Ray ; Treatment Outcome