Krüppel-like transcription factor 2 (KLF2) plays a key regulatory role in endothelial inflammation, thrombosis, angiogenesis and macrophage inflammation and polarization, and up-regulation of KLF2 expression has the potential to prevent and treatment atherosclerosis. In this study, trichostatin C (TSC) was obtained from the secondary metabolites of rice fermentation of Streptomyces sp. CPCC 203909 as a KLF2 up-regulator by using a high throughput screening model based on a KLF2 promoter luciferase reporter assay. TSC significantly inhibited the adhesion of tumor necrosis factor-α (TNFα) induced monocytes (THP-1) to human umbilical vein endothelial cells (HUVECs). Western blot results showed that TSC decreased TNFα induced the protein expression increase of vascular cell adhesion molecule-1 (VCAM-1), and thereby inhibited endothelial inflammation. The results of histone deacetylase (HDAC) overexpression and molecular docking experiments showed that TSC upregulated the expression of KLF2 by inhibiting subtypes of HDAC 4/5/7. In conclusion, this study suggests that TSC up-regulates the expression of KLF2 through inhibiting HDAC 4/5/7 and thus inhibits TNFα induced endothelial inflammation, and it has the potential to prevent and treat atherosclerosis.

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Background/Aims: Mean nocturnal baseline impedance (MNBI) is a new reflux metric for mucosal integrity. It remains unclear whether MNBI can help identify evidence against pathological reflux by the Lyon Consensus in patients with refractory gastroesophageal reflux disease (GERD) symptoms. Methods: Three hundred and forty-nine patients with refractory GERD symptoms enrolled in this study were subjected to high-resolution manometry, 24-hour multichannel intraluminal impedance-pH (MII-pH) monitoring, and endoscopy. Conventional indexes (ie, reflux events and acid exposure time) and the novel index (MNBI) of MII-pH monitoring were extracted and analyzed. The value of MNBI in diagnosing patients with evidence against pathologic reflux was evaluated by receiver-operating-characteristic analysis. Results: There were 102 (29.2%) patients with evidence against pathologic reflux, 149 (42.7%) with inconclusive or borderline evidence and 98 (28.1%) with conclusive evidence for pathologic reflux. The MNBI was significantly higher while the proportion of pathological MNBI was significantly lower in subjects with evidence against pathologic reflux than in patients with inconclusive or borderline evidence and in patients with conclusive evidence for pathologic reflux (2444.3 [1977.9-2997.4] vs 1992.8 [1615.5-2253.6] and vs 1772.3 [758.6-2161.3], both P < 0.001; 42.2% vs 79.7% and vs 80.0%, both P < 0.05). When identifying evidence against pathologic reflux in patients with refractory GERD symptoms, the MNBI yielded an area under the curve of 0.749 (P < 0.001) at a cutoff value of 1941.8 Ω. Conclusions The MNBI has a good diagnostic value for evidence against pathological reflux in patients with refractory GERD symptoms. For its simplicity and reproducibility, we believe that MNBI should be referred to in reports of impedance-pH tracings by physicians.

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

OBJECTIVE: To evaluate the effects of cardiopulmonary fitness on arteriosclerotic cardiovascular disease (ASCVD) events in patients with different risks of ASCVD. METHODS: This study enrolled 544 non ASCVD patients who underwent cardiopulmonary exercise testing in Peking University Third Hospital from September 2016 to April 2018. ASCVD overall risk assessment was conducted according to "Chinese Guidelines for the Prevention and Treatment of Adult Dyslipidemia". Peak oxygen uptake (VO₂peak), the classic indicator of cardiopulmonary fitness, was accurately determined by cardiopulmonary exercise testing in all the patients. All of the patients were followed up clinically. RESULTS: In the study, 506 patients completed the follow-up (250 lowrisk patients, 93 moderaterisk patients and 163 highrisk patients). The median follow-up period was 19 months (9-28 months), and 51 patients developed ASCVD events during the follow-up period, of whom, 33 cases developed myocardial infarction, unstable angina or coronary revascularization, and 18 cases ischemic stroke, transient ischemic attack or carotid vascular revascularization. The patients were divided into the ASCVD group (n=51) and the non ASCVD group (n=455) based on the presence or absence of ASCVD events. VO₂peak [16.3 (3.6) mL/(kg·min) vs. 19.1 (3.2) mL/(kg·min), P<0.001] in the ASCVD group were significantly lower than that in the non ASCVD group. Logistic regression analysis found VO₂peak [OR 0.893 (95%CI: 0.831-0.959), P=0.002] and ASCVD risk stratification [OR 1.428 (95%CI:1.028-1.878), P=0.031] were both independently associated with the occurrence of ASCVD events, which meant that every 1 mL/(kg·min) of increase in VO₂peak, the risk of ASCVD events was reduced by 11%. The patients were divided into low, moderate, and high VO₂peak according to the tertiles of their VO₂peak [14.4 mL/(kg·min), and 23.0 mL/(kg·min)]. Logistic regression analyses were performed using ASCVD events as a dependent variable in the patients with highrisk and low/moderate-risk of ASCVD respectively. In the patients with highrisk of ASCVD, the results suggested that the incidence of ASCVD events was significantly decreased in the patients with moderate VO2 peak [OR 0.210 (95%CI: 0.054-0.814), P=0.024] and high VO2 peak [OR 0.146 (95%CI:0.025-0.870), P=0.035], but no significant effect of VO2 peak elevation on the incidence of ASCVD events was found in the low/moderate-risk ASCVD patients. CONCLUSION High cardiopulmonary fitness can significantly reduce the occurrence of ASCVD events in patients with high-risk of ASCVD.
Adult ; Atherosclerosis ; Cardiovascular Diseases ; Humans ; Risk Assessment ; Stroke

Objective:To investigate and analyze the current situation, screening, clinical characteristics, prevention and treatment of bleeding esophageal varices in cirrhotic patients with portal hypertension in Tibet region.Methods:Clinical data of cirrhotic patients with portal hypertension through March 2017 to February 2020 from Tibet region were collected and analyzed retrospectively.Results:511 cases with liver cirrhosis were included in the study, of which 185 cases (36.20%) had compensated cirrhosis and 326 cases (63.80%) had decompensated cirrhosis. Further analysis of the etiological data of liver cirrhosis showed that 306 cases (59.88%) were of chronic hepatitis B, 113 cases (22.11%) of alcoholic liver disease, and 68 cases (13.31%) of chronic hepatitis B combined with alcoholic liver disease. Among patients with compensated liver cirrhosis, 48 cases (25.95%) underwent endoscopic examination of which 33 diagnosed as high-risk variceal bleeding. However, none of these 33 cases had received non-selective β-blocker therapy, and only four patients had received endoscopic variceal banding therapy. Among patients with decompensated liver cirrhosis, 83 cases (25.46%) had a history of upper gastrointestinal bleeding, 297 cases (91.10%) had ascites, 23 cases (7.05%) had hepatic encephalopathy, and 3 cases (0.92%) had hepatorenal syndrome. Among the patients with a history of upper gastrointestinal bleeding, 42 cases (50.60%) had received secondary preventive treatment for bleeding esophageal varices, including 39 cases of endoscopic treatment, 1 case of endoscopic combined drug treatment, 3 cases of interventional treatment, and 2 cases of surgical treatment.Conclusion:Chronic hepatitis B and alcoholic liver diseases are the main causes of liver cirrhosis in Tibet region. Moreover, this region lacks screening, prevention and treatment for bleeding esophageal varices in cirrhotic patients with portal hypertension. Therefore, it is necessary to increase the screening of high-risk groups to prevent and improve the first-time bleeding, and promote multidisciplinary team to prevent and treat re-bleeding.

BACKGROUNDUrine output (UO) is an essential criterion of the Kidney Disease Improving Global Outcomes (KDIGO) definition and classification system for acute kidney injury (AKI), of which the diagnostic value has not been extensively studied. We aimed to determine whether AKI based on KDIGO UO criteria (KDIGOUO) could improve the diagnostic and prognostic accuracy, compared with KDIGO serum creatinine criteria (KDIGOSCr).

METHODSWe conducted a secondary analysis of the database of a previous study conducted by China Critical Care Clinical Trial Group (CCCCTG), which was a 2-month prospective cohort study (July 1, 2009 to August 31, 2009) involving 3063 patients in 22 tertiary Intensive Care Units in Mainland of China. AKI was diagnosed and classified separately based on KDIGOUOand KDIGOSCr. Hospital mortality of patients with more severe AKI classification based on KDIGOUOwas compared with other patients by univariate and multivariate regression analyses.

RESULTSThe prevalence of AKI increased from 52.4% based on KDIGOSCrto 55.4% based on KDIGOSCrcombined with KDIGOUO. KDIGOUOalso resulted in an upgrade of AKI classification in 7.3% of patients, representing those with more severe AKI classification based on KDIGOUO. Compared with non-AKI patients or those with maximum AKI classification by KDIGOSCr, those with maximum AKI classification by KDIGOUOhad a significantly higher hospital mortality of 58.4% (odds ratio [OR]: 7.580, 95% confidence interval [CI]: 4.141-13.873, P< 0.001). In a multivariate logistic regression analysis, AKI based on KDIGOUO (OR: 2.891, 95% CI: 1.964-4.254, P< 0.001), but not based on KDIGOSCr (OR: 1.322, 95% CI: 0.902-1.939, P = 0.152), was an independent risk factor for hospital mortality.

CONCLUSIONUO was a criterion with additional value beyond creatinine criterion for AKI diagnosis and classification, which can help identify a group of patients with high risk of death.

Acute Disease ; mortality ; Aged ; Creatinine ; blood ; Critical Illness ; mortality ; Female ; Hospital Mortality ; Humans ; Kaplan-Meier Estimate ; Kidney Diseases ; blood ; mortality ; pathology ; urine ; Logistic Models ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; Risk Factors

Objective To investigate the expression levels of serum vasohibin-1(VASH-1)in type 2 diabetes mellitus(T2DM)patients at different stages of urinary albumin to creatinineratio(UACR)and to attempt to investigate the relationship between VASH-1 and inflammation and fibrosis in the pathogenesis of diabetic nephropathy(DN), one of the microvascular complications of T2DM. Methods 486 patients with T2DMwere divided into four groups:normal albuminuria [ UACR<30 mg/ g, n = 134], microalbuminuria [ UACR at 30-300 mg/ g, n = 122], clinical albuminuria [UACR > 300 mg/ g, n = 106 ], and clinical albuminuria hypertensive [ UACR > 300 mg/ g, with hypertension, n=124] groups. Age, course, serum levels ofVASH1, inflammation markers(CRP, ESR)and fibrosis marker( TGF-β1) with other biochemical indicators were measured, and 130 normal control subjects were also included. Results Compared with normal control group, the levels of UACR, HbA1C ,ESR, CRP, TGF-β1 and VASH-1 in groups ofnormal albuminuria, microalbuminuria, clinical albuminuria, and clinical albuminuria hypertensive were significantly higher(P<0. 05). Pearson correlation analysis showed that levels of VASH-1 were positively correlated with UACR, HbA1C ,ESR, CRPand TGF-β1( r = 0. 521, 0. 261, 0. 519, 0. 523, 0. 479, P<0. 001), while multivariate regression analysis showed that levels of UACR, HbA1C ,ESR, CRP and TGF-β1 were important factors affecting serum VASH-1 levels. Conclusion Serum levels of VASH-1 may become new biomarkers of early diagnosis of DN. Consequently, VASH-1 level may provide a new pattern and direction of inflammation and fibrosis for consideration in diabetic kidney damage.