Ursolic acid (UA), a natural triterpenoid widely distributed within fruits and edible plants, has been proven to relieve alcoholic liver disease (ALD). However, the mechanisms involved largely remain unclear. This study investigated whether the beneficial effects of UA on ALD could be related to gut-liver axis (GLA) modulation. Special attention was paid to the contribution of gut microbiome manipulation. UA ameliorated intestinal oxidative stress and barrier dysfunction induced by alcohol. As a consequence of gut leakiness amelioration, the related endotoxemia-mediated liver toll-like receptor 4 pathway induction and the subsequent reactive oxygen species overproduction were reverted. UA also counteracted alcohol-induced gut dysbiosis. A fecal microbiota transplantation study indicated that liver injury as well as ileum oxidative stress and gut barrier dysfunction of recipient mice were partly ameliorated as a result of microbiome remodeling. These results suggest that dietary UA alleviates ALD through GLA homeostasis modulation. Gut microbiome manipulation contributes to the hepatoprotective activity and GLA modulating effect of UA.
AbstractBackgroud: To describe the frequency and distribution characteristics of gastrointestinal symptoms of coronavirus disease 2019 (COVID-19) patients.Methods: As a cohort study, all confirmed COVID-19 patients with gastrointestinal symptoms at Xiangyang No.1 people’s hospital were included until February 21st, 2020. Course of disease no less than 21 days.Gastrointestinal symptoms relevant data were extracted and analyzed. The frequency histograms of the symptoms were plotted. Main symptom characteristics were summarized.Results: Of 50 included patients with gastrointestinal symptoms, 21 were male, 29were female. The mean age was 53 (SD 16) years. Course of disease ranged from 21 to 34 days with a median of 26 days. Among all patients, 16 were critically ill and five died, 12 discharged. Thirty-one clinical symptoms occurred 3168 times in total, 6 gastrointestinal symptoms occurred 439 (13.86%) times and 25 non-gastrointestinal symptoms occurred 2 729(86.14%) times. All symptoms and non-gastrointestinal symptoms distributed in 1 to 34 days, reached peak on 6th day of follow up, first seven days were the fastigium and decreasing in the rest days. Gastrointestinal symptoms mainly distributed in 1 to 34 days, reached a peak of 36 times per day on 6th of follow-up with a fastigium during 6 to 12 day, showed a trend of rise first and then fall. Nausea, vomit and abdominal discomfort occurred 133, 70 and 62 times, respectively.Conclusions: A symptom frequency to time distribution model could describe the disease process quantitatively, indicating the change law of gastrointestinal symptoms and the organ damages in gastrointestinal system, could help us to better understand and treat the new disease. Females showed higher incidence of gastrointestinal symptoms, whether there is a sex difference in susceptibility needs to be further confirmed.Trial regitration: retrospectively registeredAuthors Guoxin Huang and Shengduo Pei contributed equally to this work.
Abstract Anterior circulation large artery occlusion (AC-LAO) related acute ischemic stroke (AIS) is particularly common in clinics in China. We retrospectively analyzed 787 consecutively hospitalized AIS patients with AC-LAO in Hebei Province, China. AC-LAO was defined as a complete occlusion of at least one intracranial internal carotid artery (ICA) or middle cerebral artery (MCA) based on computed tomography or magnetic resonance angiography. Among eight subtypes of AC-LAO, unilateral MCA occlusion is the most common one (49.8%, n = 392), while bilateral ICA/unilateral MCA occlusion is the least (0.3%, n = 2). Compared with unilateral MCA and unilateral ICA occlusion, patients with tandem ICA/MCA and bilateral ICA/MCA occlusion had poor outcomes after suffering AIS. Age (OR 1.022; 95%CI, 1.007 to 1.036) was an independent risk factor for single artery progressed to multiple artery occlusion, while ApoA1 (OR 0.453; 95% CI, 0.235 to 0.953) was a protective factor. Patients with unilateral MCA occlusion were prone to artery-to-artery embolism infarction subtype, unilateral ICA occlusion group were the most vulnerable to hypoperfusion/impaired emboli clearance subtype. Our results suggested various AC-LAO subtypes have different clinical characteristics and prognosis and were prone to different subtypes of infarction. Customized preventive measures based on AC-LAO subtypes may be more targeted preventions of stroke recurrences for AIS patients and could improve their prognoses.
AIM: To study the current density of transient outward potassium current (I_(to)) in cells from the epicardial zone of the 1-week and 2-month infarcted rabbit heart. METHODS: Rabbits were infarcted by ligation of the left anterior descending coronary artery, 1 week as well as 2 months later, the single ventricular myocytes were isolated enzymatically from the infracted area of 1-week infracted rabbit heart (PMI-1 week) and 2-month infracted heart (PMI-2 months), region remote from the infracted zone of 2-month infracted heart (REM-2 months) and free wall of left ventricule from noninfarcted heart (CON). I_(to) was recorded using whole cell patch-clamp techniques. (RESULTS:) Membrane capacitance of myocytes in REM-2 months group was signifitantly larger than that in CON. I_(to)current density (at +60 mV) was significantly reduced in PMI-1 week [(7.5±2.4) pA/pF, n=12] and PMI-2 months [(10.6±4.1) pA/pF, n=18] compared with CON [(17.4±5.2) pA/pF, n=16], P0.01. Nevertheless, there was an significant increase in PMI-2M compared with PMI-1W, P0.05. I_(to) current density was also significantly decreased in REM-2 months [(13.2±4.1) pA/pF, n=23] compared with CON (P0.05), while there was an significant increase in REM-2 months compared with PMI-2 months, P0.05. CONCLUSION: The results indicate that the reduction and change of I_(to) in infarcted rabbit heart are heterogenous. These changes may underlie the abnormally long transmembrane action potentials of these arrhymogenic surviving ventricular fibers of the infarcted heart, thus contributing to reentrant arrhythmias in the infarcted heart. By 2 months after myocardial infarction, the depressed I_(to) of infracted area had returned to nearly normal, suggesting the presence of reverse remodeling.
Objective To evaluate the clinical feature of pediatric patients with bronchiolitis,and compare their treatment response between different dosage of nebulised Budesonide Suspension for Inhalation.Methods The data of the children diagnosed and administrated between 2011.1-2011.5 were collected and analyzed by soft ware SPSS 19.0.The patients were randomly divided into 0.5mg group(nebulised Budesonide Suspension for Inhalation 0.5mg once)and 1mg group(nebulised Budesonide Suspension for Inhalation 1mg once).The clinical score,respiratory frequency,oxygen saturation,length of stay,the cost were evaluated.Results 30 minutes after the treatment,The clinical score in 1mg group(6.28±1.16)was statistically lower than that(6.91±1.03)in the 0.5mg group(P=0.007),the respiratory frequency in 1mg group(55.7±7.1)was statistically lower than that(60.23±6.2)in the 0.5mg group(P=0.003),the oxygen saturation in 1mg group(96.7±2.5%)was statistically higher than that(94.3±1.8%)in the 0.5mg group(P0.001).60 minutes after the treat,The clinical score in 1mg group(5.14±1.58)was statistically lower than that(6.25±1.37)in the 0.5mg group(P0.001),the respiratory frequency in 1mg group(51.5±7.3)was statistically lower than that(55.3±6.4)in the 0.5mg group(P=0.016),the oxygen saturation in 1mg group(97.2±2.6%)was statistically higher than that(95.6±2.3%)in the 0.5mg group(P=0.004)the length of stay in 1mg group(6.42±1.89) was statistically shorter than that(8.71±2.53) in the 0.5mg group(P0.001),the cost of hospitalization in 1mg group(2142±164$)was statistical cheaper than that(2573±189$)in 0.5mg group(P0.001).Conclusion The treatment response of the patients with bronchiolitis in 1mg group are better than that in 0.5mg group,These include faster changing in clinical score,respiratory frequency,oxygen saturation;shorter hospital day and less cost.
Introduction: It is crucial to identify predictors of mortality in the early stage of acute ischemic stroke for the oldest old (aged ≥80 years) because of their poor overall survival outcomes. However, limited data are available as the oldest old have often been excluded from previous clinical studies. Hence, we aimed to assess the predictive effect of red blood cell distribution width on in-hospital mortality and the dose-response relationship between the red blood cell distribution width and in-hospital mortality in oldest old with acute ischemic stroke. Methods: A retrospective cohort study was performed in two tertiary hospitals. Patients aged ≥80 years admitted due to acute ischemic stroke from January 1, 2014, to January 31, 2020, were included in the study. We divided the eligible patients into 3 groups with tertiles of red blood cell distribution width. Restrictive cubic spline and robust locally weighted regression analysis were performed to test the dose-response relationship between red blood cell distribution width and the in-hospital mortality risk. All-cause in-hospital mortality was the main study outcome. Results: Overall, 606 patients were included in the final analysis. Red blood cell distribution width was categorized into 3 groups (T1: <13.7%, T2: 13.8–15.7%, and T3: >15.7%). The rationality of this categorization was then validated with restricted cubic spline and robust locally regression smoothing scatterplot, respectively. After adjusting for demographic and clinical features, a higher red blood cell distribution width was independently associated with in-hospital mortality and the hazard ratio (HR) was 3.31 (95% CI 2.47–4.45, p < 0.001). There was a positive dose-response relationship between red blood cell distribution width and mortality risk. Sensitivity analysis identified no conspicuous change in the HR. Conclusions: Red blood cell distribution width may be a valuable and simple measure for predicting in-hospital mortality in oldest old patients with acute ischemic stroke.
The aim of this study was to evaluate the efficacy and safety of recombinant human adenovirus-p53 (rhAd‑p53) combined with neoadjuvant chemotherapy in treatment of locally advanced cervical cancer (LACC). A total of 40 patients with LACC (stage IB2 to IIIA) were randomized into 2 groups (n=20 each): PVB group (cisplatin + vincristine + bleomycin, intravenously) and combined group (rhAd‑p53 gene therapy + neoadjuvant chemotherapy). Both groups underwent a course of chemotherapy; the only exception was the injection of the rhAd‑p53 solution 1x1012 VP intratumorally at an interval of three days thrice in the combined group thereafter. The tumor sizes and adverse events in both groups were observed. The expression of vascular endothelial growth factor (VEGF), protein p53 and micro‑vessel density (MVD) in tumor tissue was respectively determined by immunohistochemistry. The evaluation was performed three weeks after the completion of chemotherapy. The efficacy was 75% in the PVB group versus 95% efficacy in the combined group; the tumor size was reduced by 11.42±2.78 cm2 in PVB group versus the significant shrinkage of 15.25±4.00 cm2 in the combined group (P<0.05). The expression of VEGF, p53 and MVD was downregulated in both the PVB and combined groups, with significantly statistical differences versus the control. No additional adverse events were evidenced in the combined group. Therefore, intratumoral injection of rhAd‑p53 combined with neoadjuvant chemotherapy has advantage over conventional chemotherapy for its high efficacy, safety and synergism in the therapy for LACC.
To establish and validate an MRI T2∗WI-based radiomics nomogram model and to discriminate hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma (ICCA).174 patients were retrospectively collected, who were diagnosed with primary hepatic carcinoma by surgery or puncture pathology and received preoperative MRI scans including T2∗WI scans. There were 113 cases of HCC and 61 cases of mass-type ICCA. T2∗WI was used for feature extraction, the extent of the lesions was manually outlined at the largest lesions layer of the T2∗WI, and the feature dimension reduction was performed by the mRMR and LASSO to obtain the optimal feature set. The radiomics features and clinical risk factors were combined to establish the radiomics nomogram model. In both training and validation groups, calibration curves and ROC curves were applied to validate the efficacy of the established model. Finally, calibration curves were applied to assess the degree of fitting and DCA to assess the clinical utility of the established model.The radiomics model had the AUC of 0.90 (95% CI, 0.85-0.96) and 0.91 (95% CI, 0.83-0.99) in the training and validation groups, respectively; the AUC of the radiomics nomogram was 0.97 (95% CI, 0.94-0.99) in the training group and 0.95 (95% CI, 0.95-0.99) in the validation group. DCA suggested the clinical application value of the nomogram model.Radiomics nomogram model based on MRI T2∗WI scan without enhancement can be used to discriminate HCC from ICCA.
Objective To explore the relationship between the serum HBV viral load and HBV serum markers in patients with hepatitis.Methods The serum levels of HBV-DNA copies and HBV serum markers 222 patients with chronic hepatitis B were examined and analyzed.HBV-DNA copies were detected by fluorescence quantitative PCR(FQ-PCR) and HBV serum markers by chemiluminescent immunoassay.The paired analysis was carried out.Results The serum contents of HBV viral load group A(HBsAg+,HBeAg+,HBcAb+) and group D(HBsAg+,HBeAg+) was higher than that in other groups.High-levels viremia(HBV viral load105 copies/ml) was found both in group A and group D(91.9%,77.8%).Conclusion There was a positive good correlation between the level of serum HBV-DNA and HBeAg content.Simultaneous determination of serum HBV viral load and HBV serum markers is necessary in determining the HBV infection and viral replication.
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