ObjectiveTo explore the mechanism of plumbagin as a novel ferroptosis inducer in bladder cancer inhibition. MethodBladder cancer T24 cells were used in this study. The effect of different concentrations of plumbagin （0.1， 1， 2， 3， 6， 12， 24， 48 μmol·L^-1） on the viability of T24 cells was detected by cell counting kit-8 （CCK-8）. The effect of different concentrations of plumbagin （1.5， 3， 6 μmol·L^-1） on the apoptosis of T24 cells was detected by annexin V-fluorescein isothiocyanate （Annexin V FITC）/PI apoptosis kit. Different inhibitors （ferroptosis inhibitor Fer-1， apoptosis inhibitor VAD， and necroptosis inhibitor Nec-1） were used in combination with plumbagin （6 μmol·L^-1）. Reactive oxygen species （ROS） fluorescent probe （DCFH-DA）， malonaldehyde （MDA）， and glutathione （GSH） kits were used to detect the effects of different concentrations of plumbagin （1.5， 3， 6 μmol·L^-1） on the level of ROS and the content of MDA and GSH in T24 cells， respectively. The effect of different concentrations of plumbagin （1.5， 3， 6 μmol·L^-1） on peroxide levels in T24 cells was detected by C11-BODIPY fluorescent probe. Western blot was used to detect the effect of different concentrations of plumbagin （1.5， 3， 6 μmol·L^-1） on the protein expression of solute carrier family 7 member 11 （SLC7A11）， glutathione peroxidase 4 （GPX4）， nuclear factor E₂-related factor-2 （Nrf-2）， and Kelch-like ECH-associated protein 1 （Keap1）. ResultCompared with the blank group， plumbagin could inhibit the activity of T24 cells （P<0.05） with IC₅₀ of 3.52 μmol·L^-1. At the concentrations of 1.5， 3， 6 μmol·L^-1， plumbagin significantly promoted the apoptosis of T24 cells （P<0.05） as compared with the blank group. Compared with the plumbagin group at 6 μmol·L^-1， the ferroptosis inhibitor and apoptosis inhibitor groups could reverse the inhibitory effect of 6 μmol·L^-1 plumbagin on the proliferation of T24 cells （P<0.05）. Compared with the blank group， the plumbagin groups at 1.5， 3， 6 μmol·L^-1 showed increased content of ROS， MDA， and lipid peroxides in T24 cells， decreased GSH level， and reduced SLC7A11， GPX4， and Nrf-2/Keap1 （P<0.05）. Conclusionplumbagin can induce ferroptosis， and its mechanism is related to the Nrf-2/Keap1 signaling pathway.

Introduction: SABINA III assessed short-acting β2-agonist (SABA) prescription patterns and their association with asthma-related outcomes globally. Herein, we examined SABA prescription and clinical outcomes in the Malaysian cohort of SABINA III. Methods: In this observational, cross-sectional study, patients (≥12 years) were recruited between July and December 2019 from 15 primary and specialty care centres in Malaysia. Prescribed asthma treatments and severe exacerbation history within 12 months prior and asthma symptom control during the study visit were evaluated. Associations of SABA prescription with asthma control and severe exacerbation were analysed using multivariable regression models. Results: Seven hundred thirty-one patients (primary care, n=265 [36.3%]; specialty care, n=466 [63.7%]) were evaluated. The prevalence of SABA over-prescription (≥3 SABA prescriptions/year) was 47.4% (primary care, 47.1%; specialty care, 47.6%), 51.8% and 44.5% among all patients and patients with mild and moderate-to-severe asthma, respectively. Altogether 9.0% (n=66) purchased SABA without a prescription; among them, 43.9% (n=29) purchased ≥3 inhalers. The mean (standard deviation) number of severe asthma exacerbations was 1.38 (2.76), and 19.7% (n=144) and 25.7% (n=188) had uncontrolled and partly controlled symptoms, respectively. Prescriptions of ≥3 SABA inhalers (vs 1–2) were associated with lower odds of at least partly controlled asthma (odds ratio=0.42; 95% confidence interval [CI]=0.27–0.67) and higher odds of having severe exacerbation(s) (odds ratio=2.04; 95% CI=1.44–2.89). Conclusion The prevalence of SABA over-prescription in Malaysia is high, regardless of the prescriber type, emphasising the need for healthcare providers and policymakers to adopt latest evidence-based recommendations to address this public health concern.
Asthma ; Malaysia

Arabidopsis thaliana is an important and long-established model species for plant molec-ular biology,genetics,epigenetics,and genomics.However,the latest version of reference genome still contains a significant number of missing segments.Here,we reported a high-quality and almost complete Col-0 genome assembly with two gaps(named Col-XJTU)by combining the Oxford Nanopore Technologies ultra-long reads,Pacific Biosciences high-fidelity long reads,and Hi-C data.The total genome assembly size is 133,725,193 bp,introducing 14.6 Mb of novel sequences compared to the TAIR1 0.1 reference genome.All five chromosomes of the Col-XJTU assembly are highly accurate with consensus quality(QV)scores＞60(ranging from 62 to 68),which are higher than those of the TAIR10.1 reference(ranging from 45 to 52).We completely resolved chro-mosome(Chr)3 and Chr5 in a telomere-to-telomere manner.Chr4 was completely resolved except the nucleolar organizing regions,which comprise long repetitive DNA fragments.The Chr1 cen-tromere(CEN1),reportedly around 9 Mb in length,is particularly challenging to assemble due to the presence of tens of thousands of CEN180 satellite repeats.Using the cutting-edge sequencing data and novel computational approaches,we assembled a 3.8-Mb-long CEN1 and a 3.5-Mb-long CEN2.We also investigated the structure and epigenetics of centromeres.Four clusters of CEN180 monomers were detected,and the centromere-specific histone H3-like protein(CENH3)exhibited a strong preference for CEN 180 Cluster 3.Moreover,we observed hypomethylation patterns in CENH3-enriched regions.We believe that this high-quality genome assembly,Col-XJTU,would serve as a valuable reference to better understand the global pattern of centromeric polymorphisms,as well as the genetic and epigenetic features in plants.

Objective: To compare the efficacy and safety of pro-urokinase and reteplase in the treatment of patients with acute ST elevation myocardial infarction (STEMI). Methods: STEMI patients, who received intravenous thrombolytic therapy in Henan STEMI registry between September 2016 and August 2018, were eligible for this study. A total of 5479 patients from 66 hospitals were screened and patients were divided into pro-urokinase group (n=638) and reteplase group (n=702) according to thrombolytic drugs. Data including patient demographics, risk factors, medical histories, patient information at admission, in-hospital treatment, time delays, and clinical events were collected. The clinical recanalization rate, in-hospital mortality, in-hospital death or treatment withdrawal, in-hospital main adverse cardiovascular and cerebrovascular events (MACCE, death or treatment withdrawal, congestive heart failure, reinfarction and ischemic stroke) and post-thrombolysis bleeding were compared between the two groups. Bleeding events were evaluated with Bleeding Academic Research Consortium (BARC) criteria. Results: The median age [61.8 (53.2, 69.0) vs. 62.6 (52.1, 69.8), P=0.833] or the proportion of women [23.0% (147/638) vs. 25.1% (176/702), P=0.385] were similar between the pro-urokinase and reteplase groups. Clinical recanalization rates were similar between the pro-urokinase and reteplase groups [82.1% (524/638) vs. 84.9% (596/702), P=0.172], and there was no difference in the median time from onset to thrombolysis [194.5 (135.0,290.0) min vs. 190 (126.0,292.0) min, P=0.431] and the median recanalization time [95 (67.5,120.0) min vs. 95 (71.0,119.0) min, P=0.561] between the two groups. There was no significant difference in in-hospital mortality [5.5% (35/638) vs. 5.1% (36/702), P =0.770], in-hospital all-cause mortality, treatment withdrawal [8.9% (57/638) vs.7.7% (54/702), P=0.410], and in-hospital MACCE [13.0% (83/638) vs. 10.4% (73/702), P=0.137] between pro-urokinase and reteplase groups. However, the incidence of post-thrombolysis bleeding was significantly higher in reteplase group than in pro-urokinase group [7.8% (55/702) vs. 3.8% (24/638), P=0.002]. Further analysis found that the incidence of oral bleeding and the BARC grades 1-2 bleeding were significantly higher in reteplase group than in pro-urokinase group, whereas the incidence of cerebral hemorrhage was similar between the two groups [0.6% (4/638) vs. 0.4% (3/702), P=0.715]. The comparison of efficacy and safety outcomes between the two groups after adjusting for baseline characteristics using general linear mixed models was consistent with those before the adjustment. There was no significant difference in in-hospital mortality, in-hospital death or treatment withdrawal, in-hospital MACCE after adjusting for baseline characteristics and post-thrombolysis bleeding between the two groups. Conclusions: Pro-urokinase and reteplase have similar clinical efficacy in the treatment of STEMI. In terms of safety, the incidence of cerebral hemorrhage is similar, while the incidence of BARC grades 1-2 bleeding and oral bleeding is higher in reteplase group than in pro-urokinase group, which has no impact on in-hospital outcomes.
Female ; Fibrinolytic Agents/therapeutic use* ; Hospital Mortality ; Humans ; Myocardial Infarction/drug therapy* ; Recombinant Proteins ; ST Elevation Myocardial Infarction/drug therapy* ; Thrombolytic Therapy ; Tissue Plasminogen Activator ; Treatment Outcome ; Urokinase-Type Plasminogen Activator

This is a policy brief article on the prediction of Covid-19 outbreak and its prevention and control for the possible second wave in the Lao PDR. Compartmental dynamic modeling was created to reflect the natural history of Covid-19. This included susceptible, symptomatic and asymptomatic states and recovery or death. The simulation was done for one year and with two scenarios: 1) high transmission level (R0=5.2) and 2) mid -transmission level (R0=2.0). The model output showed that the size of the outbreak depended on the transmission level, and could reach to 85% of the Lao population with high transmission scenario. However, disease burden was predicted to be smaller with the interventions. Among these, voluntary home quarantine was found to be the most effective, but the predication reverses in the mid-level transmission scenario. Social distancing is much more effective. If there are imported COVID-19 cases, a new wave could occur in two weeks to 2 months, depending on the size of pandemic and efficacy of the rest of interventions. Mid-level lockdown would result in new epidemic starting by July 2020, but the number of infected people would be less if travel bans and social distancing are maintaining. Only high-level lockdown would be able to stop community transmission in the country.

Acupuncture Therapy ; Aged ; Aneurysm, Dissecting ; complications ; Brain ; diagnostic imaging ; pathology ; Cerebral Infarction ; etiology ; therapy ; Female ; Glasgow Coma Scale ; Humans ; Postoperative Complications ; etiology ; therapy ; Tomography, X-Ray Computed

Objective To evaluate the efficacy and safety of Houpu Paiqi mixture in treatment of functional dyspepsia (FD)with abdominal distension symptom.Methods From July 2014 to June 2015 , in nine centers,a total of 162 FD patients with abdominal distension symptom and met Rome Ⅲpostprandial distress syndrome (PDS)diagnostic criteria were enrolled.All patients were randomly divided into trial group and control group,81 patients in either group.The patients of trial group and control group took Houpu Paiqi mixture or placebo,respectively,25 mL per time,twice daily,and both the courses of treatment were two weeks.Before and after the treatment,the improvement of main symptoms,total clinical efficacy rate and efficacy of traditional medicine between two groups were compared.Chi square test,Fisher exact probability method and Wilcoxon test were performed for statistical analysis.Results According to the results of per-protocol (PP)analysis,the total efficacy rate of trial group and control group was 69.4% (50/72)and 59.2% (42/71),respectively,and there was no statistically significant difference in total efficacy rate between the two groups (χ2 =1 .650,P =0.199 ). And there was no statistically significant difference in the improvement of PDS main symptoms(postprandial fullnessand early satiety)between the two groups (56.3% ±27.9% vs 54.4% ±32.1%,t =0.606,P =0.727 ).For those with baseline symptom score over 14,median early satiety score of trial group after the treatment was 0,which was lower than that of control group,and the difference was statistically significant (Z =-2.370,P =0.018).The total efficacy rate of traditional medicine of trial group was 80.8% (59/73 )and that of control group was 72.0% (54/75 ),and the difference was not statistically significant (χ2 = 0.676,P =0.411 ).Conclusion Houpu Paiqi mixture has certain efficacy in FD with abdominal distension,and could be used for the treatment of PDS-predominant FD.

A 28-year-old female patient was admitted to the Second Affiliated Hospital, Zhejiang University School of Medicine, with sudden headache and vomiting for 1 day. CT scan conducted at emergency revealed subarachnoid hemorrhage, whereas digital subtraction angiography demonstrated a wide-neck aneurysm located at A1 segment of the left anterior cerebral artery. The aneurysm was totally coiled using stent assistance, which, however, was recanalized at 3 month follow-up. This patient was then subjected to aneurysm and parent artery occlusion after bypass of the bilateral A3 segments, who recovered well and discharged without ischemic complications.
Adult ; Anastomosis, Surgical ; Aneurysm, Ruptured ; surgery ; Angiography, Digital Subtraction ; Anterior Cerebral Artery ; surgery ; Female ; Humans ; Intracranial Aneurysm ; surgery ; Recurrence ; Stents ; Subarachnoid Hemorrhage ; surgery ; Tomography, X-Ray Computed

AIM: To study the chemical constituents of stems of Gymnema sylvestre (Retz.) Schult. METHODS: Chromatographic techniques using silica gel, C18 reversed phase silica gel, and prep-HPLC were used. The structures were elucidated on the basis of MS and spectroscopic analysis (1D and 2D NMR), as well as chemical methods. RESULTS: Seven compounds were isolated and their structures were elucidated as conduritol A (1), stigmasterol (2), lupeol (3), stigmasterol-3-O-β-D-glucoside (4), the sodium salt of 22α-hydroxy-longispinogenin-3-O-β-D-glucopyranosyl-(1→3)-β-D-glu-curono-pyranosyl-28-O-α-L-rhamnopyranoside (5), oleanolic acid-3-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside (6), and the sodium salt of 22α-hydroxy-longispinogenin 3-O-β-D-glucuronopyranosyl-28-O-α-L-rhamnopyranoside (7). The inhibition activities of compounds 1, 5-7 on non-enzymatic glycation of protein in vitro were evaluated. CONCLUSION Compound 7 is a new triterpenoid saponin. It was shown that compounds 1, 5-7 have weak inhibition activities for non-enzymatic glycation of protein in vitro.
Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Gymnema sylvestre ; chemistry ; Molecular Structure ; Plant Stems ; chemistry

BACKGROUNDThe role of gastro-protecting agents on symptomatic chronic gastritis is unclear. This multicenter, open, randomized trial was designed to compare the comprehensive effects of gefarnate with sucralfate on erosive gastritis with dyspeptic symptoms.

METHODSTotally 253 dyspepsia patients confirmed with erosive gastritis were enrolled from six centers in China. They randomly received either daily 300 mg gefarnate or 3 g sucralfate for six weeks. The primary endpoint was the effective rate of both treatments on endoscopic erosion at week six.

RESULTSGefarnate showed an effective rate of 72% and 67% on endoscopic score and dyspeptic symptom release, which is statistically higher than sucralfate (40.1% and 39.3%, P < 0.001, intension-to-treat). For histological improvement, gefarnate showed both effective in decreasing mucosal chronic inflammation (57.7% vs. 24.8%, P < 0.001, intension-to-treat) and active inflammation (36.4% vs. 23.1%, P < 0.05, intension-to-treat) than the control. A significant increase of prostaglandins and decrease of myeloperoxidase in mucosa were observed in gefarnate group. Severity of erosion is non-relevant to symptoms but Helicobacter pylori (H. pylori) status does affect the outcome of therapy.

CONCLUSIONSGefarnate demonstrates an effective outcome on the mucosal inflammation in patients with chronic erosive gastritis. Endoscopic and inflammation score should be the major indexes used in gastritis-related trials.

Adolescent ; Adult ; Aged ; Anti-Ulcer Agents ; therapeutic use ; Dyspepsia ; drug therapy ; Female ; Gastritis ; drug therapy ; Gefarnate ; therapeutic use ; Humans ; Male ; Middle Aged ; Sucralfate ; therapeutic use ; Treatment Outcome ; Young Adult