ObjectiveTo explore the clinical efficacy and mechanism of Bupi Qingfei prescription （BPQF） in treating stable bronchiectasis in the patients with syndromes of lung-spleen Qi deficiency and phlegm-heat accumulation in the lungs. MethodsA randomized， double-blind， placebo-controlled trial was conducted. Patients were randomized into BPQF and placebo control （PC） groups. On the basis of conventional Western medicine treatment， the BPQF granules and placebo were respectively administered at 10 g each time， twice a day， for a course of 24 weeks. The TCM symptom scores， Quality of Life Questionnaire for Bronchiectasis （QOL-B） scores， lung function indicators， T lymphocyte subsets， level of inflammatory factors in the sputum， level of neutrophil elastase （NE） in the sputum， and occurrence of adverse reactions were observed before and after treatment in the two groups. ResultsA total of 64 patients completed the study， encompassing 32 in the BPQF group and 32 in the PC group. After treatment， the BPQF group showed decreased TCM symptom scores （P<0.01）， increased QOL-B scores （P<0.01）， and declined levels of tumor necrosis factor （TNF）-α and NE （P<0.05， P<0.01）. The PC group showed decreased TCM symptom （except spleen deficiency） scores （P<0.01）， increased the QOL-B health cognition and respiratory symptom domain scores （P<0.05， P<0.01）， and a declined TNF-α level （P<0.01）. Moreover， the BPQF group had lower TCM symptom （except chest tightness） scores （P<0.05， P<0.01）， higher QOL-B （except treatment burden） scores （P<0.05， P<0.01）， and lower levels of interleukin-6 and TNF-α （P<0.05） than the PC group. Neither group showed serious adverse reactions during the treatment process. ConclusionBPQF can ameliorate the clinical symptoms of stable bronchiectasis patients who have lung-spleen Qi deficiency or phlegm-heat accumulation in the lungs by regulating the immune balance and inhibiting airway inflammatory responses.

ObjectiveTo observe the effect of Weichang'an prescription-containing serum on ferroptosis of human gastric cancer cells and explore the possible mechanism. MethodsSD rats were administrated with 18， 36， 72 g·kg^-1·d^-1 Weichang'an prescription by gavage for preparation of serum samples containing different doses of Weichang'an prescription， which were then used to treat MKN-45 cells. The cell proliferation was examined by the cell counting kit-8 （CCK-8）. In addition， inhibitors of apoptosis， necroptosis， and ferroptosis were added， and the survival of the cells treated with the serum samples was observed. The fluorescent probe dichlorodihydrofluorescein diacetate （DCF-DA） and the lipid peroxidation sensor C11-BODIPY were employed to detect the intracellular levels of reactive oxygen species （ROS） and lipid peroxidation， respectively. The levels of ferrous ion （Fe²⁺）， glutathione （GSH）， and malondialdehyde （MDA） were detected by enzyme-linked immunosorbent assay （ELISA）. Real-time PCR and Western blotting were employed to determine the expression of nuclear factor erythroid 2-related factor 2 （Nrf2）， aldo-keto reductase family 1 member B1 （AKR1B1）， glutathione peroxidase 4 （GPX4）， acyl-CoA synthetase long-chain family member 4 （ACSL4）， signal transducer and activator of transcription 3 （STAT3）， and mitogen-activated protein kinase （MAPK）. ResultsCompared with the blank group， Weichang'an prescription-containing serum decreased the viability of MKN-45 cells （P<0.05， P<0.01） in a time- and dose-dependent manner. Compared with the Weichang'an prescription group， the apoptosis inhibitor+Weichang'an prescription group and the ferroptosis inhibitor+Weichang'an prescription group showed increased cell viability （P<0.05， P<0.01）. Compared with the blank group， Weichang'an prescription elevated the levels of ROS， lipid peroxidation， and intracellular Fe²⁺ and MDA （P<0.05， P<0.01） and lowered the level of GSH （P<0.05， P<0.01） in a dose-dependent manner. Compared with the blank group， Weichang'an prescription down-regulated the mRNA and protein levels of Nrf2， AKR1B1， and GPX4 （P<0.05， P<0.01） and up-regulated the mRNA and protein levels of ACSL4 （P<0.05， P<0.01） in a dose-dependent manner. Compared with the blank group， Weichang'an prescription down-regulated the protein levels of p-STAT3 and p-ERK （P<0.05， P<0.01） in a dose-dependent manner. ConclusionThe Weichang'an prescription-containing serum can promote the ferroptosis and inhibit the proliferation of MKN-45 cells by regulating the STAT3 and MAPK pathways.

Objective To understand the mortality and potential life loss due to coronary heart disease (CHD) and stroke in Wujiang District, Suzhou from 2011 to 2022, and to provide strategies and basis for the prevention and treatment of CHD and stroke. Methods We collected the data of death cases due to CHD and stroke from the death monitoring system in Suzhou from 2011 to 2022. The mortality of CHD and stroke, potential years of life lost (potential years of life lost , PYLL), average years of life lost (average years of life lost , AYLL) and potential years of life lost rate (potential years of life lost rate , PYLLR) were calculated to analyze the development trend of death and disease burden of CHD and stroke. Results From 2011 to 2022, the crude mortality of CHD was 31.91/10 million, and that of stroke was 118.93/10 million. CHD and stroke mortality rates both showed an upward trend（P＜0.05, a statistically significant trend）. From 2011 to 2022, the mortality rate of CHD and stroke in Wujiang District increased rapidly with the increase of age. From 2011 to 2022, the disease burden caused by CHD totaled 11005 person-years, with PYLLR of 1.26% and AYLL of 12.34 years per person. The PYLL caused by stroke was 13 587.5 people-years, the PYLLR was 1.55%, and the AYLL was 8.93 years per person. PYLL, PYLLR and AYLL all decreased in women（P<0.05）, with no significant change in men（P>0.05）. Conclusion From 2011 to 2022, the mortality rate of CHD and stroke in Wujiang District appeared a tendency towards a rise, effective intervention and prevention measures should be taken among elderly and male residents.

OBJECTIVE: To investigate the frequency and related factors of ineffective triggering (IT) and double triggering (DT) in patients with acute brain injury undergoing invasive mechanical ventilation. METHODS: A retrospective cohort study was conducted using data from a single-center observational trial. Patients with acute brain injury [traumatic brain injury, stroke, and post-craniotomy for brain tumors] undergoing mechanical ventilation in the intensive care unit (ICU) of Beijing Tiantan Hospital, Capital Medical University between June 2017 and July 2019 were retrospectively analyzed. Demographic and clinical data were collected. Respiratory parameters and waveforms during the first 3 days of mechanical ventilation were recorded, with 15-minute waveform segments collected 4 times daily. Airway occlusion pressure (P_0.1) was measured via end-expiratory hold at the end of each recording. IT and DT were identified based on airway pressure, flow, and esophageal pressure waveforms, and the ineffective triggering index (ITI) and DT incidence were calculated. Multivariate Logistic regression was used to identify factors associated with IT and DT. RESULTS: A total of 94 patients with acute brain injury were ultimately enrolled, including 19 cases of traumatic brain injury (20.2%), 39 cases of stroke (41.5%), and 36 cases of post-craniotomy for brain tumor (38.3%). Supratentorial injury was observed in 49 patients (52.1%), while infratentorial injury was identified in 45 patients (47.9%). A total of 94 patients with 1 018 datasets were analyzed; 684 (67.2%) datasets were on pressure support ventilation (PSV), and 334 (32.8%) were on mandatory ventilation. IT was detected in 810 (79.6%) datasets, with a median incidence of 2.1% (0.3%, 12.0%). Datasets demonstrating IT were characterized by lower P_0.1, higher tidal volume (VT), reduced respiratory rate (RR), and decreased minute ventilation (MV) compared to those without IT. The proportion of datasets exhibiting IT was higher during PSV than in mandatory ventilation [83.8% (573/684) vs. 71.0% (237/334), P < 0.05], while, the prevalence of ITI ≥ 10% was lower [23.8% (163/684) vs. 33.5% (112/334), P < 0.05]. DT was detected in 305 datasets (30%), with a median incidence of 0.6% (0.4%, 1.3%). Datasets exhibiting DT were characterized by higher VT, reduced RR, and lower pressure support levels. The incidence of DT was lower in PSV compared to mandatory ventilation modes [0% (0%, 0.3%) vs. 0% (0%, 0.5%), P < 0.05]. The post-craniotomy for brain tumors group exhibited higher ITI, lower RR, reduced MV, and a greater proportion of infratentorial lesions, compared to the TBI group. The infratentorial lesion group demonstrated higher ITI and incidence of DT compared to the supratentorial lesion group [ITI: 3.1% (0.7%, 17.8%) vs. 1.5% (0%, 8.3%), incidence of DT: 0% (0%, 0.5%) vs. 0% (0%, 0%), both P < 0.05]. After adjusting for confounding factors through multivariate logistic regression analysis, infratentorial lesion [odds ratio (OR) = 2.029, 95% confidence interval (95%CI) was 1.465-2.811, P < 0.001], lower P_0.1 (OR = 0.714, 95%CI was 0.616-0.827, P < 0.001), and mandatory ventilation (OR = 1.613, 95%CI was 1.164-2.236, P = 0.004) were independently associated with IT. Additionally, infratentorial lesion (OR = 1.618, 95%CI was 1.213-2.157, P = 0.001), large tidal volume (OR = 1.222, 95%CI was 1.137-1.314, P < 0.001), lower pressure support levels (OR = 0.876, 95%CI was 0.829-0.925, P < 0.001), and mandatory ventilation (OR = 2.750, 95%CI was 1.983-3.814, P < 0.001) were independently associated with DT. CONCLUSION IT and DT were common in patients with acute brain injury. Infratentorial lesions and mandatory ventilation were independently associated with both IT and DT.
Humans ; Respiration, Artificial/methods* ; Retrospective Studies ; Brain Injuries/therapy* ; Intensive Care Units ; Male ; Female ; Middle Aged ; Brain Injuries, Traumatic/therapy* ; Logistic Models ; Aged ; Adult

Geminiviruses cause substantial crop yield losses worldwide. The replication initiator protein (Rep) encoded by geminiviruses is indispensable for geminiviral replication. The Rep protein encoded by beet severe curly top virus (BSCTV, genus Curtovirus, family Geminiviridae) induces VARIANT IN METHYLATION 5 (VIM5) expression in Arabidopsis leaves upon BSCTV infection. VIM5 functions as a ubiquitination-related E3 ligase to promote the proteasomal degradation of methyltransferases, resulting in reduction of methylation levels in the BSCTV C2-3 promoter. However, the specific domains of Rep responsible for VIM5 induction remain poorly characterized. Although Rep proteins from several geminiviruses act as viral suppressors of RNA silencing (VSRs), whether BSCTV Rep also possesses VSR activity remains to be illustrated. In this study, we employed a transient expression system in the 16c-GFP transgenic and the wild-type Nicotiana benthamiana plants to analyze the VSR and the VIM5-inducing activities of different truncated Rep proteins haboring distinct domains. We found that the N-terminal domain (amino acids 1-180) of Rep suppressed GFP silencing in 16c-GFP transgenic N. benthamiana leaves. The minimal N-terminal fragment (amino acids 1-104) induced VIM5 expression upon co-infiltration, while C-terminal truncations lacked VIM5-inducing activity. Our results indicate that the N-terminal domain of Rep encoded by BSCTV mediates the suppression of RNA silencing and induces VIM5 expression. Thus, our findings contribute to a better understanding of interactions between geminiviral Rep and plant hosts.
Geminiviridae/genetics* ; Nicotiana/metabolism* ; Arabidopsis/metabolism* ; RNA Interference ; Viral Proteins/metabolism* ; Arabidopsis Proteins/metabolism* ; Plants, Genetically Modified/metabolism* ; Protein Domains ; Plant Diseases/virology* ; Methyltransferases/metabolism* ; Ubiquitin-Protein Ligases/metabolism* ; DNA Helicases/genetics*

OBJECTIVE To explore the effects of levosimendan on cardiac function， hemodynamics and prognosis of patients with septic shock complicated with myocardial depression， and evaluate the safety of levosimendan. METHODS Patients with septic shock complicated with myocardial depression who were admitted to the Department of Critical Care Medicine of Chongqing University Three Gorges Hospital from April 2021 to August 2023， underwent adequate fluid resuscitation， had a mean arterial pressure （MAP） ≥65 mmHg， and received pulse indicator continuous cardiac output （PiCCO） monitoring were enrolled. The patients were randomly divided into dobutamine group and levosimendan group according to a random number table， with 20 patients in each group. Both groups received intravenous infusion of Norepinephrine bitartrate injection at a dose of 0.1-2.0 μg/（kg·min）. On this basis， the dobutamine group additionally received intravenous infusion of Dobutamine hydrochloride injection at a dose of 5- 10 μg/（kg·min） for 3 to 7 days， while the levosimendan group additionally received intravenous infusion of Levosimendan injection at a dose of 0.1-0.2 μg/（kg·min） for 24 hours. Heart rate （HR） and hemodynamic parameters [systolic blood pressure， diastolic blood pressure， MAP， central venous pressure （CVP）]， PiCCO monitoring parameters [cardiac function index （CFI）， cardiac index （CI）， stroke volume index （SVI）， extravascular lung water index， global end-diastolic volume index， pulmonary vascular permeability index （PVPI）， global ejection fraction （GEF）， systemic vascular resistance index， left ventricular contractility index]， and prognosis indicators [death within 3 days after administration， mechanical ventilation time，intensive care unit （ICU） stay time， 28-day mortality rate] were compared between the two groups before treatment and at 24 and 72 hours after treatment. Adverse reactions were E-mail：recorded for both groups. RESULTS Compared with before treatment in the same group， CFI， CI and GEF at 24 hours after treatment， CI and GEF at 72 hours after treatment in the dobutamine group， as well as SVI at 24 hours after treatment and SVI and GEF at 72 hours after treatment in the levosimendan group were significantly increased； PVPI at 72 hours after treatment in the dobutamine group was significantly decreased （P＜0.05）. Compared with the dobutamine group during the same period， patients in the levosimendan group had significantly lower HR and significantly higher CVP at 24 hours after treatment （P＜0.05）. Within 3 days after administration， there were no deaths in either group； there were no statistically significant differences in mechanical ventilation time， ICU stay time， 28-day mortality rate， or the incidence of adverse reactions between the two groups （P＞0.05）. CONCLUSIONS For patients with septic shock complicated with myocardial depression who have undergone adequate fluid resuscitation and have a MAP of ≥65 mmHg， levosimendan is comparable to dobutamine in improving cardiac function and hemodynamic parameters， without affecting patients’ prognosis or increasing the risk of adverse reactions such as hypotension.

Objective To investigate the epidemiological characteristics and changing trend of malignant tumor death in Danjiangkou City, the water source area along the middle route of South-to-North Water Diversion Project. Methods The surveillance data of cancer death cases in Danjiangkou City from 2015 to 2022 were collected, and the mortality rate, gender mortality rate, age-specific mortality rate and the rank of cancer cause of death were calculated. Joinpoint regression model was used to analyze the trend of malignant tumor mortality and standardized mortality. Annual percentage change (APC) and average annual percentage change (AAPC) were calculated to analyze the trend changes. Results From 2015 to 2022, a total of 6 254 deaths from malignant tumors were reported in Danjiangkou City, with a crude mortality rate of 178.57/100 000 and a standardized mortality rate of 152.77/100 000. There were 4 366 male deaths, and the crude mortality and standardized mortality were 244.70/100 000 and 212.87/100 000 , respectively. There were 1 888 female deaths, and the crude mortality rate and the standardized mortality rate were 109.89/100 000 and 92.69/100 000, respectively. The crude death rate of malignant tumors in the whole population in Danjiangkou City showed an increasing trend from 2015 to 2022, and the difference was statistically significant (AAPC=5.18%, t=4.07, P<0.05). The crude mortality rates of malignant tumors in both men and women showed an upward trend, and the differences were statistically significant (AAPC =5.56% and 4.35%, both P<0.05). The standardized mortality rates of malignant tumors in the whole population, women and men remained stable, and the differences were not statistically significant (AAPC=0.68, 1.59 and -0.74, all P>0.05). The trend analysis of age-specific mortality of malignant tumors showed that the age-specific mortality of malignant tumors in the whole population, men and women showed an increasing trend with age, and the differences were statistically significant (AAPC =9.22%, 9.40% and 8.53%, P<0.05). The mortality rate of malignant tumors in 0-, 1-, 10-, 45- and 70- age groups decreased year by year (AAPC =-79.62%, -7.19%, -65.99%, -8.88%, and -5.83%, all P<0.05). The mortality rate in the age group of over 75 years old showed an increasing trend (AAPC =12.24%, P<0.05), and the differences were statistically significant. The top 10 malignant tumor deaths in the whole population were lung cancer, gastric cancer, liver cancer, esophageal cancer, colorectal cancer , leukemia , pancreatic cancer , breast cancer , brain malignant tumor and cervical cancer, accounting for 88.49% of all malignant tumor deaths. Mortality rates in lung cancer (AAPC =6.75%), esophageal cancer (AAPC=11.24%), colorectal cancer (AAPC =12.95%), leukemia (AAPC=8.10%), pancreatic cancer (AAPC=15.11%), breast cancer (AAPC=13.11%) and brain malignancies (AAPC=11.16%) showed an increasing trend, and the differences were statistical significant (P<0.05). Conclusion Malignant tumor is the main cause of death in Danjiangkou City. The death rate increases year by year and increases with age. Lung cancer, stomach cancer and liver cancer are the main causes of death. Men and the elderly are high-risk groups of malignant tumors. Early detection and treatment of malignant tumors should be strengthened to reduce the incidence and death.

Objective In recent decades,China has implemented a series of policies to address air pollution.We aimed to assess the health effects of these policies on stroke burden attributable to ambient fine particulate matter(PM2.5). Methods Joinpoint regression was applied to explore the temporal tendency of stroke burden based on data from the Global Burden of Disease 2019 study. Results The age-standardized rates of disability-adjusted life year(DALY)for stroke attributable to ambient PM2.5 in China,increased dramatically during 1990-2012,subsequently decreased at an annual percentage change(APC)of-1.98[95%confidence interval(CI):-2.26,-1.71]during 2012-2019.For ischemic stroke(IS),the age-standardized DALY rates doubled from 1990 to 2014,and decreased at an APC of-0.83(95%CI:-1.33,-0.33)during 2014-2019.Intracerebral hemorrhage(ICH)showed a substantial increase in age-standardized DALY rates from 1990 to 2003,followed by declining trends,with APCs of-1.46(95%CI:-2.74,-0.16)during 2003-2007 and-3.33(95%CI:-3.61,-3.06)during 2011-2019,respectively.Conversely,the age-standardized DALY rates for subarachnoid hemorrhage(SAH)generally declined during 1990-2019. Conclusion Our results clarified the dynamic changes of the ambient PM2.5-attributable stroke burden in China during 1990-2019,highlighting the health effects of air quality improvement policies.

Objective:To compare the prevalence and progression of subclinical atherosclerosis (SA) in populations with different cardiovascular disease (CVD) risks in China, and clarify the relationship between CVD risk stratification and SA.Methods:All participants were from Beijing Community-Based Cohort of Atherosclerosis. A total of 1 462 participants underwent carotid ultrasound and coronary computed tomography scan during 2008-2009 and 2013-2014. After excluding 191 participants with history of CVD and incomplete baseline data, 1 271 participants were included in final analysis. The 10-year CVD risk for participants were calculated based on the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) equation, and risk stratification was performed. The prevalence and progression of SA was determined by carotid intima-media thickness (cIMT), carotid plaque score and coronary artery calcification (CAC) score.Results:In the participants included in this study, 536 (42.2%), 418 (32.9%) and 317 (24.9%) were classified to have low, intermediate and high 10-year risk, respectively. With the rising level of 10-year risk, the proportion of patients with SA and SA progression increased. In low, intermediate and high CVD risk groups, the proportions of participants with CAC were 16.4%, 36.4% and 52.0% (trend P<0.001); and 15.4%, 36.4% and 53.6% had progression of CAC during follow-up, respectively (trend P<0.001); compared with low-risk group, RRs for CAC progression of intermediate and high-risk groups were 2.316 (95% CI: 1.714-3.129) and 3.322 (95% CI: 2.472-4.463), respectively (trend P<0.001). The trend of relationship between CVD risk stratification and cIMT and carotid plaque progression were consistent with CAC. Conclusions:This current study shows CVD risk stratification is closely related to the prevalence and progression of atherosclerosis in Chinese population. However, many people with low CVD risk have atherosclerotic change in their carotid and coronary artery.