BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

OBJECTIVE: To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score. METHODS: The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion. RESULTS: Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m², NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m², albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01). CONCLUSIONS The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.

Objective: To investigate the role of inflammatory biomarkers in the relationship between blood lead levels and blood pressure changes. Methods: A total of 9 910 people aged 18-79 years who participated in the China National Human Biomonitoring in 2017-2018 were included in this study. A self-made questionnaire was used to collect demographic characteristics, lifestyle and other information, and the data including height, weight and blood pressure were determined through physical examination. Blood and urinary samples were collected for the detection of blood lead and cadmium levels, urinary arsenic levels, white blood cells, neutrophils, lymphocytes, and hypersensitive C-reactive protein (hs-CRP). Weighted linear regression models were used to evaluate the associations between blood lead, inflammatory biomarkers and blood pressure. Mediation analysis was performed to investigate the role of inflammation in the relationship between blood lead levels and blood pressure changes. Results: The median (Q₁, Q₃) age of all participants was 45.4 (33.8, 58.4)years, including 4 984 males accounting for 50.3%. Multivariate logistic regression model analysis showed that after adjusting for age, gender, residence area, BMI, education level, smoking and drinking status, family history of hypertension, consumption frequency of rice, vegetables, and red meat, fasting blood glucose, total cholesterol, triglycerides, blood cadmium and urinary arsenic levels, there was a positive association between blood lead levels, inflammatory biomarkers and blood pressure (P<0.05). Each 2.71 μg/L (log-transformed) increase of the lead was associated with a 2.05 (95%CI: 0.58, 3.53) mmHg elevation in systolic blood pressure (SBP), 2.24 (95%CI: 1.34, 3.14) mmHg elevation in diastolic blood pressure (DBP), 0.25 (95%CI: 0.05, 0.46) mg/L elevation in hs-CRP, 0.16 (95%CI: 0.03, 0.29)×10⁹/L elevation in white blood cells, and 0.11 (95%CI: 0.02, 0.21)×10⁹/L elevation in lymphocytes, respectively. Mediation analysis showed that the levels of hs-CRP significantly mediated the association of blood lead with SBP, with a proportion about 3.88% (95%CI: 0.45%, 7.32%). The analysis also found that the levels of hs-CRP and neutrophils significantly mediated the association of blood lead with SBP, with a proportion about 4.10% (95%CI: 1.11%, 7.10%) and 2.42% (95%CI: 0.07%, 4.76%), respectively. Conclusion: This study suggests that inflammatory biomarkers could significantly mediate the association of blood lead levels and blood pressure changes.
Adult ; Male ; Humans ; Blood Pressure/physiology* ; C-Reactive Protein/analysis* ; Lead ; Arsenic/analysis* ; Cadmium ; Biomarkers ; Hypertension/epidemiology* ; China/epidemiology*

Multidrug resistance (MDR) is the main cause of clinical treatment failure and poor prognosis in cancer. Targeting P-glycoprotein (P-gp) has been regarded as an effective strategy to overcome MDR. In this work, we reported our preclinical studies of the triazolo[1,5-a]pyrimidine-based compound WS-716 as a highly potent, specific, and orally active P-gp inhibitor. Through direct binding to P-gp, WS-716 inhibited efflux function of P-gp and specifically reversed P-gp-mediated MDR to paclitaxel (PTX) in multiple resistant cell lines, without changing its expression or subcellular localization. WS-716 and PTX synergistically inhibited formation of colony and 3D spheroid, induced apoptosis and cell cycle arrest at G2/M phase in resistant SW620/Ad300 cells. In addition, WS-716 displayed minimal effect on the drug-metabolizing enzyme cytochrome P4503A4 (CYP3A4). Importantly, WS-716 increased sensitivity of both pre-clinically and clinically derived MDR tumors to PTX in vivo with the T/C value of 29.7% in patient-derived xenograft (PDX) models. Relative to PTX treatment alone, combination of WS-716 and PTX caused no obvious adverse reactions. Taken together, our preclinical studies revealed therapeutic promise of WS-716 against MDR cancer, the promising data warrant its further development for cancer therapy.

Objective: : A role of diffusion-weighted imaging (DWI) in the diagnosis of cerebral venous thrombosis (CVT) is not wellunderstood. This study evaluates the effectiveness of DWI in the diagnosis of CVT. Methods: : Literature search was conducted in electronic databases for the identification of studies which reported the outcomes of patients subjected to DWI for CVT diagnosis. Random-effects meta-analyses were performed to achieve overall estimates of important diagnostic efficiency indices including hyperintense signal rate, the sensitivity and specificity of DWI in diagnosing CVT, and the apparent diffusion coefficient (ADC) of DWI signal areas and surrounding tissue. Results: : Nineteen studies (443 patients with 856 CVTs; age 40 years [95% confidence interval (CI), 33 to 43]; 28% males [95% CI, 18 to 38]; symptom onset to DWI time 4.6 days [95% CI, 2.3 to 6.9]) were included. Hyperintense signals on DWI were detected in 40% (95% CI, 26 to 55) of the cases. The sensitivity of DWI for detecting CVT was 22% (95% CI, 11 to 34) but specificity was 98% (95% CI, 95 to 100). ADC values were quite heterogenous in DWI signal areas. However, generally the ADC values were lower in DWI signal areas than in surrounding normal areas (mean difference−0.33×10-3 mm2/s [95% CI, −0.44 to −0.23]; p<0.00001). Conclusion : DWI has a low sensitivity in detecting CVT and thus has a high risk of missing many CVT cases. However, because of its high specificity, it may have supporting and exploratory roles in CVT diagnosis.

Objective: : A role of diffusion-weighted imaging (DWI) in the diagnosis of cerebral venous thrombosis (CVT) is not wellunderstood. This study evaluates the effectiveness of DWI in the diagnosis of CVT. Methods: : Literature search was conducted in electronic databases for the identification of studies which reported the outcomes of patients subjected to DWI for CVT diagnosis. Random-effects meta-analyses were performed to achieve overall estimates of important diagnostic efficiency indices including hyperintense signal rate, the sensitivity and specificity of DWI in diagnosing CVT, and the apparent diffusion coefficient (ADC) of DWI signal areas and surrounding tissue. Results: : Nineteen studies (443 patients with 856 CVTs; age 40 years [95% confidence interval (CI), 33 to 43]; 28% males [95% CI, 18 to 38]; symptom onset to DWI time 4.6 days [95% CI, 2.3 to 6.9]) were included. Hyperintense signals on DWI were detected in 40% (95% CI, 26 to 55) of the cases. The sensitivity of DWI for detecting CVT was 22% (95% CI, 11 to 34) but specificity was 98% (95% CI, 95 to 100). ADC values were quite heterogenous in DWI signal areas. However, generally the ADC values were lower in DWI signal areas than in surrounding normal areas (mean difference−0.33×10-3 mm2/s [95% CI, −0.44 to −0.23]; p<0.00001). Conclusion : DWI has a low sensitivity in detecting CVT and thus has a high risk of missing many CVT cases. However, because of its high specificity, it may have supporting and exploratory roles in CVT diagnosis.

OBJECTIVE: To investigate the clinical application and efficacy of ¹²⁵Ⅰ radioactive seeds implantation in the treatment of recurrent salivary gland carcinoma after external radiotherapy. METHODS: From July 2004 to July 2016, 43 cases of recurrent salivary gland carcinoma of the neck after external radiotherapy or surgery combined with external radiotherapy were treated. According to the conventional segmentation radiotherapy for head and neck cancer (once a day, 1.8-2.0 Gy each time, 5 days per week), the cumulative radiation dose of the patients in this group was calculated. In the study, 26 patients received 50-60 Gy, 7 patients received less than 50 Gy, 4 patients received 60-70 Gy, and 6 patients received more than 80 Gy (range: 80-120 Gy). The interval between the last external irradiation and local recurrence was 4-204 months, and the median interval was 48 months. Among them, 25 cases were treated with ¹²⁵Ⅰ radioactive seeds implantation only and 18 cases were treated with ¹²⁵Ⅰ radioactive seeds implantation after operation. The prescription dose was 100-140 Gy. The control rate, survival rate and disease-free survival rate were recorded to evaluate the side effects. RESULTS: The median follow-up time was 27 months (ranging from 2.5 to 149.0 months). Among them, the median follow-up time of adenoid cystic carcinoma patients was 31 months (range: 2.5-112.0 months), and the median follow-up time of mucoepidermoid carcinoma patients was 18 months (range: 5-149 months). The local control rates for 1, 3 and 5 years were 66.5%, 48.8% and 42.7%, respectively. The 1-, 3- and 5- year survival rates were 88.0%, 56.7% and 45.8%, respectively. The disease-free survival rates of 1, 3 and 5 years were 58.3%, 45.4% and 38.1%, respectively. There was no statistically significant difference in local control rate, survival rate, and disease-free survival between the radioactive seeds implantation group and the radioactive seeds implantation group after surgical resection. There were 2 cases of acute radiation reaction Ⅰ/Ⅱ and 3 cases of reaction Ⅲ or above. In the late stage of radiotherapy, there were 8 cases with Ⅰ/Ⅱ grade reaction and 3 cases with Ⅲ grade or above reaction. The incidence of radiation reactions of Grade Ⅲ and above was 7%. CONCLUSION ¹²⁵Ⅰ radioactive seeds implantation provides an alternative method for the treatment of recurrent salivary gland carcinoma after external radiotherapy. The local control rate and survival rate are improved on the premise of low incidence of side effects.
Brachytherapy/adverse effects* ; Humans ; Iodine Radioisotopes/therapeutic use* ; Neoplasm Recurrence, Local/radiotherapy* ; Salivary Gland Neoplasms/radiotherapy* ; Salivary Glands

In December 2019, coronavirus disease 2019 (COVID-19), a new de novo infectious disease, was first identified in Wuhan, China and quickly spread across China and around the world. The etiology was a novel betacoronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Lu et al., 2020). On Mar. 11, 2020, World Health Organization (WHO) characterized COVID-19 as a global pandemic. As of Mar. 22, 2020, over 292 000 confirmed COVID-19 cases have been reported globally. To date, COVID-19, with its high infectivity, has killed more people than severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) combined (Wu and McGoogan, 2020).
Adult ; Betacoronavirus ; COVID-19 ; COVID-19 Testing ; China ; Clinical Laboratory Techniques ; Coronavirus Infections/diagnostic imaging* ; Female ; Fever/virology* ; Humans ; Lymphocyte Count ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral/diagnostic imaging* ; Radiography, Thoracic ; SARS-CoV-2 ; Tomography, X-Ray Computed ; Treatment Outcome

Objective To establish and evaluate a rat model of inhalation lung injury induced by ship smog.Methods A rat model of inhalation lung injury was established by analyzing the composition of ship materials after combustion.Fortytwo healthy male Wistar rats were randomly divided into normal control group and 2,6,12,24,48 and 72h groups (6 each)after inhalation,these rats were killed at each time point,and the changes of arterial blood gas,coagulation function,the lung water content (％) were detected.Macroscopic and microscopic changes in lung tissues were observed to judge the degree of lung injury.Results The main components after combustion of 7 kinds of nonmetal materials on ship included CO,CO2,H2S,NOx and other harmful gases in this study,AIKE in one gas detector was used to monitor O2,CO,CO2 and H2S,and their concentrations remained relatively stable within 15 minutes,and the injury time was 15 minutes.The rats presented with shortness of breath and mouth breathing.Smoke inhalation caused a significant hypoxemia,the concentration of blood COHb reached a peak value 2h and the lung water content (％) did 6h after inhalation (P＜0.05).It is metabolic acidosis in the early stage after inhalation,but metabolic acidosis combined with respiratory acidosis in the later period.Histopathological observation showed diffuse hemorrhage,edema and inflammatory cell infiltration in the lung tissue as manifestations of lung injury,and the injury did not recover at 72h after inhalation,the change of blood coagulation function was not statistically significant.Conclusion A rat model of inhalation lung injury induced by ship smog has been successfully established,and has the advantages of easy replication,stability and reliability,thus can be used to research and treat inhalation lung injury induced by ship smog in naval war environment and other cases.

Objectives: To explore the clinical experience for a bridge therapy of percutaneous balloon aortic valvuloplasty (PBAV) in treating the patients with severe aortic stenosis (AS). Methods: A total of 37 patients with severe AS who were not suitable for surgical valvular replacement received PBAV in our hospital from 2011-03 to 2017-03 were retrospectively studied. The patient's mean age was (74±12) years, their clinical and anatomical features, efficacy and safety of operation were observed and the outcomes were evaluated by follow-up study. Results: Patients presented the high surgical risk and worse cardiac function, 50% of them had bicuspid leaflet morphology with severe calcification [HU850=(856.0±658.2) mm3]. Balloon size was chosen by the intra-operative supra-annular diameters; at 7 days after operation, aortic valve orifice area (AVOA) was increased from (0.37±0.10) cm2to (0.87±1.10) cm2, the mean trans-aortic valve gradient pressure decreased form (55.1±22.9) mmHg to (44.8±17.8) mmHg, P<0.001 and LVEF elevated form(35.8±14.3)% to(41.0±12.2)%,P<0.001.There were 4 patients died in hospital,1 received permanent pacemaker and 1 developed severe aortic valve regurgitation. The patients were followed-up for (16.5±11.1)months after operation, 13/37 (35.1%) patients were in transition to surgical or transcatheter aortic valve replacement (TAVR). Conclusions: PBAV may have good early clinical efficacy in severe AS patients who were not suitable for surgical valvular replacement and TAVR; PBAV could be expected to become a bridge therapy, smaller supra-annular diameter was safe and effective for patients having bicuspid leaflet with severe calcification.