BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

Objective To investigate the role of RNA-binding motif protein X-linked(RBMX)in regulating the proliferation,migration,invasion and glycolysis in human bladder cancer cells.Methods A lentivirus vectors system and RNA interference technique were used to construct bladder cancer 1376 and UC-3 cell models with RBMX overexpression and knockdown,respectively,and successful cell modeling was verified using RT-qPCR and Western blotting.Proliferation and colony forming ability of the cells were evaluated using EdU assay and colony-forming assay,and cell migration and invasion abilities were determined using Transwell experiment.The expressions of glycolysis-related proteins M1 pyruvate kinase(PKM1)and M2 pyruvate kinase(PKM2)were detected using Western blotting.The effects of RBMX overexpression and knockdown on glycolysis in the bladder cancer cells were assessed using glucose and lactic acid detection kits.Results RT-qPCR and Western blotting confirmed successful construction of 1376 and UC-3 cell models with RBMX overexpression and knockdown.RBMX overexpression significantly inhibited the proliferation,clone formation,migration and invasion of bladder cancer cells,while RBMX knockdown produced the opposite effects.Western blotting results showed that RBMX overexpression increased the expression of PKM1 and decreased the expression of PKM2,while RBMX knockdown produced the opposite effects.Glucose consumption and lactate production levels were significantly lowered in the cells with RBMX overexpression(P<0.05)but increased significantly following RBMX knockdown(P<0.05).Conclusion RBMX overexpression inhibits bladder cancer progression and lowers glycolysis level in bladder cancer cells by downregulating PKM2 expression,suggesting the potential of RBMX as a molecular target for diagnosis and treatment of bladder cancer.

OBJECTIVE To evaluate the cost-effectiveness of using Bacillus Calmette-Guérin （BCG） versus epirubicin for intravesical perfusion after transurethral resection of bladder tumor （TUR-BT） in patients with intermediate- to high-risk non-muscle- invasive bladder cancer （NMIBC）. METHODS From the perspective of China’s health system， a Markov cohort model was constructed based on the ChiCTR-IIR-16008357 study. Quality-adjusted life years （QALYs） were used as the health outcome measure， with the willingness-to-pay（WTP） threshold set at one time the per capita gross domestic product of China in 2023 （89 358 yuan/QALY）. A cost-utility analysis was used to compare the incremental cost-effectiveness ratio （ICER） of the BCG regimen relative to the epirubicin regimen for intravesical perfusion after TUR-BT in patients with intermediate- to high-risk NMIBC in China. In addition， sensitivity analysis was performed. RESULTS The incremental cost of the BCG regimen compared to the epirubicin regimen was 34 309.51 yuan， with an incremental utility of 0.800 QALYs， resulting in an ICER of 42 871.33 yuan/QALY， which is below the WTP threshold. When the WTP threshold was 89 358 yuan/QALY， the probability that the BCG regimen would be acceptable was 77.70% in the probabilistic sensitivity analysis， higher than that of the epirubicin regimen， and the acceptability of the BCG regimen increased with increasing in the WTP threshold. CONCLUSIONS When the WTP threshold was set at one time the per capita gross domestic product of China in 2023， compared to epirubicin， BCG used for intravesical perfusion after TUR-BT in patients with intermediate- to high-risk NMIBC demonstrated better cost-effectiveness.

Objective To investigate the role of RNA-binding motif protein X-linked(RBMX)in regulating the proliferation,migration,invasion and glycolysis in human bladder cancer cells.Methods A lentivirus vectors system and RNA interference technique were used to construct bladder cancer 1376 and UC-3 cell models with RBMX overexpression and knockdown,respectively,and successful cell modeling was verified using RT-qPCR and Western blotting.Proliferation and colony forming ability of the cells were evaluated using EdU assay and colony-forming assay,and cell migration and invasion abilities were determined using Transwell experiment.The expressions of glycolysis-related proteins M1 pyruvate kinase(PKM1)and M2 pyruvate kinase(PKM2)were detected using Western blotting.The effects of RBMX overexpression and knockdown on glycolysis in the bladder cancer cells were assessed using glucose and lactic acid detection kits.Results RT-qPCR and Western blotting confirmed successful construction of 1376 and UC-3 cell models with RBMX overexpression and knockdown.RBMX overexpression significantly inhibited the proliferation,clone formation,migration and invasion of bladder cancer cells,while RBMX knockdown produced the opposite effects.Western blotting results showed that RBMX overexpression increased the expression of PKM1 and decreased the expression of PKM2,while RBMX knockdown produced the opposite effects.Glucose consumption and lactate production levels were significantly lowered in the cells with RBMX overexpression(P<0.05)but increased significantly following RBMX knockdown(P<0.05).Conclusion RBMX overexpression inhibits bladder cancer progression and lowers glycolysis level in bladder cancer cells by downregulating PKM2 expression,suggesting the potential of RBMX as a molecular target for diagnosis and treatment of bladder cancer.

Objectives:To evaluate the cost-effectiveness of typical pharmaceutical smoking cessation intervention strategies in China in the context of primary cancer prevention.Methods:Markov cohort simulation models were established to simulate the burden of 12 smoking caused cancer, including lung cancer, oral cancer, nasopharyngeal cancer, laryngeal cancer, esophageal cancer, gastric cancer, pancreatic cancer, liver cancer, kidney cancer, bladder cancer, cervical cancer, and acute myeloid leukemia. Taking incremental cost effectiveness ratio (ICER) as the main indicator, the model sets one year as the cycling period for 50 periods and simulates the cohort of 10 000 thirty-five-year-old current smokers with various smoking cessation strategies. To ensure the robustness of conclusion, univariate sensitivity analysis, probability sensitivity analysis, and age-group sensitivity analysis were conducted.Results:The results showed that varenicline intervention was the most cost-effective intervention. Compared to the next most effective option, incremental cost of each additional quality-adjusted life year is 11 140.28 yuan, which is below the threshold of willingness to pay (1 year GDP per capita). The value of ICER increased as the increasing age group of adopting intervention, but neither exceeded the threshold of willingness to pay. One-way sensitivity analysis showed that the value of discount rate, the hazard ratio and cost of intervention strategy had a greater impact on the result of ICER.Conclusion:In China, the use of varenicline to quit smoking is highly cost effective in the context of cancer primary prevention, especially for younger smokers.

Objective:To explore the effect of the developmental stages and quality on pregnancy outcome and birth outcome, and provide evidence for single blastocyst selection in frozen-thawed cycles.Methods:A retrospective cohort study analysis was performed on the data of patients with a total of 893 cycles who underwent single blastocyst transfer in frozen-thawed cycles in the Center for Reproductive Medicine, Qingyuan People's Hospital from January 2013 to June 2021. The cycles were divided into day 5 (D5) and day 6 (D6) groups according to the time of blastocyst formation. Then the two groups were divided into four subgroups according to the quality of blastocyst, namely, D5 good-quality embryo subgroup, D5 non-good-quality embryo subgroup, D6 good-quality embryo subgroup and D6 non-good-quality embryo subgroup. The general data, clinical outcomes and neonatal outcomes of each group were compared.Results:1) The clinical pregnancy rate [60.14% (332/552)], the implantation rate [60.14% (332/552)] and the live birth rate [47.64% (263/552)] in D5 group were significantly higher than those in D6 group [45.75% (156/341), 45.75% (156/341), 36.36% (124/341), all P<0.001], but there were no significant differences in body mass index, duration of infertility, intimal thickness of transplantation day and miscarriage rate between the two groups (all P>0.05). In addition, there were also no significant differences in birth weight, low birth weight rate, fetal macrosomia rate and male/female ratio (all P>0.05). 2) There were significant differences in clinical pregnancy rate [61.00% (294/482), 54.29% (38/70), 51.00% (127/249), 31.52% (29/92)] and live birth rate [48.96% (236/482), 38.57% (27/70), 41.37% (103/249), 22.83% (21/92)] among D5 good-quality embryo subgroup, D5 non-good-quality embryo subgroup, D6 good-quality embryo subgroup and D6 non-good-quality embryo subgroup (all P<0.001). D5 good-quality embryo subgroup had the highest clinical pregnancy rate and live birth rate, while D6 non-good-quality embryo subgroup had the lowest clinical pregnancy rate and live birth rate. There were also no significant differences in birth weight, fetal macrosomia rate and male/female ratio among the four subgroups (all P>0.05), while there was a significant difference in low birth weight rate [5.08% (12/236), 0 (0/27), 4.85% (5/103), 23.81% (5/21)] among the four subgroups ( P=0.014). 3) There were no significant differences in clinical pregnancy rate and live birth rate between D5 non-good-quality embryo subgroup and D6 good-quality embryo subgroup (all P>0.05). The clinical pregnancy rate and the live birth rate of 4BC in D5 were lower than those of 4AA, 4AB and 4BA in D6, while the miscarriage rate of 4BC in D5 was higher than that of 4AA, 4AB and 4BA in D6, but there were no significant differences (all P>0.05).The clinical pregnancy rate and the live birth rate of 4BC in D5 were higher than those of 4BB in D6, but there were no significant differences (all P>0.05). Conclusion:In the frozen-thawed cycle of single blastocyst transplantation, D5 good-quality blastocysts are preferred. When faced with D5 non-good-quality embryos and D6 good-quality embryos, the optimal choice was D6 4AA>D6 4BA>D6 4AB>D5 4BC>D6 4BB.

Objective:To explore the effect of the developmental stages and quality on pregnancy outcome and birth outcome, and provide evidence for single blastocyst selection in frozen-thawed cycles.Methods:A retrospective cohort study analysis was performed on the data of patients with a total of 893 cycles who underwent single blastocyst transfer in frozen-thawed cycles in the Center for Reproductive Medicine, Qingyuan People's Hospital from January 2013 to June 2021. The cycles were divided into day 5 (D5) and day 6 (D6) groups according to the time of blastocyst formation. Then the two groups were divided into four subgroups according to the quality of blastocyst, namely, D5 good-quality embryo subgroup, D5 non-good-quality embryo subgroup, D6 good-quality embryo subgroup and D6 non-good-quality embryo subgroup. The general data, clinical outcomes and neonatal outcomes of each group were compared.Results:1) The clinical pregnancy rate [60.14% (332/552)], the implantation rate [60.14% (332/552)] and the live birth rate [47.64% (263/552)] in D5 group were significantly higher than those in D6 group [45.75% (156/341), 45.75% (156/341), 36.36% (124/341), all P<0.001], but there were no significant differences in body mass index, duration of infertility, intimal thickness of transplantation day and miscarriage rate between the two groups (all P>0.05). In addition, there were also no significant differences in birth weight, low birth weight rate, fetal macrosomia rate and male/female ratio (all P>0.05). 2) There were significant differences in clinical pregnancy rate [61.00% (294/482), 54.29% (38/70), 51.00% (127/249), 31.52% (29/92)] and live birth rate [48.96% (236/482), 38.57% (27/70), 41.37% (103/249), 22.83% (21/92)] among D5 good-quality embryo subgroup, D5 non-good-quality embryo subgroup, D6 good-quality embryo subgroup and D6 non-good-quality embryo subgroup (all P<0.001). D5 good-quality embryo subgroup had the highest clinical pregnancy rate and live birth rate, while D6 non-good-quality embryo subgroup had the lowest clinical pregnancy rate and live birth rate. There were also no significant differences in birth weight, fetal macrosomia rate and male/female ratio among the four subgroups (all P>0.05), while there was a significant difference in low birth weight rate [5.08% (12/236), 0 (0/27), 4.85% (5/103), 23.81% (5/21)] among the four subgroups ( P=0.014). 3) There were no significant differences in clinical pregnancy rate and live birth rate between D5 non-good-quality embryo subgroup and D6 good-quality embryo subgroup (all P>0.05). The clinical pregnancy rate and the live birth rate of 4BC in D5 were lower than those of 4AA, 4AB and 4BA in D6, while the miscarriage rate of 4BC in D5 was higher than that of 4AA, 4AB and 4BA in D6, but there were no significant differences (all P>0.05).The clinical pregnancy rate and the live birth rate of 4BC in D5 were higher than those of 4BB in D6, but there were no significant differences (all P>0.05). Conclusion:In the frozen-thawed cycle of single blastocyst transplantation, D5 good-quality blastocysts are preferred. When faced with D5 non-good-quality embryos and D6 good-quality embryos, the optimal choice was D6 4AA>D6 4BA>D6 4AB>D5 4BC>D6 4BB.

OBJECTIVE: To test the performance of CHADS-VASc score in predicting stroke recurrence in first-ever ischemic stroke survivors without atrial fibrillation (AF). METHODS: A total of 768 patients were included in this study, including 475 male (61.85%) and 293 female patients (38.15%) with a mean age of 61.52±12.59 years (17-90 years). The baseline information of the patients was collected by face-to-face questionnaire survey and electronic medical record review, and their follow-up information was collected by telephone follow-up once every 3 months. Chi-square test and Wilcoxon rank sum test were used to compare the baseline characteristics between the patients regularly followed up and those withdrawn from the study. The area under the ROC curve (AUC), sensitivity, specificity, positive likelihood ratio and other indicators of CHADS-VASc score were determined, and C-index based on Cox proportional hazards model was used to evaluate the performance of CHADS- VASc score in predicting the risk of stroke recurrence in patients at different time points during the follow-up. RESULTS: The 1-year, 3-year, and 5-year recurrence rate of stroke was 10.59%, 20.45%, and 29.46% in these patients, respectively. The AUC value, Optimal Operating Point (OOP) and the corresponding positive likelihood ratios (LR+) for predicting stroke recurrence were 0.558 (95%: 0.492-0.624), 4.5, and 1.256 at 1 year; 0.574 (95%: 0.517-0.630), 4.5, and 1.397 at 3 years; and 0.604 (95%: 0.548-0.661), 4.5, and 1.655 at 5 years, respectively. Sensitivity analysis of congestive heart failure showed that the predictive effect of CHADS-VASc score was basically unchanged. CONCLUSIONS CHADS-VASc score can be used to predict the 3-year and 5-year risk of stroke recurrence in first-ever ischemic stroke survivors without AF. The score has a better prediction ability for long-term stroke recurrence, but the prediction value remains low, suggesting the need to further improve the score or establish a new score for predicting stroke recurrence.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Atrial Fibrillation ; Brain Ischemia ; Female ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Risk Assessment ; Risk Factors ; Stroke ; Survivors ; Young Adult

OBJECTIVE: To investigate the association between alcohol drinking and all-cause death in patients with ischemic stroke. METHODS: Between January, 2010 and July, 2018, consecutive patients with first-episode ischemic stroke admitted in the West China Hospital, Sichuan University were enrolled, and all the patients were followed up every 3 months.Chi-square test was used to compare the differences in the baseline characteristics between the pre-stroke drinkers and the nondrinkers.The Cox regression model was used to analyze the effects of drinking status, drinking years, drinking frequency, average single alcohol intake before stroke and drinking status during the follow-up period on the mortality of patients after discharge. RESULTS: A total of 855 patients with ischemic stroke were enrolled, and deaths occurred in 140 of these patients.Chi-square test showed significant differences in gender ( < 0.001), weekly physical exercise time (=0.035), smoking ( < 0.001), and heart disease ( < 0.001) between the pre-stroke drinkers and nondrinkers.Multivariate Cox regression analysis showed that drinking during the follow-up period (=0.001), drinking for less than 28 years before stroke (=0.035) and a moderate drinking frequency (5 to 20 times per month for males and 4 to 9 times per month for females; =0.030) were associated with a lowered risk of death after discharge.No significant effects of pre-stroke drinking status or average single alcohol intake were found on death after ischemic stroke. CONCLUSIONS The drinking years and drinking frequency before stroke and drinking status during the follow-up period are related to the all-cause mortality in patients with ischemic stroke.Investigations of the more specific variables of drinking behaviors during the follow-up period are needed to further clarify the association between drinking and death after ischemic stroke.
Alcohol Drinking ; adverse effects ; Brain Ischemia ; etiology ; China ; Female ; Follow-Up Studies ; Humans ; Male ; Risk Factors ; Stroke ; etiology

Objective To explore the measurement of(1,3)-β-D glucan in plasma for the diagnosis of pulmonary fungal infections in pulmonary tuberculosis patients. Methods 40 pulmonary tuberculosis patients with pulmonary fungal infections in Guangzhou chest hospital from January 2015 to December 2015 were enrolled as a test group,among which 35 were confirmed and 5 were suspected pulmonary fungal infections. 52 pulmonary tuber-culosis patients without fungal infections were selected as a control group.(1,3)-β-D glucan content(G test)in this 92 patients plasma were detected. The results of G tests were compared with those from etiological diagnosis to assess the performance of G test. Results 13 strains of candida albicans,13 strains of aspergillus,2 strains of candida tropicalis,2 strains of candida glabrata and 6 strains of other yeast were obtained from patients of test group,but no fungal identified from those of control group. The median of G test in test group and in control group was 126.1 and 29.56 pg/mL,respectively,the level in test group was significantly higher than that in control group (P<0.001). 35 cases were identified as positive and 5 were negative in test group by G test ,while 41 cases were identified as negative and 11 were positive in control group. The sensitivity,specificity,positive predictive value, negative predictive value ,concordance and Youden index of G test were 87.5%,78.85%,76.09%,89.13%, 82.6%and 0.663,respectively. Conclusions Candida albicans and aspergillus are more common pathogens than the other fungi isolated from pulmonary tuberculosis patients with pulmonary fungal infection. G test ,used in pul-monary tuberculosis with pulmonary fungal infections diagnosis,is reliable and fast,and has a higher sensitivity, specificity and accuracy.