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 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 effects of Setaria italica extract on improving insomnia model mice and to explore its potential mechanisms. METHODS The mice were randomly assigned into blank group， model group， positive control group （diazepam， 2.6 mg/kg）， and S. italica extract low-dose， medium-dose and high-dose groups （1.2， 2.4， 4.8 g/kg）， with 10 mice in each group. Except for the blank group， all other groups received intraperitoneal injection of para-chlorophenylalanine （PCPA） to establish the insomnia model. After modeling， the blank group and model group were given a constant volume of normal saline intragastrically， and administration groups were given relevant medicine intragastrically， with a volume of 0.01 mL/g， once a day， for 7 consecutive days. After the administration， the open-field test was conducted to observe the praxiological changes of mice， and to determine the levels of 5-hydroxytryptamine （5-HT） and 5-hydroxyindoleacetic acid （5-HTAA） in the hippocampal tissue， as well as the contents of 5-HT， brain-derived neurotrophic factor （BDNF）， interleukin-2 （IL-2）， IL-6， B-cell lymphoma-2 （Bcl- 2）， and Bcl-2-associated X protein （Bax） in the serum. The expression of phosphoinositide 3-kinase/protein kinase B/nuclear factor- κB （PI3K/Akt/NF-κB） signaling pathway related protein was determined in the hippocampus of mice. RESULTS Compared with the model group， the total exercise time of mice in S. italica extract high-dose group was significantly prolonged， but the total rest time was significantly shortened （P＜0.01）； the number of standing times and modification times were significantly reduced （P＜ 0.01）. The contents of 5-HT， BDNF， and Bcl-2 in serum， and Bcl-2/Bax were significantly increased， while the contents of IL-2， IL-6， and Bax were significantly reduced （P＜0.05 or P＜ 0.01）. The content of 5-HTAA in the hippocampal tissue and 202104010910029）；the phosphorylation levels of PI3K and Akt proteins were increased significantly， while the phosphorylation level of NF-κB p65 protein was decreased significantly （P＜0.05）.CONCLUSIONS High-dose of S. italica extract demonstrates significant therapeutic effects on insomnia in mice， and the mechanism of which may be associated with the regulation of PI3K/Akt/NF-κB signaling pathway.

Objective:To investigate the therapeutic effect of open suture and selective suture in patients with high complexity anal fistula and its effect on anal function and complications.Methods:Prospectively selected 174 patients with high complex anal fistula who were hospitalized in the Anorectal Surgery Department of the Second People′s Hospital of Yibin City from December 2018 to December 2021 as the study subjects, including 138 males and 36 females, aged from 26 to 45 years, with an average of (35.20 ± 8.86) years. According to the admission order of patients, grouped them into single and double numbers, with single numbers being the control group ( n=87) and double numbers being the observation group ( n=87). The control group was treated with traditional incision and thread hanging therapy, while the observation group was treated with selective suture through incision and thread hanging therapy. Compared the surgical time, blood loss, surgical cost, wound healing time, and anal function at 6 months after surgery between the two groups of patients. Compared the treatment effects of two groups of patients at 6 months after surgery. Compared the postoperative complications within 6 months and recurrence within 1 year between the two groups. The measurement data subject to normal distribution were expressed by mean ± standard deviation( ± s). The two groups were compared by independent sample t test, and the count data were compared by Chi-square test. Rank sum test was used for comparison of hierarchical data. Results:The surgical time in the observation group was higher than that in the control group [(44.30 ± 8.11) min vs (42.18 ± 7.25) min, ( t=-2.44, P<0.05], and the surgical cost was higher than that in the control group [(1184.81 ± 372.68) yuan vs (835.28 ± 320.03) yuan, t=-8.75, P<0.001]. There was no statistically significant difference in blood loss data between the two groups [(19.57 ± 6.07) mL vs (18.35 ± 5.25) mL, t=-1.88, P>0.05]. The length of wound healing time in the observation group was lower than that in the control group [(24.18 ± 4.35) d vs (29.35 ± 5.08) d, t=11.09, P<0.001]. The anal function score of the observation group at 6 months after surgery was lower than that of the control group [(4.80 ± 1.21) score vs (6.71 ± 1.35) score, t=14.72, P<0.001]. All patients did not experience any loss of follow-up. In the comparison of treatment effects 6 months after surgery, the observation group had a better efficacy rating than control group ( Z=3.86, P<0.001). At 6 months after surgery, the incidence of complications in the observation group was lower than that in the control group [2.30% (2/87) vs 10.34% (9/87), χ2=4.76, P<0.05]. One year after surgery, the recurrence rate in the observation group was lower than that in the control group [2.30% (2/87) vs 10.34% (9/87), χ2=4.76, P<0.05]. Conclusion:The application of incision and thread-drawing selective suture in the treatment of patients with high complex anal fistula is beneficial to the treatment effect of patients, reduces postoperative complications, and protects the anal function of patients, with good use value.

OBJECTIVE To study the impr ovement effects of Dianxianqing granule on blood-brain barrier （BBB）injury in Alzheimer’s disease （AD）model mice by regulating NLR family pyrin domain containing 3（NLRP3）inflammasome signaling pathway. METHODS Totally 125 mice were randomly divided into sham operation group （n＝25）and modeling group （n＝100） by body weight. AD model was induced by intracerebroventricular injection of β-amyloid 25-35 in model group. Sham operation group was given normal saline with same method. The 100 model mice were randomly divided into model group ，Donepezil hydrochloride tablets group （positive control 1，1.3 mg/kg，i.g.），MCC950 group [positive control 2（selective NLRP 3 inhibitor），10 mg/kg，i.p.] and Dianxianqing granule group （12.48 g/kg by crude drug ，i.g.）by body weight ，with 25 mice in each group. Second day after modeling ，administration groups were given relevant medicine ，once a day ，for consecutive 21 d. Sham operation group and model group were given intragastric administration of water and intraperitoneal injection of normal saline. At last administration，the learning and memory ability was determined by Y maze test ，and blood-brain barrier permeability was measured by Evans blue leakage assay. The expressions of NLRP 3，anti-ionized calcium-binding adapter molecule 1（IBA-1），nuclear factor kappa B （NF-κB）p65，p53 upregulated modulator of apoptosis （PUMA），occludin（ocln），zonula occluden- 1（ZO-1）and claudin-5 （cldn5） in cerebral tissue were determined. RESULTS Compared with model group ， spontaneous alternate response rate ，protein expressions of ocln ，cldn5 lnzyxyqy2003@163.com and ZO- 1 in cerebral tissue were increased significantly in administration groups （P＜0.05 or P＜0.01）；Evans blue E-mail：jiadg2003@126.com content and protein expressions of NLRP 3，IBA-1，PUMA and NF-κB p65 in cerebral tissue were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Dianxianqing granule can improve BBB injury of AD model m ice by inhibiting NLRP 3 inflammasome signaling pathway.

Objective:To investigate the significance and mechanism of ten-eleven translocation (Tet1) against Mycobacterium marinum ( Mm) infection in mice. Methods:SPF wild-type C57BL/6 and Tet1-knockout (Tet1KO) mice were injected intravenously with Mm. All mice were monitored and the abscesses formed in tail were observed and quantified. Pathological changes in mouse tail tissues were observed using hematoxylin and eosin (HE) staining and transmission electron microscopy and the differences between the two groups were analyzed. Immunohistochemistry staining was used to detect the expression and distribution of TNF-α and TGF-β in mouse tail tissues. Moreover, mouse tail tissues were cultured on 7H10 plates for bacterial counting. The expression of NF-κBp65 and TGF-β was detected by Western blot. Results:Obvious lesions including abscesses and ulcers were formed in the Mm-infected C57BL/6, but only scattered small abscesses were observed in Mm-infected Tet1KO mice. During Mm infection, the bacterial load was gradually increased in C57BL/6 mice, but decreased in Tet1KO mice. Histopathological examination showed that obvious inflammatory cell infiltration and typical granulomatous lesions were found in Mm-infected C57BL/6 mice, while no significant inflammatory cell infiltration was detected in Mm-infected Tet1KO mice. Immunohistochemistry staining demonstrated that the expression of TNF-α and TGF-β was lower in Mm-infected Tet1KO mice than in Mm-infected C57BL/6 mice. Moreover, the expression of phosphorylated NF-κBp65 and TGF-β was significantly reduced in Mm-infected Tet1KO mice as compared with that in Mm-infected C57BL/6 mice. Conclusions:Deletion of Tet1 could alleviate the inflammatory damage mediated by Mm and enhance the host immune response to bacteria.

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 investigate the effect of different turnover intervals in preventing stress injury to patients in emergency room. Methods: The 200 eligible patients from July 2016 to July 2017 were divided into 4 groups by random number table method, 50 patients per group, named as the conventional group, test group 1, test group 2 and test group 3. Turning frequency was used for 2.0 h in the conventional group, and 2.5 h, 3.0 h and 3.5 h in the first, second and third groups, respectively. The average body pressure of the shoulder blade, left and right lateral ankle and sacral tail between the four groups at different turning time, the incidence of stress injuries, the comprehensive satisfaction of patients with turn-over nursing were compared. Results: There was no statistically significant difference in the body pressure value of the main compression site between the four groups (P>0.05), and the incidence of stress injury was 2.0% (1/50), 2.0% (1/50), 2.0% (1/50), and 4.0% (2/50), respectively (P>0.05). The comprehensive satisfaction degree of the patients in the four groups was 71.0%(71/100), 75.0%(81/108), 79.8% (83/104), and 86.6% (97/112), respectively, with statistically significant differences (χ²=8.517, P< 0.05). For each of the two groups, only the general group and the experimental group showed statistically significant differences in the comprehensive satisfaction degree of the patients in the three groups (χ²=7.824, P< 0.01). Conclusions It shows that the 3.5 h turning-over interval can effectively prevent stress injuries, improve patient satisfaction, and reduce the workload of nursing staff without affecting patient treatment, nursing, and stress injury prevention.

Objective To evaluate the geometric and dosimetric accuracy of autosegmentation software for contouring the organ-at-risk ( OAR) of esophageal cancer, and discuss its clinical feasibility. Methods A total of 10 patients were enrolled, and single and multi-template were adopted respectively to auto-delineate corresponding OARs on target CT images based on image registration. The geometric consistency including volume difference (ΔV) , dice similarity ( DSC) and position difference (Δx, Δy,Δz) between the two autosegmentation method and manual were compared using Wilcoxon signed-rank test. And the correlation between DSC and OAR volume was analyzed. In addition, to evaluate the clinical feasibility of autosegmentation, the dose distributions of all OARs were compared using Friedman test. Results The average DSC of all OARs obtained by single and multi-template were 0.82 ± 0.17 and 0.92 ± 0.54, respectively, with statistically significant difference (Z= -2.803- -2.497, P<0.05). A positive correlation between DSC of the autosegmentation and OAR volume was found by spearman analysis, and the single-template was not good enough for the spinal cord with smaller volume. The positional deviations of multi-template group were less than 0.5 cm in three directions, which were better than single-template group. The main dosimetric indexes of single-template and multiple-template were similar to manual coutours. V20 of whole lung were 23.2％, 22.4％ and 22.1％, Dmeanof whole lung were (11.3 ±4.0), (11.1 ±4.5) and (11.0 ±4.3) Gy, Dmaxof spinal cord were (40.3 ±4.8), (38.2 ±6.7) and (39.4 ± 5.3) Gy, respectively, and V30 of heart were 16.0％, 15.8％ and 15.5％, respectively. There was no statistical difference between the three methods (P>0.05), and all of the dosimetric indexes were in line with the requirements of clinical dose limits. Conclusions The autosegmentation software can achieve satisfactory precision for the OARs of the esophageal cancer patients, and the multi-template method is better than the single-template, which is more suitable for clinical application.