Objective:To investigate the association between baseline hemoglobin level and early neurologic deterioration(END)after intravenous thrombolysis in patients with acute ischemic stroke(AIS).Methods:Data of AIS patients who received intravenous thrombolytic therapy at multiple hospitals across the country between January 2017 and July 2020 were collected from the online database Acute Stroke Patients for Stroke Management Quality Evaluation(CASE-Ⅱ,NCT04487340).Binary logistic regression analysis was used to study the factors affecting the occurrence of END after intravenous thrombolytic therapy,and the correlation between baseline hemoglobin level and END was investigated by limiting cubic spline curve analysis.Results:A total of 8162 patients were included.Patients with END had lower baseline hemoglobin levels(136 and 140 g/L,P<0.01)and higher rates of anemia(24.2%and 16.9%,P<0.01)compared with non-END patients.Binary logistic regression analysis showed that baseline hemoglobin level(OR=0.995,95%CI:0.991-0.999,P<0.05)and anemia(OR=1.238,95%CI:1.055-1.454,P<0.01)were independently correlated with the occurrence of END after intravenous thrombolysis in AIS patients.Restricted cubic spline regression showed that there was a U-shaped relationship between hemoglobin level and the risk of END after intravenous thrombolysis in AIS patients(P<0.01),although this relationship was only significant in male patients(P<0.05)and not in female patients(P>0.05).Conclusion:There is a correlation between baseline hemoglobin level and the risk of END in AIS patients after intravenous thrombolysis,especially in male patients,in whom both lower and higher hemoglobin level may increase the risk of END.

Objective:To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China.Methods:This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis.Results:Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) ( Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS ( Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion:Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.
Humans ; Benzydamine ; Esophageal Neoplasms/drug therapy* ; Esophageal Squamous Cell Carcinoma/drug therapy* ; Molecular Docking Simulation ; Phosphorylation ; Cell Proliferation ; Cell Line, Tumor ; Apoptosis ; Cyclin-Dependent Kinase 2

Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

OBJECTIVE: To investigate the effect of working time on the prognosis of patients with ischemic stroke undergoing intravenous thrombolysis. METHODS: Clinical data of 3050 patients with ischemic stroke received intravenous thrombolysis from 71 hospitals in Zhejiang Province during June 2017 and September 2018 were retrospective analyzed. Whole day of Saturday and Sunday were defined as weekend; whole day of Monday to Friday were defined as weekdays; Monday to Friday 8:00-17:00 were defined as daytime of weekdays; Monday to Friday 17:01-07:59 on next day were defined as nights of weekdays; unconventional working time were defined as weekend and nights of weekdays. Good outcome was defined as mRS 0-2 at 3 months. Univariate analyses of baseline and prognostic variables in group of weekend and weekdays, nights of weekdays and daytime of weekdays, unconventional working time and daytime of weekdays were performed. Binary logistic regression was used to investigate whether weekend, nights of weekdays and unconventional working time were independent predicting factors of outcome after intravenous thrombolysis, respectively. RESULTS: There was no difference in 7-day mortality, 3-month mortality and good outcome at 3-month between weekend group and weekdays group, nights of weekdays group and daytime of weekdays group, unconventional working time group and daytime of weekdays group (all >0.05). Binary logistic regression results showed that weekends, nights of weekdays and unconventional working time were not independent predicting factors for outcome after intravenous thrombolysis (all >0.05). CONCLUSIONS The working time has not affected the outcomes of patients with ischemic stroke undergoing intravenous thrombolysis in studied hospitals of Zhejiang province.
Brain Ischemia ; drug therapy ; Humans ; Prognosis ; Retrospective Studies ; Stroke ; drug therapy ; Thrombolytic Therapy ; Time Factors

OBJECTIVE: To compare the time delay between in-hospital stroke and out-of-hospital stroke patients, and to explore the influence factors for the prognosis of in-hospital stroke patients treated by intravenous thrombolysis. METHODS: Clinical data of 3050 patients with ischemic stroke who received intravenous thrombolysis in 71 hospitals in Zhejiang province from June 2017 to September 2018 were analyzed. Differences of time delay including door to imaging time (DIT), imaging to needle time (INT) and door to needle time (DNT) between in-hospital stroke (=101) and out-of-hospital stroke (=2949) were observed. The influencing factors for the outcome at 3 month after intravenous thrombolysis in patients with in-hospital stroke were analyzed using binary logistic regression analysis. RESULTS: Patients with in-hospital stroke had longer DIT[53.5 (32.0-79.8) min vs. 20.0 (14.0-28.0) min, <0.01], longer IDT[47.5(27.3-64.0)min vs. 36.0(24.0-53.0)min, <0.01], and longer DNT[99.0 (70.5-140.5) min vs. 55.0 (41.0-74.0) min, <0.01], compared with patients with out-of-hospital stroke; patients in comprehensive stroke center had longer DIT[59.5(44.5-83.3) min vs. 37.5(16.5-63.5) min, <0.01], longer DNT[110.0(77.0-145.0) min vs. 88.0 (53.8-124.3) min, <0.05], but shorter INT[36.5(23.8-60.3)min vs. 53.5 (34.3-64.8) min, <0.05], compared with patients in primary stroke center. Age (=0.934, 95% 0.882-0.989, <0.05) and baseline National Institute of Health Stroke Scale score (=0.912, 95% 0.855-0.973, <0.01) were independent risk factors for prognosis of in-hospital stroke patients. CONCLUSIONS In-hospital stroke had longer DIT and DNT than out-of-hospital stroke, which suggests that a more smooth thrombolysis process of in-hospital stroke should be established.
Administration, Intravenous ; Brain Ischemia ; drug therapy ; Fibrinolytic Agents ; therapeutic use ; Hospitals ; statistics & numerical data ; Humans ; Prognosis ; Stroke ; drug therapy ; Thrombolytic Therapy ; statistics & numerical data ; Time Factors ; Treatment Outcome

OBJECTIVE: To investigate the effect of treatment time on the outcome of patients with ischemic stroke undergoing reperfusion therapy. METHODS: The clinical data of 3229 ischemic stroke patients who received intravenous thrombolysis with or without arterial thrombolysis from 71 hospitals in Zhejiang province from June 2017 to September 2018 were retrospectively reviewed. The good outcome was defined as modified Rankin Scale (mRS) ≤ 2. Binary logistic regression analysis was used to investigate the association of door to needle time (DNT), or door to reperfusion time (DRT) with the outcomes in patients treated by intravenous thrombolysis or bridging arterial thrombolysis, respectively. RESULTS: Binary logistic regression showed that DNT (=0.994, 95%:0.991-0.997, <0.01) or DRT (=0.989, 95%:0.983-0.995, <0.01) were independently associated with good outcomes, respectively. Every hour decreases in DNT resulted in a 4.7%increased probability of functional independence (mRS 0-2) in patients treated by intravenous thrombolysis; Every hour decreases in DRT was associated with a 11.4%increased probability of functional independence in patients treated by intravenous thrombolysis with arterial thrombolysis. CONCLUSIONS Good outcomes are associated with lower DNT in ischemic stroke patients treated by intravenous thrombolysis or lower DRT in patients treated by intravenous thrombolysis bridging arterial thrombolysis.
Brain Ischemia ; drug therapy ; Fibrinolytic Agents ; therapeutic use ; Humans ; Reperfusion ; Retrospective Studies ; Stroke ; drug therapy ; Thrombolytic Therapy ; Time Factors ; Treatment Outcome

OBJECTIVE: To investigate the effect of emergency medical service (EMS) on the prognosis of ischemic stroke patients treated with intravenous thrombolysis. METHODS: Clinical data of 2123 ischemic stroke patients treated with intravenous thrombolysis in 70 hospitals in Zhejiang province were retrospectively analyzed. There were 808 patients sent to the hospital by ambulance (EMS group) and 1315 patients by other transportations (non-EMS group). Good outcome was defined as modified Rankin Scale (mRS) ≤ 2 at 3-month. The onset to needle time (ONT), onset to door time (ODT), door to needle time (DNT) and outcome were compared between EMS group and non-EMS group. Binary logistic regression was used to explore the influencing factors for the outcome at 3-month. RESULTS: Compared with the non-EMS group, patients in the EMS group were older, with higher baseline National Institute of Health Sroke Scale (NIHSS) score, and had a higher proportion of atrial fibrillation (all <0.05), but there were no significant differences in ONT, ODT and DNT between two groups (all >0.05). Binary logistic regression showed that EMS was not independently associated with good outcome (=0.856, 95%:0.664-1.103, >0.05). CONCLUSIONS EMS had not improve the outcome of patients receiving intravenous thrombolysis in Zhejiang province.
Administration, Intravenous ; Brain Ischemia ; drug therapy ; Emergency Medical Services ; Fibrinolytic Agents ; therapeutic use ; Humans ; Prognosis ; Retrospective Studies ; Stroke ; drug therapy ; Thrombolytic Therapy ; statistics & numerical data ; Treatment Outcome

OBJECTIVETo investigate the effect of tirofiban on hemorrhagic transformation and neurological outcome in patients with acute cerebral infarct treated with endovascular therapy.

METHODSOne hundred and fifteen patients with acute cerebral infarct who received endovascular stent mechanical thrombectomy in the Second Affiliated Hospital, Zhejiang University School of Medicine during October 2013 and April 2017 were included in the study. Among 115 patients, 30 received tirofiban treatment. Hemorrhagic transformation and neurological outcomes were assessed using the ECASS Ⅱ criteria and modified Rankin scale (mRS), respectively. Unfavorable outcome was defined as mRS>2. Binary logistic regression model was used to analyze the independent predictors of hemorrhagic transformation and neurological outcome.

RESULTSBinary logistic regression analysis showed that tirofiban treatment did not increase the risk of hemorrhagic transformation (=0.437, 95%:0.168-1.132,>0.05); baseline NIHSS (=1.136, 95%:1.014-1.273,<0.05), recanalization (=0.060, 95%:0.010-0.365,<0.01), hypertension (=4.233, 95%:1.320-13.570,<0.05) and onset to treatment time(=1.006, 95%:1.001-1.011,<0.05) were independently associated with unfavorable outcome, while such association was not observed in tirofiban treatment (=1.923, 95%:0.536-6.568,>0.05).

CONCLUSIONSTirofiban appears to be safe for patients with acute cerebral infarct receiving endovascular therapy.

OBJECTIVETo investigate the association of serum folate level with the severity of white matter hyperintensity (WMH) and presence of cerebral microbleeds (CMB).

METHODSClinical data of WMH patients from the second affiliated Hospital, Zhejiang University school of Medicine during July 2011 and February 2016 were retrospectively reviewed. According to Fazekas score based on T2-Flair images, patients were classified into mild WMH (0-3) and severe WMH (4-6). The presence of CMB was assessed on susceptibility weighted imaging (SWI). Binary logistic analysis was conducted to identify the independent predictors for severe WMH and the presence of CMB.

RESULTSTwo hundred and twenty eight patients with WMH were included, among whom 149(65.35%)had severe WMH. In patients with high folate (≥ 15.68 nmol/L), low folate (6.8-15.67 nmol/L) and folate deficiency (<6.8 nmol/L), the proportions of severe WMH were 52.88%, 73.33% and 89.47%, respectively. Binary logistic regression analysis revealed that compared with high folate group, severe WMH was more common in groups with low folate (=2.109, 95%:1.112-4.001,<0.05) and folate deficiency (=6.383, 95%:1.168-34.866,<0.05). Eighty-eight(48.09%) of 183 patients receiving SWI scan presented with CMB. Although the subjects with CMB had lower serum folate level than those without CMB(13.42 vs 16.51 nmol/L,<0.01), binary logistic regression analysis did not reveal the independent association between serum folate level and the presence of CMB after adjusting for hyperhomocysteinemia (>0.05).

CONCLUSIONSLower serum folate level is independently associated with severe WMH, but not with the CMB concurrence.