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

BACKGROUND: The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections. METHODS: This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups. RESULTS: A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups. CONCLUSION: The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs. REGISTRATION ClinicalTrials.gov , NCT05173493.
Humans ; Helicobacter Infections/drug therapy* ; Helicobacter pylori/pathogenicity* ; Male ; Female ; Prospective Studies ; Middle Aged ; Anti-Bacterial Agents/adverse effects* ; Adult ; Aged ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

Objective: To evaluate the application effect of oral health management program based on behavior change wheel (BCW) theory, so as to provide a reference for improving children s awareness of oral self management and the development of healthy oral behaviors. Methods: A total of 120 children aged 5-6 from 2 kindergartens in Yubei District in Chongqing City, selected by convenience sampling method from September 2023 to March 2024, were divided into a experimental group and a control group (60 each). Children in the experimental group were given an oral health education programme based on BCW theory (promoted health awareness, cultivated healthy behavior ability, strengthened awareness and ability, and provided opportunitiess) on the basis of conventional oral health education, and children in the control group were given conventional oral health education; data were collected before and 3 months after the intervention, respectively. Comparisons between groups were made using the Mann-Whitney U test and χ 2 test. Results: Before intervention, there were no significant differences in plaque index [2.00(1.00,2.00), 2.00(1.00,2.00)] and the number of filled teeth [0.00(0.00,1.00), 0.00( 0.00 ,1.00)] between the experimental group and the control group ( Z=-0.88, -0.42, P >0.05). After intervention, the plaque index of the experimental group [1.00(0.00,1.00)] was lower than that of the control group [1.00(0.25,2.00)] and before intervention, and the number of filling teeth in the experimental group [1.00(0.00,2.00)] was higher than that of the control group [1.00(0.00,1.00)] and before intervention, the differences were statistically significant ( Z =-3.14, -5.48; -2.08, -3.02, P <0.05). Before intervention, there were no significant differences in oral health behavior report rate and oral health knowledge mastery rate between the two groups ( χ 2=0.30-0.91, 0.15-1.43, P > 0.05 ). After intervention, the report rates of health tooth brushing (method, frequency and duration) and preventive behavior (using fluoride toothpaste, pit and fissure sealing prevention and fluoride application prevention) in the experimental group were better than those in the control group and before intervention, and the differences were statistically significant ( χ 2=4.88-9.38, 9.13- 22.63 , P <0.05). The mastery rates of oral health knowledge in the experimental group were better than that in the control group, and the differences were statistically significant ( χ 2=4.62-8.54, P <0.05). Conclusion Oral health management programs based on the BCW theory are more conducive to improving children s oral hygiene, as well as enhancing children s basic oral knowledge and promoting the development of oral health behaviors.

The xylitol dehydrogenase(XDH)is a crucial enzyme involved in the xylose utilization in pentose-catabolizing yeasts and fungi.In addition to producing xylulose,XDH can also be employed to develop a biosensor for monitoring xylitol concentration.In this study,the gene encoding the thermophilic fungus Talaromyces emersonii XDH(TeXDH)was heterologously expressed in Escherichia coli BL21(DE3)at 16 ℃ in the soluble form.Recombinant TeXDH with high purity was purified by using a Ni-NTA affinity column.Size-exclusion chromatography and SDS-PAGE analysis demonstrated that the puri-fied recombinant TeXDH exists as a native trimer with a molecular mass of approximately 116 kD,and is composed of three identical subunits,each with a molecular weight of around 39 kD.The TeXDH strictly preferred NAD+as a coenzyme to NADP+.The optimal temperature and pH of the TeXDH were 40 ℃and 10.0,respectively.After EDTA treatment,the enzyme activity of TeXDH decreased to 43.26％of the initial enzyme activity,while the divalent metal ions Mg2+or Ca2+could recover the enzyme activity of TeXDH,reaching 103.32％and 110.69％of the initial enzyme activity,respectively,making them the optimal divalent metal ion cofactors for TeXDH enzyme.However,the divalent metal ions of Mn2+,Ni2+,Cu2+,Zn2+,Co2+,and Cd2+significantly inhibited the activity of TeXDH.ICP-MS and molecular doc-king studies revealed that 1 mol/L of TeXDH bound 2 mol/L Zn2+ions and 1 mol/L Mg2+ion.Further-more,TeXDH exhibited a high specificity for xylitol,laying the foundation for the development of future xylitol biosensors.

Objective To investigate the predictive value of serum circular RNA(circRNA)CDYL and circRNA ACAP2 expression levels for major adverse cardiovascular events(MACE)in pa-tients with acute myocardial infarction(AMI).Methods A total of 98 AMI patients were enrolled into the observation group,and divided into MACE group(n=45)and no-MACE group(n=53)based on whether they experienced MACE.Another 98 healthy individuals who underwent physical ex-amination during the same period were selected as the control group.The expression levels of serum cir-cRNA CDYL and circRNA ACAP2 were compared among groups.Multivariate logistic regression analysis was used to identify factors influencing the occurrence of MACE in AMI patients.Receiver operating characteristic(ROC)curve analysis was conducted to evaluate the predictive value of serum circRNA CDYL and circRNA ACAP2 levels for MACE in AMI patients.Results The serum circRNA CDYL level in the observation group was significantly lower than that in the control group,while the circRNA ACAP2 level was significantly higher(P＜0.05).The circRNA CDYL level in the MACE group was significantly lower,and the circRNA ACAP2 level was significantly higher than that in the no-MACE group(P＜0.05).Heart rate and circRNA ACAP2 were identified as independent risk factors for MACE in AMI patients,whereas circRNA CDYL served as independent protective factor(P＜0.05).The area under the ROC curve(AUC)for predicting MACE in AMI patients using se-rum circRNA CDYL,circRNA ACAP2 and their combination were 0.814,0.821 and 0.921,re-spectively.The sensitivity and specificity of combined prediction using serum circRNA CDYL and circRNA ACAP2 were 91.11％and 79.25％,respectively.The combined prediction efficacy of serum circRNA CDYL and circRNA ACAP2 was superior to their individual prediction(Zcombined-circRNA CDYL=1.975,Zcombined-circRNAACAP2=2.064,P=0.048,0.039).Conclusion Serum circRNA CDYL lev-el is down-regulated and circRNA ACAP2 level is up-regulated in AMI patients,and circRNA ACAP2 is an independent risk factor for MACE,while circRNA CDYL is a independent protective factor.The combined value of circRNA CDYL and circRNA ACAP2 in predicting the occurrence of MACE is higher.

Objective:To investigate the status quo of negative social expectation and its influencing factors in patients with primary liver cancer, in order to improve the negative social cognition, therapeutic effect.Methods:This was a cross-sectional study, the convenience sampling method was used to select the patients with primary liver cancer who were hospitalized in hepatobiliary and pancreatic medical center of People′s Hospital of Xinjiang Uygur Autonomous Region from September 2022 to June 2024 as the research objects. The General Information Questionnaire, Cancer-related Negative Social Expectations Scale and Cancer Loneliness Scale were used to investigate the patients. Multiple linear stepwise regression analysis was used to investigate the influencing factors of negative social expectations in patients with primary liver cancer.Results:A total of 290 questionnaires were distributed, and 277 valid questionnaires were collected. Among the patients, there were 161 males and 116 females, aged <45 years with 43 cases, 45-60 years with 138 cases, over 60 years with 96 cases.The total score of negative social expectation in patients with primary liver cancer was (20.70 ± 2.70) points. Multiple linear stepwise regression analysis showed that age, education level, residence style, family history of tumor, Child-Pugh grade of liver function and loneliness were the influencing factors of negative social expectation in patients with primary liver cancer ( t values were -4.57-7.55, all P<0.05), accounting for 42.2% of total variation. Conclusions:The negative social expectation of patients with primary liver cancer is above the medium level, so the medical staff should pay more attention and give targeted intervention to ensure the effective implementation of clinical treatment measures.

The xylitol dehydrogenase(XDH)is a crucial enzyme involved in the xylose utilization in pentose-catabolizing yeasts and fungi.In addition to producing xylulose,XDH can also be employed to develop a biosensor for monitoring xylitol concentration.In this study,the gene encoding the thermophilic fungus Talaromyces emersonii XDH(TeXDH)was heterologously expressed in Escherichia coli BL21(DE3)at 16 ℃ in the soluble form.Recombinant TeXDH with high purity was purified by using a Ni-NTA affinity column.Size-exclusion chromatography and SDS-PAGE analysis demonstrated that the puri-fied recombinant TeXDH exists as a native trimer with a molecular mass of approximately 116 kD,and is composed of three identical subunits,each with a molecular weight of around 39 kD.The TeXDH strictly preferred NAD+as a coenzyme to NADP+.The optimal temperature and pH of the TeXDH were 40 ℃and 10.0,respectively.After EDTA treatment,the enzyme activity of TeXDH decreased to 43.26％of the initial enzyme activity,while the divalent metal ions Mg2+or Ca2+could recover the enzyme activity of TeXDH,reaching 103.32％and 110.69％of the initial enzyme activity,respectively,making them the optimal divalent metal ion cofactors for TeXDH enzyme.However,the divalent metal ions of Mn2+,Ni2+,Cu2+,Zn2+,Co2+,and Cd2+significantly inhibited the activity of TeXDH.ICP-MS and molecular doc-king studies revealed that 1 mol/L of TeXDH bound 2 mol/L Zn2+ions and 1 mol/L Mg2+ion.Further-more,TeXDH exhibited a high specificity for xylitol,laying the foundation for the development of future xylitol biosensors.

Objective:To investigate the status quo of negative social expectation and its influencing factors in patients with primary liver cancer, in order to improve the negative social cognition, therapeutic effect.Methods:This was a cross-sectional study, the convenience sampling method was used to select the patients with primary liver cancer who were hospitalized in hepatobiliary and pancreatic medical center of People′s Hospital of Xinjiang Uygur Autonomous Region from September 2022 to June 2024 as the research objects. The General Information Questionnaire, Cancer-related Negative Social Expectations Scale and Cancer Loneliness Scale were used to investigate the patients. Multiple linear stepwise regression analysis was used to investigate the influencing factors of negative social expectations in patients with primary liver cancer.Results:A total of 290 questionnaires were distributed, and 277 valid questionnaires were collected. Among the patients, there were 161 males and 116 females, aged <45 years with 43 cases, 45-60 years with 138 cases, over 60 years with 96 cases.The total score of negative social expectation in patients with primary liver cancer was (20.70 ± 2.70) points. Multiple linear stepwise regression analysis showed that age, education level, residence style, family history of tumor, Child-Pugh grade of liver function and loneliness were the influencing factors of negative social expectation in patients with primary liver cancer ( t values were -4.57-7.55, all P<0.05), accounting for 42.2% of total variation. Conclusions:The negative social expectation of patients with primary liver cancer is above the medium level, so the medical staff should pay more attention and give targeted intervention to ensure the effective implementation of clinical treatment measures.

OBJECTIVES: To isolate potassium ion channel Kv4.1 inhibitor from centipede venom, and to determine its primary and spatial structure. METHODS: Ion-exchange chromatography and reversed-phase high-performance liquid chromatography were performed to separate and purify peptide components of centipede venom, and their inhibiting effect on Kv4.1 channel was determined by whole-cell patch clamp recording. The molecular weight of isolated peptide Kv4.1 channel inhibitor was identified with MALDI-TOF, its primary sequence was determined by Edman degradation sequencing and two-dimensional mass spectrometry, its patial structure was established based on iterative thread assembly refinement online analysis. RESULTS: A peptide SsTx-P2 was separated from centipede venom with the molecular weight of 6122.8, and its primary sequence consists of 53 amino acid residues, showed as NH₂-ELTWDFVRTCCKLFPDKSECTKACATEFTGGDESRLKDVWPRKLRSGDSRLKD-OH. Peptide SsTx-P2 potently inhibited the current of Kv4.1 channel transiently transfected in HEK293 cell, with 1.0 μmol/L SsTx-P2 suppressing 95% current of Kv4.1 channel. Its spatial structure showed that SsTx-P2 shared a conserved helical structure. CONCLUSIONS The study has isolated a novel peptide SsTx-P2 from centipede venom, which can potently inhibit the potassium ion channel Kv4.1, and its spatial structure displays a certain degree of conservation.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.