Stearoyl-coenzyme A desaturase 1 (SCD1) catalyzes the rate-limiting step of de novo lipogenesis and modulates lipid homeostasis. Although numerous SCD1 inhibitors were tested for treating metabolic disorders both in preclinical and clinic studies, the tissue-specific roles of SCD1 in modulating obesity-associated metabolic disorders and determining the pharmacological effect of chemical SCD1 inhibition remain unclear. Here a novel role for intestinal SCD1 in obesity-associated metabolic disorders was uncovered. Intestinal SCD1 was found to be induced during obesity progression both in humans and mice. Intestine-specific, but not liver-specific, SCD1 deficiency reduced obesity and hepatic steatosis. A939572, an SCD1-specific inhibitor, ameliorated obesity and hepatic steatosis dependent on intestinal, but not hepatic, SCD1. Mechanistically, intestinal SCD1 deficiency impeded obesity-induced oxidative stress through its novel function of inducing metallothionein 1 in intestinal epithelial cells. These results suggest that intestinal SCD1 could be a viable target that underlies the pharmacological effect of chemical SCD1 inhibition in the treatment of obesity-associated metabolic disorders.

Objective:To analyze the current status of registrations in randomized controlled trials (RCTs) of endovascular therapy for ischemic stroke.Methods:The ClinicalTrials.gov database was searched for RCTs of endovascular therapy for ischemic stroke from January 1, 1994 to June 30, 2024. The registration time, sites, sample size, complete status and design types, contents, and outcome evaluation methods of the trails were analyzed.Results:(1) A total of 195 RCTs were included. Number of RCTs registrations during 1994-2004, 2005-2014 and 2015-2024 were 2, 21 and 172, respectively. RCTs registration sites mainly concentrated in China, the United States and France, with 90 (46.1%), 29 (14.9%) and 24 (12.3%) registrations, respectively. There were 43 RCTs with sample size≤100 (22.1%), 143 RCTs with sample size of 100-1000 (73.3%), and 9 RCTs with sample size ≥1000 (4.6%). Fifty-seven RCTs were completed (29.2%, the average time from registration to trial completion was 1044 days); 91 RCTs (46.7%) were in the recruitment or pre-recruitment states; 23 RCTs (11.8%) were suspended or terminated. (2) RCTs design types included parallel design ( n=189, 96.9%), factorial design ( n=2, 1.0%), group-sequential design ( n=2, 1.0%), cross-over design ( n=1, 0.5%), and single-arm design ( n=1, 0.5%). Forty-four open trials (22.6%) and 151 blinded trials (77.4%) were recorded; among the blind trials, 108 RCTs (71.5%) were single-blind design, 19 (12.6%) were double-blind design, and 24 RCTs (15.9%) were triple-blind design. (3) A total of 69 RCTs (35.4%) focused on drug use, including 23 trails related to arterial thrombolysis drugs (mainly alteplase and tenecteplase); 67 RCTs (34.4%) were about endovascular therapy and perioperative management, among which 27 trials compared the efficacy of endovascular therapy, intravenous thrombolysis or placebo; 49 RCTs (25.1%) were about equipment use during treatment. (4) Outcome evaluation method: modified Rankin scale was most frequently used (153 RCTs), followed by National Institutes of Health Stroke Scale (100 RCTs). Conclusions:In the past decade, the number of RCTs about endovascular treatment for ischemic stroke has increased rapidly, and most of them were multi-center and blinded RCTs investigating the selection of arterial thrombolytic drugs, optimization of thrombectomy devices, and perioperative management. China is particularly prominent in this area of research.

With the rapid development of artificial intelligence(AI)technology and its extensive application in the medical field,Al has gradually been applied to all aspects of cerebrovascular disease diagnosis and treatment,including but not limited to prevention,prediction,diagnosis,treatment,and prognosis assessment.This article reviewed the current application of Al technology in the field of cerebrovascular disease diagnosis and treatment and discussed the improvement of the diagnostic and therapeutic process with AI technology application.It provides novel insights and strategies for the clinical management of cerebrovascular diseases.

With the rapid development of artificial intelligence(AI)technology and its extensive application in the medical field,Al has gradually been applied to all aspects of cerebrovascular disease diagnosis and treatment,including but not limited to prevention,prediction,diagnosis,treatment,and prognosis assessment.This article reviewed the current application of Al technology in the field of cerebrovascular disease diagnosis and treatment and discussed the improvement of the diagnostic and therapeutic process with AI technology application.It provides novel insights and strategies for the clinical management of cerebrovascular diseases.

Objective:To analyze the current status of registrations in randomized controlled trials (RCTs) of endovascular therapy for ischemic stroke.Methods:The ClinicalTrials.gov database was searched for RCTs of endovascular therapy for ischemic stroke from January 1, 1994 to June 30, 2024. The registration time, sites, sample size, complete status and design types, contents, and outcome evaluation methods of the trails were analyzed.Results:(1) A total of 195 RCTs were included. Number of RCTs registrations during 1994-2004, 2005-2014 and 2015-2024 were 2, 21 and 172, respectively. RCTs registration sites mainly concentrated in China, the United States and France, with 90 (46.1%), 29 (14.9%) and 24 (12.3%) registrations, respectively. There were 43 RCTs with sample size≤100 (22.1%), 143 RCTs with sample size of 100-1000 (73.3%), and 9 RCTs with sample size ≥1000 (4.6%). Fifty-seven RCTs were completed (29.2%, the average time from registration to trial completion was 1044 days); 91 RCTs (46.7%) were in the recruitment or pre-recruitment states; 23 RCTs (11.8%) were suspended or terminated. (2) RCTs design types included parallel design ( n=189, 96.9%), factorial design ( n=2, 1.0%), group-sequential design ( n=2, 1.0%), cross-over design ( n=1, 0.5%), and single-arm design ( n=1, 0.5%). Forty-four open trials (22.6%) and 151 blinded trials (77.4%) were recorded; among the blind trials, 108 RCTs (71.5%) were single-blind design, 19 (12.6%) were double-blind design, and 24 RCTs (15.9%) were triple-blind design. (3) A total of 69 RCTs (35.4%) focused on drug use, including 23 trails related to arterial thrombolysis drugs (mainly alteplase and tenecteplase); 67 RCTs (34.4%) were about endovascular therapy and perioperative management, among which 27 trials compared the efficacy of endovascular therapy, intravenous thrombolysis or placebo; 49 RCTs (25.1%) were about equipment use during treatment. (4) Outcome evaluation method: modified Rankin scale was most frequently used (153 RCTs), followed by National Institutes of Health Stroke Scale (100 RCTs). Conclusions:In the past decade, the number of RCTs about endovascular treatment for ischemic stroke has increased rapidly, and most of them were multi-center and blinded RCTs investigating the selection of arterial thrombolytic drugs, optimization of thrombectomy devices, and perioperative management. China is particularly prominent in this area of research.

Diffuse large B-cell lymphoma (DLBCL) can be caused by multiple factors, including virus and autoimmune function, which in turn trigger persistent activation of the B-cell receptor (BCR) signaling pathway and other related signaling pathways, which collectively promote malignant B-cell proliferation and lead to tumor formation. Studies have shown significant progress in the treatment of primary and relapsed/refractory DLBCL with Bruton tyrosine kinase inhibitor (BTKi) in combination with chemotherapy, immunotherapy and small molecule inhibitors in the setting of poor outcome with BTKi monotherapy. This article reviews the progress of BTKi combined regimens in DLBCL.

The FMS-like tyrosine kinase 3 (FLT3) gene mutation is the most common genetic mutation in acute myeloid leukemia (AML) and is associated with poor prognosis. Various targeted inhibitors have been developed for FLT3 mutations and have shown promising clinical efficacy. However, the emergence of resistance poses new challenges for targeted therapy in AML. This article provides an overview of the pathological and prognostic role of FLT3 mutations in AML, the current research progress on commonly used FLT3 inhibitors (type I and type II), the mechanisms of FLT3 inhibitor resistance, and strategies for overcoming resistance.

OBJECTIVE To study the pharmacokinetics of paeoniflorin， hesperidin， naringenin， formononetin and enoxolone from Chitong xiaoyanling granules in rats. METHODS Six male SD rats fasted but not deprived of water for 12 h were given Chitong xiaoyanling granules （5.0 g/kg） intragastrically at one time. Blood was collected from inner canthus of rats at different time points after administration. Plasma samples were pretreated with acetonitrile precipitated protein （sulfamethoxazole as internal standard）， and the concentrations of 5 ingredients in plasma were determined by liquid chromatography-tandem mass spectrometry （LC-MS/MS）. The pharmacokinetic parameters of each ingredient were calculated using DAS 3.0 software. RESULTS After intragastric administration of Chitong xiaoyanling granules， tmax and t1/2 of formononetin were the shortest among 5 ingredients （0.25 h and 0.39 h， respectively）. For naringenin and enoxolone， the tmax was shorter， but t1/2 was longer， and there was an obvious double-peak phenomenon in the drug-time curve of naringenin. Compared with the other three components， cmax and AUC of paeoniflorin and hesperidin were not directly proportional to the content of in vitro components. CONCLUSIONS Formononetin， naringin and enoxolone in Chitong xiaoyanling granules were absorbed rapidly in rats， while paeoniflorin and hesperidin were absorbed slowly.

Objective: To investigate the seroprevalence and influencing factors of serum neutralizing antibodies among SARS-CoV-2 infected individuals, so as to provide the evidence for developing the health management and COVID-19 vaccination strategy among SARS-CoV-2 infected individuals. Methods: Recovered SARS-CoV-2 infected individuals from January 1st, 2020 to February 10th, 2021 in Zhejiang Province were recruited in March 2021. Participants' demographics, underlying diseases, date of definitive diagnosis and severity of clinical symptoms were collected using questionnaire surveys, and serum neutralizing antibody against SARS-CoV-2 was detected using a fluorescent immunoassay. In addition, factors affecting the seropositivity of neutralizing antibody against SARS-CoV-2 were identified using a multivariable logistic regression model. Results: A total of 559 SARS-CoV-2 infected individuals were enrolled, including 480 confirmed cases and 79 asymptomatic carriers, with an median (interquartile range) age of 47.00 (22.00) years, and all participants had never received COVID-19 vaccination. The median (interquartile range) duration from diagnosis to serum sampling was 387.00 (11.00) days, and the seroprevalence of neutralizing antibody against SARS-CoV-2 was 83.90%. The serum neutralizing antibody against SARS-CoV-2 was all positive 9 months after diagnosis, and the seroprevalence of neutralizing antibody against SARS-CoV-2 appeared no tendency towards a decline with time within 14 months after diagnosis (P>0.05). Multivariable logistic regression analysis showed that women were 1.892 times (95%CI: 1.169-3.064) more likely to produce serum neutralizing antibodies against SARS-CoV-2 than men, and mild, common and severe/critically ill SARS-CoV-2 infected cases were 2.438 (95%CI: 1.305-4.557), 4.481 (95%CI: 2.318-8.663), and 23.525 (95%CI: 2.990-185.068) times more likely to produce serum neutralizing antibodies against SARS-CoV-2 than asymptomatic carrier, respectively. Conclusions The seroprevalence of neutralizing antibody was 100.00% among SARS-CoV-2 infected individuals within 9 months after diagnosis. Individuals' gender and severity of clinical symptoms correlate with the seroprevalence of neutralizing antibody against SARS-CoV-2.

Objective:To explore the effects of habit reversal training on the use of inhaled corticosteroids (ICS) in patients with bronchial asthma.Methods:Select 89 patients with bronchial asthma using ICS admitted to the respiratory department of the Anhui No.2 Provincial People′s Hospital from 2016 January - 2019 January, and they were randomly divided into control group and study group, 45 cases in control group and 44 cases in study group. Patients in the control group received usual care and propaganda measures, the patients in the study group were intervened by the behavioral habit reversal training consisting of consciousness practice, behavior evaluation, antagonistic action training, anxiety management, follow-up and social support.. Asthma control test questionnaire (ACT), self-developed evaluation method of ICS inhalation technique, bronchial asthma quality of life questionnaire (AQLQ), were used to evaluate the difference of inhaled glucocorticoid corticosteroid therapy before and after the intervention.Results:The ICS inhalation technique scores (6.24±0.82) were higher than those of the control group (4.13±0.67), the difference was statistically significant ( t=-13.307, P<0.05). ACT scores of the study group were better than those of the control group ( Z=-2.780, P=0.005), the difference was statistically significant ( P<0.05). After intervention, AQLQ total scores in the study group, and the asthma symptoms, psychological status, and scores of the self-health dimension in AQLQ in the study group were (211.74±29.84), (51.09±6.49), (39.57±5.24), (24.36±3.41), higher than those in the control group(191.18±27.91), and (43.18±5.73), (31.21±4.62), (19.94±2.84), the difference was statistically significant ( t value was -7.988 - -3.358, P<0.05). Conclusion:Habit reversal training can effectively enhance the technical level of bronchial asthma patients operating ICS device, further improve the status of asthma control, improve the quality of life of patients, and improve the quality of nursing services for such patients.