Objective To investigate the dynamic functional connectivity differences between insomnia patients and healthy controls in triple brain networks[the significant network(SN),the default mode network(DMN),and the executive control network(ECN)]using functional magnetic resonance imaging,and uncover their associations with cognitive ability.Methods Dynamic functional connectivity analysis was performed on functional magnetic resonance imaging data from 40 insomnia patients and 40 healthy controls.The changes in dynamic functional connectivity values were studied for SN,DMN,ECN[including the left executive control network(LECN)and the right executive control network(RECN)];the similarities and differences in time characteristic indicators such as time score,average dwell time,and conversion rate were explored;and their associations with clinical information were analyzed.Results The SN-LECN and DMN-RECN dynamic functional connectivity was significantly higher in insomnia patients than in healthy controls(P=0.013,0.047),while the RECN-LECN and RECN internal functional connectivity strength was lower in insomnia patients than in healthy controls(P<0.001).Additionally,the fractional time in state 2 in insomnia group was significantly higher than that in healthy controls(P<0.001),and it was positively correlated with the Pittsburgh sleep quality index(r=0.524,P=0.001).Conclusion Insomnia patients exhibit significant abnormalities in triple brain network dynamic functional connectivity,which may be related to abnormalities in cognitive control and sensory processing in insomnia patients.These findings provide a new perspective for further research on the neural mechanisms and potential intervention strategies for insomnia.

Small cell neuroendocrine cervical carcinoma(SCNECC)is a rare gynecological malignancy characterized by early invasion and metastasis,resulting in a poorer prognosis compared to cervical squamous cell carcinoma and adenocarcinoma.The clinical management of SCNECC remains in the exploratory phase.Recently,as this uncommon tumor has garnered increasing attention both domestically and internationally,some progress has been made in improving its prognosis.This article summarizes the advancements in combined modality therapy for SCNECC,discussing and providing insights into key issues related to current treatment strategies of surgery,radiotherapy and chemotherapy,as well as targeted and immunotherapies.

Background::An evidence gap still exists regarding the efficacy and safety of tegoprazan in patients with erosive esophagitis (EE) in China. This study aimed to verify the efficacy and safety of tegoprazan vs. esomeprazole in patients with EE in China. Methods::This study was a multicenter, randomized, double-blind, parallel, active-controlled, non-inferiority phase III trial of patients with EE randomized 1:1 to tegoprazan 50 mg/day vs. esomeprazole 40 mg/day. This study was conducted in 32 sites between October 24, 2018 and October 18, 2019. The primary endpoint was the cumulative endoscopic healing rate at week 8. The secondary endpoint included endoscopic healing rate at week 4, changes in the reflux disease questionnaire (RDQ) and gastroesophageal reflux disease health-related quality of life (GERD-HRQL) scores, and symptom improvement. Results::A total of 261 patients were randomized: 132 to the tegoprazan group and 129 to the esomeprazole group. The cumulative endoscopic healing rate at 8 weeks in the tegoprazan group was non-inferior to that of the esomeprazole group (91.1% vs. 92.8%, difference: -1.7%, 95% confidence interval [CI]: -8.5%, 5.0%, P = 0.008). There were no statistically significant differences in the changes in RDQ (total, severity, and frequency) and GERD-HRQL scores between the two groups (all P >0.05). The percentages of days without symptoms, including daytime and nighttime symptoms based on patients' diaries, were similar between the two groups (all P >0.05). In the tegoprazan and esomeprazole groups, 71.5% (93/130) and 61.7% (79/128) of the participants reported adverse events (AEs), 2.3% and 0 experienced serious AEs, while 70.0% and 60.2% had treatment-emergent AEs, respectively. Conclusion::Tegoprazan 50 mg/day demonstrated non-inferior efficacy in healing EE, symptom improvement, and quality of life, and it has similar tolerability compared with esomeprazole 40 mg/day.

Objective:To comprehensively evaluate the cost and cost-effectiveness of the colorectal cancer screening program for key populations in Zhejiang Province from 2020 to 2022, and provide reference for optimizing colorectal cancer screening strategies.Methods:Based on the colorectal cancer screening program for key populations in Zhejiang Province from 2020 to 2022, parameters such as initial screening positivity rates, colonoscopy compliance rates, and detection rates for colorectal-related lesions among residents aged 50-74 were obtained. Questionnaire surveys assessed program costs and direct medical costs associated with colorectal cancer-related lesions. From a health system perspective, the cost-effectiveness ratio was calculated using the Early Detection Cost Index (EDCI) and the cost per detected case, followed by sensitivity analysis.Results:A total of 5 881 364 screenings were completed from 2020 to 2022. The initial screening positive rate (positive for either questionnaire or fecal immunochemical testing ) was 16.83%, with a colonoscopy compliance rates of 33.96% ( n=336 150). Detection rates for non-advanced adenomas, advanced adenomas, and colorectal cancer were 24.83% ( n=83 453), 11.91% ( n=40 033), and 1.01% ( n=3 397), respectively. Initial screening positivity rates and detection rates increased with age, while colonoscopy compliance rates decreased with age. Cost analysis showed a total project investment of 378 730 457 yuan, with initial screening costing 146 633 103 yuan (38.72%) and diagnostic colonoscopy 232 097 354 yuan (61.28%). The average cost per initial screening and diagnostic colonoscopy was 24.93 and 690.46 yuan, respectively. Direct medical costs for non-advanced adenomas, advanced adenomas, and colorectal cancer at stages Ⅰ, Ⅱ, Ⅲ, and Ⅳ were 4 921, 8 380, 42 547, 62 156, 66 720, and 72 334 yuan, respectively. Cost-effectiveness analysis indicated that screening needed to detect one case of colorectal cancer required 1 731 people and cost 111 490 yuan; the cost per detected advanced adenoma was 9 460 yuan, and the EDCI was 0.09. Costs decreased with increasing age per detected colorectal lesion. Sensitivity analysis showed that increasing colonoscopy compliance could reduce the cost-effectiveness ratio. Conclusions:The colorectal cancer screening program for key populations in Zhejiang Province demonstrates cost-effectiveness. Improving colonoscopy compliance can enhance overall screening effectiveness and economic benefits.

Objective To observe changes of white matter function in adolescent smoker(AS)with resting-state functional MRI(rs-fMRI)fractional amplitude of low-frequency fluctuation(fALFF)technique.Methods Forty-five adolescents(AS group)and 45 control subjects(control group)were prospectively enrolled,and brain rs-fMRI were acquired.Brain regions with fALFF being different between groups were observed,and the correlations with clinical indicators were analyzed.Results Compared with that in control group,fALFF of the right superior longitudinal fasciculus significantly elevated in AS group(FDR correct Q＜0.05),in which the peak of the cluster was positively correlated with score of Fagerstr?m test for nicotine dependence(FTND)(r=0.294,P=0.049).Conclusion White matter function changed in AS,presenting as significantly increased fALFF in right superior longitudinal fasciculus,which was positively correlated with nicotine dependence.

Aim To investigate the therapeutic effects of a newly developed Tadalafil tablets on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,as well as its influence on the activation of the NF-κB signaling pathway in myo-cardial cells.Methods SD rats were randomly divid-ed into 4 groups:the sham operation group(Sham),the model group(AAC),the tadalafil new tablet treat-ment group(N-Tad,5 mg·kg-1),and the positive control drug treatment group(Cialis,10 mg·kg-1g).The AAC model group and treatment group rats under-went blunt dissection and constrictive ligation of the abdominal aorta at the left renal artery branch point during surgery,while the Sham group rats only had their arteries separated without any constrictive liga-tion.Rats in the treatment groups received either N-Tad or Cialis via gavage three days after modeling,while rats in the sham group and the model group re-ceived physiological saline daily for 8 weeks.Small an-imal ultra-high-resolution echocardiography and hemo-dynamic assessment were applied to evaluate left ven-tricular function in each group of rats,and the calcula-tion of the left ventricular mass index was conducted.By employing Western blot and RT-PCR.we assessed the impact of this treatment on the expression of the hy-pertrophy factor atrial natriuretic peptide(ANP),phosphorylated NF-κB p65 protein(p-NF-κB p65),and phosphorylated IκB-α in the left heart tissue of rats and in H9c2 cardiomyocytes.Results Compared to the Sham group,the AAC rats exhibited a significant decrease in left heart function,an increase in left ven-tricular mass index,and a notable increase in ANP and p-p65 expression in the left heart tissue(P＜0.05).Both N-Tad and Cialis treatments could significantly enhance left ventricular function,decrease left ventric-ular mass index,and inhibit the expression of ANP and phosphorylated NF-κB p65 in rats with myocardial hy-pertrophy(P＜0.05).Notably,the therapeutic effect of low-dose N-Tad was comparable to that of high-dose Cialis.At the cellular level,Tadalafil significantly in-hibited the activation of the NF-κB signaling pathway and reduced the expression of associated proteins in H9c2 cardiomyocytes.Conclusions N-Tad can sig-nificantly inhibit p65 and IκB-α phosphorylation,and the activation of the NF-κB signaling pathway,reduce ANP expression,and improve pathological myocardial hypertrophy,as well as mitigate left heart function damage caused by abdominal aortic constriction.

Objective To investigate the status and developmental trends of clinical trials for weight control drugs in China,and to provide data support for sponsors,researchers,and regulatory authorities.Methods The drug clinical trial registration and information platform of the National Medical Products Administration was utilized to search for registered clinical trials of weight control drugs from November 2012 to June 2024.The search employed"overweight","obesity",and"weight loss"as keywords.The information collected included project registration time,drug name,dosage form,drug classification,indications,trial staging,study progress,design type,lead unit,and sponsor.Microsoft Office Excel software was employed for data entry,organization,and extraction.Results A total of 95 registered clinical trials of weight control drugs were identified,comprising 40 domestic multicenter trials,47 domestic single-center trials,and 8 international multicenter trials.Regarding trial phasing,46(48.4％)were phase Ⅰ clinical trials,17(17.9％)were phase Ⅱ clinical trials,19(20.0％)were phase Ⅲ clinical trials,and 13(13.7％)were bioequivalence trials.The drug categorization encompassed 22 chemical drugs,20 biological products,and 1 traditional Chinese medicine/natural drug.Concerning drug dosage forms,there were 32 items of injectable dosage forms,8 items of tablets,2 items of capsules,and 1 item of chewable tablets.Conclusions Registered clinical trials for weight-loss medications in China are predominantly concentrated in regions with developed medical resources.Injectable biologics constitute most test drugs,with most drugs in the early stages of research and development.The examination of the safety and efficacy of these drugs remains to be substantiated,and it is anticipated that a considerable period will elapse before their approval and market introduction.

Aim To investigate the therapeutic effects of a newly developed Tadalafil tablets on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,as well as its influence on the activation of the NF-κB signaling pathway in myo-cardial cells.Methods SD rats were randomly divid-ed into 4 groups:the sham operation group(Sham),the model group(AAC),the tadalafil new tablet treat-ment group(N-Tad,5 mg·kg-1),and the positive control drug treatment group(Cialis,10 mg·kg-1g).The AAC model group and treatment group rats under-went blunt dissection and constrictive ligation of the abdominal aorta at the left renal artery branch point during surgery,while the Sham group rats only had their arteries separated without any constrictive liga-tion.Rats in the treatment groups received either N-Tad or Cialis via gavage three days after modeling,while rats in the sham group and the model group re-ceived physiological saline daily for 8 weeks.Small an-imal ultra-high-resolution echocardiography and hemo-dynamic assessment were applied to evaluate left ven-tricular function in each group of rats,and the calcula-tion of the left ventricular mass index was conducted.By employing Western blot and RT-PCR.we assessed the impact of this treatment on the expression of the hy-pertrophy factor atrial natriuretic peptide(ANP),phosphorylated NF-κB p65 protein(p-NF-κB p65),and phosphorylated IκB-α in the left heart tissue of rats and in H9c2 cardiomyocytes.Results Compared to the Sham group,the AAC rats exhibited a significant decrease in left heart function,an increase in left ven-tricular mass index,and a notable increase in ANP and p-p65 expression in the left heart tissue(P＜0.05).Both N-Tad and Cialis treatments could significantly enhance left ventricular function,decrease left ventric-ular mass index,and inhibit the expression of ANP and phosphorylated NF-κB p65 in rats with myocardial hy-pertrophy(P＜0.05).Notably,the therapeutic effect of low-dose N-Tad was comparable to that of high-dose Cialis.At the cellular level,Tadalafil significantly in-hibited the activation of the NF-κB signaling pathway and reduced the expression of associated proteins in H9c2 cardiomyocytes.Conclusions N-Tad can sig-nificantly inhibit p65 and IκB-α phosphorylation,and the activation of the NF-κB signaling pathway,reduce ANP expression,and improve pathological myocardial hypertrophy,as well as mitigate left heart function damage caused by abdominal aortic constriction.

Objective:To comprehensively evaluate the cost and cost-effectiveness of the colorectal cancer screening program for key populations in Zhejiang Province from 2020 to 2022, and provide reference for optimizing colorectal cancer screening strategies.Methods:Based on the colorectal cancer screening program for key populations in Zhejiang Province from 2020 to 2022, parameters such as initial screening positivity rates, colonoscopy compliance rates, and detection rates for colorectal-related lesions among residents aged 50-74 were obtained. Questionnaire surveys assessed program costs and direct medical costs associated with colorectal cancer-related lesions. From a health system perspective, the cost-effectiveness ratio was calculated using the Early Detection Cost Index (EDCI) and the cost per detected case, followed by sensitivity analysis.Results:A total of 5 881 364 screenings were completed from 2020 to 2022. The initial screening positive rate (positive for either questionnaire or fecal immunochemical testing ) was 16.83%, with a colonoscopy compliance rates of 33.96% ( n=336 150). Detection rates for non-advanced adenomas, advanced adenomas, and colorectal cancer were 24.83% ( n=83 453), 11.91% ( n=40 033), and 1.01% ( n=3 397), respectively. Initial screening positivity rates and detection rates increased with age, while colonoscopy compliance rates decreased with age. Cost analysis showed a total project investment of 378 730 457 yuan, with initial screening costing 146 633 103 yuan (38.72%) and diagnostic colonoscopy 232 097 354 yuan (61.28%). The average cost per initial screening and diagnostic colonoscopy was 24.93 and 690.46 yuan, respectively. Direct medical costs for non-advanced adenomas, advanced adenomas, and colorectal cancer at stages Ⅰ, Ⅱ, Ⅲ, and Ⅳ were 4 921, 8 380, 42 547, 62 156, 66 720, and 72 334 yuan, respectively. Cost-effectiveness analysis indicated that screening needed to detect one case of colorectal cancer required 1 731 people and cost 111 490 yuan; the cost per detected advanced adenoma was 9 460 yuan, and the EDCI was 0.09. Costs decreased with increasing age per detected colorectal lesion. Sensitivity analysis showed that increasing colonoscopy compliance could reduce the cost-effectiveness ratio. Conclusions:The colorectal cancer screening program for key populations in Zhejiang Province demonstrates cost-effectiveness. Improving colonoscopy compliance can enhance overall screening effectiveness and economic benefits.