Purpose: This study aimed to assess the impact of aerobic exercise at different intensities over an eight-week period on the expression and activation of cortical synaptic proteins, with the potential to reduce anxiety and improve memory in young mice. Methods: Seven-week-old C57BL/6 mice were subjected to treadmill exercises at low (n = 10), moderate (n = 10), and high intensity (n = 10) for eight weeks. Behavioral assessments were conducted to evaluate anxiety and cognitive function. To explore the underlying mechanisms, we measured the phosphorylated levels of extracellular signal-regulated kinase (ERK), cyclic adenosine monophosphate response-binding protein (CREB), protein kinase (AKT), adenosine monophosphate activated protein kinase (AMPK), synapsin (S9, S549, S609), and PSD-95 in the cortex, as these are associated with synaptic strength. Additionally, the expression of doublecortin (DCX), a neurogenic factor, was analyzed in the hippocampus. Results: Exercise led to reductions in depressive and anxiety-related behaviors and elevated the levels of phosphorylated ERK, CREB, AKT, AMPK, synapsin (S9, S549, S609), and PSD-95 in the cortex of young mice. Furthermore, exercise increased DCX expression in the hippocampus. Moderate-intensity exercise yielded more pronounced effects than other intensities. Conclusion The findings of this research indicate that consistent moderate-intensity exercise increases synaptic strength and reduces depression and anxiety in young mice by activating multiple factors.

Purpose: This study aimed to assess the impact of aerobic exercise at different intensities over an eight-week period on the expression and activation of cortical synaptic proteins, with the potential to reduce anxiety and improve memory in young mice. Methods: Seven-week-old C57BL/6 mice were subjected to treadmill exercises at low (n = 10), moderate (n = 10), and high intensity (n = 10) for eight weeks. Behavioral assessments were conducted to evaluate anxiety and cognitive function. To explore the underlying mechanisms, we measured the phosphorylated levels of extracellular signal-regulated kinase (ERK), cyclic adenosine monophosphate response-binding protein (CREB), protein kinase (AKT), adenosine monophosphate activated protein kinase (AMPK), synapsin (S9, S549, S609), and PSD-95 in the cortex, as these are associated with synaptic strength. Additionally, the expression of doublecortin (DCX), a neurogenic factor, was analyzed in the hippocampus. Results: Exercise led to reductions in depressive and anxiety-related behaviors and elevated the levels of phosphorylated ERK, CREB, AKT, AMPK, synapsin (S9, S549, S609), and PSD-95 in the cortex of young mice. Furthermore, exercise increased DCX expression in the hippocampus. Moderate-intensity exercise yielded more pronounced effects than other intensities. Conclusion The findings of this research indicate that consistent moderate-intensity exercise increases synaptic strength and reduces depression and anxiety in young mice by activating multiple factors.

Purpose: This study aimed to assess the impact of aerobic exercise at different intensities over an eight-week period on the expression and activation of cortical synaptic proteins, with the potential to reduce anxiety and improve memory in young mice. Methods: Seven-week-old C57BL/6 mice were subjected to treadmill exercises at low (n = 10), moderate (n = 10), and high intensity (n = 10) for eight weeks. Behavioral assessments were conducted to evaluate anxiety and cognitive function. To explore the underlying mechanisms, we measured the phosphorylated levels of extracellular signal-regulated kinase (ERK), cyclic adenosine monophosphate response-binding protein (CREB), protein kinase (AKT), adenosine monophosphate activated protein kinase (AMPK), synapsin (S9, S549, S609), and PSD-95 in the cortex, as these are associated with synaptic strength. Additionally, the expression of doublecortin (DCX), a neurogenic factor, was analyzed in the hippocampus. Results: Exercise led to reductions in depressive and anxiety-related behaviors and elevated the levels of phosphorylated ERK, CREB, AKT, AMPK, synapsin (S9, S549, S609), and PSD-95 in the cortex of young mice. Furthermore, exercise increased DCX expression in the hippocampus. Moderate-intensity exercise yielded more pronounced effects than other intensities. Conclusion The findings of this research indicate that consistent moderate-intensity exercise increases synaptic strength and reduces depression and anxiety in young mice by activating multiple factors.

Purpose: This study aimed to assess the impact of aerobic exercise at different intensities over an eight-week period on the expression and activation of cortical synaptic proteins, with the potential to reduce anxiety and improve memory in young mice. Methods: Seven-week-old C57BL/6 mice were subjected to treadmill exercises at low (n = 10), moderate (n = 10), and high intensity (n = 10) for eight weeks. Behavioral assessments were conducted to evaluate anxiety and cognitive function. To explore the underlying mechanisms, we measured the phosphorylated levels of extracellular signal-regulated kinase (ERK), cyclic adenosine monophosphate response-binding protein (CREB), protein kinase (AKT), adenosine monophosphate activated protein kinase (AMPK), synapsin (S9, S549, S609), and PSD-95 in the cortex, as these are associated with synaptic strength. Additionally, the expression of doublecortin (DCX), a neurogenic factor, was analyzed in the hippocampus. Results: Exercise led to reductions in depressive and anxiety-related behaviors and elevated the levels of phosphorylated ERK, CREB, AKT, AMPK, synapsin (S9, S549, S609), and PSD-95 in the cortex of young mice. Furthermore, exercise increased DCX expression in the hippocampus. Moderate-intensity exercise yielded more pronounced effects than other intensities. Conclusion The findings of this research indicate that consistent moderate-intensity exercise increases synaptic strength and reduces depression and anxiety in young mice by activating multiple factors.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

BACKGROUND: Neoadjuvant chemoradiotherapy followed by radical surgery has been a common practice for patients with locally advanced rectal cancer, but the response rate varies among patients. This study aimed to develop a ResNet-Vision Transformer based magnetic resonance imaging (MRI)-endoscopy fusion model to precisely predict treatment response and provide personalized treatment. METHODS: In this multicenter study, 366 eligible patients who had undergone neoadjuvant chemoradiotherapy followed by radical surgery at eight Chinese tertiary hospitals between January 2017 and June 2024 were recruited, with 2928 pretreatment colonic endoscopic images and 366 pelvic MRI images. An MRI-endoscopy fusion model was constructed based on the ResNet backbone and Transformer network using pretreatment MRI and endoscopic images. Treatment response was defined as good response or non-good response based on the tumor regression grade. The Delong test and the Hanley-McNeil test were utilized to compare prediction performance among different models and different subgroups, respectively. The predictive performance of the MRI-endoscopy fusion model was comprehensively validated in the test sets and was further compared to that of the single-modal MRI model and single-modal endoscopy model. RESULTS: The MRI-endoscopy fusion model demonstrated favorable prediction performance. In the internal validation set, the area under the curve (AUC) and accuracy were 0.852 (95% confidence interval [CI]: 0.744-0.940) and 0.737 (95% CI: 0.712-0.844), respectively. Moreover, the AUC and accuracy reached 0.769 (95% CI: 0.678-0.861) and 0.729 (95% CI: 0.628-0.821), respectively, in the external test set. In addition, the MRI-endoscopy fusion model outperformed the single-modal MRI model (AUC: 0.692 [95% CI: 0.609-0.783], accuracy: 0.659 [95% CI: 0.565-0.775]) and the single-modal endoscopy model (AUC: 0.720 [95% CI: 0.617-0.823], accuracy: 0.713 [95% CI: 0.612-0.809]) in the external test set. CONCLUSION The MRI-endoscopy fusion model based on ResNet-Vision Transformer achieved favorable performance in predicting treatment response to neoadjuvant chemoradiotherapy and holds tremendous potential for enabling personalized treatment regimens for locally advanced rectal cancer patients.
Humans ; Rectal Neoplasms/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Neoadjuvant Therapy/methods* ; Aged ; Adult ; Chemoradiotherapy/methods* ; Endoscopy/methods* ; Treatment Outcome

BACKGROUND: It is inaccurate to reflect the level of dust exposure through working years. Furthermore, identifying a predictive indicator for lung function decline is significant for coal miners. The study aimed to explored whether club cell secretory protein (CC16) levels can reflect early lung function changes. METHODS: The cumulative respiratory dust exposure (CDE) levels of 1,461 coal miners were retrospectively assessed by constructed a job-exposure matrix to replace working years. Important factors affecting lung function and CC16 were selected by establishing random forest models. Subsequently, the potential of CC16 to reflect lung injury was explored from multiple perspectives. First, restricted cubic spline (RCS) models were used to compare the trends of changes in lung function indicators and plasma CC16 levels after dust exposure. Then mediating analysis was performed to investigate the role of CC16 in the association between dust exposure and lung function decline. Finally, the association between baseline CC16 levels and follow-up lung function was explored. RESULTS: The median CDE were 35.13 mg/m³-years. RCS models revealed a rapid decline in forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), and their percentages of predicted values when CDE exceeded 25 mg/m³-years. The dust exposure level (<5 mg/m³-years) causing significant changes in CC16 was much lower than the level (25 mg/m³-years) that caused changes in lung function indicators. CC16 mediated 11.1% to 26.0% of dust-related lung function decline. Additionally, workers with low baseline CC16 levels experienced greater reductions in lung function in the future. CONCLUSIONS CC16 levels are more sensitive than lung indicators in reflecting early lung function injury and plays mediating role in lung function decline induced by dust exposure. Low baseline CC16 levels predict poor future lung function.
Uteroglobin/blood* ; Humans ; Dust/analysis* ; Occupational Exposure/analysis* ; Male ; Middle Aged ; Adult ; Retrospective Studies ; Lung Injury/chemically induced* ; Coal Mining ; Biomarkers/blood* ; China/epidemiology* ; Air Pollutants, Occupational ; Female

Objective To investigate the infection status and changing trend of hepatitis C virus(HCV)infection in hospitalized patients in medical institutions,and provide reference for formulating HCV infection prevention and control strategies.Methods HCV infection surveillance results from cross-sectional survey data reported to China Healthcare-associated Infection(HAI)Surveillance System in 2020 were summarized and analyzed,HCV positive was serum anti-HCV positive or HCV RNA positive,survey result was compared with the survey results from 2003.Results In 2020,1 071 368 inpatients in 1 573 hospitals were surveyed,738 535 of whom underwent HCV test,4 014 patients were infected with HCV,with a detection rate of 68.93％and a HCV positive rate of 0.54％.The positive rate of HCV in male and female patients were 0.60％and 0.48％,respectively,with a statistically sig-nificant difference(x2=47.18,P＜0.001).The HCV positive rate in the 50-＜60 age group was the highest(0.76％),followed by the 40-＜50 age group(0.71％).Difference among all age groups was statistically signifi-cant(x2=696.74,P＜0.001).In 2003,91 113 inpatients were surveyed.35 145 of whom underwent HCV test,resulting in a detection rate of 38.57％;775 patients were infected with HCV,with a positive rate of 2.21％.In 2020,HCV positive rates in hospitals of different scales were 0.46％-0.63％,with the highest in hospital with bed numbers ranging 600-899.Patients'HCV positive rates in hospitals of different scales was statistically signifi-cant(X2=35.34,P＜0.001).In 2020,12 provinces/municipalities had over 10 000 patients underwent HCV-rela-ted test,and HCV positive rates ranged 0.19％-0.81％,with the highest rate from Hainan Province.HCV posi-tive rates in different departments were 0.06％-0.82％,with the lowest positive rate in the department of pedia-trics and the highest in the department of internal medicine.In 2003 and 2020,HCV positive rates in the depart-ment of infectious diseases were the highest,being 7.95％and 3.48％,respectively.Followed by departments of orthopedics(7.72％),gastroenterology(3.77％),nephrology(3.57％)and general intensive care unit(ICU,3.10％)in 2003,as well as departments of gastroenterology(1.35％),nephrology(1.18％),endocrinology(0.91％),and general intensive care unit(ICU,0.79％)in 2020.Conclusion Compared with 2003,HCV positive rate decreased significantly in 2020.HCV infected patients were mainly from the department of infectious diseases,followed by departments of gastroenterology,nephrology and general ICU.HCV infection positive rate varies with gender,age,and region.

Objective:To observe the clinical efficacy and safety of Tongren Niuhuang Qingxin Pills combined with telmisartan tablets in the treatment of hypertensive vertigo syndrome of phlegm-heat disturbance.Methods:Randomized controlled trial was conducted. Totally 80 patients with hypertension vertigo and phlegm-heat disturbance syndrome were selected from March 2021 to August 2022 at Beijing Tongrentang Hospital of Traditional Chinese Medicine as the observation objects. They were randomly divided into two groups using a random number table method, with 40 cases in each group. The control group received oral telmisartan tablets, while the experimental group received Tongren Niuhuang Qingxin Pills in addition to the control group. Both groups were treated for 28 days and followed up for 1 month. The patients' room blood pressure before and after treatment was measured, and TCM syndrome scores were evaluated. The dizziness assessment rating scale (DARS) was used to evaluate the severity of dizziness, adverse reactions during treatment were recorded, drug safety was observed, and clinical efficacy was evaluated.Results:The total effective rate of the experimental group was 85.0% (34/40), and that of the control group was 7.5% (3/40), with statistical significance between the two groups ( χ2=48.32, P<0.001). Compared with before treatment, the experimental group had SBP [(136.63 ± 6.01) mmHg vs. (159.30 ± 9.01) mmHg, t=-21.00] and DBP [(84.48 ± 4.36) mmHg vs. (95.30 ± 3.75) mmHg, t=-13.80] after treatment; after treatment, SBP [(137.34 ± 6.39) mmHg vs. (158.00 ± 10.06) mmHg, t=-5.28] and DBP [(86.08 ± 4.43) mmHg vs. (95.18 ± 6.61) mmHg, t=-8.09] decreased in the control group ( P<0.01), but there was no statistical significance between the two groups after treatment ( P>0.05). After treatment, the TCM syndrome scores in the experimental group (8.68 ± 3.39 vs. 15.12 ± 3.03, Z=-6.61) were lower than those in the control group ( P<0.001), and DARS score [(8.53 ± 3.93) vs. (12.20 ± 3.95), Z=-3.63] was lower than that in the control group ( P<0.001). After treatment, the therapeutic effect index of TCM syndromes in the experimental group improved compared to before treatment in the same group. The therapeutic effect index of each symptom, from high to low, was as follows: rotation of oneself or visual objects>numbness of limbs>dry stool>dizziness and dizziness>liking cold drinks>bitter and dry mouth>red urine>red tongue, yellow coating, and greasy tongue>vomiting sticky and turbid phlegm>tinnitus>smooth pulse. There were no significant adverse reactions during the treatment of the two groups. Conclusion:Tongren Niuhuang Qingxin Pills combined with telmisartan can reduce the blood pressure of patients with hypertensive vertigo syndrome of phlegm-heat disturbance, improve the vertigo symptoms and TCM syndromes of patients, and the efficacy evaluation is superior to that of telmisartan alone.

Objective To explore the cut-off value of three dimensional(3D)vena contracta area(VCA)in diagnosing severe tricuspid regrugitation(TR)under different etiologies and its accuracy and practicality in clinical application.Methods From Mar 2019 to May 2021,ninety-two patients with confirmed TR underwent two dimensional(2D)and 3D transthoracic echocardiography.The correlation and consistency between 3D VCA 3D calculated based on the proximal isokinetic surface area(PISA)effective regurgitant orifice area(EROA)was calculated.Comprehensive 2D multi-parameter method was used as a reference method to calculate the cut-off value of the diagnosis of severe TR.Results A total of 85 patients were ultimately included.3D VCA and 3D PISA EROA had similar and acceptable correlations in both primary TR and secondary TR(primary TR:r=0.831,P<0.01;secondary TR:r=0.806,P<0.01).Bland-Altman analysis showed that 3D VCA overestimated TR compared with 3D PISA EROA(62%overestimated in the total patient population,51%overestimated in primary TR,and 74%overestimated in secondary TR).In secondary TR,the cut-off value of 3D VCA for diagnosing severe TR was 0.45 cm2(sensitivity 89%,specificity 82%);combining clinical symptoms,positive 2D PISA EROA results and 3D VCA results for severe TR,the chi-square value was higher than those only included clinical symptoms or incorporated clinical symptoms and positive 2D PISA EROA results(42.168 vs.26.059 and 16.759,P<0.01).Conclusion 3D VCA would overestimate TR,and had high and incremental diagnostic value for evaluating severe TR in secondary TR.