ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, S_max) alternated with one minute at low speed (50%-55% S_max), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.

INTRODUCTION: During the coronavirus disease 2019 (COVID-19) pandemic, contact tracers were under immense pressure to deliver effective and timely contact tracing, raising concerns of higher susceptibility to burnout. Our study aimed to determine burnout prevalence among hospital-based contact tracers and associated risk factors, so that interventions to reduce burnout risk could be formulated. METHODS: One hundred and ninety-six active contact tracers across three hospitals within a healthcare cluster were invited to complete an anonymous online survey. To identify burntout, data such as demographics, work-related variables and contact tracing-related variables were collected using the Copenhagen Burnout Inventory. Associated factors were identified using multivariate statistics. Open-ended questions were included to understand the challenges and potential improvements through qualitative analysis. RESULTS: A total of 126 participants completed the survey, giving a completion rate of 64%, and almost half of these participants (42.9%) reported burnout. Protective factors included being on work-from-home arrangements (adjusted odds ratio [OR] 0.22, 95% confidence interval [CI] 0.08-0.56), perception of being well supported by their institution (adjusted OR 0.25, 95% CI 0.08-0.80) and being married (adjusted OR 0.28, 95% CI 0.12-0.64). Risk factors included having an administrative role pre-COVID-19 (adjusted OR 3.62, 95% CI 1.33-9.83). Work-related burnout was related to being activated for more than 1 day in the preceding week (unadjusted OR 3.25, 95% CI 1.33-7.94) and multiple activations in a day (unadjusted OR 3.54, 95% CI 1.44-4.41). Biggest challenges identified by participants were language barrier (62.7%), followed by workflow-related issues (42.1%). CONCLUSION Our study demonstrated burnout and other challenges faced by a team of mostly hospital-based administrative staff redeployed on a part-time basis to ensure timely contact tracing. To mitigate burnout, we recommend choosing staff on work-from-home arrangements and ensuring adequate manpower and rostering arrangements.
Humans ; COVID-19/epidemiology* ; Burnout, Professional/epidemiology* ; Singapore/epidemiology* ; Female ; Male ; Cross-Sectional Studies ; Adult ; Middle Aged ; Risk Factors ; Surveys and Questionnaires ; Contact Tracing/methods* ; SARS-CoV-2 ; Prevalence ; Pandemics

OBJECTIVE: Huachansu injection (HCSI), a promising anti-cancer Chinese medicine injection, has been reported to have the potential for reducing the toxicity of chemotherapy and improving the quality of life for colorectal cancer (CRC) patients. The objective of this study is to explore the synergistic and detoxifying effects of HCSI when used in combination with irinotecan (CPT-11). METHODS: To investigate the effect of HCSI on anti-CRC efficacy and intestinal toxicity of CPT-11, we measured changes in the biological behavior of LoVo cells in vitro, and anti-tumor effects in LoVo cell xenograft nude mice models in vivo. Meanwhile, the effect of HCSI on intestinal toxicity and the uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) expression was investigated in the CPT-11-induced colitis mouse model. Subsequently, we measured the effect of HCSI and its 13 constituent bufadienolides on the expression of UGT1A1 and organic anion transporting polypeptides 1B3 (OATP1B3) in HepG2 cells. RESULTS: The combination index (CI) results showed that the combination of HCSI and CPT-11 exhibited a synergistic effect (CI < 1), which significantly suppressing the LoVo cell migration, enhancing G2/M and S phase arrest, and inhibiting tumor growth in vivo. Additionally, the damage to intestinal tissues was attenuated by HCSI in CPT-11-induced colitis model, while the increased expression of UGT1A1 in HepG2 cells and in mouse was observed. CONCLUSION The co-therapy with HCSI alleviated the intestinal toxicity induced by CPT-11 and exerted an enhanced anti-CRC effect. The detoxifying mechanism may be related to the increased expression of UGT1A1 and OATP1B3 by HCSI and its bufadienolides components. The findings of this study may serve as a theoretical insights and strategies to improve CRC patient outcomes. Please cite this article as: Jiang B, Meng ZY, Hu YJ, Chen JJ, Zong L, Xu LY, Zhang XQ, Zhang JX, Han YL. Huachansu injection enhances anti-colorectal cancer efficacy of irinotecan and alleviates its induced intestinal toxicity through upregulating UGT1A1-OATP1B3 expression in vitro and in vivo. J Integr Med. 2025; 23(5):576-590.
Irinotecan/therapeutic use* ; Animals ; Glucuronosyltransferase/genetics* ; Humans ; Colorectal Neoplasms/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Nude ; Mice ; Up-Regulation/drug effects* ; Male ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Hep G2 Cells ; Cell Line, Tumor ; Intestines/drug effects* ; Amphibian Venoms

The development of animal early embryos commences with the reprogramming of terminally differentiated gametes into totipotent zygotes following fertilization. During the initial stages of embryonic development, the transcriptional levels of zygotic genome remain silent and maternal gene products dominate the regulation of development. As embryonic development progresses, the maternal gene products undergo phased degradation while the zygotic genome gradually activates transcription, marking the transition from the maternal regulation to the zygotic genome regulation in early embryonic development, which is also referred to as the maternal-zygotic transition (MZT). Zygotic genome activation (ZGA) is a critical turning process in this transition, and its accurate occurrence is crucial for early embryonic development and cell fate decisions. However, the regulatory factors and molecular mechanisms of ZGA remain poorly understood. Studies have shown that ZGA varies greatly among different species and may be affected by a variety of regulatory factors such as DNA methylation, histone modification, non-coding RNA, chromatin remodeling and ZGA related factors. Here, we review the research progress of the above regulatory factors affecting ZGA, which can provide valuable insights for further investigations into the ZGA related mechanisms of early embryos.

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.

Background::Breast cancer (BC) risk-stratification tools for Asian women that are highly accurate and can provide improved interpretation ability are lacking. We aimed to develop risk-stratification models to predict long- and short-term BC risk among Chinese women and to simultaneously rank potential non-experimental risk factors.Methods::The Breast Cancer Cohort Study in Chinese Women, a large ongoing prospective dynamic cohort study, includes 122,058 women aged 25-70 years old from the eastern part of China. We developed multiple machine-learning risk prediction models using parametric models (penalized logistic regression, bootstrap, and ensemble learning), which were the short-term ensemble penalized logistic regression (EPLR) risk prediction model and the ensemble penalized long-term (EPLT) risk prediction model to estimate BC risk. The models were assessed based on calibration and discrimination, and following this assessment, they were externally validated in new study participants from 2017 to 2020.Results::The AUC values of the short-term EPLR risk prediction model were 0.800 for the internal validation and 0.751 for the external validation set. For the long-term EPLT risk prediction model, the area under the receiver operating characteristic curve was 0.692 and 0.760 in internal and external validations, respectively. The net reclassification improvement index of the EPLT relative to the Gail and the Han Chinese Breast Cancer Prediction Model (HCBCP) models for external validation was 0.193 and 0.233, respectively, indicating that the EPLT model has higher classification accuracy.Conclusions::We developed the EPLR and EPLT models to screen populations with a high risk of developing BC. These can serve as useful tools to aid in risk-stratified screening and BC prevention.

Objective To investigate the effects of α1-antitrypsin(AAT)on motor function in adult mice with immature brain white matter injury.Methods Five-day-old C57BL/6J mice were randomly assigned to the sham surgery group(n=27),hypoxia-ischemia(HI)+ saline group(n=27),and HI+AAT group(n=27).The HI white matter injury mouse model was established using HI methods.The HI+AAT group received intraperitoneal injections of AAT(50 mg/kg)24 hours before HI,immediately after HI,and 72 hours after HI;the HI+saline group received intraperitoneal injections of the same volume of saline at the corresponding time points.Brain T2-weighted magnetic resonance imaging scans were performed at 7 and 55 days after modeling.At 2 months of age,adult mice were evaluated for static,dynamic,and coordination parameters using the Catwalk gait analysis system.Results Compared to the sham surgery group,mice with HI injury showed high signal intensity on brain T2-weighted magnetic resonance imaging at 7 days after modeling,indicating significant white matter injury.The white matter injury persisted at 55 days after modeling.In comparison to the sham surgery group,the HI+saline group exhibited decreased paw print area,maximum contact area,average pressure,maximum pressure,paw print width,average velocity,body velocity,stride length,swing speed,percentage of gait pattern AA,and percentage of inter-limb coordination(left hind paw → left front paw)(P<0.05).The HI+saline group showed increased inter-paw distance,percentage of gait pattern AB,and percentage of phase lag(left front paw → left hind paw)compared to the sham surgery group(P<0.05).In comparison to the HI+saline group,the HI+ AAT group showed increased average velocity,body velocity,stride length,and swing speed(right front paw)(P<0.05).Conclusions The mice with immature brain white matter injury may exhibit significant motor dysfunction in adulthood,while the use of AAT can improve some aspects of their motor function.[Chinese Journal of Contemporary Pediatrics,2024,26(2):181-187]

Objective To analyze the latent categories of traditional Chinese medicine(TCM)constitution of college students,and to explore the moderating effects of latent categories of TCM constitution on the the associations between self-efficacy and depression-anxiety symptoms.Methods An investigation was carried out in two universities of Guangdong Province with 30-item TCM constitution scale,General Self-Efficacy Scale(GSES)and Kessler Psychological Distress Scale,and then a total of 1 097 valid samples were obtained.Correlation analysis,latent profile analysis,and hierarchical regression analysis were used for statistical analysis.Results(1)Four latent categories of TCM constitution were obtained in the college students:generally-balanced type(32.0%),highly-balanced type(17.4%),generally-biased type(36.9%)and highly-biased type(13.7%).There were statistically significant differences in the subscale scores of TCM constitution scale among the college students with various latent categories of TCM constitution(all P＜0.001).(2)Hierarchical regression analysis showed that the self-efficacy negatively predicted the symptoms of depression and anxiety(β value being-0.268,-0.161 respectively,P＜0.001);with the generally-balanced type as reference,the generally-biased type and the highly-biased type positively predicted the symptoms of depression and anxiety,and the highly-balanced type negatively predicted the symptoms of depression and anxiety(all P＜0.001).(3)The latent categories of TCM constitution had moderating effects on the self-efficacy and depression-anxiety symptoms:the depression-anxiety symptoms were relieved with the increase of self-efficacy in the college students with the TCM constitution being generally-biased type,highly-biased type and generally-balanced type(all P＜0.01);in the college students with highly-balanced type,the symptoms of depression(β=0.005,P=0.907)and anxiety(β=0.007,P=0.878)did not change with the increase of self-efficacy.Conclusion Obvious heterogeneity of TCM constitution is presented in the population of college students.The measures of enhancement of self-efficacy and the correction of TCM to promote the psychological health of college students should be performed with reference to the characteristics of their TCM constitution types.

Objective: To establish and validate a nomogram model for predicting the risk of microvascular invasion(MVI) in hepatocellular carcinoma. Methods: The clinical data of 210 patients with hepatocellular carcinoma who underwent hepatectomy at Department of Hepatobiliary and Pancreatic Surgery,the Affiliated Hospital of Qingdao University from January 2013 to October 2021 were retrospectively analyzed. There were 169 males and 41 females, aged(M(IQR)) 57(12)years(range:30 to 80 years). The patients were divided into model group(the first 170 cases) and validation group(the last 40 cases) according to visit time. Based on the clinical data of the model group,rank-sum test and multivariate Logistic regression analysis were used to screen out the independent related factors of MVI. R software was used to establish a nomogram model to predict the preoperative MVI risk of hepatocellular carcinoma,and the validation group data were used for external validation. Results: Based on the modeling group data,the receiver operating characteristic curve was used to determine that cut-off value of DeRitis ratio,γ-glutamyltransferase(GGT) concentration,the inverse number of activated peripheral blood T cell ratio (-aPBTLR) and the maximum tumor diameter for predicting MVI, which was 0.95((area under curve, AUC)=0.634, 95%CI: 0.549 to 0.719), 38.2 U/L(AUC=0.604, 95%CI: 0.518 to 0.689),-6.05%(AUC=0.660, 95%CI: 0.578 to 0.742),4 cm(AUC=0.618, 95%CI: 0.533 to 0.703), respectively. Univariate and multivariate Logistic regression analysis showed that DeRitis≥0.95,GGT concentration ≥38.2 U/L,-aPBTLR>-6.05% and the maximum tumor diameter ≥4 cm were independent related factors for MVI in hepatocellular carcinoma patients(all P<0.05). The nomogram prediction model based on the above four factors established by R software has good prediction efficiency. The C-index was 0.758 and 0.751 in the model group and the validation group,respectively. Decision curve analysis and clinical impact curve showed that the nomogram model had good clinical benefits. Conclusions: DeRitis ratio,serum GGT concentration,-aPBTLR and the maximum tumor diameter are valuable factors for preoperative prediction of hepatocellular carcinoma with MVI. A relatively reliable nomogram prediction model could be established on them.
Female ; Humans ; Male ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Neoplasm Invasiveness ; Nomograms ; Retrospective Studies ; Risk Factors ; Adult ; Middle Aged ; Aged ; Aged, 80 and over

Oxidative stress, due to the disruption of the balance between reactive oxygen species (ROS) generation and the antioxidant defense system, plays an important role in the pathogenesis of rheumatoid arthritis (RA). Excessive ROS leads to the loss of biological molecules and cellular functions, release of many inflammatory mediators, stimulate the polarization of macrophages, and aggravate the inflammatory response, thus promoting osteoclasts and bone damage. Therefore, foreign antioxidants would effectively treat RA. Herein, ultrasmall iron-quercetin natural coordination nanoparticles (Fe-Qur NCNs) with excellent anti-inflammatory and antioxidant properties were constructed to effectively treat RA. Fe-Qur NCNs obtained by simple mixing retain the inherent ability to remove ROS of quercetin and have a better water-solubility and biocompatibility. In vitro experiments showed that Fe-Qur NCNs could effectively remove excess ROS, avoid cell apoptosis, and inhibit the polarization of inflammatory macrophages by reducing the activation of the nuclear factor-κ-gene binding (NF-κB) pathways. In vivo experiments showed that the swollen joints of mice with rheumatoid arthritis treated with Fe-Qur NCNs significantly improved, with Fe-Qur NCNs largely reducing inflammatory cell infiltration, increasing anti-inflammatory macrophage phenotypes, and thus inhibiting osteoclasts, which led to bone erosion. This study demonstrated that the new metal-natural coordination nanoparticles could be an effective therapeutic agent for the prevention of RA and other diseases associated with oxidative stress.