Rheumatoid arthritis （RA） is a common chronic systemic autoimmune disease with synovitis as the main manifestation， which often causes joint swelling and pain or even deformity. It is considered to be an incurable lifelong disease. Although the current Western medicine treatment can alleviate the progression of the disease， it has the clinical limitations of liver injury， cardiovascular complications， and other adverse reactions， along with easy recurrence. Traditional Chinese medicine （TCM） has a long history and has the advantages of individualized treatment and fewer adverse reactions. It can effectively relieve the symptoms of joint swelling and pain in RA patients and slow down the progression of bone destruction， which has attracted wide concern in the medical community. Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathway is an important intracellular pathway involved in cell proliferation， differentiation， apoptosis， immune regulation， and other biological behaviors， and plays an important role in the pathophysiological process of RA. In recent years， many studies have confirmed that TCM monomers and compounds can inhibit inflammation and angiogenesis by regulating the JAK/STAT signaling pathway， induce apoptosis and inhibit proliferation of fibroblast-like synoviocytes （FLS）， regulate immune response， and thus exert an effect in the treatment of RA. However， there is still a lack of comprehensive and systematic induction and overview. Therefore， by searching the relevant literature in China National Knowledge Infrastructure （CNKI） and PubMed databases from 2009 to 2024， this study described the mechanism of the JAK/STAT signaling pathway in the occurrence and development of RA and summarized the research progress of TCM monomers and compounds in regulating the JAK/STAT signaling pathway in RA intervention. The study aims to provide new ideas and strategies for the clinical treatment of RA with TCM and the research and development of new drugs.

Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.

The Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutation is one of the most prevalent activating alterations in cancer. It indicates a poor overall prognosis due to its highly invasive nature. Although several KRAS inhibitors have been developed in recent years, a significant clinical challenge has emerged as a substantial proportion of patients eventually develop resistance to these therapies. Therefore, identifying determinants of drug resistance is critical for guiding treatment strategies. This review provides a comprehensive overview of the mutation landscape and molecular mechanisms of KRAS activity in various cancers. Meanwhile, it summaries the progress and prospects of small molecule KRAS inhibitors undergoing clinical trials. Furthemore, this review explores potential strategies to overcome drug resistance, with the ultimate goal of steering toward patient-centric precision oncology in the foreseeable future.
Humans ; Drug Resistance, Neoplasm/drug effects* ; Proto-Oncogene Proteins p21(ras)/metabolism* ; Mutation/genetics* ; Neoplasms/genetics* ; Antineoplastic Agents/therapeutic use*

Objective: To identify optimal recommendations for 24 hour movement behaviors in relation to obesity indicators among children and adolescents, so as to provide scientific evidences for targeted obesity prevention strategies. Methods: From April to June 2024, 242 participants (96 children aged 6-11, 146 adolescents aged 12-18) were recruited from two schools(one combined junior and senior high school, one consistent school for 12 years) in Tianjin for performing physical examination. Obesity indicators including body mass index Z scores (BMI Z ), waist-to-hip ratio (WHR), body fat percentage (FAT), and fat mass index (FMI) were measured. Measurement of 24 hour movement behaviors using an accelerometer, comprised moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), sedentary behavior (SB), and sleep (SLP). The optimal movement duration and interval for children and adolescents were determined through optimal time zone analysis. Results: Significant associations were found between 24 hour movement behaviors and BMI Z ( F =2.35) and WHR ( F =3.55) in children, as well as BMI Z ( F = 3.57 ), FAT ( F =2.44), and WHR ( F = 3.61 ) in adolescents (all P <0.05). The results of optimal time zone analysis showed that optimal daily durations were MVPA 63( 40- 70) min, LPA 257(220-270) min, SB 467(390-600) min, SLP 653(590-680) min for children, and MVPA 65(40-70) min, LPA 262(220-270) min, SB 484(440-600) min, SLP 629(510-670) min for adolescents. Conclusion The recommended amount of 24 hour movement for children and adolescents based on obesity indicators could provide reference for informing the development of Chinesespecific guidelines,and promote healthy lifestyles among children and adolescents.

Objective:To evaluate the association between heatwaves and fall-related mortality.Methods:A total of 61 421 fall-related mortality from 2013 to 2022 in 7 provinces of China were included in a time-stratified case-crossover design, with daily meteorological data derived from the fifth generation European Reanalysis dataset produced by the European Centre for Medium-Range Weather Forecasts. Conditional logistic regression chimeric distributed lag nonlinear model was used to analyze the association between heatwaves and fall-related mortality and stratified analysis was conducted according to gender and age.Results:Heatwaves were associated with an increased risk of fall-related morality. The risk of fall-related mortality during heatwaves was higher than during non-heatwave periods ( OR=1.11, 95% CI: 1.05-1.18). The attributable fraction of fall-related motality due to heatwaves was 10.25% (95% CI: 4.49%-15.36%). For each 1 ℃ increase above the heatwave threshold, the risk of fall-related mortality increased by 34% ( OR=1.34, 95% CI: 1.02-1.76). The effect of heatwave duration on fall-related mortality was not statistically significant. Stratified analyses indicated that women experienced a higher risk of fall-related mortality during heatwaves ( OR=1.13, 95% CI: 1.04-1.22) compared to man ( OR=1.10, 95% CI: 1.04-1.17). Conclusions:Heatwave increases the risk of fall-related mortality, and the intensity of heatwaves modify this risk. Women are vulnerable populations.

Executive function(EF) is an advanced cognitive function of the central nervous system, and is closely related to an individual's capacity for daily living and adaptation. Patients with attention deficit hyperactivity disorder (ADHD) typically exhibit significant executive dysfunction. While most existing studies on the executive function of individuals with ADHD are cross-sectional, and little is known about the longitudinal maturation process of related brain structures and functional connectivity patterns. The findings indicate that ADHD patients exhibit differential developmental trajectories in brain structural and functional connectivity compared with typically developing group.Furthermore, there is a lifespan association between abnormal brain network development and ADHD symptoms. This article aims to elucidate the characteristics of executive function deficits in ADHD patients across different developmental stages, examining their relationship with the nervous system’s development from a development perspective.

BACKGROUND:Osteoporotic trabecular structures are insufficient to maintain screw holding force,often leading to spinal fixation failure.Currently,the following four aspects are mainly used to solve this problem:(1)screw material;(2)surface coating treatment;(3)screw channel solidification strategy;(4)screw shape.The screw channel of the modified cortical bone trajectory screw placement technique has been proven to have a good fixation effect,but there is an urgent need to develop matching screws.OBJECTIVE:To compare the biomechanical performance differences of various types of spinal cortical bone thread screws in the modified cortical bone trajectory fixation of lumbar vertebrae using the finite element method.METHODS:The L4 vertebral models were constructed based on the CT data of three adult wet lumbar specimens(two males and one female)and subjected to finite element analysis.In the modified cortical bone trajectory fixation technique,fully cortical bone thread screws(single thread screws)with lengths of 45 mm and diameters of 5.5 mm and 4.5 mm were used and considered as groups A and B,which were compared with those of the traditional pedicle screw technique group(group C,6.0 mm diameter,45 mm length,double-threaded screw)and the cortical bone trajectory screw group(group D,4.5 mm diameter,45 mm length,double-threaded screw).Axial pull-out force,screw stability(determined by the displacement ratio of upper,lower,left,and right loads),and anti-spin-out torque were measured to compare fixation strength of each group of screws.RESULTS AND CONCLUSION:(1)Axial pull-out force:Group A＞group B(P=0.003),and both group A and group B were greater than the group C(P＜0.001,P=0.003)and group D(all P＜0.001).(2)Screw stability:When load was applied in the upward and downward directions on the screw,the load displacement ratio of the four screw double threads was greater in group A than in group B(P＞0.05);both group A and group B were greater than the group C(all P＜0.001)and the group D(all P＜0.001).(3)Anti-spin-out torque:Group A＞group B(P=0.008),and both group A and group B were greater than the group C(P=0.008,P=0.131).(4)It is indicated that during modified cortical bone trajectory fixation of lumbar vertebrae,the novel spinal cortical bone thread screw demonstrates superior biomechanical performance compared to double thread screws applied in the clinically classic pedicle screw trajectory and cortical bone trajectory.Additionally,the novel spinal cortical bone thread screw(D=5.5 mm,L=45 mm)becomes the optimal adaptation for the modified cortical bone trajectory screw path.

Objective This study aims to analyze the application and effect of a competency-based blended teaching model in obstetrics and gynecology education.Methods The study included 90 interns undergoing training in the Department of Obstetrics and Gynecology at Zhongshan Torch Development Zone People's Hospital from March 2023 to July 2024.The partici-pants were randomly divided into two groups using a random number table method.The control group received traditional teaching methods,while the observation group received a competency-based blended teaching model.The teaching effects were compared between the two groups.Results At the end of the rotation,both groups showed varying degrees of improvement in theoretical examination scores,practical skills scores,and CTDI-CV scores.The observation group showed significantly greater improvement compared to the control group(P＜0.05).At the end of the rotation,the scores of clinical basic competency,teamwork ability,and other dimensions of the Student Job Competency Evaluation Scale were significantly higher in the observation group compared to the control group(P＜0.05).The differences were statistically significant.Conclusion The application of a competency-based blended teaching model in obstetrics and gynecology education has significant effects,improving teaching quality and enab-ling medical students to achieve better assessment results.It also enhances critical thinking skills and job competency.This mod-el has high value for promotion and application.

Executive function(EF) is an advanced cognitive function of the central nervous system, and is closely related to an individual's capacity for daily living and adaptation. Patients with attention deficit hyperactivity disorder (ADHD) typically exhibit significant executive dysfunction. While most existing studies on the executive function of individuals with ADHD are cross-sectional, and little is known about the longitudinal maturation process of related brain structures and functional connectivity patterns. The findings indicate that ADHD patients exhibit differential developmental trajectories in brain structural and functional connectivity compared with typically developing group.Furthermore, there is a lifespan association between abnormal brain network development and ADHD symptoms. This article aims to elucidate the characteristics of executive function deficits in ADHD patients across different developmental stages, examining their relationship with the nervous system’s development from a development perspective.

Objective::To report a fetus with ARCN1-related syndrome caused by a novel de novo heterozygous variant, highlighting the importance of early genetic diagnosis in prenatal care. Methods::The clinical and genetic data of a fetus with a complex combination of clinical signs and a novel de novo heterozygous variant were collected and have been summarized in this study. The potential pathogenic variant was identified throughout the whole exome sequencing and the effects of candidate variants were further validated by a minigene splicing assay. Results::Prenatal systematic ultrasound detected fetal growth restriction. Genetic analysis identified a novel de novo heterozygous variant within the ARCN1 gene—c.1241 +5G>A-located in intron 8. In vitro minigene splicing assays demonstrated that the variant led to two abnormal transcripts. The longer transcript retained 189 base pairs of intron 8, resulting in a truncated protein of 414 amino acids (p.Ser415*). The shorter transcript involved exon 8 skippings, producing a truncated protein of 407 amino acids (p.Ile378Serfs*31). Conclusion::A novel de novo heterozygous variant of the ARCN1 gene, namely NM_001655.5: c.1241 +5G>A, was discovered and identified in a fetus with rhizomelic short stature, microretrognathia, and developmental delays.