Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, joint destruction, and functional impairment. Angiogenesis plays a key role in the pathological progression of RA with dysfunction of endothelial cells to promote synovial inflammation, sustain pannus formation, subsequently leading to joint damage. Colquhounia Root Tablets (CRT), a Chinese patent drug, has shown a satisfying clinical efficacy in treating RA, while the underlying mechanism by which CRT inhibits RA-associated angiogenesis remains unclear. In this study, we applied a research approach combining transcriptomic data analysis, bio-network mapping, and in vivo and in vitro experiments to explore the molecular mechanisms of CRT in suppressing angiogenesis in RA. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences (ratification number: IBTCMCACMS21-2307-06). Network analysis identified that key genes such as nucleotide-binding oligomerization domain-containing protein 2 (NOD2), SMAD family member 3 (SMAD3), and vascular endothelial growth factor A (VEGFA) significantly enriched in pathways related to NOD-like receptor signaling and VEGF signaling, indicating that CRT may inhibit angiogenesis by regulating vascular endothelial cell function with modulating angiogenesis-related pathways. In vivo data showed that CRT significantly reduced the positive expression of CD31 and VEGF in the ankle joint of adjuvant-induced arthritis (AIA) rats. In vitro data further confirmed that CRT effectively inhibited VEGF-induced migration, invasion, and tube formation in HUVECs, while significantly reduced the expression of angiogenesis-related factors VEGF/CD31/Ang-1, as well as the positive expression of VEGF and CD31 in HUVECs. Furthermore, CRT markedly decreased the protein expression of NOD2, VEGFA, and SMAD3. In conclusion, these findings indicate that CRT may inhibit the RA-related angiogenesis by targeting the NOD2/SMAD3/VEGF signaling axis to improve endothelial cell function, enriching the scientific connotation of CRT in inhibiting pathological angiogenesis in RA and also offer new insights for clinical prevention and treatment of RA.

ObjectiveTo understand the infection characteristics of multidrug-resistant organisms (MDROs) in hospitalized patients in a tertiary sentinel hospital in Shanghai, so as to provide an evidence for the development of targeted prevention and control measures. MethodsData of MDROs strains and corresponding medical records of some hospitalized patients in a hospital in Shanghai from 2021 to 2023 were collected, together with an analysis of the basic information, clinical treatment, underlying diseases and sources of sample collection. ResultsA total of 134 strains of MDROs isolated from hospitalized patients in this hospital were collected from 2021 to 2023 , including 63 strains of methicillin-resistant Staphylococcus aureus (MRSA), 57 strains of carbapenem-resistant Acinetobacter baumannii (CRAB), and 14 strains of carbapenem-resistant Klebsiella pneumoniae (CRKP). Of the 134 strains, 30 strains were found in 2021, 47 strains in 2022 and 57 strains in 2023. The male-to-female ratio of patients was 2.05∶1, with the highest percentage (70.90%) in the age group of 60‒<90 years. The primary diagnosis was mainly respiratory disease, with lung and respiratory tract as the cheif infection sites. There was no statistically significant difference in the distribution of strains between different genders and infection sites (P>0.05). However, the differences in the distribution of strains between different ages and primary diagnosis were statistically significant (P<0.05). Patients who were admitted to the intensive care unit (ICU), had urinary tract intubation, were not artery or vein intubated, were not on a ventilator, were not using immunosuppresants or hormones, and were not applying radiotherapy or chemotherapy were in the majority. There was no statistically significant difference in the distribution of strains for whether received radiotherapy or chemotherapy or not (P>0.05), while the differences in the distribution of strains with ICU admission history, urinary tract intubation, artery or vein intubation, ventilator use, and immunosuppresants or hormones use or not were statistically significant (all P<0.05). The type of specimen was mainly sputum, the hospitalized ward was mainly comprehensive ICU, the sampling time was mainly in the first quarter throughout the year, the number of underlying diseases was mainly between 1 to 2 kinds, the application of antibiotics ≥4 kinds, and those who didn’t receive any surgery recently accounted for the most. There were statistically significant differences in the distribution of strains between different specimen types, wards occupied and history of ICU stay (P<0.05), but no statistically significant difference in the distribution of strains between different sampling times, number of underlying diseases and types of antibiotics applied (P>0.05). ConclusionThe situation of prevention and control on MDROs in this hospital is still serious. Focus should be placed on high-risk factors’ and infection monitoring and preventive measures should be strengthened to reduce the incidence rate of MDROs infection.

Neuroscience is a significant frontier discipline within the natural sciences and has become an important interdisciplinary frontier scientific field. Brain is one of the most complex organs in the human body, and its structural and functional analysis is considered the “ultimate frontier” of human self-awareness and exploration of nature. Driven by the strategic layout of “China Brain Project”, Chinese scientists have conducted systematic research focusing on “understanding the brain, simulating the brain, and protecting the brain”. They have made breakthrough progress in areas such as the principles of brain cognition, mechanisms and interventions for brain diseases, brain-like computation, and applications of brain-machine intelligence technology, aiming to enhance brain health through biomedical technology and improve the quality of human life. Due to limited understanding and comprehension of neuroscience, there are still many important unresolved issues in the field of neuroscience, resulting in a lack of effective measures to prevent and protect brain health. Therefore, in addition to actively developing new generation drugs, exploring non pharmacological treatment strategies with better health benefits and higher safety is particularly important. Epidemiological data shows that, exercise is not only an indispensable part of daily life but also an important non-pharmacological approach for protecting brain health and preventing neurodegenerative diseases, forming an emerging research field known as motor neuroscience. Basic research in motor neuroscience primarily focuses on analyzing the dynamic coding mechanisms of neural circuits involved in motor control, breakthroughs in motor neuroscience research depend on the construction of dynamic monitoring systems across temporal and spatial scales. Therefore, high spatiotemporal resolution detection of movement processes and movement-induced changes in brain structure and neural activity signals is an important technical foundation for conducting motor neuroscience research and has developed a set of tools based on traditional neuroscience methods combined with novel motor behavior decoding technologies, providing an innovative technical platform for motor neuroscience research. The protective effect of exercise in neurodegenerative diseases provides broad application prospects for its clinical translation. Applied research in motor neuroscience centers on deciphering the regulatory networks of neuroprotective molecules mediated by exercise. From the perspectives of exercise promoting neurogenesis and regeneration, enhancing synaptic plasticity, modulating neuronal functional activity, and remodeling the molecular homeostasis of the neuronal microenvironment, it aims to improve cognitive function and reduce the incidence of Parkinson’s disease and Alzheimer’s disease. This has also advanced research into the molecular regulatory networks mediating exercise-induced neuroprotection and facilitated the clinical application and promotion of exercise rehabilitation strategies. Multidimensional analysis of exercise-regulated neural plasticity is the theoretical basis for elucidating the brain-protective mechanisms mediated by exercise and developing intervention strategies for neurological diseases. Thus,real-time analysis of different neural signals during active exercise is needed to study the health effects of exercise throughout the entire life cycle and enhance lifelong sports awareness. Therefore, this article will systematically summarize the innovative technological developments in motor neuroscience research, review the mechanisms of neural plasticity that exercise utilizes to protect the brain, and explore the role of exercise in the prevention and treatment of major neurodegenerative diseases. This aims to provide new ideas for future theoretical innovations and clinical applications in the field of exercise-induced brain protection.

OBJECTIVE To evaluate the efficacy and safety of high-dose ilaprazole combined with amoxicillin for newly diagnosed elderly patients with Helicobacter pylori （Hp） infection， and analyze independent risk factors for failure of Hp infection eradication treatment. METHODS Totally 200 cases of newly diagnosed elderly patients with Hp infection in Xinxiang Central Hospital from August 1， 2021 to December 1， 2024 were selected and randomly divided into control group and study group， with 100 cases in each group. The control group was treated with classic quadruple therapy regimen （Amoxicillin capsules+ Clarithromycin tablets+Bismuth potassium citrate tablets+Ilaprazole enteric-coated tablets）. The study group was treated with high- dose Ilaprazole enteric-coated tablets+Amoxicillin capsules. All patients were administered medication for 2 weeks. Hp eradication rates in the two groups were compared using intention-to-treat （ITT） and per-protocol （PP） analyses. The incidence of adverse reactions in both groups was also recorded. The multiple-factor Logistic regression analysis was used to identify independent risk factors for failure of Hp infection eradication treatment. RESULTS In ITT and PP analyses， there was no significant difference of Hp eradication rates between the two groups （P＞0.05）. There was no significant difference in incidence of mild to moderate adverse reactions between the two groups （P＞0.05）. BMI ≤18.5 kg/m2， BMI ＞23.9 kg/m2， rural residence， concomitant diabetes and concomitant heart disease were identified as independent risk factors influencing the failure of Hp infection eradication treatment （P＜0.05）. CONCLUSIONS The efficacy and safety of high-dose ilaprazole combined with amoxicillin are comparable to classic quadruple therapy regimen in treating newly diagnosed elderly patients with Hp infection. Independent risk factors influencing the failure of Hp infection eradication treatment include BMI ≤18.5 kg/m2， BMI ＞23.9 kg/m2， rural residence， concomitant diabetes and concomitant heart disease.

OBJECTIVE To construct an evaluation index system for the core competencies of ethics committee members of drug clinical trial institution， providing a basis for optimizing the training system for committee members， improving the quality of ethical review， and fully safeguarding the safety and rights of subjects. METHODS Using methods such as literature research and expert consultation， a preliminary core competency evaluation index system was constructed. The Delphi method was employed to revise and validate it， ultimately forming an evaluation index system for the core competencies of ethics committee members. Based on this system， a questionnaire survey was conducted among 90 ethics committee members from 29 drug clinical trial institutions nationwide， comparing their importance rating and self-assessment scores of the core competency indexes. RESULTS The evaluation system constructed included 4 primary indicators （ethics and professional knowledge， ethics review ability， communication and expression ability， moral integrity and work style） and 39 secondary indicators （familiarity with the content of clinical trial-related laws and regulations， ability to complete project ethics review and identify ethical defects in research protocols within a short period of time， ability to judge the scientific value of clinical research， etc.）. The results of questionnaire survey showed that the interviewed ethics committee members had significant capability gaps in dimensions such as regulatory knowledge， ethical norms， review efficiency， risk judgment， and problem analysis. The differences between the importance rating scores of corresponding secondary indicators and the self-assessment scores were all no less than 0.38. CONCLUSIONS This study has developed a quantifiable and stratified core competency assessment tool for ethics committee members. It can provide a scientific framework for committee member training， qualification certification， and standardized management of ethics committees.

Chemotherapy-induced complications, particularly lethal cardiovascular diseases, pose significant challenges for cancer survivors. The intertwined adverse effects, brought by cancer and its complication, further complicate anticancer therapy and lead to diminished clinical outcomes. Simple supplementation of cardioprotective agents falls short in addressing these challenges. Developing bi-functional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events simultaneously. Drug repurposing was naturally endowed with co-therapeutic potential of two indications, implying a unique chance in the development of bi-functional agents. Herein, we further proposed a novel "trilogy of drug repurposing" strategy that comprises function-based, target-focused, and scaffold-driven repurposing approaches, aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional agent. Through function-based repurposing, a cardioprotective agent, carvedilol (CAR), was identified as a potential neddylation inhibitor to suppress lung cancer growth. Employing target-focused SAR studies and scaffold-driven drug design, we synthesized 44 CAR derivatives to achieve a balance between anticancer and cardioprotection. Remarkably, optimal derivative 43 displayed promising bi-functional effects, especially in various self-established heart failure mice models with and without tumor-bearing. Collectively, the present study validated the practicability of the "trilogy of drug repurposing" strategy in the development of bi-functional co-therapy agents.

Objective: To investigate the prospective effects of intake of each food group on the development of lung function of pupils,so as to provide theoretical basis for promoting the healthy development of lung function and preventing chronic respiratory diseases in Chinese children. Methods: A cluster stratified sampling method was used to select a total of 893 pupils in grades 2-5 from Chengdu in November 2021. Dietary data of respondents were collected using a food frequency questionnaire within the past year,then the food group intake was categorized into T1, T2 and T3 from low to high by the trichotomous method, and anthropometric measurements including lung capacity were obtained in 2022. Logistic regression models and test for trend were used to analyze the prospective effects of intake of each food group on lung function development of pupils. Results: Among male students, consumption of vegetables [118.6(50.5, 188.2)g/d] and milk and dairy products [200.0(73.3, 250.0)g/d] were higher in the excellent lung capacity group than in the non excellent lung capacity group [90.0(37.1, 192.9), and 178.6(35.7, 250.0)g/d],with statistically significant differences ( Z =-1.98, -2.24); among girls, the group with excellent lung capacity consumed less staple food [391.1(273.6, 511.4)g/d] than the group with non excellent lung capacity [407.4(309.5, 594.3)g/d], and the group with excellent lung capacity consumed more aquatic products [31.2(14.6, 69.8)g/d] and milk and dairy products [215.0(107.1, 250.1) g/d ] than that of the non excellent lung capacity [19.4(10.7, 58.3), 114.3(35.7, 250.0)g/d] ( Z =-2.01, -3.33, -5.10)( P < 0.05 ). After adjusting for energy, body mass index Z score(BMI Z ), mother s education level, averge family income monthly, whether presence of smokers in the living environment, and whether participation in physical activities during the past week, among male students, T3 group of vegetable intake ( OR =0.48, 95% CI = 0.27-0.86), T2 group of bean and soy product intake ( OR = 0.52 , 95% CI =0.27-0.96)，T2 and T3 groups of milk and dairy products intake (T2： OR =0.54, 95% CI =0.31-0.93; T3： OR = 0.52 , 95% CI =0.30-0.90) were negatively associated with non excellent lung capacity ( P <0.05). Among girls, T3 group of aquatic product intake( OR =0.52, 95% CI =0.28-0.97), T2 and T3 groups of milk and dairy product (T2: OR =0.44, 95% CI =0.25- 0.76 ;T3: OR =0.33, 95% CI =0.19-0.59) were negatively associated with nonexcellent lung capacity, whereas the T2 group of red meat intake ( OR =2.51, 95% CI =1.37-4.67) was positively associated with non excellent lung capacity. Non excellent lung capacity was found to be negatively associated with vegetable and milk and dairy product intake in boys by test for trend; in girls, milk and dairy products intake was negatively associated with non excellent lung capacity, whereas red meat intake was positively associated with non excellent lung capacity ( t =-1.13，-0.44；-3.03，1.95, P trend <0.05). Conclusions Milk and dariy products intakes reduce the risk of non excellent lung capacity in pupils, vegetables intakes reduce the risk of non excellent lung capacity in boys, and the intake of red meat increases the risk of non excellent lung capacity in girls. Promoting rational food choices is necessary for children to improve healthy lung development.

OBJECTIVE To investigate the regulatory effect of autophagy on the resistance of human liver cancer cell Huh7 to lenvatinib. METHODS Using human liver cancer cell Huh7 as subject， the lenvatinib-resist cell model （Huh7-LR） was generated by the low-dose gradient method combined with long-term administration. The sensitivity of parental cell Huh7 and drug-resistant cell Huh7-LR to lenvatinib was detected by using CCK-8 assay and flow cytometry. Western blot assay and GFP-mCherry-LC3 plasmid transfection were performed to detect the expression levels of autophagic protein Beclin-1， autophagic adapter protein sequestosome 1 （p62）， microtubule-associated protein 1 light chain 3 （LC3） and autophagic level. Furthermore， an autophagy activation model was constructed by cell starvation， the protein expression of p62 and autophagy level were detected by using Western blot assay and GFP-mCherry-LC3 plasmid transfection， and the effect of autophagy activation on the sensitivity of Huh7-LR cells to lenvatinib was detected by flow cytometry. RESULTS Compared with parental cells， the drug resistance index of Huh7-LR cells was 6.2； protein expression of p62 was increased significantly， while apoptotic rate， protein expression of Beclin-1 and LC3Ⅱ/ LC3Ⅰ ratio were all reduced significantly （P＜0.05 or P＜0.01）； the level of autophagy was decreased to some extent. Autophagy activation could significantly increase the protein expression of p62 in Huh7-LR cells （P＜0.05） and autophagy level， and significantly increase its apoptotic rate （P＜0.05）. CONCLUSIONS Autophagy is involved in lenvatinib resistance， and activating autophagy can reverse the resistance of liver cancer cells to lenvatinib to some extent.

BACKGROUND:A previous study by our group found that protein phosphatase 2Cm(PP2Cm)null mice developed significantly fewer symptoms of renal failure relative to wild-type mice,and thus it was speculated that PP2Cm may play an important protective role in the development of renal fibrosis,however,the molecular mechanisms remain undefined. OBJECTIVE:To investigate the effect of the PP2Cm gene on the transcriptome of human renal tubular epithelial cells. METHODS:Cultured human renal tubular epithelial cells were transfected with the PP2Cm gene into human renal tubular epithelial cells using plasmids.The expression of PP2Cm in the cells was detected by fluorescence quantitative PCR assay and western blot assay,and subsequently,cell RNA was separately extracted for transcriptome sequencing to look for differentially expressed genes between transfected and control groups.The resulting differential genes were further subjected to GO analysis and KEGG analysis using bioinformatics methods. RESULTS AND CONCLUSION:There were 796 differentially expressed genes,553 of which were downregulated genes and 243 upregulated genes,in human renal tubular epithelial cells transfected with the PP2Cm gene compared with untransfected blank cells by sequencing analysis.GO analysis results showed that the upregulated genes were significantly enriched in cellular biosynthetic processes,protein translation,intrinsic apoptotic signaling pathways,and so on.The downregulated expressed genes were significantly enriched in endothelial cell proliferation,cell adhesion and other signaling pathways.KEGG analysis results showed that the significantly up-regulated genes were enriched in metabolism-related signaling pathways such as amino acid metabolism and biosynthesis.The downregulated expressed genes were significantly enriched in signaling pathways such as pantothenate and coenzyme A biosynthesis.Our results show that PP2Cm overexpression can affect a number of signaling pathways related to a range of biological processes in renal tubular epithelial cells,which may be important in metabolism-related signaling pathways such as amino acid metabolism and biosynthesis.

Objective To investigate the detection rate and grading diagnostic value of ultra-wide field swept-source optical coherence tomography angiography(UWF SS-OCTA)combined with ultra-wide field scanning laser ophthalmoscopy(UWF SLO)in diabetic retinopathy(DR)lesions.Methods In this cross-sectional study,diabetic patients attending the Ophthalmology Department of Sichuan Provincial Peoples Hospital were recruited.All participants underwent UWF SS-OC-TA,UWF SLO and fundus fluorescein angiography to detect DR lesions,including microaneurysms(MA),intraretinal hem-orrhages(IRH),nonperfusion areas(NPAs),intraretinal microvascular abnormalities(IRMAs),venous beading(VB),neovascularization elsewhere(NVE),neovascularization of the optic disc(NVD),and vitreous hemorrhage(VH).The re-sults of the combination of three imaging examinations(triple imaging)were used as the standards,evaluating the detec-tion rate and severity grading consistency in DR lesions of pairwise combinations of different imaging modalities.Results A total of 101 patients(175 eyes)were included.Compared with the triple imaging results,the detection rates of UWF SS-OCTA combined with UWF SLO for MA,IRH,NPAs,IRMAs,NVE,NVD and VH were 91％,83％,77％,69％,27％,10％and 12％,respectively,with Kappa values of 0.812,1.000,1.000,1.000,0.986,0.970 and 1.000.Compared with the triple imaging results,the combination of UWF SS-OCTA and UWF SLO demonstrated excellent consistency in grading the severity of DR(Kappa=0.943).Conclusion UWF SS-OCTA combined with UWF SLO can accurately identify MA,IRH,NPAs,IRMAs,NVE,NVD and VH,demonstrating high accuracy in DR screening and grading diagnosis,making it suitable for large-scale screening and management of DR in clinical practice.