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.

Chemotherapy based on cisplatin or its combination therapy is a common cancer treatment method. However， the non-specific side effects of cisplatin， poor pharmacokinetic properties of small molecule drugs， and susceptibility to drug resistance greatly limit the clinical application of cisplatin as first-line anti-tumor drug. With the development of nanocarrier technology， liposomes have become an ideal carrier for delivering cisplatin drugs due to their excellent properties of targeting， reducing toxicity， and enhancing efficacy. This paper reviews the status of cisplatin liposome both domestically and internationally which have entered clinical trials， including L-NDDP，SPI-077®， Lipoplatin®，LiPlaCis，SLIT and ILC， etc. Currently， only Lipoplatin® and ILC are showing good potential in cancer therapy. Although cisplatin liposome has made some progress in reducing systemic toxicity and improving treatment efficiency in clinical research， there is still potential for further improvement in tumor targeting and reducing side effects. In the future， more low-toxicity and efficient cisplatin liposomes can be developed through formulation technologies such as co-delivery liposome， stimuli-responsive liposome and targeting liposome.

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.

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*

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.

Objective:To analyze the correlation between the grouping and weighting of two sets of disease combination systems, namely diagnosis-related groups(DRG) and diagnosis-intervention packet(DIP), and to establish a multidimensional analysis and evaluation mode by applying DRG, DIP, and clinical pathway to guide the standardized diagnosis and treatment and management of disease types.Methods:DRG grouping and DIP simulation full enrollment were applied to patients discharged from a tertiary Grade A general hospital in 2019. The correlation analysis between DRG, DIP, and clinical pathway inclusion(entry), correlation analysis between relative weight of DRG group and DIP standard score, and correlation analysis between clinical pathway entry and cost structure of the two disease groups were conducted by using chi-square test, Pearson correlation analysis, t-test, structural change value, degree of structural change, and incremental contribution rate. Results:Among the 130 395 patients, 41 460 cases entered the clinical pathway, 127 535 cases were enrolled in DRG, and 104 227 cases were enrolled in DIP. There was a correlation between the enrollment of DRG, DIP, and clinical pathway( P<0.05), and there was also a correlation between the relative weight of DRG groups and the enrollment of clinical pathway. The relative weight of the DRG disease group was positively correlated with the DIP standard score( r2=0.761 7, P<0.001). There was a significant difference in hospitalization costs between patients with and without clinical pathway access for some diseases( P<0.05), and different cost categories had different impacts on the total costs. Conclusions:The weight assignment and value orientation of DRG and DIP disease types are consistent, and the multi-dimensional fusion evaluation mode for DRG-DIP-clinical pathway is feasible. The correlation analysis of DRG, DIP, and clinical pathways can serve as the basis for disease classification and cost structure evaluation, which could help to carry out hospital′s refined management and optimize disease structure.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Objective·To measure the parameters of the uterine artery,umbilical artery and middle cerebral artery in a rat model of preeclampsia(PE)by Doppler ultrasound,and compare the pathological changes in placental blood vessels and pregnancy outcomes,in order to provide an effective method and reference for evaluating placental function in PE animal models.Methods·PE(n=8)and normal pregnancy(NP,n=8)groups in Sprague-Dawley(SD)rat models were established by intraperitoneal injections of N'-nitro-L-arginine methylesterhydrochloride(L-NAME)and 0.9%sodium chloride solution.Blood pressure and proteinuria indexes were detected to evaluate whether the model was successfully established.On gestational day 19(GD19),Doppler ultrasound was utilized to measure the parameters of the uterine artery,umbilical artery and the fetal middle cerebral artery in both the PE and NP groups.After termination of the pregnancies,placental function was evaluated through the pathology of placental blood vessels and the quality of the fetuses and placentas.Results·In the PE group,both blood pressure(GD15:P=0.001;GD19:P=0.001)and proteinuria(GD15:P=0.001;GD19:P=0.001)were significantly higher than those in the NP group.The pulsatility index(PI)of the umbilical artery and uterine artery was notably elevated in the PE group compared to the NP group(both P=0.000).Furthermore,the resistance index(RI)of the fetal middle cerebral artery was significantly lower than that in the PE group(P=0.000).While the number of fetal rats did not differ significantly,the quality of placental and fetal rats was notably lower in the PE group(P=0.006 and P=0.000,respectively).Immunohistochemical staining of placental tissue revealed that the number of placental micro vessel densities in the PE group was less than that in the NP group(P=0.001).Correlation analysis revealed that placental micro vessel density,fetal quality and placental quality were inversely related with the RI of the umbilical artery and the PI and RI of the uterine artery,and positively correlated with the S/D,PI and RI of the fetal middle cerebral artery(all P<0.05).Conculsion·Doppler ultrasound assessment of the uterine artery,umbilical artery and middle cerebral artery indices in L-NAME-induced PE rat models effectively reflects pregnancy outcomes and placental vascular pathology.This method is valuable for evaluating placental vascular perfusion in PE rat models,offering practicality and convenience for research involving animal models.

Digital therapeutics(DTs)refers to a non-drug intervention method that uses electronic devices such as computers,smartphones,and wearable devices to evaluate and intervene through software programs and Internet technologies.It has been confirmed that there is a good therapeutic effect on a variety of mental disorders.Digital therapeutics can improve the insomnia problems of insomniacs,enhance the attention and work memory ability of patients with attention deficit hyperactivity disorder,and can also alleviate symptoms such as depression and anxiety disorder.Digital therapy will develop towards personalized treatment,popular treatment,fragmented treatment,and entertainment treatment in the future and have broad development prospects.

Objective:To evaluate the feasibility and safety of a novel transjugular intrahepatic portosystemic shunt (TIPS) puncture set for transjugular intrahepatic portal puncture in swine.Methods:Thirteen domestic swine were randomly divided into experimental group ( n=7) and control group ( n=6) and received transjugular intrahepatic portal puncture with the novel puncture set and the R?sch-Uchida Transjugular Liver Access Set (RUPS-100), respectively. Three swines in each group were randomly selected and sacrificed immediately after the procedure and the rest were sacrificed 1 week later. The intraoperative technical success rate, puncture attempts, procedure time, fluoroscopy time, vital signs and occurrence of complications related to the procedure as well as the changes of liver and kidney function before, immediately after and 1 week after the procedure were compared between two groups. Independent sample t test, paired t test, Mann-Whitney U test, chi-square test or Fisher′s exact test were performed to compare the differences between groups. Results:The technical success rate was 100% for both groups. No significant difference in portal puncture attempts [2.0 (1.0, 5.0) vs. 2.0(1.0, 5.5), P>0.999], procedure time [(47.7±20.6) vs. (52.5±28.0)min, P=0.729] and fluoroscopy time [(725.1±489.2) vs. (763.7±562.4)s, P=0.897] was observed between two groups. In addition, no significant difference of the major liver and kidney function between two groups before, immediately after and 1 week after procedure ( P>0.05 at all time points). No significant difference of the major liver and kidney function change in two groups during perioperative period was identified (all P>0.05). Furthermore, no significant difference of non-target puncture occurrence was observed between two groups ( P>0.999). In the meantime, no significant difference of occurrence of small hematomas around hepatic hilar was discovered among swine sacrificed immediately after procedure between two groups ( P>0.999). No other major complications were identified in either group. Conclusion:The novel TIPS puncture set is feasible and safe to perform transjugular intrahepatic portal puncture in swine.