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.

OBJECTIVE To evaluate the efficacy and safety of rituximab （RTX） in the treatment of primary Sjögren syndrome （pSS）. METHODS Randomized controlled trials （RCTs） on the effects of RTX （trial group） versus placebo （control group） in the treatment of pSS were searched from the Cochran Library， PubMed， Embase， Medline， Web of Science， VIP， CNKI， Wanfang， and other databases during the inception to February 2024. After literature screening and quality evaluation， meta-analysis was performed by using RevMan 5.3 software. RESULTS Seven RCTs were finally included， involving a total of 518 patients. Results of meta-analysis showed that European League Against Rheumatism Sjögren syndrome disease activity index （ESSDAI） score [MD＝－1.17， 95%CI（－1.52， －0.82）， P＜0.000 01] and oral dryness visual analogue scale （VAS） score [MD＝－3.97， 95%CI （－5.08， －2.86）， P＜0.000 01] in the trial group were significantly lower than the control group； unstimulated salivary flow rate [SMD＝0.64， 95%CI（0.41， 0.87）， P＜0.000 01] and Schirmer score [MD＝0.19， 95%CI（0.18， 0.20）， P＜0.000 01] were significantly higher than the control group. There was no statistical significance in response rate [RD＝0.10， 95%CI（－0.04， 0.23）， P＝0.16]， fatigue VAS score [MD＝－12.50， 95%CI（－35.14， 10.15）， P＝0.28]， European League Against Rheumatism Sjögren syndrome patient reported index （ESSPRI） score [MD＝0.33， 95%CI（－0.53， 1.18）， P＝0.46]， Short-form 36 health survey physical component summary （SF36-PCS） score [MD＝0.90， 95%CI（－2.97， 4.78）， P＝0.65]， SF-36 mental component summary （SF36-MCS） score [MD＝0.11， 95%CI（－0.41， 0.63）， P＝0.68]， total salivary gland ultrasound score [SMD＝－1.91， 95%CI（－4.01， 0.19）， P＝0.07] or the incidence of adverse drug reactions [OR＝1.15，95%CI（0.62，2.13），P＝0.66] between 2 groups. CONCLUSIONS RTX has advantages in the improvement of ESSDAI score， unstimulated salivary flow rate， Schirmer score and oral dryness VAS score in pSS patients， and has a good safety profile. However， it did not exhibit significant improvement in fatigue VAS score， ESSPRI score， SF36-PCS score， SF36-MCS score or response rates.

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*

The liver performs multiple life-sustaining functions. Hepatic diseases, including hepatitis, cirrhosis, and hepatoma, pose significant health and economic burdens globally. Along with the advances in nanotechnology, mesoporous silica nanoparticles (MSNs) exhibiting diversiform size and shape, distinct morphological properties, and favorable physico-chemical features have become an ideal choice for drug delivery systems and inspire alternative thinking for the management of hepatic diseases. Initially, we introduce the physiological structure of the liver and highlight its intrinsic cell types and correlative functions. Next, we detail the synthesis methods and physicochemical properties of MSNs and their capacity for controlled drug loading and release. Particularly, we discuss the interactions between liver and MSNs with respect to the passive targeting mechanisms of MSNs within the liver by adjusting their particle size, pore diameter, surface charge, hydrophobicity/hydrophilicity, and surface functionalization. Subsequently, we emphasize the role of MSNs in regulating liver pathophysiology, exploring their value in addressing liver pathological states, such as tumors and inflammation, combined with multi-functional designs and intelligent modes to enhance drug targeting and minimize side effects. Lastly, we put forward the problems, challenges, opportunities, as well as clinical translational issues faced by MSNs in the management of liver diseases.

Arthritis, encompassing osteoarthritis (OA), rheumatoid arthritis (RA), and gouty arthritis (GA), is a prevalent inflammatory disease that significantly impacts quality of life. Natural products (NPs), derived from animals, plants, marine organisms, and microorganisms, have demonstrated beneficial effects in arthritis treatment both domestically and internationally. These natural compounds offer advantages in drug discovery due to their skeletal diversity, structural complexity, and multi-effect, multi-target, and low-toxicity properties compared to conventional small-molecule medicines. However, unclear mechanisms have hindered the development and clinical application of NPs. This review summarizes recent experimental studies from the past decade on natural medicine for arthritis treatment, emphasizing key NPs with therapeutic effects on OA, RA, and GA. It examines the effects and molecular mechanisms of NPs acting on different cells to treat arthritis. Furthermore, this review provides insights into the future prospects of NP research in this field, which is crucial for advancing NP-based arthritis treatments.
Humans ; Biological Products/therapeutic use* ; Animals ; Arthritis, Rheumatoid/drug therapy* ; Arthritis, Gouty/drug therapy* ; Arthritis/drug therapy* ; Osteoarthritis/drug therapy*

Objective To investigate the association between urinary lead and nonalcoholic fatty liver disease(NAFLD).Methods The participants,aged≥18 years,were selected from the 2017-2020 National Health and Nutrition Examination Survey(NHANES),with the exclusion of the participants with a lack of liver transient elastography data and urinary lead markers and those with hepatitis B,hepatitis C,and significant alcohol consumption.A total of 2 492 participants were enrolled and divided into NAFLD group with 852 participants and non-NAFLD group with 1 640 participants.High-performance liquid chromatography-electrospray ionization-tandem mass spectrometry and online solid-phase extraction combined with isotope dilution were used to measure urinary lead level.The independent-samples t test or the Wilcoxon rank sum test was used for comparison of continuous data between two groups,and the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups.Multivariate Logistic regression analysis,restricted cubic spline,subgroup analysis,and interaction analysis were used to investigate the association between urinary lead and NAFLD.Results The NAFLD group had a significantly higher urinary lead level than the non-NAFLD group(Z=-2.023,P=0.043).After adjustment of the covariates of age,sex,race,marital status,education,family income-to-poverty ratio,body mass index,smoking,drinking,diabetes mellitus,hypertension,and hyperlipidemia,there was a significant increase in the risk of NAFLD in the Q3 urinary lead group(odds ratio[OR]=1.360,95%confidence interval[CI]:1.019-1.817,P=0.037).There was a positive dose-response relationship between urinary lead and the risk of NAFLD(P=0.047),which was a non-linear relationship(Pnon-linear=0.037).There was a significant interaction between urinary lead and race,and for every quartile increase in urinary lead,the risk of NAFLD in Mexican-Americans was increased by 32.40%(OR=1.324,95%CI:1.017-1.632,P<0.05).Conclusion Urinary lead level is significantly associated with the risk of NAFLD.

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.

Head and neck squamous cell carcinoma (HNSCC) is the seventh most common malignant tumor in the world, with a 5-year survival rate of only about 50%. Thus, discovering more effective diagnostic and therapeutic approaches is an urgent need. The metabolic reprogramming of tumor cells is a key feature in the development of HNSCC, which widely exhibits alterations in glycolytic metabolism, lipid metabolism, and amino acid metabolism compared with normal cells. Metabolic reprogramming affects the energy supply and biosynthesis of tumor cells. It also participates in the regulation of the tumor microenvironment and promotes key biological processes such as proliferation, invasion, and metastasis of HNSCC. With the progressive understanding of the complexity of tumor biology, targeted-therapy strategies against metabolic reprogramming in HNSCC are emerging as a promising therapeutic approach. These metabolically targeted therapies have performed well in preclinical studies, but their clinical application requires further validation. In the future, we need to deeply explore the more complex features of metabolic reprogramming and its biological significance in HNSCC, with the aim of discovering more effective diagnostic and therapeutic targets, as well as providing new strategies to improve the prognosis of HNSCC patients.

Objective:To evaluate the efficacy and safety of febuxostat in the treatment of hyperuricemia with hypertension.Methods:Randomized controlled trials (RCT) on the treatment of hyperuricemia with hypertension using febuxostat were retrieved from Medline, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Database, and VIP Database from January 2013 to July 2023, according to the retrieval strategy. Two trained researchers completed the literature screening, quality evaluation, and data extraction. Meta-analysis was performed using RevMan 5.3. The fixed-effect model or random-effects model was used to analyze the research data, and subgroup analysis was conducted to identify the source of heterogeneity.Results:A total of 5 RCTs involving 456 patients (228 in the experimental group and 228 in the control group) were included in the meta-analysis, all of which were English-language literatures and foreign studies. In the treatment of hyperuricemia with hypertension, febuxostat showed a statistically significant difference in reducing serum uric acid (sUA) levels compared to control drugs [MD(95% CI)=-1.31(-2.55, -0.07), P=0.040]; there was no statistically significant difference in reducing systolic blood pressure (SBP) [SMD(95% CI)=-0.12(-0.51, 0.27), P=0.540] or diastolic blood pressure (DBP) [SMD(95% CI)=-0.15(-0.40, 0.09), P=0.220]. Subgroup analysis showed that the difference in intervention drugs in the control group may be the cause of heterogeneity in sUA levels, and the difference in intervention time may be the cause of heterogeneity in SBP levels among different studies. There was no statistically significant difference in the incidence of adverse reactions between the febuxostat group and the control group [RD (95% CI) =-0.01(-0.08, 0.06), P=0.770]. Conclusion:Febuxostat has a significant advantage in improving sUA levels and is relatively safe in the treatment of hyperuricemia with hypertension, but it does not show significant advantages in blood pressure control.

Objective To establish and validate a Nomogram model for predicting the overall survival(OS)of the patients with intrahepatic cholangiocarcinoma(ICC)based on domestic multicenter data,and screen the beneficiaries of adjuvant chemotherapy based on the prediction model.Methods From December 2011 to December 2017,the data of 278 patients with postoperative pathological diagnosis of ICC from 4 medical centers in our country were collected retrospectively COX regression model was used to screen the independent risk factors of OS and constructed a Nomogram model.This model was used to stratify the risk of OS for all patients and to screen the beneficiaries of adjuvant chemotherapy.Results A total of 278 patients were enrolled,and 23 cases(8.3%)received adjuvant chemotherapy.COX multivariate analysis showed that drinking history,ECOG score,method of hepatectomy,lymph node status,number of tumors,and tumor differentiation were independent risk factors for postoperative OS.The Nomogram model had a C-index of 0.690(95%CI:0.646-0.734)in the training cohort and 0.740(95%CI:0.863-0.617)in the validation cohort.According to risk stratification by Nomogram model,in the high-risk group there was a statistically significant difference in survival between adjuvant chemotherapy and non-adjuvant chemotherapy(P=0.033),whereas in the low-risk group,there was no significant difference in survival(P=0.59).Conclusions Nomogram model based on independent risk factors of OS demonstrated excellent predictive capability for survival and could be used to screen,and identify the patients with ICC who benefit from adjuvant chemotherapy.