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.

ObjectiveTo evaluate the clinical efficacy of Fuzheng Huaji Formula （扶正化积方） for chronic hepatitis B to reduce the incidence of liver cirrhosis and hepatocellular carcinoma. MethodsA retrospective cohort study was conducted， collecting medical records of 118 patients with chronic hepatitis B and 234 patients with hepatitis B-related cirrhosis who visited the hospital between January 1， 2014， and December 31， 2018. The use of Fuzheng Huaji Formula was designated as the exposure factor. Patients receiving antiviral treatment for hepatitis B without concurrent Fuzheng Huaji Formula therapy were included in the western medicine group， while those receiving antiviral treatment combined with Fuzheng Huaji Formula for a cumulative treatment lasting longer than 3 months were included in the combined treatment group. The follow-up observation period was five years. Kaplan-Meier survival analysis was used to assess the cumulative incidence of cirrhosis in patients with chronic hepatitis B and the cumulative incidence of hepatocellular carcinoma in patients with hepatitis B-related cirrhosis. Univariate and multivariate Cox regression analyses were employed to examine the factors influencing the occurrence of cirrhosis and hepatocellular carcinoma. ResultsAmong patients with chronic hepatitis B， there were 55 cases in the combined treatment group and 63 cases in the western medicine group； among patients with hepatitis B-related cirrhosis， there were 110 cases in the combined treatment group and 124 cases in the western medicine group. Five-year follow-up outcomes for chronic hepatitis B patients showed that the cumulative incidence of cirrhosis was 5.45% （3/55） in the combined treatment group and 17.46% （11/63） in the western medicine group， with a statistically significant difference between groups （Z = 2.003， P = 0.045）. Five-year follow-up outcomes for hepatitis B-related cirrhosis patients showed that the cumulative incidence of hepatocellular carcinoma was 8.18% （9/110） in the combined treatment group and 22.58% （28/124） in the western medicine group， also showing a statistically significant difference （Z = 3.007， P = 0.003）. Univariate and multivariate Cox regression analyses indicated that treatment with Fuzheng Huaji Formula is an independent protective factor in preventing the progression of chronic hepatitis B to cirrhosis and the progression of hepatitis B-related cirrhosis to hepatocellular carcinoma （P＜0.05）. ConclusionCombining Fuzheng Huaji Formula with antiviral therapy for hepatitis B can effectively intervene in the disease progression of chronic hepatitis B， reducing the incidence of cirrhosis and hepatocellular carcinoma.

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.

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 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.

Objective To observe the expression and trends of tight junction proteins Occludin and zonula occlu-den-1(ZO-1)in blood-brain barrier(BBB)of rats with traumatic brain injury(TBI),and to explore the interven-tion effect of cannabidiol(CBD)on the BBB.Methods The TBI model of rat was prepared by modified"Feeney free fall method"and randomly divided into three groups:the sham-operated group(Sham group),the model group(TBI+vehicle group)and the CBD intervention group(TBI+CBD group),with 24 rats in each group.Each group was subdivided into six time points:8 h,1,2,3,5 and 7 d after injury.The expression of Occludin and ZO-1,which are closely related to the permeability of BBB,was detected by immunohistochemistry,immuno-fluorescence staining and Western blot at different points.The permeability of BBB was detected by sodium fluores-cein assay.Results The results of immunohistochemistry showed that compared with Sham group,the positive ex-pression of Occludin and ZO-1 decreased with time after brain trauma(P<0.05),and both reached the lowest level at 2 d.The expression levels of Occludin and ZO-1 were up-regulated after 1 d of CBD intervention(P<0.05).Immunofluorescence staining showed a similar trend to Western blot results,with Occludin and ZO-1 fluo-rescence expression intensity and protein expression reduced after TBI compared with Sham group(P<0.05).And the expression levels of Occludin and ZO-1 were up-regulated after 2 d of CBD intervention(P<0.05).The results of fluorescein sodium experiment showed that the BBB integrity of brain tissue was destroyed after TBI,and the permeability increased after TBI(P<0.01).The permeability of BBB decreased after CBD intervention(P<0.05).Conclusion The expression of tight junction proteins Occludin and ZO-1 decreases after TBI,and the permeability of BBB is disrupted,and CBD intervention reverses the disruption of the BBB by TBI.

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.

Since the first Drug Administration Law was issued in 1984， the drug regulation of China has undergone a forty- year process. During these four decades， China’s drug regulatory system has gradually transitioned from being extensive to refined， and the concept of supervision has become increasingly scientific. This paper first outlines the historical evolution of China’s drug regulatory laws and regulations since the founding of the People’s Republic of China， with a focus on the historical origins of the revision of the Drug Administration Law during 1984-2001. It also clarifies the new challenges faced by drug regulation as the industry innovates and develops， as well as the corresponding reform of the drug review and approval system. The paper summarizes the reform achievements of drug regulation. By studying and analyzing the challenges faced by drug regulation in terms of regulatory capacity， regulatory resources， and regulatory system in the context of internationalization of the industry， the paper proposes policy suggestions such as establishing a cross-regional regulatory system， reforming the review mechanism， strengthening the construction of the review team， and enhancing transparency in regulatory practices， with the aim of promoting the high-quality development of the pharmaceutical industry.

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.

Polygonum multiflorum （PM）， a commonly used Chinese herbal medicine in clinical practice， has been associated with frequent reports of liver injury in recent years， and the medication safety of PM has attracted more and more attention in China and globally. This article reviews the recent research advances in the signaling pathways and mechanisms of PM in causing drug-induced liver injury （DILI） and aims to provide new ideas for the proper and rational use of PM in clinical practice. The results show that PM is involved in the regulation of various signaling pathways， and it leads to the death of hepatocytes by destroying mitochondrial function， exacerbating bile acid accumulation， and inducing immune response， oxidative stress， and endoplasmic reticulum stress， thereby inducing the development and progression of DILI through multiple targets， pathways， and levels.