Background: The European League of Rheumatology(EULAR)guidelines recommend Janus kinase (JAK) inhibitors for patients with moderate to severe rheumatoid arthritis (RA) who are insensitive or under-responsive to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). But there was no recommendation for which one was preferred in five currently approved JAK inhibitors. The objective of this network meta-analysis study was to evaluate the efficacy of five JAK inhibitors as monotherapy and combination therapy in patients with moderate-to-severe active rheumatoid arthritis.Methods: The randomized controlled trials (RCTs) of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy or combined with csDMARD in the treatment of active RA were searched in database of PubMed, Embase, Web of Science and Cochrane Library, up to December 2023. The control group included placebo or csDMARD. Outcome indicators included American College of Rheumatology 20% response (ACR20), ACR50, ACR70 and the percentage of patients achieving 28-joint disease activity score using C-reactive protein (DAS28(CRP))<2.6 at 12 weeks and 24 weeks. The statistical analysis was performed by Stata14 and RevMan5.4. Data processing, network evidence plots, surface under the cumulative ranking curve (SUCRA) ranking, league plots and funnel plots were generated. Risk ratio (RR) and 95% confidence interval (95%CI) as effect sizes to analyze the statistics.Results: This study included thirty-six RCTs with 16,713 patients. All JAK inhibitors were more effective than placebo in ACR20 (RRs ranging between 1.74 and 3.08), ACR50 (RRs ranging between 2.02 and 7.47), ACR70 (RRs ranging between 2.68 and 18.13), DAS28(CRP) < 2.6 (RRs ranging between 2.70 and 7.09) at 12 weeks. Upadacitinib 30 mg and upadacitinib 15 mg showed relatively good efficacy according to their relative SUCRA ranking. All JAK inhibitors were more effective than csDMARD or placebo in ACR20 (RRs ranging between 1.16 and 1.86), ACR50 (RRs ranging between 1.69 and 2.84), ACR70 (RRs ranging between 1.50 and 4.47), DAS28(CRP) < 2.6 (RRs ranging between 2.28 and 7.56) at 24 weeks. Upadacitinib 15 mg + csDMARD and baricitinib 4 mg + csDMARD showed relatively good efficacy according to their relative SUCRA ranking. The safety analysis results such as serious infection, malignancy, major adverse cardiovascular event (MACE), and venous thromboembolic events (VTE) showed no statistical difference.Conclusion: This NMA study indicated that all JAK inhibitors performed better than placebo. Based on the results of this study, upadacitinib 30 mg, upadacitinib 15 mg, upadacitinib 15 mg + csDMARD and baricitinib 4 mg + csDMARD were recommended treatment options with relatively good efficacy and safety. However, attention should be paid to monitoring the occurrence of adverse events in high-risk RA patients with medication. Combination therapy with csDMARD might be more suitable for the maintenance of long-term efficacy. However, in clinical practice, it is still necessary to select the appropriate therapeutic regimen based on the actual clinical situation.

Polymyxin B is served as a last-line agent for Carbapenem-resistant organisms (CRO) infections. This study aimed to establish a population pharmacokinetic (PK) model in patients with/without continuous renal replacement therapy (CRRT), to investigate the relationship between clinical covariates and polymyxin B PK parameters, and to optimize polymyxin B dosing regimens. Blood samples were obtained for each patient at steady state. The plasma concentrations of polymyxin B were determined using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Population PK models were developed using Pirana program and Monte Carlo simulations were conducted. A total of 63 patients accounting for 189 blood samples were included and divided into modeling (n = 49) and validation (n = 14) groups. A two-compartment model described the data well. CRRT, creatinine clearance (CLCR) and Sequential Organ Failure Assessment (SOFA) score were identified as significant covariates of polymyxin B clearance. Monte Carlo simulations indicated that a maintain dose of 75-100 mg q12h was required to meet the target drug exposure in patients receiving CRRT with SOFA ≤ 11 (minimum inhibitory concentration ≤ 1 mg·L^-1). For patients without CRRT, dosage strategy should be adjusted on the basis of different renal functions and SOFA scores. This is the first population PK study that demonstrated CRRT, CLCR and SOFA score had significant effects on polymyxin B clearance in critically ill patients with/without CRRT. More PK data are urgently needed to clarify polymyxin B PK characteristics in patients with/without CRRT.

Objective: The aim of this study was to compare the efficacy and safety of anti-tau protein monoclonal antibodies for Alzheimer’s disease (AD). Tau protein aggregation, a key pathological feature of AD, is closely associated with neurodegeneration and cognitive decline. Targeting tau protein has emerged as a promising therapeutic strategy. By investigating the effects of monoclonal antibodies on cognitive function, disease progression, and overall quality of life in patients with AD, which can provide valuable insights into their potential as a therapeutic option for this devastating neurodegenerative disorder.Methods: The randomized controlled trials (RCTs) investigating the efficacy of Gosuranemab, Semorinemab, Tilavonemab, and Zagotenemab in Alzheimer’s disease (AD) were systematically searched across PubMed, Embase, Web of Science and Cochrane Library, up to May 2024. The control group included placebo. The efficacy indicators were change in the Mini Mental State Examination (MMSE), Clinical Dementia Rating Scale Sum of Boxes (CDR-SB), Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog), Alzheimer’s Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL) from baseline until the time of efficacy observation. Statistical analysis was conducted using Stata 14 and RevMan 5.4. The purpose of data processing, including generating network evidence plots, surface under the cumulative ranking curve (SUCRA) ranking, league plots, and funnel plots, is to visually summarize and evaluate the relative effectiveness and safety and potential publication bias of multiple interventions. Mean differences (MD) and 95% confidence interval (95%CI) as effect sizes to analyze continuous variables.Results: This study encompassed six RCTs involving 2,193 patients. Semorinemab were more effective than placebo in MMSE and ADAS-Cog scores (MDs ranging between 0.52 and 3.21; MDs ranging between 0.17 and 3.30). Placebo showed relatively good efficacy according to SUCRA ranking on change in CDR-SB and ADCS-ADL scores (75.7 and 79.5%). Tilavonemab and Semorinemab exhibited efficacy similar to that of a placebo in the analysis of the two indicators. Tilavonemab showed a lower incidence of AE, SAE, fall, and urinary tract infections than placebo, and the differences were statistically significant. Most safety analysis results showed no statistical difference.Conclusion: The results indicated that anti-tau protein monoclonal antibodies, such as Semorinemab and Tilavonemab, showed promise in terms of efficacy and safety for managing AD. Further studies are needed to confirm these findings, assess long-term effects, and refine treatment protocols.Systematic review registration: https://www.crd.york.ac.uk/prospero/#myprospero, CRD42024583388.

Nanoparticle-based drug delivery systems hold great promise for improving the effectiveness of anti-tumor therapies. However, their clinical translation remains hindered by several significant challenges, including intricate preparation processes, limited drug loading capacity, and concerns regarding potential toxicity. In this context, pure drug-assembled nanosystems (PDANSs) have emerged as a promising alternative, attracting extensive research interest due to their simple preparation methods, high drug loading efficiency, and suitability for large-scale industrial production. This innovative approach presents new opportunities to enhance both the safety and therapeutic efficacy of cancer treatments. This review comprehensively explores recent progress in the application of PDANSs for cancer therapy. It begins by detailing the self-assembly mechanisms and fundamental principles underlying PDANS formation. The discussion then advances to strategies for assembling single pure drug nanoparticles, as well as the co-assembly of multiple drugs. Subsequently, the review addresses the therapeutic potential of PDANSs in combination treatment modalities, encompassing diagnostic and therapeutic applications. These include combinations of chemotherapeutic agents, phototherapeutic approaches, the integration of chemotherapy with phototherapy, and the synergistic use of immunotherapy with other treatment methods. Finally, the review highlights the potential of PDANSs in advancing tumor therapy and their prospects for clinical application, providing key insights for future research aimed at optimizing this technology and broadening its utility in cancer treatment.