Objective: Our study aimed to identify potential correlations between anti-tumor efficacy and immune-related adverse events (irAEs) in non-small-cell lung cancer (NSCLC).Methods: We conducted a comprehensive search of online electronic databases up to March 2023 to identify any correlations between irAEs and immune checkpoint inhibitor (ICI) efficacy in NSCLC. We used meta-analysis RevMan 5.3 software to calculate pooled results.Results: Our meta-analysis of 54 studies revealed that patients who experienced irAEs achieved a significantly higher objective response rate (p < 0.00001) and longer progression-free survival (PFS) (p < 0.00001) and overall survival (OS) (p < 0.00001) than those who did not experience irAEs. Additionally, patients with ≥2 irAEs had better PFS, whereas no significant difference was observed between patients with or without squamous cell carcinoma. Subgroup analysis of irAE types indicated that irAEs (thyroid dysfunction and gastrointestinal, skin, or endocrine irAEs) were associated with better PFS and OS. However, no significant differences were observed between patients with pneumonitis or hepatobiliary irAEs.Conclusion: Our study showed that the occurrence of irAEs was a strong predictor of survival efficacy in patients with NSCLC treated with ICIs. Specifically, patients with ≥2 irAEs and those with thyroid dysfunction and gastrointestinal, skin, or endocrine irAEs achieved a better survival benefit.Systematic Review Registration: Website: https://www.crd.york.ac.uk/prospero/, Identifier: CRD42023421690

Background: The implanted vascular access ports (PORTs) were compared with peripherally inserted central catheters (PICCs) as the administration of chemotherapy regarding different clinical effects and adverse effects. Which is better is debatable. Hence, the current study was conducted to assess the safety and efficacy of these two optimal vascular access strategies.Methods: The following electronic databases were searched: PubMed, Embase, and the Cochrane Library updated in May 2023. Studies on the differences in complication rates in patients with cancer using either PICC or PORT for chemotherapy were included. Meta-analysis Revman 5.3 software was used for statistical analysis.Results: A total of 22 articles were retrieved. The results suggested that PORT has a superior safety profile, with lower incidences of overall adverse effects (OR=2.72, 95% CI=1.56–4.72 P=0.0004), catheter-related thrombosis (OR=2.84, 95% CI=1.97–4.11, P<0.00001), and allergic reactions (OR=6.26, 95% CI=1.86–21.09, P=0.003) than typically expected with PICC. Moreover, PICC was non-inferior to the PORT group with respect to DVT (OR=2.00, 95% CI=0.86–4.65, P=0.11) and infection (OR=1.55, 95% CI=0.75–3.22, P=0.24).Conclusion: PORT achieved safety benefits compared with chemotherapy through PICC. Therefore, PORT is regarded as safe and effective vascular access for the administration of chemotherapy. When considering economic factors and some key elements, more high-quality research would help verify these clinical benefits.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identififier CRD42023421690.

Background:Medication therapy management (MTM) services is a method that can effectively improve patients’ conditions, but the efficacy of economic and humanistic outcomes remain unclear. This systematic review and meta-analysis aim to use economic, clinical and humanistic outcomes to evaluate the multi-benefits of MTM services.Method:A systematic review and meta-analysis was conducted by retrieving PubMed, EMBASE, the Cochrane Library andClinicalTrial.govfrom the inception to April 2022. There were two reviewers screening the records, extracting the data, and assessing the quality of studies independently.Results:A total of 81 studies with 60,753 participants were included. MTM services were more effective in clinical outcomes with decreasing the rate of readmission (OR: 0.78; 95% CI: 0.73 to 0.83; I²= 56%), emergency department visit (OR: 0.88; 95% CI: 0.81 to 0.96; I²= 32%), adverse drug events (All-cause: OR: 0.68; 95% CI: 0.56 to 0.84; I²= 61%; SAE: OR: 0.51; 95% CI: 0.33 to 0.79; I²= 35%) and drug-related problems (MD: −1.37; 95% CI: −2.24 to −0.5; I²= 95%), reducing the length of stay in hospital (MD: −0.74; 95% CI: −1.37 to −0.13; I²= 70%), while the economic and humanistic outcomes were less effective.Conclusion:Our systematic review and meta-analysis demonstrated that MTM services had great ability to improve patients’ clinical conditions while the efficacy of economic and humanistic outcomes, with some of the outcomes showing high degree of heterogeneity and possible publication bias, required more future studies to provide stronger evidence.Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=349050], identifier [CRD42022349050].

Various factors, including genetic polymorphisms, drug–drug interactions, and patient characteristics influence the blood concentrations of tacrolimus in renal transplant patients. In the present study, we established a population pharmacokinetic model to explore the effect of combined use of Wuzhi capsules/echinocandins and the patients’ biochemical parameters such as haematocrit on blood concentrations and target doses of tacrolimus in renal transplant patients with different CYP3A5 genotypes. The aim of the study was to propose an individualised tacrolimus administration regimen for early renal transplant recipients. In this retrospective cohort study, we included 240 renal transplant recipients within 21 days of surgery (174 males and 66 females, mean age 39.4 years), who received tacrolimus alone (n = 54), in combination with Wuzhi capsules (99) or caspofungin (57) or micafungin (30). We collected demographic characteristics, clinical indicators, CYP3A5 genotypes, and 1950 steady-state concentrations of tacrolimus and included them in population pharmacokinetic model. An additional 110 renal transplant recipients and 625 steady-state concentrations of tacrolimus were included for external validation of the model. The population pharmacokinetic model was established and Monte Carlo was used to simulate probabilities for achieving the target concentration for individual tacrolimus administration. A two-compartment model of first-order absorption and elimination was developed to describe the population pharmacokinetics of tacrolimus. CYP3A5 genotypes and co-administration of Wuzhi capsules, as well as time after renal transplantation and haematocrit, were important factors affecting the clearance of tacrolimus. We found no obvious change in trend in the scatter plot of tacrolimus clearance rate vs. haematocrit. The Monte Carlo simulation indicated the following recommended doses of tacrolimus alone: 0.14 mg⋅kg⁻¹⋅d⁻¹ for genotype CYP3A5*1*1, 0.12 mg⋅kg⁻¹⋅d⁻¹ for CYP3A5*1*3, and 0.10 mg⋅kg⁻¹⋅d⁻¹ for CYP3A5*3*3. For patients receiving the combination with Wuzhi capsules, the recommended doses of tacrolimus were 0.10 mg⋅kg⁻¹⋅d⁻¹ for CYP3A5*1*1, 0.08 mg⋅kg⁻¹⋅d⁻¹ for CYP3A5*1*3, and 0.06 mg⋅kg⁻¹⋅d⁻¹ for CYP3A5*3*3 genotypes. Caspofungin or micafungin had no effect on the clearance of tacrolimus in renal transplant recipients. The population pharmacokinetics of tacrolimus in renal transplant patients was evaluated and the individual administration regimen of tacrolimus was simulated. For early kidney transplant recipients receiving tacrolimus treatment, not only body weight, but also CYP3A5 genotypes and drugs used in combination should be considered when determining the target dose of tacrolimus.

Background: Immune checkpoint inhibitors (ICIs), either as monotherapy or in combination with chemotherapy, have improved the therapeutic outcome for non-small cell lung cancer (NSCLC). However, the efficacy of combination therapies, such as programmed cell death 1(PD-1)/its ligand (PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, in targeting different pathways remains unclear. We performed a meta-analysis to determine whether the addition of a CTLA-4 inhibitor to PD-1/PD-L1 therapy improves the efficacy of PD-1/PD-L1 monotherapy in NSCLC.Methods: We systematically searched various electronic databases for suitable trials. Only randomized controlled trials (RCTs) comparing the clinical efficacy of PD-1/PD-L1 with and without CTLA-4 were included in the analyses. The meta-analysis software RevMan 5.3 was used for statistical analyses.Results: A total of seven RCTs were retrieved. The results suggested that the combination of CTLA-4 and PD-1/PDL-1 inhibitors did not show enhanced efficacy over PD1/PDL-1 inhibitor monotherapy as determined by overall survival (OS) (HR = 0.98, 95% CI = 0.84–1.14, p = 0.79), progression-free survival (PFS) (HR = 0.92, 95% CI = 0.81–1.06, p = 0.25), and objective response rate (ORR) (HR = 1.08, 95% CI = 0.96–1.21, p = 0.19). Furthermore, the combination immunotherapy was associated increased toxicity as evidenced by increased incidence of any type adverse events (AEs) (RR = 1.06, 95% CI = 1.00–1.13, p = 0.03), grade ≥3 immune-mediated AEs (RR = 1.58, 95% CI = 1.36–1.82, p < 0.05), and treatment discontinuation (RR = 1.83, 95% CI = 1.46–2.28, p < 0.05).Conclusion: Combining anti-CTLA-4 with anti-PD-1/PD-L1 therapy did not improve the therapeutic efficacy, and was associated with greater toxicity than anti-PD-1/PD-L1 monotherapy in patients with advanced NSCLC. Further investigation of the combination immunotherapy in specific subsets of patients is warranted to identify and define the patient-specific benefits of this combination.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42023435399

The present study aims to evaluate phytochemical and pharmacological potential of total protoflavones from Macrothelypteris viridifrons. In the phytochemical study, an HPLC analysis method was established, and the optimal extraction and purification conditions were analyzed. The extractive condition was optimized as follows: the backflow extraction with 20 folds of 70% ethanol at 80◦C for 1 h twice. Moreover, by combining the alkali-extraction and acid-precipitation method with the macroporous resin purification technology, the final purity rate of total protoflavones was no less than 54.85%. In the pharmacological study, the total protoflavones from M. viridifrons showed a significant tumor-inhibitory effect in the H22 hepatoma cells transplantation model with a higher inhibitory rate of 55.76% in high dosage (100mg/kg) treatment group compared with the positive control group (20 mg/kg cyclophosphamide). Taken of all, these results support that protoflavones are the material basis of M. viridifrons as an anticancer folk medicine.