Correction for 'An ROS-sensitive tegafur-PpIX-heterodimer-loaded in situ injectable thermosensitive hydrogel for photodynamic therapy combined with chemotherapy to enhance the tegafur-based treatment of breast cancer' by Zhiqiang Zhang et al., Biomater. Sci., 2021, 9, 221-237, https://doi.org/10.1039/D0BM01519A.

Supersaturation is a widely employed strategy to improve the oral bioavailability of poorly soluble drugs, but its application is usually limited by rapid recrystallization. This study aimed to investigate the solubilization and crystallization-inhibitory effects of various polymers, including HPMCAS-LG, HPC-SL, HP-55, PVP K30, HPMC, and Eudragit® L100-55, on the BCS II drug efonidipine hydrochloride (EFH). Eudragit® L100-55 demonstrated the most effective ability to generate and maintain supersaturation of EFH in pH 6.8 phosphate buffered saline. An organic solvent-free aqueous processing strategy was successfully employed to prepare amorphous solid dispersions (ASDs) of EFH. In vitro solubility studies showed that the Eudragit® L100-55 ASDs achieved significantly higher maximum drug concentrations than crude EFH and maintained supersaturation for a prolonged duration. Consequently, in vitro studies using everted gut sacs showed that the optimized ASD enhanced the apparent permeability of EFH by nearly threefold compared to the crude drug, while the apparent permeability was comparable to that of Landel®. Pharmacokinetic studies in beagle dogs confirmed a significant improvement in oral absorption. The relative bioavailability of the optimized Eudragit® L100-55 ASD was approximately 1.5-fold higher than that of Landel®, although slightly lower Cmax and delayed tmax values were observed, indicating a slower but more sustained absorption process. The prolonged MRT further supported extended systemic exposure. the relative bioavailability of the optimized Eudragit® L100-55 ASD were 1.5 times higher than that of Landel®. The prolonged tmax and MRT suggest modified drug release characteristics. The findings demonstrate that Eudragit® L100-55-based ASDs prepared via aqueous processing represent a promising strategy for enhancing the intestinal absorption and oral bioavailability of EFH by effectively generating and stabilizing its supersaturated state. The enhancement is primarily attributed to sustained supersaturation, which maintains a higher concentration gradient and promotes absorptive flux across the intestinal membrane.

PurposeImmunotherapy as a neoadjuvant treatment approach has achieved certain therapeutic effects in various types of cancer. However, in the specific cancer type of hepatocellular carcinoma (HCC), standardized protocols for neoadjuvant immunotherapy remain to be defined. This systematic review and meta-analysis focus on evaluating the efficacy and safety of neoadjuvant immunotherapy in the treatment of HCC, aiming to provide a robust basis for clinical decision-making.MethodsThis study systematically searched databases such as PubMed, EMBASE, the Cochrane Library, and conference proceedings to identify clinical trials focusing on patients with HCC undergoing neoadjuvant immunotherapy. The Review Manager 5.4 software was applied to estimate the odds ratio (OR) of effect sizes and their corresponding 95% confidence intervals (CI).ResultsImmune checkpoint inhibitors (ICIs) demonstrate significant efficacy in improving pathological outcomes and safety profiles in patients with resectable hepatocellular carcinoma (HCC). Specifically, ICIs significantly increase the pathological complete response (pCR) rate (OR = 0.23, 95% CI [0.14, 0.37], p < 0.00001) and major pathological response (MPR) rate (OR = 0.47, 95% CI [0.32, 0.70], p = 0.0002). They also markedly enhance the objective response rate (ORR) (OR = 0.42, 95% CI [0.28, 0.63], p < 0.0001). Furthermore, ICIs potentially improve the surgical resection rate (OR = 3.91, 95% CI [2.05, 7.45], p < 0.0001) and reduce the incidence of grade 3–4 treatment-related adverse events (TRAEs) (OR = 0.27, 95% CI [0.17, 0.44], p < 0.00001), indicating both therapeutic benefits and acceptable toxicity profiles.ConclusionNeoadjuvant immunotherapy shows promise in the treatment of resectable HCC. Nonetheless, to further validate its efficacy, more large-scale, well-designed clinical trials are necessary to provide conclusive evidence.Systematic review registrationThis comprehensive review adheres to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards and has been carried out as per a preregistered protocol (PROSPERO registration number: CRD42024560660).

The intricate physiological microenvironment of the diabetic wound characterized by overexpressed reactive oxygen species (ROS), persistent inflammation, angiogenetic dysfunction, and bacterial infection impeded the healing process. Herein, a photo-crosslinking composite hydrogel was fabricated based on the methacrylate modification of sesbania gum (SG) and γ-polyglutamic acid (γ-PGA), which could trigger free radical polymerization to form interpenetrating polymer network under 365 nm UV. Meanwhile, the micronized traditional Chinese medicine Huoxue Tongluo extract (HXTL) was encapsulated into the hydrogel to prepare the wound dressing (H-SGPGA). The 1H NMR and FT-IR successfully confirmed the synthesis of the methacrylate SG (SGMA) and γ-PGA (γ-PGAMA). Then, the enhanced mechanical properties, ROS scavenging (DPPH: 88.2 % ± 0.9 %; ABTS+: 90.5 % ± 0.4 %) and the antibacterial capacity (97.04 % ± 0.58 % against S. aureus) of H-SGPGA was investigated and confirmed in vitro. Finally, in the S. aureus infected diabetic wound model, the in vivo result demonstrated that the H-SGPGA significantly accelerated the diabetic wound repair process (8.31 % ± 5.54 % wound area on day 12) by promoting epidermis regeneration (79.13 % ± 5.99 %), collagen deposition (71.4 % ± 9.1 %), and angiogenesis (294.1 % ± 29.6 % of control group). Therefore, the composite H-SGPGA provided a potential treatment as the hydrogel dressing for the diabetic wound.

Hematopoietic progenitor kinase 1 (HPK1), also known as MAP4K1, is a hematopoietic-specific serine/threonine kinase and a member of the MAP4K family of mammalian Ste20-associated protein kinases, which share a highly similar protein structure, and play important roles in the regulation of cell survival, cell migration, apoptosis and autophagy. HPK1 is a negative regulator of T-cell, B-cell and dendritic cell-mediated immune responses, and HPK1 kinase deficiency increases cytokine secretion and enhances T-cell signaling, viral clearance and tumor growth inhibition. Thus, HPK1 may be implicated in the development and progression of human malignant tumors and is a potent target for anti-tumor immunotherapy. In this review, we summarized the biological rationale and potential of HPK1 as a candidate target for tumor immunotherapy, as well as recent research advances in HPK1 inhibitors, with a special emphasis on HPK1 small molecule inhibitors currently under preclinical and clinical investigation.

Background: The global prevalence of type 2 diabetes mellitus (T2DM) continues to rise, with patients facing significantly elevated risks of cardiovascular complications, particularly heart failure (HF). Objective: This examination sought to methodically examine cardiovascular sequelae, notably heart failure, among users of dipeptidyl peptidase 4 (DPP-4) inhibitors when compared with nonusers. Methods: Cochrane, Embase, and PubMed databases, which compared the use of DPP-4 inhibitors and reported cardiovascular outcomes and heart failure events in patients with type 2 diabetes mellitus (T2DM), were searched using specific terms. Studies were included if they satisfied the following inclusion criteria: they were randomized trials comparing DPP-4 inhibitor use in patients with T2DM; study duration was longer than 24 weeks; and they reported cardiovascular outcomes as their main or secondary end points. Stata 15 MP (StataCorp LLC, College Station, Texas, USA) was used to analyze the data, and odds ratios (ORs) with 95% CIs were used to represent the results. Results: A total of 79,010 participants with T2DM were included. A total of 37,895 patients were assigned to the DPP-4 inhibitor group, whereas 41,115 patients were assigned to the control group. Results of the analysis showed that during a mean follow-up period ranging from 24 to 302 weeks, heart failure incidence did not differ significantly between T2DM patients treated with DPP-4 inhibitors and those who were not (OR = 1.06; 95% CI, 0.96–1.18; P = 0.452). Major adverse cardiovascular events (including nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death; OR = 1.01; 95% CI, 0.95–1.08; P = 0.354), stroke (OR = 1.01; 95% CI, 0.78–1.30; P = 0.968), myocardial infarction (OR = 0.89; 95% CI, 0.73–1.07; P = 0.49), and all-cause mortality (OR = 1.03; 95% CI, 0.96–1.11; P = 0.309) were also similarly manifested in both groups. Conclusions: The present analysis showed that treatment with DPP-4 inhibitors did not significantly increase cardiovascular outcomes and heart failure in these patients with T2DM, indicating that these drugs may be safe to use in terms of cardiovascular events.

Aims: This study aimed to characterize the pharmacokinetics of imatinib in paediatric patients with hepatic impairment, a population for whom evidence-based dosing guidance is currently lacking, in order to inform safe and effective prescribing across a range of clinical scenarios. Methods: Using PK-Sim® software, we integrated physiological, physicochemical, and clinical pharmacokinetic data to develop a physiologically based pharmacokinetic (PBPK) model for imatinib in adults with normal hepatic function. This model was subsequently extrapolated to predict imatinib disposition in children with hepatic impairment, enabling estimation of age- and liver-function-specific doses that maintain plasma concentrations within the therapeutic window. Results: A PBPK framework was first established and verified against clinical pharmacokinetic data obtained from adults and children with varying degrees of hepatic impairment. The final paediatric model, stratified into 12 age- and liver-function subgroups, predicted exposure to imatinib that rose progressively as hepatic function declined. To maintain concentrations within the therapeutic window, dose recommendations were derived: 260–340 mg/m 2 /d. For children with normal hepatic function, 260 mg/m 2 /d. For mild or moderate impairment, and 200 mg/m 2 /d. For severe hepatic dysfunction. Conclusion: Hepatic impairment in children significantly elevates systemic imatinib exposure, resulting in a corresponding increase in adverse-event incidence.

Background Finerenone,a nonsteroidal mineralocorticoid antagonist,is a novel therapeutic agent for renal protection in patients with diabetic kidney disease,joining the ranks of angiotensin-converting enzyme inhibitors and sodium-glucose cotransporter 2 inhibitors in providing renal protection for such patients.Recently,two meta-analyses focusing on patients with chronic kidney disease have yielded conflicting conclusions regarding the impact of finerenone on the decline of estimated glomerular filtration rate(eGFR).In light of this,the present meta-analysis specifically targets the population with type 2 diabetes,aiming to thoroughly investigate the efficacy and safety of finerenone.Objective To systematically evaluate the efficacy and safety of finerenone in patients with type 2 diabetes and kidney disease.Methods A computerized search was conducted in the Cochrane Library,Web of Science,Embase,and PubMed databases,covering the period from their inception to April 2024.Literature was screened and data extracted according to the inclusion and exclusion criteria.Meta-analysis was performed using Revman 5.3,comparing indicators such as the urine albumin-to-creatinine ratio and estimated glomerular filtration rate in type 2 diabetes patients treated with finerenone.Results A total of 7 articles were ultimately included,involving 15 528 patients.The results showed that compared with the control group,intervention group(using finerenone)had statistically significant differences in the urine albumin-to-creatinine ratio(SMD=-0.46,95%CI=-0.48 to-0.39,P<0.05),estimated glomerular filtration rate(SMD=-0.15,95%CI=-0.19 to-0.10,P<0.05),renal composite endpoint(OR=0.83,95%CI=0.75 to 0.92,P<0.05),all-cause mortality(OR=0.88,95%CI=0.78 to 0.99,P<0.05),and end-stage renal disease(OR=0.88,95%CI=0.78 to 0.99,P<0.05).Compared with the control group,intervention group significantly increased the risk of hyperkalemia(OR=2.13,95%CI=1.89 to 2.39,P<0.05).Conclusion Finerenone can significantly improve renal composite endpoint events in patients with type 2 diabetes and kidney disease,reduce the urine albumin-to-creatinine ratio,and slow down the decline of estimated glomerular filtration rate;however,attention should be paid to the risk of hyperkalemia during treatment.

Purpose To evaluate the efficacy and safety of combination therapy with sodium-glucose cotransporter2(SGLT-2) inhibitors and glucagon-like peptide-1(GLP-1) receptor agonists in the treatment of type 2 diabetes mellitus (T2DM). Methods To construct an exhaustive database of randomized controlled trials (RCTs) concerning SGLT-2 inhibitors and GLP-1 agonists, a methodical search was undertaken across a range of databases, such as Embase, PubMed, and the Cochrane Central Register of Controlled Trials, from their inception to January 2023. Following this, a meta-analysis was executed to amalgamate the collected data, which allowed for the calculation of standardized mean differences (SMDs), odds ratios (ORs), and 95% confidence intervals (CIs) for a spectrum of outcomes. This analytical approach was designed to yield a quantitative evaluation of the therapeutic efficacy and safety profile of SGLT-2 inhibitors and GLP-1 agonists for the treatment of diabetes mellitus. Results When compared to GLP-1 agonist therapy alone, the combination therapy did not significantly reduce fasting plasma glucose (FPG) levels (95% confidence interval [CI]: -0.27, 0.10; p=0.35), body weight (95% CI: -0.18, 0.18; p=1.00), Glycosylated Hemoglobin, Type A1C (HbA1c) (95% CI: -0.29, 0.07; p=0.22), or systolic blood pressure (SBP) values (95% CI: -0.29, 0.06; p=0.21). In contrast, when compared to SGLT-2 inhibitor therapy alone, combination therapy significantly decreased FPG by 0.24 mmol/L (95% CI: -0.43, -0.05; p=0.01), HbA1c by 0.45% (95% CI: -0.72, -0.18; p=0.001), and SBP by 0.12 mmHg (95% CI: -0.24, 0.00; p=0.05). However, the combination therapy failed to demonstrate a significant reduction in body weight when compared with either SGLT-2 inhibitor therapy (95% CI: -0.20, 0.05; p=0.24) or GLP-1 agonist therapy (95% CI: -0.18, 0.18; p=1.00). Additionally, the combination therapy did not increase the incidence of hypoglycemia. It should be noted that data regarding mortality and cardiovascular outcomes were limited. Conclusions The combination treatment of SGLT-2 inhibitors and GLP-1 receptor agonists effectively reduces HbA1c, FPG, and SBP without elevating the risk of hypoglycemia when compared to monotherapy with SGLT-2 inhibitors. However, these beneficial effects were not observed when the combination therapy was compared with GLP-1 receptor agonist treatment alone.

Diabetic wounds present significant burdens to both patients and the healthcare system due to their prolonged inflammatory phase and adverse microenvironment. Traditional Chinese medicine (TCM), particularly Scutellaria baicalensis extract (SE), has shown promise in wound healing. Herein, sesbania gum (SG) was oxidized and formed hydrogel with carboxymethyl chitosan (CMCS) through the imine bond. Then, SE was loaded into the hydrogel as a wound dressing (CMCS−OSG@SE hydrogel). In vitro experiments demonstrated the mechanical properties and ROS scavenging efficiency of the hydrogel, as well as the release of SE and its biocompatibility. In an vivo study, diabetic mice with S. aureus infection were used, and the CMCS−-OSG@SE hydrogel dressing accelerated wound healing by promoting epidermal regeneration and collagen deposition. This composite polysaccharide hydrogel loaded with SE shows great potential for diabetic wound treatment.

Background:To investigate the safety and efficiency of dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with diabetic kidney disease. Methods:We conducted a comprehensive literature search across multiple databases, including Embase, PubMed, CNKI, and the Cochrane Central Register of Controlled Trials, from inception to January 2024. The search focused on randomized controlled trials (RCTs) that directly compared DPP-4 inhibitors with placebos or other glucose-lowering therapies. A meta-analysis was performed to pool data and quantify the therapeutic effects and safety profile of DPP-4 inhibitors in DKD. Results:Twenty-three RCTs with 16,378 participants were included. DPP-4 inhibitors significantly reduced urinary albumin-to-creatinine ratio (UACR) and HbA1c levels compared to controls (UACR: SMD -0.23, 95% CI: -0.41, -0.06; p = 0.01; HbA1c: SMD -0.32, 95% CI: -0.51, -0.14; p = 0.0006). A higher proportion of patients in the DPP-4 inhibitor group achieved at least a 30% reduction in UACR (OR = 1.73, 95% CI: 1.10, 2.73; p = 0.02). However, estimated glomerular filtration rate (eGFR) and serum creatinine (SCr) changes were similar between groups (eGFR: p = 1.00; SCr: p = 0.67). No significant differences were found in all-cause mortality (OR = 0.94, 95% CI: 0.83, 1.06; p = 0.31) or hypoglycemia risk (OR = 1.10, 95% CI: 0.80, 1.52; p = 0.54) between the DPP-4 inhibitor and control groups. Conclusions:DPP-4 inhibitors exhibit renoprotective properties, indicated by significant reductions in UACR and HbA1c levels. They do not appear to increase the risk of hypoglycemia, presenting a favorable safety profile when compared to placebo or alternative antidiabetic agents.

Hyponatremia can worsen the outcomes of patients with liver cirrhosis. However, it remains unclear about how to predict the risk of death in cirrhotic patients with hyponatremia. Patients with liver cirrhosis and hyponatremia were screened. Eligible patients were randomly divided into the training (n = 472) and validation (n = 471) cohorts. In the training cohort, the independent predictors for in-hospital death were identified by logistic regression analyses. Odds ratios (ORs) were calculated. An artificial neural network (ANN) model was established in the training cohort. Areas under curve (AUCs) of ANN model, Child-Pugh, model for end-stage liver disease (MELD), and MELD-Na scores were calculated by receiver operating characteristic curve analyses. In multivariate logistic regression analyses, ascites (OR = 2.705, P = 0.042), total bilirubin (OR = 1.004, P = 0.003), serum creatinine (OR = 1.004, P = 0.017), and international normalized ratio (OR = 1.457, P = 0.005) were independently associated with in-hospital death. Based on the four variables, an ANN model was established. Its AUC was 0.865 and 0.810 in the training and validation cohorts, respectively, which was significantly larger than those of Child-Pugh (AUC = 0.757), MELD (AUC = 0.765), and MELD-Na (AUC = 0.769) scores. An ANN model has been developed and validated for the prediction of in-hospital death in patients with liver cirrhosis and hyponatremia.

OBJECTIVE:To assess the long-term effectiveness of Huangqi (Radix Astragali Mongolici, HQ)-based Traditional Chinese Medicine (TCM) in the treatment of diabetic peripheral neuropathy (DPN). METHODS:Nine databases were searched to retrieve available randomized controlled trials that compared HQ-based TCM and Western Medicines in the treatment of DPN. The methodological quality of the included studies was assessed using the Cochrane bias risk tool, and RevMan 5.4 was used for data analysis. The effect estimates of interest were risk ratio (RR), mean difference (MD) or standardized mean difference (SMD) with 95% confidence interval (CI). RESULTS:The results from 48 available studies assessing 3759 patients demonstrated that cases administered HQ-based TCM [RR = 1.30, 95% CI (1.21, 1.40), P < 0.000 01] or HQ-based TCM combined with Western Medicines [RR = 1.25, 95% CI (1.19, 1.31), P < 0.000 01] exhibited higher total efficacy rates than individuals who received Western Medicine alone. The results showed that the HQ-based TCM group had decreased Toronto Clinical Scoring System scores [MD =－1.50, 95% CI (－1.83, －1.17), P < 0.000 01], and reduced serum interleukin 6 [SMD = －0.57, 95% CI (－0.87, －0.27), P = 0.0002] and tumor necrosis factors-α levels [SMD = －0.60, 95% CI (－0.95, －0.25), P = 0.0009]. In addition, both HQ-based TCM and HQ-based TCM combined with Western Medicine increased nerve conduction velocity and decreased glycaemia compared with Western Medicine alone. In terms of blood lipids, oxidative stress and adverse drug reactions, there were no significant differences between the HQ-based TCM groups and the Western Medicine control group. CONCLUSION:The current Meta-analysis revealed that HQ-based TCM yields higher efficacy and safety than Western Medicine alone for the treatment of DPN, although further well-designed RCTs are required to validate these findings.

PURPOSE:This meta-analysis sought to assess the relationship between dipeptidyl peptidase-4 inhibitors (DPP-4) and the risk of pancreatitis and pancreatic cancer by synthesizing data from randomized, controlled trials, in light of the conflicting findings from observational studies and previous meta-analyses. METHODS:Cochrane, Embase, ClinicalTrials.gov, and PubMed databases that compared the use of DPP-4 inhibitors and that reported pancreatitis and pancreatic cancer events in patients with diabetes mellitus Type 2 (T2DM) were searched using specific terms. Studies were included if they satisfied the following inclusion criteria: They were randomized trials comparing DPP-4 inhibitors use in patients with T2DM; The study's duration was longer than 24 weeks; And they reported pancreatitis and pancreatic cancer events. Stata 15 MP was used to analyze the data, and odds ratios (OR) with 95% confidence intervals (CI) were used to represent the results. FINDINGS:A total of 81,737 participants with T2DM were included in the analysis. The results showed that during a mean follow-up period of 24 to 520 weeks, The use of DPP-4 inhibitors was not associated with an increased risk of pancreatitis (Peto-OR 0.97; 95% CI: 0.74, 1.27) or pancreatic cancer (Peto-OR = 0.88; 95% CI: 0.59, 1.30). IMPLICATIONS:Current evidence fails to validate a significant correlation between DPP-4 therapy and pancreatitis or pancreatic cancer. However, subgroup analyses showed that sitagliptin was associated with a significant reduction in pancreatitis risk compared to the control group; furthermore, when comparing different types of control medications, a significant decrease in pancreatic cancer risk was observed among DPP-4 users compared to GLP-1 users.

Background: The novel class of oral antidiabetic agents known as dipeptidyl peptidase 4 (DPP-4) inhibitors has garnered endorsement from the United States Food and Drug Administration for management of patients afflicted with type 2 diabetes mellitus (T2DM). This examination sought to methodically examine cardiovascular sequelae, notably heart failure, amongst users of DPP-4 inhibitors when compared to non-users.Methods: Cochrane, Embase, and PubMed database that compared the use of DPP-4 inhibitors and that reported cardiovascular outcomes and heart failure events in patients with T2DM were searched using specific terms. Studies were included if they satisfied the following inclusion criteria: They were randomized trials comparing DPP-4 inhibitors use in patients with T2DM; The studies duration was longer than 24 weeks; And they reported cardiovascular outcomes as their main or second endpoints. Stata 15 MP was used to analyze the data, and odds ratios (OR) with 95% confidence intervals (CI) were used to represent the results.Results: A total number of 79,010 participants with T2DM were included. 37,895 patients were assigned to the DPP-4 inhibitor group whereas 40,640 patients were assigned to the control group. Results of this analysis showed that during a mean follow-up period ranging from 24 to 302 weeks, the primary endpoint (heart failure) was not significantly different in the treatment of T2DM patients with versus without DPP-4 inhibitors (OR: 1.06, 95% CI: 0.96,1.18; P = 0.452). MACE (include nonfatal myocardial infarction (MI), nonfatal stroke, cardiovascular death) (OR: 1.01, 95% CI: 0.95,1.08; P = 0.354), stroke (OR: 0.71, 95% CI: 0.41,1.22; P = 0.292), MI (OR: 0.89, 95% CI: 0.73,1.07; P = 0.49) and all-cause mortality (OR: 1.03, 95% CI: 0.96,1.11; P = 0.309) were also similarly manifested in both groups.Conclusion: The current analysis showed that treatment with DPP-4 inhibitors did not significantly increase cardiovascular outcomes and heart failure in these patients with T2DM indicating that those drugs might be safe to use in terms of cardiovascular events.Funding: We do not have any fundings.Declaration of Interest: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence the work submitted, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled, “ Cardiovascular events and heart failure in patients with type 2 diabetes treated with dipeptidyl peptidase-4 inhibitors: An update systematic review and meta-analysis. ” .

Direct oral anticoagulants (DOACs) could effectively prevent the occurrence of cancer-associated venous thromboembolism (CAVTE), which incidence rate was estimated to be 4–20%. But the efficacy and safety remain controversial between DOACs and low molecular weight heparin (LMWH). PubMed, Cochrane Library, Embase, ClinicalTrials.gov databases for randomized controlled trials (RCTs) were systematically searched from inception to March 15, 2022. A random-effects model was used to report the odds ratio (OR) and 95% confidence interval (CI) for both direct and network meta-analyses. Seven studies were included totaling 3242 patients. A lower rate of recurrence VTE was noted in the DOACs compared with LMWH (OR 0.62, 95% CI 0.47–0.82, I2 = 0.0%). The aspect of major bleeding (MB) was similar (OR 1.30, 95% CI 0.77–2.18, I2 = 34.9%). When assessing clinically relevant nonmajor bleeding (CRNMB) (OR 1.61, 95% CI 1.17–2.22, I2 = 20.7%) and clinically relevant bleeding (CRB) (OR 1.39, 95% CI 1.11–1.74, I2 = 0.0%), a higher risk of events was observed in DOACs. In subgroup analyses, the MB of gastrointestinal and genitourinary malignancies had a higher rate in the DOACs. For ranking, apixaban ranked the first in prevention of VTE and reducing MB events. Edoxaban had the highest risk drug in MB. In terms of CRNMB and CRB, LMWH showed the lowest risk. Compared with LMWH, DOACs seemed to have a decreased risk of recurrence VTE while increasing CRNMB and CRB. DOACs and LMWH were equivalent to the aspect of MB, but DOACs had a higher MB risk in patients with gastrointestinal and genitourinary malignancies. Apixaban may be the lowest risk compared to the other DOACs in precaution of VTE and reducing bleeding events. Los anticoagulantes orales directos (ACOD) son eficaces en la prevención de la tromboembolia venosa (TEV) relacionada con el cáncer, cuya tasa de incidencia se estima en 4-20%. Sin embargo, la eficacia y seguridad de ACOD y heparina de bajo peso molecular (HBPM) siguen siendo controvertidas. Desde el inicio hasta el 15 de marzo de 2022 se realizaron búsquedas sistemáticas en las bases de datos de ensayos controlados aleatorios (ECA) en PubMed, The Cochrane Library, Embase, ClinicalTrials.gov. Se utilizó el modelo de efectos aleatorios para informar la razón de probabilidades (RP) y los intervalos de confianza (IC) de 95% para los metaanálisis directos y de red. Se incluyeron siete estudios con un total de 3.242 pacientes. En comparación con HBPM, los ACOD tienen una tasa más baja de recurrencia de TEV (OR 0,62, IC 95%: 0,47 a 0,82, I2 = 0,0%). La frecuencia de hemorragias mayores fue similar (OR 1,30, IC 95% 0,77 a 2,18, I2 = 34,9%). Se observó un mayor riesgo de eventos en los ACOD. Cuando se evaluaron las hemorragias no mayores clínicamente relevantes (CRNMB) (OR 1,61, IC 95%: 1,17 a 2,22, I2 = 20,7%) y las hemorragias clínicamente relevantes (OR 1,39, IC 95%: 1,11 a 1,74, I2 = 0,0%), En los análisis de subgrupos, las hemorragias mayores en las neoplasias malignas gastrointestinales y genitourinarias fueron más frecuentes con los ACOD. Apixabán ocupó el primer lugar en la prevención de TEV y la reducción de eventos hemorrágicos mayores. Edoxabán tuvo el mayor riesgo de hemorragias mayores. Las HBPM demostraron tener menor riesgo de hemorragias mayores clínicamente relevantes y hemorragias clínicamente relevantes. En comparación con la HBPM, el tratamiento con ACOD se asociaba a un menor riesgo de recurrencia de TEV, mientras que aumentaba el riesgo de sufrir hemorragias mayores clínicamente relevantes y hemorragias clínicamente relevantes. Los ACOD y LMWH comportaban un riego equivalente de sufrir hemorragias mayores. Sin embargo, los ACOD tenían un mayor riesgo de hemorragias mayores en pacientes con neoplasias malignas gastrointestinales y genitourinarias. En comparación con otros ACOD, apixabán tuvo un riesgo más bajo de eventos hemorrágicos cuando se usaba en prevención de la TEV.

Background: Human albumin (HA) infusion is potentially effective for the management of hyponatremia in liver cirrhosis, but the current evidence is very limited. Methods: In this retrospective study, 2414 cirrhotic patients who were consecutively admitted to our hospital between January 2010 and June 2014 were included in the Hospitalization outcome cohort, and 339 cirrhotic patients without malignancy who were consecutively admitted to our department between December 2014 and April 2021 were included in the Long-term outcome cohort. The development and improvement of hyponatremia were compared between patients who received HA infusion during hospitalizations and did not. Logistic and Cox regression analyses were performed to evaluate the association of development and improvement of hyponatremia during hospitalizations with the outcomes. Odds ratios (ORs) and hazard ratios (HRs) were calculated. Results: In the two cohorts, HA infusion significantly decreased the incidence of hyponatremia and increased the rate of improvement of hyponatremia in cirrhotic patients during hospitalizations. In the Hospitalization outcome cohort, the development of hyponatremia during hospitalizations was significantly associated with increased in-hospital mortality (OR = 2.493, p < 0.001), and the improvement of hyponatremia during hospitalizations was significantly associated with decreased in-hospital mortality (OR = 0.599, p = 0.014). In the Long-term outcome cohort, the development of hyponatremia during hospitalizations was significantly associated with decreased long-term survival (HR = 0.400, p < 0.001), and the improvement of hyponatremia during hospitalizations was not significantly associated with long-term survival (HR = 1.085, p = 0.813). Conclusions: HA infusion can effectively prevent the development of hyponatremia and improve hyponatremia in cirrhotic patients during hospitalizations, which may influence the patients’ outcomes.

The aim of this work is to develop a novel simultaneous in vitro dissolution - in situ perfusion system (SDPS) as a potential tool to evaluate the in vivo performance of solid oral formulation in rat. The innovative nitrendipine (NTD) tablet of Bayotensin mite (R) made in Germany was used as reference listed drug (RLD), and five generic products from Chinese market were compared with RLD using the in vitro dissolution test method specified by the orange book and the SDPS method developed in this study. Four self-prepared NTD tablets with different proportions of microcrystalline cellulose/starch were employed to investigate the discriminatory ability of the SDPS for formulation. In addition, the predictivity of the SDPS in relation to data from in vivo pharmaceutics studies was evaluated. The 45-min dissolution test and multiple-pH dissolution profiles of generic product 1 and 2 have no difference compared with the RLD, but their dissolution profiles from the SDPS showed statistically significant differences. A biexponential formula successfully described the concentration profiles of self-prepared formulations in SDPS experiments. The k(dis) (0.08 +/- 0.01 similar to 0.2 +/- 0.03 min(-1)) and k(a) (about 2.30 x 10(-3) min(-1)) values calculated by the formulas of F1-F3 suggested that the used excipients had no effect on the intestinal absorption of NTD, and it might be the property of active pharmaceutical ingredient that led to the difference among the generics. Furthermore, the in vivo rat pharmacokinetics study results of F1-F3 showed a good correlation (R-2 = 0.99) with the SDPS data. In summary, the SDPS is a promising tool to detect the unexpected quality changes of pharmaceutical products in weakly regulated markets, facilitate formulation screening, and potentially reduce animal testing for estimating the in vivo absorption behavior of solid oral formulations. The absorption performance of generic drugs in vivo should be further investigated.

Abstract Purpose Given the inter-individual variability in dose-corrected concentrations observed in olanzapine used, this study aimed to find factors that may have contributed to the variation in patients.Methods The trough plasma concentrations of olanzapine were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). All the patients enrolled were on steady olanzapine doses for at least two weeks. Our study simultaneously investigated the association of gender, co-treatment, kidney function, body weight, and UGT1A4, UGT2B7, UGT2B15, CYP1A2, CYP2D6 variants on olanzapine dose-corrected concentrations (C/DOLZ) in 117 Chinese patients with schizophrenia.Results Multiple linear regression analyses suggested that gender, co-treatment with sodium valproate, and UGT1A4 variants had significantly affected C/DOLZ in inpatients with schizophrenia (P༜0.05). Females showed higher C/DOLZ levels compared to males, co-treatment with VPA exhibited lower C/DOLZ levels, UGT1A4 variants showed its significance (P = 0.005) in the multiple linear regression,Conclusions The results revealed that gender, co-treatment with VPA, and UGT1A4 variants significantly influenced C/DOLZ levels. This study provided some combined effects, especially genotype and co-treatment information, for clinicians to remind them when prescribing OLZ. The variability of C/DOLZ levels suggests that TDM could be a helpful tool in addition to a thorough clinical follow-up.

Psoriasis is an autoimmune disorder disease with abnormally activated T lymphocytes and thickening of the epidermis. The mechanism of the action of tacrolimus and paclitaxel are matched with the two only known pathogenesis of psoriasis. However, there has been no report on tacrolimus combined with paclitaxel in the treatment of psoriasis until now. The O/O ointment was prepared for the topical application to overcome poor solubility, poor skin penetration, and erratic absorption of the two drugs. A high-speed shearing method was adopted to prepare the ointment, in which propylene carbonate was used to solve tacrolimus and paclitaxel completely. The ointment showed excellent stability, slow release of the drugs, better retention in psoriatic skin, and good skin tolerance. The therapeutic efficacy of ointment was evaluated with imiquimod induced psoriatic model, and the level of expression of psoriatic biochemical markers was evaluated using the PASI score and immunohistochemistry. The cumulative PASI score was 10.8 for the imiquimod induced group, 7.8 for the tacrolimus ointment group, 8.3 for the paclitaxel ointment and 5.3 for the tacrolimus-paclitaxel (1:1) ointment group, respectively. Ointment group with tacrolimus and paclitaxel indicated a significant improvement in the phenotypic features of the psoriatic skin treated. Compared with the imiquimod group, tacrolimus-paclitaxel (1:1) ointment group was significantly reduced the level of IL-17. The results confirm that tacrolimus and paclitaxel co-loaded ointment can be an effective strategy for the treatment of psoriasis.