This current study was conducted in healthy Chinese volunteers to evaluate its safety, tolerability pharmacokinetics and immunogenicity profiles of recombinant human interferon beta-1b (rIFN β-1b) by subcutaneous administration (SC).

The clinical study included four single-dose (SD) cohorts and one multiple-dose (MD) cohort. The single-dose part was designed as a double-blind, randomized, placebo-controlled, dose-escalation (4-16 MIU dose range) study. Eight participants enrolled in each single-dose cohort were allocated (3∶1) to receive either rIFN β-1b or placebo. The multiple-dose cohort was mainly designed to assess the pharmacokinetics and immunogenicity profile of rIFN β-1b, with 8 MIU dose for eight consecutive days in eight healthy volunteers. The blood concentration of rIFN β-1b and the titre of anti-drug antibody (ADA) were quantified by a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetic parameters were calculated using a non-atrioventricular model with the WinNonlin software. The safety monitoring was carried out across the trial.

All 40 healthy participants enrolled and completed the trial. In 4, 8, 12 MIU SD groups, the C_max were (63.18±34.64)、(125.17±59.19) and (214.00±89.02) pg·mL^-1, respectively; AUC_0-t were (3 247.63±1 842.60)、(7 903.33±3 427.03) and (9 740.00±2 333.47) h·pg·mL^-1, respectively; AUC_0-∞ were (4 374.00±1 087.74)、(8 861.67±3 677.13) and (10 528.33±2 344.60) h·pg·mL^-1, respectively. The mean C_max of rIFN β-1b approximately increased linearly with dose-relationship in the SD group (4-12 MIU) and the mean AUC_0-t and AUC_0-∞ showed the similar treand. The median t_max ranged from 5 to 12 hours in the SD groups. The median t_max was 4 hours in the MD group and no increase of the titre level of anti-drug antibody was found. The elimination half-life (t_1/2) was similar in all dose groups, approximately 50 hours. No serious adverse events occurred and all adverse events returned to normal or baseline level. The common adverse events were mainly influenza-like illness, injection site adverse reactions and fever, all of which were graded as mild (Grade 1) or moderate (Grade 2).

The rIFN β-1b showed safe and well-tolerated in single and multiple doses cohorts of this study. Systemic exposure of IFN β-1b increased with dose-relationship in the single-dose group. These findings support the necessity for further clinical studies.

Based on data mining, network pharmacology and molecular docking technology, we reveal the medication pattern and the molecular mechanism of action of the core pairs of medicines in traditional Chinese medicine (TCM) compounding for the treatment of autism spectrum disorders (ASD) and attention-deficit hyperactivity disorder (ADHD), and explore the possible effective ways of Chinese medicines for the treatment of co-morbidities of ASD-ADHD. By comparing the pathogenesis of ASD and ADHD and the pharmacological effects of the obtained core pairs, we are searching for the medication ideas of traditional Chinese medicine for the treatment of ASD-ADHD co-occurring disorders.

Microsoft Excel 2016, SPSS Modeler 18.0 and other software were used to perform statistical processing, association analysis, and screening of core drug pairs for the compounded prescriptions that met the inclusion criteria. On the basis of the data mining results, the targets of ASD, ADHD, and the core drug pairs were collected with the help of databases such as TCMSP, GeneCards, etc., and the part of target overlap was regarded as the key target. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the key targets using the databases. Molecular docking of the active ingredients of the core drug pairs with the key targets was performed using AutodockTools 1.5.6 and PyMol 3.1.

A total of 63 herbal prescriptions for ASD and 105 herbal prescriptions for ADHD were screened, and the visualisation network showed that the core pair of medicines for treating both diseases was Acori Tataninowii Rhizoma-Polygalae Radix. Based on the network pharmacology, it was learnt that Acori Tataninowii Rhizoma-Polygalae Radix was able to regulate ASD and ADHD through multiple pathways and targets, and the molecular docking results showed that the main active ingredients in Acori Tataninowii Rhizoma-Polygalae Radix had a good binding affinity with the key targets.

The core drug pairs in the TCM compound formula for treating ASD and ADHD are both Acori Tataninowii Rhizoma-Polygalae Radix, which may play a role in the treatment of co-morbid ASD and ADHD through different mechanisms mediated by different core targets, providing a possible direction for the treatment of co-morbid ASD and ADHD with TCM.

To establish a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for determine the concentration of busulfan in plasma of hematopoietic stem cell transplantation (HSCT) patients and apply it to clinical sample detection.

A Symmetry C₁₈ column 150.0 mm ( 4.6 mm, 3.5 μm) was used. The mobile phase consisted of phase A (10 mmol·L^-1 ammonium formate solution, containing 0.1% formic acid, v/v) and phase B (acetonitrile), and was subjected to gradient elution at a flow rate of 0.8 mL·min^-1, and the injection volume was 10 μL. The internal standard was carbamazepine. The quantitative analysis was ionized with atmospheric pressure chemical ionization source (APCI), positive ion mode, and multi reaction monitoring (MRM). Detecting ion pairs were busulfan 264.4→151.2, carbamazepine 237.1→194.0. The specificity, standard curve, precision, recovery rate, matrix effect and stability of the method were validated.

The retention times of busulfan and internal standard were 5.1 min and 5.3 min, respectively. The standard curve equation for busulfan in plasma was y=0.06x-0.04 (r=0.998 7), with a linear range of 0.1-10.0 μg·mL^-1. The relative standard deviation (RSD) of intra-day and inter-day precision were less than 10%; The recovery rate was 95.64%-104.49%, and the matrix effect was 100.11%-118.87%. The RSD of the stability of quality control samples after low-temperature storage, three freeze-thaw cycles, or room temperature storage were less than 10%. The average drug exposure of patients undergoing HSCT was (4.99±2.76) μg·mL^-1·h (range 0.66-13.77 μg·mL^-1·h).

The established LC-MS/MS method has short analysis time, good specificity, and high precision, and is suitable for the therapeutic drug monitoring of busulfan in HSCT patients.

To establish a high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method for the simultaneous determination of fluconazole, posaconazole, and linezolid in human cerebrospinal fluid.

Cerebrospinal fluid samples were precipitated with acetonitrile containing internal standard (voriconazole) and separated by Agilent C₁₈ column (2.7 μm, 4.6×150 mm). The mobile phase was 0.1% formic acid aqueous solution acetonitrile, gradient elution, flow rate 0.4 mL·min^-1, column temperature 35 ℃, and injection volume 1μL; The spray ion source, positive ion mode and multi reaction monitoring were used for the determination. The specificity, standard curve, lowerer limit of quantification(LLOQ), precision, accuracy, recovery rate and recovery rate. This method was applied to determine the concentrations of fluconazole, posaconazole, and linezolid in clinical cerebrospinal fluid.

The methodological results showed that fluconazole (0.4-32 μg·mL^-1, r=0.999 6) in cerebrospinal fluid samples, posaconazole (0.04-3.2 μg·mL^-1, r=0.9992) and linezolid (0.2-16 μg·mL^-1, r=0.9989) had a good linear relationship and specificity within the linear range. The LLOQ of, posaconazole, and linezolid was 0.4、0.04 and 0.2 μg·mL^-1, respectively. The relative standard deviation (RSD) values of intra-day and inter-day precision were both less than 15%, with good stability and extraction recovery rates above 80%, unaffected by matrix effects. Additionally, the method exhibited good detection sensitivity for fluconazole, posaconazole, and linezolid in the cerebrospinal fluid of rats and clinical patients. The concentration of the 7 tested sample was within the linear range.

This method is simple, fast, and highly sensitive, and can be used for the determination of cerebrospinal fluid concentrations of fluconazole, posaconazole, and linezolid in clinical patients.

Diabetic kidney disease (DKD) is one of the common microvascular complications of diabetes mellitus. Due to its insidious onset and unclear pathogenesis, DKD is easy to progress to end-stage renal disease. Endoplasmic reticulum is the main site of protein synthesis and processing in the body. When affected by adverse factors of the body, endoplasmic reticulum stress (ERS) will be triggered, resulting in the accumulation of misfolded or unfolded proteins, resulting in imbalance of the internal environment. Studies have shown that ERS is involved in the core pathogenesis of DKD, and the renal tissue lesions caused by DKD can be effectively alleviated by regulating ERS. This article focuses on the experimental studies on the intervention of ERS with traditional Chinese medicine and its compound in the prevention and treatment of DKD, in order to provide new ideas and reference for clinical treatment of DKD.

To explore the value of texture features in magnetic resonance imaging (MRI) for predicting post-stroke cognitive impairment (PSCI) in elderly patients, and to analyze its correlation with the efficacy of PSCI drug therapy, providing a basis for selecting the timing and optimizing clinical drug intervention plans.

A retrospective analysis was conducted on the data of stroke patients admitted from January 2020 to January 2024. The data was divided into a training set (n=160) and a validation set (n=56) according to the data source. Collect PSCI standardized medication treatment data (including cholinesterase inhibitors, memantine, and combination therapy regimens) for all patients from baseline to cognitive assessment. After preprocessing of T1 weighted imaging (T1w) images, texture features were measured in the hippocampus and entorhinal cortex. Patients with high hippocampal kurtosis (≥ 2.5) and low hippocampal kurtosis were grouped and analyzed. A PSCI prediction and efficacy prediction model was constructed and validated based on drug treatment information. As a result, a total of 327 patients were included in this study, including 211 males and 116 females. The accuracy of the prediction model in the training set and validation set is 90% and 77%, respectively; Covariance analysis showed that there were differences (P<0.05) in hippocampal kurtosis, entorhinal cortex kurtosis, and entorhinal cortex deficit anomaly (IDM) between PSCI patients and non PSCI patients. The effective rate of donepezil treatment showed that the group with high hippocampal kurtosis was significantly higher than the group with low kurtosis (76.31% vs. 41.22%, P<0.01); Patients with IDM ≥ 0.4 in the entorhinal cortex showed better efficacy with combination therapy (donepezil+memantine) compared to monotherapy (82.13% vs. 58.28%, P<0.05). After optimizing the model and incorporating drug treatment factors, the validation set AUC increased to 0.82.

Conventional clinical MRI texture features are reliable early predictors of PSCI and are significantly associated with the efficacy of PSCI drug therapy. They can be combined with drug therapy information to construct more accurate prediction and efficacy evaluation models, providing imaging support for individualized drug intervention in PSCI.

This systematic review and Meta-analysis compared the efficacy and safety of dexibuprofen with ibuprofen across diverse clinical settings.

A comprehensive literature search was performed across multiple databases (PubMed, Embase, Web of Science, Scopus, Cochrane Library, and CNKI) to identify all relevant clinical trials comparing dexibuprofen and ibuprofen. Statistical analyses were conducted using RevMan 5.4.

A Meta-analysis incorporating 21 randomized controlled trials demonstrated that dexibuprofen showed no statistically significant differences in efficacy compared to ibuprofen at full-dose (RR=1.02, 95% CI: 0.99-1.05), 70% doses (RR=0.92, 95% CI: 0.72-1.17), or 50% doses (RR=0.99, 95% CI: 0.82-1.19). Subgroup analyses indicated comparable efficacy between dexibuprofen and ibuprofen for both adult analgesia (RR=1.09, 95% CI: 0.97-1.23) and pediatric antipyresis (RR=1.01, 95% CI: 0.98-1.04). Regarding safety, full-dose dexibuprofen showed a lower risk of adverse events compared to ibuprofen (RR=0.76, 95% CI: 0.58-1.00).

Dexibuprofen demonstrates comparable efficacy to ibuprofen, exhibits good dose-sparing characteristics in the fields of analgesia and antipyresis. Furthermore, it exhibits superior safety at equivalent doses, making it suitable for patient populations requiring reduced drug exposure or those at risk of gastrointestinal adverse reactions.

With the release of guidance for adaptive design in clinical trials both domestically and internationally, designing interim analyses in clinical trials has great guiding significance for the success of clinical trials. It not only helps to improve research and development efficiency, but also has important preventive significance for clinical trials that have chosen incorrect statistical methods, resulting in serious issues such as type I error inflation and introduction of bias, which may lead to the failure of clinical trials. This article combines three cases that have occurred in current clinical trials to analyze and summarize the statistical issues related to confirmatory clinical trial interim analyses, promoting a deeper understanding of interim analyses and providing references for the high-quality design, implementation, analysis, and interpretation of results of confirmatory clinical trials..