To evaluate the safety and tolerance of a single administration versus multiple administrations of recombinant human parathyroid hormone 1-84 (PTH1-84) for injection in Chinese healthy volunteers, as well as to observe the pharmacokinetic characteristics in health individuals following drug administration.

A single center, open, single administration/multiple administration trial was designed. The healthy subjects were divided into four dose groups: 25, 50, 75 and 100 μg, in which the 25 μg dose group was only given at a single dose, and the other three dose groups continued to conduct continuous administration after a single dose. The physical signs of the subjects were recorded, and the biological samples were collected at the time specified in the scheme to calculate and analyze the pharmacokinetic parameters. The safety of different doses of recombinant PTH1-84 was evaluated by the pharmacokinetic parameters of healthy subjects and the occurrence of adverse reactions.

A total of 28 healthy subjects were included in the study, with 4 participants in the 25 μg dosage group and 8 participants in each of the remaining three groups. In the safety evaluation, no correlation between the incidence of adverse events and dosages was observed, and no serious adverse events occurred. The reported adverse reactions resolved favorably. The pharmacokinetic results indicate that recombinant human parathyroid hormone 1-84, within the dosage range of 50 to 100 μg, demonstrates a dose-dependent relationship for both AUC and C_max following single and multiple administrations. This suggests a positive correlation between drug exposure and dosage.

PTH1-84 has good clinical safety and tolerance at the experimental dose.

To analyze the characteristics and patterns of myocarditis associated with immune checkpoint inhibitors (ICIs) in China, providing a reference for rational clinical drug dosing.

Authors conducted a comprehensive search of CNKI, Wanfang, VIP, as well as PubMed and Web of Science to collect case reports of myocarditis caused by ICIs in China (up to June 2024). Data were extracted and analyzed accordingly.

A total of 143 cases in 132 literatures were includedin this study. The median age of patients was 66 years old, and the primary disease was lung cancer in the majority (28.67%). The onset time of myocarditis was 83.92% within 90 days of the first medication, with the median time of 24 days. The first symptoms of myocarditis were mainly chest tightness, shortness of breath, palpitation (59.44%) and fatigue (37.76%). Manifestations of myocarditis related cardiovascular adverse events were tachyarrhythmia (35.66%), bradyarrhythmia (19.58%), heart failure (12.59%), acute coronary syndrome (4.90%) and cardiogenic shock (4.90%). 15 (10.49%) patients died of myocarditis.

Myocarditis caused by ICIs in China mainly occurs in the early stage of immunotherapy, with the first symptoms mainly chest tightness, shortness of breath, palpitations and fatigue. During ICIs dosing, monitoring should be strengthened to identify myocarditis related cardiovascular events in time to ensure the safety of drug dosing.

To mine the security alert signals of risk signals of adverse drug events (ADEs) associated with post-marketing use of avacopan based on the FDA Adverse Event Reporting System (FAERS) database. The findings are intended to provide a reference for clinical safety in medication practices.

The study collected ADE reports related to Apixaban from the FAERS database for the period of Q4 2021 to Q2 2024. Potential safety signals associated with Apixaban were identified using various methodologies, including reporting odds ratio (ROR), proportional reporting ratio (PRR), bayesian confidence propagation neural network (BCPNN), and multi-item gamma poisson shrinker (MGPS). Weber distribution test was used to determine the occurrence rule of ADE. The reporting odds ratio was used to estimate the relative risk of arvaracopam ADE in different genders.

A total of 6 519 ADE reports involving 2 730 patients with avacopan as the primary suspected drug were collected, and 75 avacopan ADE signals were mined involving 15 systems. ADE occurs mostly within 30 days after administration of avacopan. Consistent with the description in the package insert, ADEs of hepatobiliary system, infection and infection system were commonly observed. In addition, ADEs such as epistaxis, pulmonary hemorrhage, pharyngeal swelling and deep vein thrombosis were not included in the package insert. The analysis of gender differences in the risk signals associated with arvalacopam revealed that female patients were more susceptible to conditions such as jaundice, pulmonary vasculitis, esophageal candidiasis, cheilitis, Escherichia coli urinary tract infection, etc. In contrast, male patients were more likely to have dental hypersensitivity, pulmonary hemorrhage, elevated serum ferritin, and cardiac pacemaker implantation.

In the real-world application of avacopan, it is essential to focus on the ADE related to the hepatobiliary system, respiratory system, thoracic and mediastinal systems, as well as infectious conditions. Additionally, appropriate strategies should be implemented based on gender differences to mitigate the occurrence of ADEs.

An HPLC-MS/MS method was established for the simultaneous determination of 15 components [betaine, agaritol, bergamolide, 2-(2-phenylidene) chromone, dehydrodiisoeugenol, D-(-)-quinic acid, gallic acid, protocatechuic acid, hydroxysafflor yellow A, rutin, isoquercetin, ellagic acid, luteolin and apigenin] in Qingxin Chenxiang Bawei powder (pills). The quantitative method, combined with chemometrics and entropy weight-grey correlation degree method to analyze the comprehensive quality, provides a reference for the quality control and evaluation of this preparation.

The analysis was conducted using a Shim-pack GIST-HP C₁₈ chromatographic column, with the mobile phase consisting of methanol (A) and a 0,1% formic acid aqueous solution (B). A gradient elution was employed at a column temperature of 35 ℃, with an injection column of 3 μL. Weisenxin platform was used for cluster analysis (CA), SIMCA 14.1 software was used for principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), and the compounds with variable important in projection (VIP) value greater than 1.0 were used as the criterion to screen quality differences. The entropy weight-correlation degree method was used to analyze the comprehensive quality.

The linear relationship of the 15 components was good in their respective ranges, and the linear correlation r was greater than or equal 0.999 0. Precision RSD were all lower than 3.00%. The stability and repeatability were good, RSD lower than 5.00%; The average recoveries were 93.62%~105.10%, and RSD was 1.18%~4.37%. CA and PCA analysis classified 14 batches of Qingxin Chenxiang Bawei powder (pills) into 2 categories: manufacturers D (D1~D4) were grouped into one group, manufacturers A and M (A1~A4, M1~M6) were grouped into one group. Six difference markers were screened in OPLS-DA mode, which were D-(-)-quinic acid, agaritol, 2-(2-phenylethyl) chromone, dehydrodiisoeugenol, bergamolactone and quercetin, respectively. A2 has the best comprehensive quality.

The established HPLC-MS/MS method for the simultaneous determination of 15 components in Qingxin Chenxiang Bawei powder (pill) can be used for the comprehensive quality study of Qingxin Chenxiang Bawei powder (pill) combined with chemometrics and entropy weight correlation degree method.

To set up the quality standards of Reyihan granules.

The identification items for Ocimi basilici Fructus, Roses rugosae Flos, Nardostachyos radlx Et Rhizoma, and Foeniculi fructus were established using TLC. The characteristic chromatogram was established, and the contents of gallic acid and rosmarinic acid in Reyihan granules were determined using HPLC.

The TLC identification method for Ocimi basilici Fructus, Roses rugosae Flos, Nardostachyos radlx Et Rhizoma, Foeniculi fructus had clear spots, with no interference from negative controls. There were 35 characteristic peaks in the HPLC characteristic chromatogram of Reyihan granules. Through comparison with reference standards, 13 compounds were identified. Gallic acid showed a good linear relationship within the range of 1.303 2~13.032 0 μg·mL^-1 (r=0.999 7), with an average recovery rate of 97.23% and an RSD of 1.20% (n=6). Rosmarinic acid showed a good linear relationship within the range of 2.462 4~24.624 0 μg·mL^-1 (r=0.999 3), with an average recovery rate of 102.79% and RSD of 1.10% (n=6).

This method has strong specificity, good repeatability and stability, and can achieve quality control of Reyihan granules.

To establish the 14th batch of national reference standards for histamine phosphate.

Histamine phosphate was identified using infrared spectroscopy and bioactivity assay. Its hygroscopicity, moisture content, and uniformity were also examined. Using the 13th batch of national reference standard for histamine phosphate as the standard, 4 laboratories were selected to conduct collaborative calibration of the potency of the reference standard using the cat blood pressure method.

The final combined potency of this batch of standard products was determined to be 97.8%.

This batch of reference materials can be used as the 14th batch of national reference materials for histamine phosphate, with a relative potency set at 100%, batch numbers 150510-202214.

To investigate the intestinal absorption characteristics of harmine derivative H-2-168 using Caco-2 cells model and in situ single-pass intestinal perfusion method.

The Caco-2 cell monolayer model and in situ single pass intestinal perfusion model of rat were established. The concentrations of H-2-168 in cell permeation fluid and intestinal perfusion fluid were determined by HPLC. The changes of apparent permeability coefficient (P_app) of H-2-168 in Caco-2 cell model and those of absorption rate constant (K_a) and P_app in in situ single pass intestinal perfusion model of rat under different influence factors (intestinal segment, concentration, pH and P-glycoprotein inhibitor) were investigated.

In Caco-2 cell model, P_app values at medium and high concentrations of H-2-168 were significantly higher than that at low concentration (P<0.05), but P_app at high concentration was slightly lower than that at medium concentration, showing a high concentration saturation phenomenon. H-2-168 was absorbed in the whole intestine of rats, with K_a and P_app decreased significantly with the increase of drug concentration (P<0.05). K_a and P_app at pH 7.4 were significantly higher than those at pH 5.4. There were no significant changes in the absorption parameters before and after the addition of P-glycoprotein inhibitor (P>0.05).

H-2-168 is a well-absorbed drug, and its absorption mechanism may involve active transport or facilitated diffusion, and it is not a substrate of P-glycoprotein.

To introduce the concepts and tools of risk management in the production process of traditional Chinese medicine preparations.

The differences between the productions of traditional Chinese medicine preparations and chemical drugs were studied. Combined with the characteristics of risk management and control, a match was made. Quality risk management tools such as fishbone diagrams, hazard analysis and critical control points (HACCP), as well as failure mode and effects analysis (FMEA) were used. Taking a certain traditional Chinese medicine preparation production enterprise as an example, quality risk management was carried out on the traditional Chinese medicine preparations it produced.

Through the introduction of the risk management model, the quality control of the entire production process of traditional Chinese medicine preparations has become clearer, enabling the identification of potential hazards in various aspects on a wide scale, thus improving the quality and safety level of traditional Chinese medicine preparations.

The production and quality control of traditional Chinese medicine preparations with the concept and tools of risk management has comparative advantages and is worth popularizing.