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.

The purpose of this paper is to investigate the current status of the domestic electronic submission system in relation to the comprehensive lifecycle management of drug registration. We aim to analyze the challenges encountered and propose suggestions for improving China's electronic submission system.

By employing the literature review, this study summarizes and compares the development and current status of the domestic electronic submission system. In light of the actual situation in China, it puts forward targeted suggestions for improvement.

In our country, electronic submisisons are categorized into two forms: electronic common technical document （eCTD） submission and Non-eCTD submission. Currently, we are in a transitional phase where both formats coexist. However, during the implementation process, we still face issues such as non-uniform submission format standards and insufficient capacity of provincial bureaus to receive and review eCTDs. In response to these issues, this paper proposes the following specific measures: ①deepening the reform of eCTD and expanding the implementation range of products. ②Strengthening the effective connection of drug management from market launch to post-market. ③Accelerating the standardization of document submission throughout the entire lifecycle of drugs. Through the implementation of these measures, it is expected to expedite the comprehensive electronic process of drug registration and application in our country, thereby enhancing the efficiency and quality of review and approval.

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 establish and validate a method for determining the plasma concentration of isavuconazole and to apply this method to clinical monitoring of plasma drug concentration.

The plasma samples of isavuconazole were subjected to protein precipitation using methanol. The quantification was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), with stable isotope voriconazole-d4 serving as the internal standard. An Ultimate AQ-C₁₈ chromatographic column was used with a gradient elution of methanol (containing 0.1% formic acid)-water (0.1% formic acid) with a flow rate of 0.3 mL·min^-1. The column temperature was set at 40 ℃ and the injection volume of pretreated sample was 5.0 μL. The ion source was positive electrospray ion source, with multiple reaction monitoring mode for positive ion scanning (MRM⁺). The ion pairs used for quantitative analysis were m/z 438.2→224.1 (isavuconazole) and m/z 354.2→285.1 (voriconazole-d4). After administering a loading dose to five patients, plasma samples were collected on days 4, 5, 6, 12, 13, and 14 post-initiation of treatment to measure the trough concentation of the drug.

The linear range of the isavuconazole detection quality concentration was 0.1~10 μg·mL^-1 (r=0.999 6), with a quantification limit of 0.25 μg·mL^-1. The within-batch precision and between-run precision were not higher than 11.9%, and the relative errors were between -4.83% and 6.20%. The stability relative errors were between -2.04% and 6.89%. The extraction recoveries rates of isavuconazole and voriconazole-d4, as well as the matrix effects and residual effects, do not influence the quantitative analysis of the analytes. All trough concentrations of the samples from the five patients were within the linear range of the method.

The established LC-MS/MS method for assaying of isavuconazole is simple and accurate. It can be used for the clinical monitoring the plasma concentration of isavuconazole in patients with fungal infections.

To evaluate the effect of Multi-Trace Element Injection (I) on postoperative inflammatory indexes in children with appendicitis.

A total of 68 patients who underwent laparoscopic appendectomy for perforated appendicitis in the Department of General Surgery of Fudan University affiliated pediatric hospital from March 2022 to December 2022 were randomly divided into an experimental group and a control group. The experimental group was given Multi-Trace Element Injection (I) at a dosage of 1 mL·kg^-1·d^-1 based on routine anti-infection treatment, with a 7-day treatment course. The control group only received routine anti-infection treatment. The inflammatory indexes, abdominal ultrasound and adverse reactions of children in the two groups were compared on the 4th and 7th day post-surgery.

The comparison of CRP value changes between the experimental and control groups 4 days after surgery showed that the experimental group had a baseline change of -85.2（-123，-48.2）, while the control group had a baseline change of -64.0 （-86.2，-26.5）, and the difference was statistically significant (P<0.05). Compared with preoperative levels, the change in PCT 4 days after surgery was -2.30 (-2.50, -2.0) in the experimental group and -0.880 (-2.50, -0.968) in the control group, with a statistically significant difference (P<0.05). The change in WBC count compared to preoperative levels was -7.52 (-10.7, -4.04) in the experimental group and -4.34 (-7.90, -1.19) in the control group, with no statistically significant difference (P>0.05). The comparison of CRP changes between the experimental and control groups 7 days after surgery showed that the experimental group had a baseline change of -125 (-135, -61.2), and the control group had a baseline change of -104 (-149, -76.2), with no statistically significant difference (P>0.05). The change in PCT compared to preoperative levels was -2.79 (-5.41, -1.05) in the experimental group and -1.71 (-4.08, -0.435) in the control group, with no statistically significant difference (P>0.05). The change in WBC count compared to preoperative levels was (-6.63±5.55) in the experimental group and (-6.41±6.64) in the control group, with no statistically significant difference (P>0.05). Covariate analysis showed that after controlling for the status of Multi-Trace Element Injection (I), the experimental group was significantly better than the control group in reducing CRP, PCT and WBC count (P<0.05). This indicates that Multi-Trace Element Injection (I) has a significant effect on reducing inflammation. The effect of the experimental group remained significant under the control of these covariates. There was no statistically significant difference in the incidence of adverse reactions, abdominal ultrasound findings and hospitalization days between the two groups of children (P>0.05).

The application of Multi-Trace Element Injection (I) after laparoscopic appendectomy is safe and effective, and can further reduce postoperative inflammation in children and promote infection improvement.

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 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 screen the anti-inflammatory and anti-swelling active fraction of Stellera chamaejasme Daphne odora, and to preliminarily explore its pharmacodynamics and mechanism of action.

The toe swelling model was established in SD rats. The toe swelling, serum inflammatory factors and superoxide dismutase (SOD) activity were detected by daubing different extracts of Daphne odora chamaejasme and its ointment.

The water extract and ethanol precipitation of the drug had better anti-inflammatory and detumescence effect. The content was objective and the extraction process was simple. The 80% ethanol extract showed good anti-inflammatory and detumescence activity, but the drug activity was not as good as the former extract. Two types of extracts were formulated into an ointment for the aforementioned model experiments. The results indicated that, compared to the model group, the ointment significantly inhibited the swelling degree of inflammatory paw edema induced by carrageenan in rats. The serum samples of the experimental animals were analyzed for IL-1β and other inflammatory factors. Compared with the model group, the anti-inflammatory effect of the ointment was supported by IL-1β levels and the observations from tissue pathology sections. The activity of SOD was increased.

Extract A and extract B are the effective parts of anti-inflammation and anti-swelling of Stellera chamaejasme Daphne odora.

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.

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 systematically evaluate the efficacy and safety of ferrous succinate tablets in the treatment of iron deficiency anemia during pregnancy.

Retrieved from PubMed, Embase, Cochrane Library, CNKI, Wanfang, randomized controlled trials (RCTs) about ferrous succinate versus polysaccharide iron complex capsules and ferrous sulfate tablets in the treatment of anemia during pregnancy and different dosage forms of ferrous succinate tablets for the treatment of iron-deficiency anemia in pregnancy were collected from January 2016 to April 2024. Meta-analysis was performed using RevMan 5.3 and Stata 17.0 software.

A total of 47 RCTs were retrieved with 6 655 patients. Results of meta-analysis showed that ferrous succinate tablets were significantly better than ferrous sulfate tablets in terms of overall efficacy [OR=4.65, 95%CI (3.68,5.88), P<0.000 01] and incidence of adverse reactions (P<0.05). There was no statistical significance in total response rate [OR=1.47，95％CI (0.45，4.79)，P=0.52] and specific adverse effect rates (P>0.05) between ferrous succinate tablets and polysaccharide iron complex capsules. The overall effectiveness and total incidence of adverse drug reactions in ferrous succinate sustained-release tablets were significantly better than that of ferrous succinate film-coated tablets.

The efficacy and safety of ferrous succinate tablets in treating iron deficiency anemia in pregnancy are both good.

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.