To evaluate the possibility of hepatitis B reactivation in patients with hepatitis B infection-associated rheumatoid arthritis who were treated with TNF inhibitors.

Literature search method and inclusion and exclusion criteria were established, then the databases were searched, literature meeting inclusion criteria were collected, and relevant data was extracted for analysis.

A total of 14 studies involving 534 HBV-related rheumatoid arthritis patients were included. The overall comprehensive hepatitis B reactivation rate was 0.017 5 [95%CI: 0.005 4, 0.034 0], I²=67%, P<0.01. In the subgroup analysis, the reactivation rate of hepatitis B using glucocorticoids was 0.067 6 [95%CI: 0.039 6, 0.101 2], I²=89%, P<0.01. The reactivation rate of hepatitis B without glucocorticoids was 0.045 7 [95%CI: 0.016 4, 0.084 6], I²=69%, P<0.01.

The employment of TNF inhibitors in patients with HBV-related rheumatoid arthritis had a certain rate of hepatitis B reactivation. In the subgroup analysis, the rate of hepatitis B reactivation in the target population showed a distinct regional distribution, and the rate of hepatitis B reactivation in the glucocorticoid-using subgroup was higher than that in the glucocorticoid-not subgroup.

Carboxymethyl starch sodium is the most commonly used superdisintegrant, and the degree of substitution and crosslinking density are the important quality attributes that affect its water swellability and disintegration performance. By exploring the correlation between degree of substitution, crosslinking density, and water swellability, this study aims to provide a theoretical reference for the production of disintegrant with excellent performance.

Seventeen batches of carboxymethyl starch sodium were collected. Low-field nuclear magnetic resonance technique was used to determine the crosslink density values. And the degree of substitution and water swellability value were determined by physical-chemical method. The correlation between crosslinking density, degree of substitution and water swellability was investigated by Pearson correlation.

There were significant differences in the attribute values of products from different sources. The crosslinking density was significantly negatively correlated with the degree of substitution and water swellability, and the correlation coefficients were -0.814 and -0.854. The degree of substitution was significantly positively correlated with the water swellability, and the correlation coefficient was 0.823.

The crosslinking density and the degree of substitution are the critical quality attributes that affect the disintegration of carboxymethyl starch sodium. Understanding the disintegration behavior of disintegrants is of great significance for the development of pharmaceutical solid preparations. Clarifying the relationship between the disintegration characteristics of carboxymethyl starch sodium and crosslinking density and degree of substitution will help to select the correct disintegrant for a given formulation.

To observe the adverse reactions of thalidomide in the reproductive system, such as menstrual disorders and ovarian reserve function, in women of childbearing age with rheumatic immune diseases and provide references for the safety of clinical medication.

A retrospective analysis was conducted on female patients aged 18~45 years with complete data who visited the Rheumatology and Immunology Department of the First Affiliated Hospital of Nanchang University and received thalidomide treatment from January 2018 to June 2023. The occurrence of menstrual disorders and levels of anti-Müllerian hormone (AMH) during thalidomide use were observed to analyze the potential adverse effects on reproductive system function and risk factors.

A total of 214 patients were included, with an average age of (34.81±6.45) years. The dosage of thalidomide ranged from 25 to 75 mg·d^-1, with a cumulative dose ranging from 750 to 81 000 mg. The treatment duration ranged from 1 to 36 months. The rate of menstrual cycle disorders in women of childbearing age during thalidomide use was as high as 79.59%, with a rate of amenorrhea of 18.37%. Univariate analysis showed a significant correlation between cumulative dose, treatment duration, and decreased AMH levels (P<0.05). The menstrual recovery rate after discontinuation of thalidomide was 62.5% in patients with AMH ≤ 2 ng·mL^-1, while it was 100% in patients with AMH>2 ng·mL^-1. The menstrual recovery time for both groups was within 1~2 months. Pearson correlation analysis showed a negative linear correlation between AMH and daily dose of thalidomide (r=-0.522, P<0.05), cumulative dose (r=-0.807, P<0.05), and treatment duration (r=-0.761, P<0.05). Cox regression analysis showed that a cumulative dose of thalidomide >9 g was an independent risk factor for adverse events in the reproductive system (HR=19.014, P<0.001).

The incidence of menstrual disorders and decreased ovarian reserve function is high in women of childbearing age using thalidomide. Therefore, the reproductive risks should be evaluated, and ovarian reserve function should be monitored to prevent ovarian dysfunction leading to amenorrhea and affecting fertility and quality of life.

To establish an analytical method for determination of the content and dissolution of aprepitant, prepare aprepitant solid dispersion by three different preparation methods (hot-melt extrusion, solvent-melt method and spray drying method), and investigate the effects of different processes on the physical stability of the solid dispersions.

The effects of different preparation processes on the stability of aprepitant solid dispersions were measured in terms of water content, moisture attraction, residual microcrystals, aprepitant content, related impurities, and in vitro release.

Among the three different processes, the aprepitant solid dispersion prepared by hot-melt extrusion had low water content, poor moisture attraction, drug in amorphous form, good in vitro dissolution behavior, able to dissolve and release in acid solution, resistant to crystallization and precipitation behavior due to pH change and maintained high supersaturation after transit to the intestine.

Hot-melt extrusion is the optimal preparation method for solid dispersions composed of crystallization inhibitor HPMCAS and dissolution enhancer PVP K30.

To study the development process, current situation and specific requirements of drug registration based on e-CTD format in the United States, and to provide some reference for the construction of e-CTD channel for drug registration in China.

A literature review was used to review the regulatory process of e-CTD implementation in the United States, and the data of e-CTD application and total electronic data application were compared and analyzed. To explore the similarities and differences between the traditional registration declaration format and e-CTD format in terms of organization, data requirements, application process and data review, the specific changes were analyzed.

In the process of e-CTD implementation, the United States improved and optimized the submission process and approval process by constantly issuing technical guidelines and paid attention to the training of technical personnel and protected data security. On the one hand, it is suggested that Chinese regulatory agencies improve the guidelines for drug registration application based on e-CTD format as soon as possible, increase policy support such as priority review and approval, and strengthen e-CTD knowledge training for registration personnel in enterprises and review centers. On the other hand, strengthen e-CTD knowledge training for registered personal of enterprises and agencies, enterprises should change their research and development ideas, carry out the QbD concept, formulate a registration operation team suitable for their own development needs, and actively participate in international drug registration to accumulate experience in order to promote the application of e-CTD in enterprises

HPLC was used to establish the methods for the determination of harmaline (HM) and the derivative 9-butyl-1-methyl-N-(2-hydroxy) ethyl-β- carboline-3-formamide (No.: H-2-104) in rat blood samples in order to evaluate repeated dosing toxicokinetics (TK).

The Wistar rats were randomly divided into HM low, medium, and high-dose groups and H-2-104 low, medium, and high-dose groups (35, 70, 140 mg·kg^-1) with eight rats in each group. Repeated dosing toxicity experiments were conducted to investigate the toxicokinetic profile of HM and H-2-104 in rats 28 days after the first dose to the end of administration and the kinetic parameters were calculated.

Both HM and derivative H-2-104 could be detected with good linearity in the range of 66.67~500 ng·mL^-1. The specialized properties, accuracy, precision, extraction recovery, and stability of the proposed method were in accordance with the requirements for the determination of biological samples. After the administration of HM, the C_max and AUC_0-t in rats were (301.78±67.24) ng·mL^-1, (234.18±98.35) ng·mL^-1 (low concentration); (478.65±99.74) ng·mL^-1, (710.03±208.93) ng·mL^-1 (medium concentration); (721.51±107.52) ng·mL^-1, (819.61±310.54) ng·mL^-1 (high concentration). After the administration of H-2-104, the C_max and AUC_0-t in rats were (234.84±102.03) ng·mL^-1, (198.67±38.88) ng·mL^-1 (low concentration); (298.73±87.52), (676.55±210.83) ng·mL^-1 (medium concentration); (411.81±123.71), (1 004.86±426.05) ng·mL^-1 (high concentration). After administration, T_max of the two compounds was shorter and both drugs were eliminated within 4 hours.

The first and last C_max and AUC_0-t of HM and derivative H-2-104 at each dose increased disproportionately with dose and were positively correlated with dose, exhibiting nonlinear kinetics. This study provides preliminary elucidation of the in vivo toxicokinetic behavior of HM and derivative H-2-104 in rats, and the experimental results provide support and reference for their subsequent studies.

The chemical pattern recognition technology was used to analyze the HPLC characteristic fingerprints data of Poria, screen the differential quality markers and perform quantitative analysis, so as to provide scientific basis for quality evaluation of Poria.

Welch Ultimate Plus C₁₈ chromatographic column (250 mm×4.6 mm, 5 μm) was used. Acetonitrile (containing 0.2% tetrahydrofuran)-0.1% phosphoric acid aqueous solution with gradient elution was used as mobile phase. The fingerprint of Poria was established with detection wavelength set at 222 nm, flow rate at 1 mL·min^-1, column temperature at 30 ℃, injection volume at 10 μL. The differential quality markers were identified by similarity analysis, principal component analysis (PCA), cluster analysis (CA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). The quantitative research was carried out in accordance with the requirements of "Guidelines for Validation of Analytical Methods" in Chinese Pharmacopoeia.

The similarity of 15 batches of Poria was between 0.935~0.998. Eight common peaks were calibrated and 6 were identified; The samples were classified according to the origins from PAC results, which is consistent with CA result. Pachymic acid was screened as the differential quality marker of Poria by OPLS-DA. The established method for the determination of pachymic acid was stable, reliable, durable, which meets the requirements of the Pharmacopoeia.

The methods of characteristic fingerprint combined with chemical pattern recognition technology can effectively screen the differential quality marker of Poria from different regions, providing a reference for the establishment of quality standards for Poria.