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 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.

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.

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.

Different levels of genotoxic impurities 1-methyl-4-nitroso piperazine (MNP) and 1-methyl-4-nitroso piperazine (CPNP) were detected in rifampicin and rifapentine capsules. In this study, the nitrite ions in rifampicin and rifapentine capsules were determined by solid phase extraction-ion chromatography to explore the relationship between the content of nitrite ions and the formation of above genotoxic impurities.

The method of solid phase extraction-ion chromatography used for nitrite determination was established and validated.

Nitrite ion was not detected in rifampicin and rifapentine capsules with different levels of MNP and CPNP.

It is speculated that the origin of MNP and CPNP in rifampin and rifapentine capsules was not from nitrite ion, but derived from oxidative degradation of API.