Objective:To establish ICP-MS method for determining the Class 1 and Class 2A elemental impurities in pharmaceutical excipients polysorbates according to ICH Q3D(R2)Guidelines.Class 1 elemental impurities include As,Cd,Hg and Pb;Class 2A elemental impurities include Co,Ni and V.Methods:The analysis was performed using ICP-MS with the following parameters.Plasma mode:HMI-8,carrier gas:He,sampling depth:10.0 mm.RF power:1 600 W,the carrier gas flow,the nebulizer gas flow and the auxiliary gas flow were all 0.8 L·min-1.The plasma gas flow was 15.0 L·min-1.The speed of nebulizer pump was0.10 r·min-1.The temperature of atomizer chamber was 2.0℃.Analytical method:internal standard method.Results:The correla-tion coefficient for all elemental impurities was not less than 0.999.Spiked recoveries ranged between 85%-115.0%,with RSD is not more than 5.0%.The RSD of precision rate was not more than 10.0%.The contents of 7 elemental impurities in 15 batches of the samples were all less than PDE for injection set by ICH Q3D(R2)guidelines.Conclusion:The developed ICP-MS method demonstrates high sensitivity,good precision,and accuracy,making it suitable for controlling the Class 1 and Class 2A elemental impurities in polysorbate pharma-ceutical excipients.The results shows low risks of elemental impurities in commercial pharmaceutical excipients polysorbates.

Objective:To establish ICP-MS method for determining the Class 1 and Class 2A elemental impurities in pharmaceutical excipients polysorbates according to ICH Q3D(R2)Guidelines.Class 1 elemental impurities include As,Cd,Hg and Pb;Class 2A elemental impurities include Co,Ni and V.Methods:The analysis was performed using ICP-MS with the following parameters.Plasma mode:HMI-8,carrier gas:He,sampling depth:10.0 mm.RF power:1 600 W,the carrier gas flow,the nebulizer gas flow and the auxiliary gas flow were all 0.8 L·min-1.The plasma gas flow was 15.0 L·min-1.The speed of nebulizer pump was0.10 r·min-1.The temperature of atomizer chamber was 2.0℃.Analytical method:internal standard method.Results:The correla-tion coefficient for all elemental impurities was not less than 0.999.Spiked recoveries ranged between 85%-115.0%,with RSD is not more than 5.0%.The RSD of precision rate was not more than 10.0%.The contents of 7 elemental impurities in 15 batches of the samples were all less than PDE for injection set by ICH Q3D(R2)guidelines.Conclusion:The developed ICP-MS method demonstrates high sensitivity,good precision,and accuracy,making it suitable for controlling the Class 1 and Class 2A elemental impurities in polysorbate pharma-ceutical excipients.The results shows low risks of elemental impurities in commercial pharmaceutical excipients polysorbates.

Objective Taking the medicinal excipient pectin as an example,based on the ICH Q3C risk assessment and management concept,this paper explores the control standards for residual solvents in pectin in the variety text of the Chinese Pharmacopoeia.Methods Pectin products from different processes and manufacturers were analyzed,the types of solvent residues in pectin were identified,and the solvent residues of products from different manufacturers were analyzed by gas chromatography.Results According to the product process,there was a risk of residual methanol(class 2),ethanol and isopropanol(class 3)in pectin products.In 18 batches of samples,the residual amount of methanol was measured in the range of 0.05％-0.17％,the residual amount of ethanol was in the range of 0.01％-0.38％,isopropanol was not detected,and the total amount of residual solvents was in the range of 0.07％-0.55％.Conclusions It is suggested that the residual solvent inspection item may not be listed separately in the main text of the pectin standard of the Chinese Pharmacopoeia.It is recommended that the manufacturer is required to indicate the name and limit of residual solvents under the labeling item of the standard.

Objective Exploring the ideas for coordinating the implementation of residual solvent control and ICH Q3C in the Chinese Pharmacopoeia standards for pharmaceutical excipients.Methods The relevant situation of residual solvent control in the current pharmaceutical excipient standards in Chinese pharmacopoeia was analyzed,and the progress of the International Conference on Harmonistion of Human Drug Registration Technology's Guidelines for Residual Solvents(ICH Q3C)and the coordination of foreign pharmacopoeias were compared and were analyzed.Results Proposed a coordination and implementation strategy between the Chinese Pharmacopoeia pharmaceutical excipient standards and ICH Q3C based on the association review mechanism.Conclusions The proposed coordinated implementation plan helps to improve the international integration of Chinese pharmaceutical excipient standard system,enhance the scientific and effective control of residual solvents in pharmaceutical excipients by regulatory authorities and the pharmaceutical industry,and comprehensively promote the translation and implementation of ICH Q3C guiding principles in Chinese pharmaceutical excipient standards.

Objective Taking the medicinal excipient pectin as an example,based on the ICH Q3C risk assessment and management concept,this paper explores the control standards for residual solvents in pectin in the variety text of the Chinese Pharmacopoeia.Methods Pectin products from different processes and manufacturers were analyzed,the types of solvent residues in pectin were identified,and the solvent residues of products from different manufacturers were analyzed by gas chromatography.Results According to the product process,there was a risk of residual methanol(class 2),ethanol and isopropanol(class 3)in pectin products.In 18 batches of samples,the residual amount of methanol was measured in the range of 0.05％-0.17％,the residual amount of ethanol was in the range of 0.01％-0.38％,isopropanol was not detected,and the total amount of residual solvents was in the range of 0.07％-0.55％.Conclusions It is suggested that the residual solvent inspection item may not be listed separately in the main text of the pectin standard of the Chinese Pharmacopoeia.It is recommended that the manufacturer is required to indicate the name and limit of residual solvents under the labeling item of the standard.

Objective Exploring the ideas for coordinating the implementation of residual solvent control and ICH Q3C in the Chinese Pharmacopoeia standards for pharmaceutical excipients.Methods The relevant situation of residual solvent control in the current pharmaceutical excipient standards in Chinese pharmacopoeia was analyzed,and the progress of the International Conference on Harmonistion of Human Drug Registration Technology's Guidelines for Residual Solvents(ICH Q3C)and the coordination of foreign pharmacopoeias were compared and were analyzed.Results Proposed a coordination and implementation strategy between the Chinese Pharmacopoeia pharmaceutical excipient standards and ICH Q3C based on the association review mechanism.Conclusions The proposed coordinated implementation plan helps to improve the international integration of Chinese pharmaceutical excipient standard system,enhance the scientific and effective control of residual solvents in pharmaceutical excipients by regulatory authorities and the pharmaceutical industry,and comprehensively promote the translation and implementation of ICH Q3C guiding principles in Chinese pharmaceutical excipient standards.

Objective: Cardiac magnetic resonance (CMR) is a diagnostic tool that provides precise and reproducible information about cardiac structure, function, and tissue characterization, aiding in the monitoring of chemotherapy response in patients with lightchain cardiac amyloidosis (AL-CA). This study aimed to evaluate the feasibility of CMR in monitoring responses to chemotherapy in patients with AL-CA. Materials and Methods: In this prospective study, we enrolled 111 patients with AL-CA (50.5% male; median age, 54 [interquartile range, 49–63] years). Patients underwent longitudinal monitoring using biomarkers and CMR imaging. At followup after chemotherapy, patients were categorized into superior and inferior response groups based on their hematological and cardiac laboratory responses to chemotherapy. Changes in CMR findings across therapies and differences between response groups were analyzed. Results: Following chemotherapy (before vs. after), there were significant increases in myocardial T2 (43.6 ± 3.5 ms vs. 44.6 ± 4.1 ms; P = 0.008), recovery in right ventricular (RV) longitudinal strain (median of -9.6% vs. -11.7%; P = 0.031), and decrease in RV extracellular volume fraction (ECV) (median of 53.9% vs. 51.6%; P = 0.048). These changes were more pronounced in the superior-response group. Patients with superior cardiac laboratory response showed significantly greater reductions in RV ECV (-2.9% [interquartile range, -8.7%–1.1%] vs. 1.7% [-5.5%–7.1%]; P = 0.017) and left ventricular ECV (-2.0% [-6.0%–1.3%] vs. 2.0% [-3.0%–5.0%]; P = 0.01) compared with those with inferior response. Conclusion Cardiac amyloid deposition can regress following chemotherapy in patients with AL-CA, particularly showing more prominent regression, possibly earlier, in the RV. CMR emerges as an effective tool for monitoring associated tissue characteristics and ventricular functional recovery in patients with AL-CA undergoing chemotherapy, thereby supporting its utility in treatment response assessment.

Objective:To determine the erythromycin resistance of Bordetella pertussis isolates and their ptxP1 and ptxP3 phenotypic composition and compare clinical manifestations of children with pertussis caused by the two types of strains. Methods:This was a cross-sectional study, the pertussis cases diagnosed using bacterial culture from January 2019 to December 2022 in Beijing Children′s Hospital and the First People′s Hospital of Wuhu were collected.Any suspected Bordetella pertussis colonies were identified by the slide agglutination test.The susceptibility of isolates to erythromycin was detected by the E-test and K-B test.The ptxP gene was amplified by polymerase chain reaction and sequenced to determine its genotype. t-test, Mann-Whitney U-test, Chi-square test and Fisher′s exact test were use to statistical analysis. Results:A total of 192 strains of Bordetella pertussis were identified, including 188 (97.9%) erythromycin-resistant strains.Among the 188 strains, 30.3%(57/188) belonged to the ptxP1 genotype and 69.7%(131/188) belonged to the ptxP3 genotype.In children aged below 1 year old, the incidence of paroxysmal cough caused by infection with the ptxP3 strain was higher than that with the ptxP1 strain (57.1% vs.29.4%, P<0.05), and children infected with the ptxP3 strain were more likely to develop apnea or asphyxia (23.8% vs.17.6%), post-tussive vomiting (44.4% vs.32.4%), whooping cough (72.0% vs.50.0%) and pneumonia or bronchitis (85.7% vs.73.5%) compared to those infected with the ptxP1 strain, but the differences were not statistically significant(all P>0.05). In children aged 1 year old and above, the white blood cell count of children infected with the ptxP1 strain was higher than that of infections with the ptxP3 strain [13.5(9.9, 24.5)×10 9/L, 10.3 (7.0, 16.4)×10 9/L, P<0.05], and children infected with the ptxP1 strain were more likely to contract other pathogen infections than those infected with the ptxP3 strain (17.4% vs.4.4%, P>0.05). Conclusions:ptxP3 erythromycin-resistant Bordetella pertussis has become the main pathogen of pertussis.Infants with pertussis caused by the ptxP3 erythromycin-resistant strain show more significant manifestations and a higher possibility of severe symptoms than those infected with the ptxP1 erythromycin-resistant strain.

ObjectiveTo investigate the therapeutic effect of Baihe Wuyaotang （BWT） on non-alcoholic fatty liver disease （NAFLD） and elucidate its underlying mechanism. MethodC57BL/6J mice were randomly assigned to six groups： normal control， model， positive drug （pioglitazone hydrochloride 1.95×10^-3 g·kg^-1）， and low-， medium-， and high-dose BWT （1.3，2.5 and 5.1 g·kg^-1）. Following a 12-week high-fat diet （HFD） inducement， the mice underwent six weeks of therapeutic intervention with twice-daily drug administration. Body weight was monitored weekly throughout the treatment period. At the fifth week， glucose tolerance （GTT） and insulin tolerance （ITT） tests were conducted. Subsequently， the mice were euthanized for the collection of liver tissue and serum， and the subcutaneous adipose tissue （iWAT） and epididymal adipose tissue （eWAT） were weighed. Serum levels of total triglycerides （TG） and liver function indicators，such as alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， were determined. Histological examinations， including oil red O staining， hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy， were performed to evaluate hepatic lipid deposition， pathological morphology， and ultrastructural changes， respectively. Meanwhile， Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were employed to analyze alterations， at both gene and protein levels， the insulin signaling pathway molecules， including insulin receptor substrate 1/2/protein kinase B/forkhead box gene O1 （IRS1/2/Akt/FoxO1）， glycogen synthesis enzymes phosphoenolpyruvate carboxy kinase （Pepck） and glucose-6-phosphatase （G6Pase）， lipid metabolism-related genes stearoyl-coA desaturase-1 （SCD-1） and carnitine palmitoyltransferase-1 （CPT-1）， fibrosis-associated molecules α-smooth muscle actin （α-SMA）， type Ⅰ collagen （CollagenⅠ）， and the fibrosis canonical signaling pathway transforming growth factor-β₁/drosophila mothers against decapentaplegic protein2/3（TGF-β₁/p-Smad/Smad2/3）， inflammatory factors such as interleukin（IL）-6， IL-8， IL-11， and IL-1β， autophagy markers LC3B Ⅱ/Ⅰ and p62/SQSTM1， and the expression of mammalian target of rapamycin （mTOR）. ResultCompared with the model group， BWT reduced the body weight and liver weight of NAFLD mice（P<0.05， P<0.01）， inhibited liver lipid accumulation， and reduced the weight of white fat： it reduced the weight of eWAT and iWAT（P<0.05， P<0.01） as well as the serum TG content（P<0.05， P<0.01）. BWT improved the liver function as reflected by the reduced ALT and AST content（P<0.05， P<0.01）. It improved liver insulin resistance by upregulating IRS2， p-Akt/Akt， p-FoxO1/FoxO1 expressions（P<0.05）. Besides， it improved glucose and lipid metabolism disorders： it reduced fasting blood glucose and postprandial blood glucose（P<0.05， P<0.01）， improved GTT and ITT（P<0.05， P<0.01）， reduced the expression of Pepck， G6Pase， and SCD-1（P<0.01）， and increased the expression of CPT-1（P<0.01）. The expressions of α-SMA， Collagen1， and TGF-β₁ proteins were down-regulated（P<0.05， P<0.01）， while the expression of p-Smad/Smad2/3 was downregulated（P<0.05）， suggesting BWT reduced liver fibrosis. BWT inhibited inflammation-related factors as it reduced the gene expression of IL-6， IL-8， IL-11 and IL-1β（P<0.01） and it enhanced autophagy by upregulating LC3B Ⅱ/Ⅰ expression（P<0.05）while downregulating the expression of p62/SQSTM1 and mTOR（P<0.05）. ConclusionBWT ameliorates NAFLD by multifaceted improvements， including improving IR and glucose and lipid metabolism， anti-inflammation， anti-fibrosis， and enhancing autophagy. In particular， BWT may enhance liver autophagy by inhibiting the mTOR-mediated signaling pathway.

Objective:To investigate the arsenic metabolism pattern and possible influencing factors in the population in drinking-water-borne endemic arsenic poisoning (drinking-water-borne arsenic poisoning for short) areas.Methods:In December 2004, a cluster sampling method was used to select arsenic poisoning population (arsenic poisoning group) and healthy population (control group) in drinking-water-borne arsenic poisoning area of Bayannur City, Inner Mongolia Autonomous Region as the survey subjects. A questionnaire survey was conducted. Arsenic content in drinking water at home of survey subjects, the levels of urinary arsenic and its metabolites, including [trivalent arsenic (As Ⅲ), inorganic arsenic (iAs), monomethylarsenic acid (pentavalent, MMA V), dimethylarsenic acid (pentavalent, DMA V), total arsenic (tAs), percentage of inorganic arsenic (iAs%), percentage of monomethylarsenic acid (MMA%), percentage of dimethylarsenic acid (DMA%), primary methylation index (PMI), secondary methylation index (SMI)] were tested using high performance liquid chromatography-inductively coupled plasma mass spectrometry; nail arsenic and nail selenium levels were tested using atomic fluorescence spectrometer. The influencing factors of arsenic metabolism pattern were analyzed by multiple linear regression. Results:A total of 536 survey subjects were included, including 155 individuals in the arsenic poisoning group and 381 in the control group. The water arsenic level ranged from 0.0 to 825.7 μg/L. Compared with the control group, there was no significant difference in the distribution of gender, education level and dental fluorosis in the arsenic poisoning group ( P > 0.05), but there were significant differences in the distribution of age, marital status, smoking, drinking and water arsenic ( P < 0.05). Compared with the control group, the levels of urinary As Ⅲ, iAs, MMA V, DMA V, tAs, MMA%, MMA/DMA and nail arsenic in the arsenic poisoning group were higher ( P < 0.05), while the levels of urinary DMA%, SMI and nail selenium were lower ( P < 0.05); but there was no statistically significant difference in the levels of urinary iAs% and PMI ( P > 0.05). Gender, education level, depth of wells, water arsenic, total number of wells and nail arsenic were the influencing factors of urinary As Ⅲ (β = - 19.82, - 23.83, 0.61, 0.21, 7.26, 2.98, P < 0.05). Age, depth of wells, water arsenic and nail arsenic were the influencing factors of urinary tAs (β = 3.18, 3.25, 1.31, 15.59, P < 0.05). Gender, education level, depth of wells, water arsenic, total number of wells and nail arsenic were the influencing factors of urinary iAs (β = - 20.47, - 25.90, 0.64, 0.25, 7.87, 3.11, P < 0.05). Age, gender, education level, water arsenic and nail arsenic were the influencing factors of urinary MMA V (β = 0.52, - 17.07, - 21.84, 0.22, 2.77, P < 0.05). Age, depth of wells, water arsenic and nail arsenic were the influencing factors of urinary DMA V (β = 2.35, 2.47, 0.85, 9.22, P < 0.05). Conclusions:Compared with healthy individuals, there are differences in arsenic metabolism pattern among individuals with drinking-water-borne arsenic poisoning. Age, gender, education level, depth of wells, water arsenic, total number of wells and nail arsenic may be influencing factors of different arsenic metabolism patterns.