Objective To investigate the promotion effect of human transcriptional positive cofactor 4 (PC4) overexpression on lymphatic metastasis in lung adenocarcinoma .Methods 96 samples of lung adenocarcinoma tissue were collected .The immuno‐histochemistry(IHC) and real‐time quantitative polymerase chain reaction (qRT‐PCR) were adopted for detecting the expression levels of PC4 protein and mRNA .The correlation of PC4 expression with lymphatic metastasis and TNM stage was analyzed .Re‐sults The expression of PC4 protein was positively correlated mRNA in lung adenocarcinoma (r=0 .63 ,P<0 .01);the expression of PC4 protein was positively correlated with lymph node metastasis (χ2 =8 .29 ,P<0 .01) and TNM stage (χ2 =4 .71 ,P<0 .05);the expression of PC4 mRNA was also positively correlated with lymph node metastasis (χ2 = 8 .40 ,P< 0 .01) and TNM stage (χ2 =5 .10 ,P<0 .05) .Conclusion PC4 overexpression is found to be closely associated with the lymph node metastasis and TNM stage .PC4 may facilitate the lymph node metastasis of lung adenocarcinoma .

Taking plastic packaging materials as an example, this paper mainly summarizes the general principles of pharmacopoeias and guiding principles of relevant government departments related to the compatibility studies of drugs and packaging materials at home and abroad, with much reference to relevant monographs and literature. The purpose and specific methods of extraction and interaction studies are summarized and discussed. The existing problems and solutions in compatibility research are also proposed in this review to provide some refe-rence for researchers in relevant fields.

2,6-dimethylbenzenamine was determined as a genotoxic impurity in lidocaine hydrochloride injection, and 2-chloro-N-(2,6- dimethylphenyl) acetamide was determined as potential genotoxic impurity. An LC-MS/MS method was established to research the profiling of genotoxic impurities in active pharmaceutical ingredients (API), homemade preparation and reference preparation on column Agilent ZORBAX Eclipse Plus C18(4.6 mm250 mm，5 μm). The results show that in the homemade preparation the 2,6-dimethylbenzenamine and the 2-chloro-N-(2,6-dimethylphenyl) acetamide may be degraded under oxidation condition and alkaline condition in addition to the introduction from API preparation process. This study provides guidance for genotoxic risk assessment and prescription process optimization of lidocaine hydrochloride.

As one of the most important biological drugs, protein and peptide drugs have been increasingly used in the prevention, diagnosis and treatment of diseases in recent years. However, most of them need to be injected and lack of long-acting formulations, which brings many troubles to patients suffering from chronic diseases. In this review, we summarized the strategies for engineering long-acting formulations for proteins and peptides via preparation means, including extended-release injection, implant, oral preparations and transdermal drug delivery systems, and analyzed their release mechanisms, research advances, advantages and shortcomings, thereby providing potential approaches for promoting the formulation improvement of these drugs.

The gas chromatography method was developed for the determination of ethylene glycol, diethylene glycol and triethylene glycol in poloxamer 188 to provide scientific basis for the quality control. The samples was separated on column VF-17ms(30 m×0. 53 mm, 1. 0 μm)with temperature programming, inlet temperature was 270 °C, detector temperature was 290 °C and the split ratio was 10 ∶1. The method showed great linearity over the range of 6-15 μg/mL(r≥0. 999). The injection precision(n=8)of the three residual impurities were 3. 3%, 3. 0%, 2. 3% and the average recoveries were 99. 05%(RSD=2. 9%, n=9), 102. 20%(RSD=4. 0%, n=9), 101. 91%(RSD=3. 1%, n=9), respectively. The analytical method is specific, accurate and sensitive, which is suitable for the determination of ethylene glycol, diethylene glycol and triethylene glycol in poloxamer 188, providing reference and guidance for the production and quality control of poloxamer 188.

Pharmaceutical excipients of animal origin, an important part in pharmaceutical excipients, are widely used in pharmaceutical preparations.However, compared with the pharmaceutical excipients of other origins, pharmaceutical excipients of animal origin have more special requirements in many aspects, such as raw materials, production, quality control, storage, supervision, etc.Chinese Pharmacopoeia 2020 first included the Guideline for Pharmaceutical Excipients of Animal Origin, which introduces the basic ideas and technical requirements for the life cycle quality control of pharmaceutical excipients of animal origin based on the risk management concept.This article illustrates the specificity of the pharmaceutical excipients of animal origin, and interprets the main contents of this guideline in conjunction with relevant domestic and foreign regulations and technical documents, thereby providing comprehensive reference for the implementation of the guideline.

Objective:To develop and validate gas chromatographic methods for the determination of residual benzene in carbomer copolymer,carbomer homopolymer and carbomer interpolymer,to address the issues of the current method in the Chinese Pharmacopoeia in the actual detection process,such as low sensitivity and poor repeatability of benzene detection in the mixed reference solution,and to optimize and improve the current stand-ards for series of carbomer pharmaceutical excipients.Methods:Samples were separated on a column DB-624(30 m ×0.530 mm,3.00 μm)with temperature programming,the inlet temperature of 140 ℃,the detector tem-perature of 250 ℃,and the split ratio of 5∶1.The external standard method was adopted for the quantitative deter-mination of residual benzene.Results:The linearity was great across the range of 0.04-1.00 μg·mL-1(r=0.996 8),the injection precision of benzene was 6.8％(n=6),and the average recovery rate was 96.89％(RSD=8.1％,n=9).Conclusion:The gas chromatographic method established in this research is more specif-ic,with higher accuracy and precision compared to the current method in the Chinese Pharmacopoeia.This optimized method is more suitable for the determination of residual benzene content in carbomer copolymer,car-bomer homopolymer and carbomer interpolymer,providing reference and guidance for the quality management and the control of carbomer.

To better promote the development of film-coated formulations and membrane agents, the present study was carried out to investigate the critical material attributes (CMAs) of different sources and models of HPMC in terms of film-coating performance and the correlation between each of the CMAs and the film-coating-related properties, using 2910 HPMC as the research target. Firstly, various analytical techniques were used to characterize the CMAs and film coating-related properties of HPMC. Secondly, the CMAs and film coating-related properties of HPMC were systematically evaluated by principal component analysis (PCA) and orthogonal partial least-squares discrimination analysis (OPLS-DA). The CMAs and film-coating-related properties of HPMC were systematically evaluated to elucidate the intrinsic relationship between the CMAs and film-coating-related properties of HPMC. The results showed that there were significant differences in viscosity, weight-average molecular weight, film tensile strength, elongation, elastic modulus, dissolution time, and flexibility of HPMCs from different manufacturers. The results of PCA and OPLS-DA analyses indicated that these 11 variables showed some correlations with each other. Both mathematical models showed better differentiation and classification of HPMC samples, and the OPLS-DA model had a better classification effect than the PCA model. Therefore, in this study, the physicochemical properties and the film-forming characteristic of HPMC were comprehensively evaluated, and the correlation between them was further established using PCA and OPLS-DA. The impact degree of different CMAs on the film coating performance of HPMC was clarified, which can be used as an important reference for the selection of excipient quality control programs in excipient production and formulation research and development.

Objective:A gas chromatography analysis system for fatty acid compositions of hydrogenated palm glycerides was established to provide a reference for quality standards of hydrogenated palm glycerides.Methods:In this test,a DB-WAX(30 m ×0.53 mm,1.0 μm)strong polarity gas chromatographic column was employed with an injection volume of 1 μL and a split ratio of 120∶1.The initial column temperature was 70℃,sustained for 2 min,ramped up to 230 ℃ at a rate of 5 ℃ per minute,and maintained for 10 min,with the inlet temperature of 250 ℃ and the detector temperature of 250 ℃.Results:In this experiment,the gas chromatograph-ic method was established successfully to determine fatty acid compositions of hydrogenated palm glycerides.The validated results indicated that the method exhibited well-suited system applicability,specificity and precision,and the RSD(％)fulfilled the requirements.The limit of detection(LOD)and limit of quantification(LOQ)values of nine fatty acid methyl esters were defined,and fatty acid compositions of seven batches of samples were checked successfully.Conclusion:The GC methodology developed in this study is suitable for the analysis and determina-tion of fatty acid compositions in hydrogenated palm glycerides,which can serve as a reference for the quality control of this pharmaceutical excipient and the establishment of quality standards.