OBJECTIVE To establish a high performance liquid chromatography (HPLC) method for the detection of related substances in somatostatin for injection. METHODS The determination was performed on a C₁₈ column with mobile phases consisting of potassium dihydrogen phosphate solution and acetonitrile by gradient elution. The detection wavelength was set at 215 nm and the column temperature was maintained at 50 ℃. RESULTS The established method can effectively separate the main components and seven major degradation impurities. The peak area of somatostatin and 7 kinds of impurities had good linear relationships with the concentration (r≥0.999 1, n=8). Relative standard deviation (RSD) of precision, stability and repeatability tests of 7 kinds of impurities were all lower than 3.6%. The average recoveries of 7 kinds of impurities ranged from 100.0% to 104.4% (n=9). The impurity content determined by the established method is higher than that determined by the European Pharmacopoeia(EP) and Chinese Pharmacopoeia(Ch.P). CONCLUSION The method is simple, accurate and stable. It can control the impurities in somatostatin for injection and provide a basis for improving the standard of this drug.

OBJECTIVE To identify and evaluate the risk signals of tislelizumab in non-small-cell lung cancer (NSCLC) patients, so as to provide basis for future management of irAEs and better tumor immunotherapy in NSCLC patients. METHODS The clinical data of NSCLC patients who received tislelizumab in Peking University People's Hospital from April 2021 to April 2023 were retrospectively analyzed. The occurrence of irAEs during tislelizumab treatment was observed, the incidence of irAEs was summarized, and the clinical features of irAEs and non-irAEs groups were compared. RESULTS Sixty-eight NSCLC patients received tislelizumab, of whom 22 (32.35%) developed 32 irAEs. The main manifestations were pulmonary toxicity (17.65%), skin toxicity (11.76%), endocrine toxicity (5.88%), gastrointestinal toxicity (4.41%), cardiovascular toxicity (4.41%), and hematological toxicity (2.94%). The median duration of irAEs was 79 d (1-706 d). Thirteen cases (59.09%) were treated with glucocorticoids. Comparison of the clinical characteristics of irAEs group and non-irAEs group showed that the incidence of irAEs in patients with hepatic insufficiency was higher (P<0.05), the other differences were not statistically significant (P>0.05). CONCLUSION irAEs involve multiple systems/organs, so attention should be paid to the management of immune-related toxicity, timely detection, and treatment of irAEs, to achieve better effects of tumor immunotherapy.

OBJECTIVE To establish the quality risk management mode based on failure mode and effect analysis (FMEA),and explore the application effect in the collinear production of external solution preparations. METHODS FMEA was performed on each link during the whole process of collinear production of external solution preparations. The high and medium risk failure modes were identified according to risk priority number (RPN), and failure causes were analyzed for formulating and implementing improvement measures. The risk level and the continuous verification effect of cleaning verification were evaluated before and after the implementation of control measures, the incidence of equipment failure, the qualified rate of first clearance, the rate of quality control compliance and the frequency of deviation treatment before and after the application of quality risk management mode were compared, and the improvement effect was examined. RESULTS A total of 21 failure modes were identified in the whole process of collinear production, of which 4 were high-risk, 11 were medium-risk and 6 were low-risk. The 15 items of medium and high risk failure modes were downgraded to low risk, and all cleaning verification indicators are controlled within the limits by continuous improvement of pollution and cross-contamination control measures, continuous supervision and research of collinear production risk control measures, continuous confirmation of equipment cleaning effect and other measures. Moreover, after the implementation of quality risk management mode, the incidence of equipment failure and the frequency of deviation treatment were reduced markedly, and the qualified rate of the first clearance and the quality control compliance rate were significantly increased, and the differences were statistically significant (P<0.05). CONCLUSION Applying the quality risk management model in the whole process of collinear preparation production can effectively reduce the risk of confusion, contamination and cross contamination, ensure the quality of collinear preparation products, and improve the operation level of the quality management system.

Targeted nano-drug delivery system (TNDDS) offers prominent advantages in drug delivery for treatment of hepatocellular carcinoma, targeting the tumor site via ligand-receptor interaction. TNDDS reduces the dosage of drug to fulfill the therapeutic index requirement, improving pharmacokinetics and biodistribution. Besides, it can sustain drug release for several days after single-dose administration. In recent years, glycyrrhetinic acid (GA) attracts much attention as a highly efficient ligand targeting to liver tumor. The superiority of GA is mainly reflected in its combination of efficient liver tumor targeting, superior anti-tumor activity and favorable biocompatibility. GA-based TNDDS to liver tumor possesses high site-specificity and therapeutic efficiency for chemotherapeutic drugs or genetic materials delivering. This paper focuses on the basic theory of GA as a ligand targeting to liver tumor and the researches advances in the development of GA-based nano-delivery systems. Through the review and summary in this paper, it is expected to systematically present current progress of GA-based liver tumor TNDDS for interested researchers, and provide references for the development of new delivery systems.

Ginkgo biloba has been widely used to treat diseases such as blood stasis blocking collaterals, chest pain, stroke, and hemiplegia. Ginkgo biloba extract 50 (GBE50) is the fifth generation of Ginkgo biloba extract (GBE). The chemical components of GBE50 include total flavonoids and terpene lactones. GBE50 shows multiple pharmacological effects such as anti-inflammatory, antioxidant stress, and antiplatelet aggregation. In clinic, it has been widely used in vascular-related diseases such as coronary heart disease, angina pectoris, stroke, and vascular dementia. The authors review the studies on the material basis, clinical application, and mechanism of GBE50, and mainly focus on the research progress in pharmacological mechanism. These might provide a fresh perspective and idea for research on GBE50 in the treatment of vascular-related diseases.

Active ingredients in Chinese medicine have great potential to be used in breast cancer treatment to improve the efficacy of existing breast cancer treatment strategies. By influencing different signaling pathways to produce different mechanisms of action, active ingredients in Chinese medicine enhance the sensitivity of tumor cells to the effects of chemical, hormonal or gene therapeutic agents, reduce toxic side effects or inhibit the efflux of anticancer drugs. In this paper, it is reviewed the strategies for the combination of Chinese herbal active ingredients with other breast cancer therapeutic agents, such as chemotherapeutic agents, hormones, gene agents, small molecule inhibitors and inorganic mixtures, and intelligently design nano-delivery systems to co-deliver Chinese herbal active ingredients and other breast cancer therapeutic agents for the synergistic treatment of breast cancer. Nanocarriers offer various advantages including improved solubility, increased stability and enhanced tumor targeting, thus overcoming the clinical application limitations of the active ingredients of TCM.

OBJECTIVE To synthesize phytanetriol by epoxidation/ring-opening reaction under catalyst-free conditions using phytol as raw material, low concentration of hydrogen peroxide as oxidant, and formic acid as oxygen carrier. METHODS The effects of the molar ratios of formic acid and hydrogen peroxide to phytol, reaction temperature, and reaction time on the yield of phytanetriol were investigated using a single-factor test and verified by 3-batch reproducibility. The chromatographic purity and structure of phytanetriol were analyzed by gas-mass spectrometry, infrared spectroscopy, and nuclear magnetic resonance spectrometry. RESULTS The optimal conditions for the epoxidation reaction system were n(HCOOH):n(H₂O₂):n(phytol)=5∶1.3∶1, temperature 55 ℃, and reaction time 2 h. The optimal conditions for the ring-opening reaction system were pH=13, temperature 105 ℃, and reaction time 0.5 h. The phytanetriol synthesis process had a yield of 86.6% in the validated experiments. The chromatographic purity was 94.6%. CONCLUSION The synthesis process is stable and can produce phytanetriol with controllable quality and better purity than commercially available products.

OBJECTIVE To excavate the key genes of drought stress response of A.sinensis, and carry out the comparative analysis with the transcriptome data of the main cultivars ‘Mingui 1’ and ‘Mingui 2’ of Angelica sinensis (Oliv.) Diels. METHODS With the fresh leaf and root tissues of two cultivars of A.sinensis as materials, a cDNA library was constructed. The Illumina HiSeq^TM 4000, a second-generation high-throughput sequencing platform, was used for sequencing analysis, and key enzyme genes in response to drought stress were screened from differentially expressed genes(DEGs). RESULTS A total of 584 423 236 clean reads were obtained from transcriptome sequencing, in which the percentage of Q20 (base amount ≥20%) and Q30 (base amount ≥30%) were above 97.47% and 92.64%, and the GC content ranged from 42.78% to 43.15%. A total of 1 894 DEGs were screened from the leaves and roots of two cultivars of A.sinensis, the numbers of which were 674 and 1 220, respectively, and they had 338 shared DEGs. The GO enrichment results showed that the annotation classification of DEGs of two cultivars of A.sinensis in the same tissue part mainly included cellular process, metabolic process and catalytic activity. KEGG analysis found that the DEGs were significantly enriched in plant-pathogen interaction, MAPK signaling pathway-plant, phenylpropanoid biosynthesis and plant hormone signal transduction pathways. The detailed classification annotation results were consistent with the trends of GO and KEGG analysis. Based on the functional annotation results, 60 drought resistance genes were excavated. HVA22C, KRP1, PUB23, DREB1B and Bp10 were selected to verify their expression levels by qRT-PCR. and the results showed their genes expression level were consistent with the transcriptome sequencing gene expression trends. CONCLUSION The two cultivars of A.sinensis have some differences in drought resistance pathways such as abscisic acid regulation, osmoregulation, scavenging of reactive oxygen species and regulation of other functional proteins, and the screened drought resistance genes can provide data references for further research on the molecular mechanisms of A.sinensis in response to drought stress.

OBJECTIVE To establish a quality consistency evaluation method reflecting the overall pharmacodynamic characteristics of multi-batch Chinese medicine compound preparations. METHODS Establish a drug absorption simulating system(DASS) standardized absorption biomimetic system module using a flipped intestinal sac model, and prepare intestinal absorption samples of Danggui buxue tang from different sources and batches; Drawing on the concept of consistency evaluation of biopharmaceuticals, a cell biological effect characterization module was established using Real-time cell analysis(RTCA) to monitor the cell response curves of 15 batches of Danggui buxue tang samples. RESULTS The combination of DASS-RTCA was used to extract the characteristic parameters of time-dependent cell response patterns (TCRPs) maps from 15 batches of Danggui buxue tang samples. The RSD of each characteristic parameter was less than 5.1%, indicating that the differences in cell effect characterization of Danggui buxue tang (DBT) were small and the similarity of TCRPs maps was high. Through similarity analysis, cluster analysis, radar chart analysis, etc., it is reflected that the quality of different batches of DBT has high consistency. CONCLUSION The quality consistency evaluation method established by DASS-RTCA can reflect the overall quality of the preparations and provide new ideas and methods for the evaluation of batch-to-batch quality consistency of traditional Chinese medicines.

OBJECTIVE This study aimed to investigate the role and potential mechanisms of Icotinib (ICO) on pulmonary fibrosis. METHODS C57BL/6 mice were randomly divided into Sham group, PF group, ICO 30 mg·kg^-1 group and ICO 60 mg·kg^-1 group, 8 rats in each group. A mouse model of PF was induced by intratracheal injection of bleomycin (3 mg·kg^-1). Hematoxylin-eosin staining and Masson trichrome staining for lung tissues were performed to observe the pathological alterations and collagen deposition. Immunohistochemical detection of lung tissue collagen type Ⅰ (collagen Ⅰ) expression. In vitro, the lung epithelial cells were divided into control group, epidermal growth factor (EGF) group, EGF combined with ICO (0.1, 1, 10 mmol·L^-1) groups. The protein expression of E-cadherin, α-SMA and nuclear transfer of NF-κB p65 were detected by immunofluorescence. The protein levels of Collagen Ⅰ, E-cadherin, α-SMA, Vimentin, phosphorylation epidermal growth factor receptor (p-EGFR), p-IκBα, p-NF-κB p65 and nuclear NF-κB p65 were detected by Western blot analysis in lung tissue and (or) cells. RESULTS The results demonstrated that ICO inhibited bleomycin-induced collagen deposition, reduced type Ⅰ collagen expression, alleviated bleomycin-induced EMT (increased E-cadherin expression and decreased Vimentin and α-SMA expression), and decreased phosphorylation of EGFR, IκBα, NF-κB p65 and nuclear translocation of NF-κB p65 in vivo. Furthermore, incubation of lung epithelial cells with EGF activated EMT and EGFR/NF-κB signaling pathway, and these effects were reversed by ICO In vitro. CONCLUSION In conclusion, ICO attenuates EGF-induced EMT in lung epithelial cells and bleomycin-induced pulmonary fibrosis in mice by downregulating EGFR/NF-κB pathway.