OBJECTIVE To establish a method based on gas chromatography-mass spectrometry (GC-MS) for simultaneous determination of a variety of soluble sugars in Ophiopohon japonicus tuberous roots and fibrous roots and to analyze the differences in the soluble sugars by multivariate statistical analysis. METHODS The optimized two-step derivatization method of methoxylation-trimethylsilylation combined with GC-MS was used to determine the soluble sugar components in 18 batches of Ophiopohon japonicus tuberous roots and fibrous roots. And the differences in the components were analyzed by multivariate statistical analysis, and the sweetness values of the tuberous roots and fibrous roots samples were converted according to the contents. RESULTS Eighteen kinds of soluble sugars were identified and 14 kinds of them were quantitatively analyzed in the tuberous roots and fibrous roots of Ophiopohon japonicus. It was found that the ingredients of the soluble sugar components in the tuberous roots and fibrous roots of Ophiopohon japonicus were basically the same, and the average of the total contents of the 14 kinds of soluble sugar components were also basically the same (88.76 mg·g^-1 in tuberous roots vs. 85.66 mg·g^-1 in fibrous roots). However, there were some differences in the contents of the components, and the contents of D-(-)-fructose and in the fibrous roots were significantly higher than those in the tuberous roots, while the contents of D-(+)-sucrose in the tuberous roots were significantly higher than those in the fibrous roots. The results of multivariate statistical analysis showed that tuberous roots and fibrous roots could be significantly differentiated by the determination of soluble sugar fractions. The difference in sweetness values between tuberous roots and fibrous roots was small by conversion. CONCLUSION With high sensitivity, good precision and accuracy, GC-MS is able to distinguish a variety of soluble monosaccharides and disaccharides with similar structures, and realize the accurate characterization and quantification of a variety of soluble sugars in Ophiopohon japonicus, and providing a basis for the study of soluble sugar fractions in different parts of Ophiopohon japonicus and its further development and utilization.

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.

OBJECTIVE To investigate the influencing factors and test methods of viable bacterial count in probiotic products of nature Bifidobacterium, and provide reference and suggestions for improving the quality control of such products. METHODS The effects of storage temperature and viable count determination method on viable count were studied, and the pretreatment methods and diluent composition were optimized, and the drug resistance genes and virulence genes of 11 strains contained in four products were analyzed by whole genome sequencing and functional genomics analysis. RESULTS The results showed that temperature had a great influence on the results of viable bacteria count of Bifidobacteria products, and the optimized method of live bacteria count could effectively improve the count results. Several strains of live bacteria products contained drug resistance genes and virulence genes. CONCLUSION It is suggested that we should pay attention to the influence of temperature on products in production storage and circulation. The count method of live bacteria can consider the characteristics of strains and production technology, and optimize the influencing factors such as pre-treatment and diluent. And there is a need for systematic safety assessment of all strains involved in commercially live bacteria product.

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.

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 investigate the penetration effect of solid microneedle in vivo and in vitro, the model drug ketoprofen was administered in the form of a patch. METHODS Using a rat skin penetration test, the effects of microneedle length, pre-treatment pressure, pre-treatment time, and types of needle on the penetration enhancement of ketoprofen in vitro were investigated. The pharmacokinetic characteristics of ketoprofen patches applied to the back of rats after different microneedle treatments were investigated, as well as the effect of the ketoprofen patch on promoting permeability in vivo. RESULTS In vitro, skin permeation tests revealed that after microneedle pretreatment, the permeation rate and permeation volume of the patch were significantly increased (P<0.05) and the permeation time lag was significantly shortened (P<0.05) after microneedle pretreatment, while the permeation promotion effect was related to the pressure, time, microneedle length and type of microneedle pretreatment. After microneedle pretreatment of the skin (pressure: 1-7 N, time: 1-5 min, microneedle length: 200 μm-300 μm), the cumulative permeation amount of the experimental drug for 24 hours increased by 1.16-3.09 times, and the permeation delay decreases by 0.20-2.50 h. As the results of in vivo pharmacokinetic in rats, ρ_max (10.86±0.80) μg·mL^-1 and AUC_0→t (108.10±17.06) μg·h·mL^-1 after 300 μm roller microneedle pretreatment of the skin, which were significantly greater than the control ρ_max (0.42±0.03) μg·mL^-1 and AUC_0→t (7.46±0.98) μg·h·mL^-1(P<0.05). ρ_max and AUC_0→t were increased by 25.9 times and 15 times. CONCLUSION Solid microneedle pretreatment of skin significantly improves in vitro penetration and in vivo skin absorption of ketoprofen patches through rat skin, with a more significant promotion effect in vivo penetration.

OBJECTIVE To analyze the key contents of paediatric regulation in the European Union (EU) and identify the characteristics of the European regulation for paediatric medicines. METHODS A literature review was conducted to analyze the EU paediatric regulation, relevant guidance documents and published literatures. RESULTS The EU has established the paediatric medicines committee, which is specifically responsible for issues related to the regulation of paediatric medicines. Moreover, the EU has systematically designed the regulation around four aspects including obligations, rewards and incentives, other initiatives for paediatric medicines research and information and transparency measures. CONCLUSION The EU attaches great importance to building a professional team for the regulation of paediatric medicines, focusing on both mandatory and incentives, and emphasizing the concepts of the whole life cycle of medicines and dynamic adjustments, which provide a comprehensive guarantee for promoting the development and availability of paediatric medicines. It deserves to be studied and learned from.

OBJECTIVE To optimize the formulation of nicorandil thermosensitive nasal gel (NIC-TNG) and further evaluate its quality. METHODS With gelling temperature and gelling time as observation indexes, the blank formulation composition of NIC-TNG was first optimized by central composite design-response surface method. Franz transdermal diffusion cell method was then used to screen the ideal permeation enhancer by using ex vivo nose mucosa of sheep as test model. The effect of pH on the chemical stability of NIC aqueous solution was investigated to establish the suitable pH of NIC-TNG. Lastly, NIC-TNG was prepared and its main quality items such as the gelation temperature and time, pH, labeled contents of the drug and preservative, cumulative erosion rate, cumulative drug release, and in vitro drug release were studied, respectively. Meanwhile, the effect of temperature on the viscosity, expansion coefficient and water holding capacity of NIC-TNG were investigated. RESULTS The optimized formulation of NIC-TNG consisted of 25 mg·mL^-1 NIC, 172.1 mg·mL^-1 F127, 5.0 mg·mL^-1 F68, 3.8 mg·mL^-1 HPMC, 5.0 mg·mL^-1 chlorobutanol and suitable amount of purified water. The gelation temperature and time, pH, labeled content of NIC and preservative were found to be 30.92 ℃, 40.82 s, 6.42, 99.18% and 98.72%, respectively. There was a good linear correlation between the in vitro cumulative erosion rate, cumulative drug release of NIC-TNG and time (r≥0.999 6). Furthermore, the in vitro release of NIC from the nasal gel showed obvious sustained release characteristics. Temperature exhibited obvious effect on the viscosity of the nasal gel. Finally, NIC-TNG showed low expansion coefficient and good water-holding capacity. CONCLUSION NIC-TNG will be expected to have good clinical application prospects due to its advantages such as reasonable formulation composition, simple preparation process, stable and controllable quality, convenient use and obvious sustained drug release behavior.

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.