OBJECTIVE To optimize the prescription pre-review system in our hospital and evaluate its application effects. METHODS Aiming at the problems of imperfect rule base and high false positive rate in the early operation of the system， optimization measures were taken， including improving the content of the rule base， adjusting the interception level and prompt mode， refining the working model of prescription review pharmacists， and strengthening clinical communication. A retrospective cohort study was conducted， with prescription data from June to December 2023 （before optimization） as the control group and June to December 2024 （after optimization） as the observation group. Through inter group comparative analysis， the actual effect of optimizing the prescription pre-approval system was evaluated. RESULTS The prescription qualified rate increased from （82.51± 4.04）% before optimization to （90.98±1.55）% after optimization； the false positive rate decreased from （20.87±1.64）% before optimization to （7.41±2.04）% after optimization. The monthly range of prescription qualified rate narrowed from 10.24% to 4.11%， and the coefficient of variation decreased from 4.92% to 1.73%. The monthly range of false positive rate slightly increased from 4.40% to 5.34%， the coefficient of variation rose from 8.32% to 26.18%. CONCLUSIONS Through multi-dimensional optimizations of the prescription pre-review system in our hospital， its prescription review efficiency has been significantly enhanced， the quality of prescriptions has steadily improved， and the accuracy of reviews has notably improved.

Serum cholinesterase(ChE)level is important for the diagnosis and prognostic evaluation of various diseases such as liver diseases and toxic diseases,and butyrylcholinesterase(BuChE)is an important component of ChE.Mutations in the BCHE gene can cause a significant reduction in the level of BuChE,with extensive reports in European and American populations and relatively few reports in Eastern countries,particularly China.This study describes a male patient,aged 35 years,who was misdiagnosed with organophosphorus pesticide poisoning due to an extreme reduction in ChE level and was given detoxification therapy,but such diagnosis was excluded by various biochemical examinations.Finally whole-exome sequencing and Sanger sequencing revealed the complex heterozygous mutations of c.1027dup and c.401dup at exon 2 of the BCHE gene,and hereditary BuChE deficiency due to these mutations is the cause of the extreme reduction in ChE level.

ObjectiveTo investigate the efficacy and safety of N-acetylcysteine （NAC） in the treatment of severe alcoholic hepatitis （SAH）， and to provide a basis for clinical medication for SAH. MethodsA prospective randomized controlled trial was conducted among 172 SAH patients with a Maddrey discriminant function score of >32 points who were recruited by The Fifth Medical Center of Chinese PLA General Hospital from June 2015 to June 2018， and these patients were divided into NAC group with 84 patients and control group with 86 patients. NAC （8 g/day， 28 days） was assessed in terms of its safety in SAH patients， its impact on 28-day biochemical parameters， and its role in improving 28- and 180-day survival rates. A further analysis was performed to investigate the effect of NAC on the 28- and 180-day survival rates of SAH patients with acute-on-chronic liver failure （ACLF-SAH patients） and those without acute-on-chronic liver failure （non-ACLF-SAH patients）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used for comparison of survival curves. Univariate and multivariate Cox proportional-hazards regression model analyses were used to investigate independent influencing factors. ResultsNo serious adverse events were observed during NAC treatment， suggesting that NAC had a good safety profile. Compared with the control group， NAC did not significantly improve the 28-day biochemical parameters （all P>0.05） and survival rate of SAH patients （P=0.081）， but it could improve the 180-day survival rate of SAH patients （67.4% vs 81.0%， χ²=4.280， P=0.039）. NAC did not improve the 28- and 180-day survival rates of ACLF-SAH patients （both P>0.05）； NAC did not improve the 28-day survival rate of non-ACLF-SAH patients （P>0.05）， but it could improve the 180-day survival rate of these patients （68.4% vs 88.9%， χ²=4.883， P=0.027）. The multivariate Cox regression survival analysis showed that NAC treatment （hazard ratio ［HR］=2.530， 95% confidence interval ［CI］： 1.334‍ ‍— 4.796， P=0.004，）， Maddrey discriminant function score （HR=3.852， 95%CI： 2.032 — 7.304， P<0.001）， and serum sodium level （HR=1.948， 95%CI： 1.079‍ ‍—‍ ‍3.517， P=0.027） were independent influencing factors for 180-day survival rate in SAH patients. ConclusionNAC has a good safety profile in the treatment of SAH and can improve the 180-day survival rate of SAH patients， and in particular， non-ACLF-SAH patients can benefit from NAC treatment in terms of middle- and long-term survival rates.

Objective:To explore the association between polymorphisms of transforming growth factor-β(TGF-β)signaling pathway and non-syndromic cleft lip with or without cleft palate(NSCL/P)among Asian populations,while considering gene-gene interaction and gene-environment interaction.Methods:A total of 1 038 Asian NSCL/P case-parent trios were ascertained from an international consortium,which conducted a genome-wide association study using a case-parent trio design to investigate the genes affec-ting risk to NSCL/P.After stringent quality control measures,343 single nucleotide polymorphism(SNP)spanning across 10 pivotal genes in the TGF-β signaling pathway were selected from the original genome-wide association study(GWAS)dataset for further analysis.The transmission disequilibrium test(TDT)was used to test for SNP effects.The conditional Logistic regression models were used to test for gene-gene interaction and gene-environment interaction.Environmental factors collected for the study in-cluded smoking during pregnancy,passive smoking during pregnancy,alcohol intake during pregnancy,and vitamin use during pregnancy.Due to the low rates of exposure to smoking during pregnancy and al-cohol consumption during pregnancy(＜3％),only the interaction between maternal smoking during pregnancy and multivitamin supplementation during pregnancy was analyzed.The threshold for statistical significance was rigorously set at P=1.46 × 10-4,applying Bonferroni correction to account for multiple testing.Results:A total of 23 SNPs in 4 genes yielded nominal association with NSCL/P(P＜0.05),but none of these associations was statistically significant after Bonferroni's multiple test correction.How-ever,there were 6 pairs of SNPs rs4939874(SMAD2)and rs1864615(TGFBR2),rs2796813(TGFB2)and rs2132298(TGFBR2),rs4147358(SMAD3)and rs1346907(TGFBR2),rs4939874(SMAD2)and rs1019855(TGFBR2),rs4939874(SMAD2)and rs12490466(TGFBR2),rs2009112(TGFB2)and rs4075748(TGFBR2)showed statistically significant SNP-SNP interaction(P＜1.46 × 10-4).In contrast,the analysis of gene-environment interactions did not yield any significant results after being cor-rected by multiple testing.Conclusion:The comprehensive evaluation of SNP associations and interac-tions within the TGF-β signaling pathway did not yield any direct associations with NSCL/P risk in Asian populations.However,the significant gene-gene interactions identified suggest that the genetic architec-ture influencing NSCL/P risk may involve interactions between genes within the TGF-β signaling path-way.These findings underscore the necessity for further investigations to unravel these results and further explore the underlying biological mechanisms.

ObjectiveTo analyze the quality and status of technical service items of radiation health technical service institutions (RHTSI) in China. Methods A total of 608 and 622 RHTSIs with radiation health technical service qualifications from 31 provinces, autonomous regions, and municipalities in the years of 2021 and 2022 were selected as the research subjects. The data of quality monitoring of radiological health technology services, comparison of radiological health testing capabilities, and investigation of the current status of technical support institutions were collected to analyze the status of technical service items which was conducted by RHTSIs from 2021 to 2022. Results A total of 622 RHTSIs in China obtained technical service institution qualifications in 2022, an increase of 14 from 608 in 2021. While a total of 404 of 622 RHTSIs conducted radiological health technology services, a decrease of 11.4% from 456 in 2021. A total of 241 804 technical service items were conducted in 2022, an increase of 39.7% from 173 064 in 2021. The median number of technical service items by non-health system RHTSIs was higher than that of the health system RHTSIs in 2021 and 2022, (203 vs 40 items, 215 vs 55 items, all P<0.01). The number of technical service institutions and technical service items conducted in different regions from high to low were the eastern, central, and western regions in 2021. The number of technical service institutions in different regions was highest in the eastern region, followed by the central and western regions, while the number of technical service items from high to low were the eastern, western, and central regions in 2022. The number of provincial, municipal, and county-level health system RHTSIs decreased by 6.5%, 26.3%, and 27.3%, respectively, in 2022 compared with 2021. The number of technical service items conducted by provincial health system RHTSIs increased by 48.6%, while those conducted by municipal and county-level health system RHTSIs decreased by 13.8% and 21.3%, respectively. Conclusion Although the number of RHTSI conducting technical services decreases in 2022 compared with 2021, the number of technical service items conducted increases. Non-medical RHTSI undertake the majority of technical service items. Within the medical institutes, the number of technical service items conducted by provincial RHTSI is higher than that of municipal and county-level RHTSI.

Objective To investigate the current situation of radiological health technical service institutions and their technical services in China, and to provide a basis for better utilizing radiological health technical service resources and strengthening institutions’ capability building. Methods From October to December 2021, we conducted quality monitoring, ability comparison, capability building surveys, and other investigations on radiation health technical services to collect information on the qualifications and technical services of radiation health service institutions. The data were pooled and analyzed using SPSS software. Results By the end of 2021, there were 608 radiological health technical service institutions across China, with 47.0% of them located in the eastern region, and the percentage of institutions in the health system (42.6%) was less than that in the non-health system (57.4%). Institutions of grade A offered 62.3% of technical services, while institutions of grade B provided 37.7% of technical services; technical services provided by the non-health system and the health system accounted for 84.2% and 15.8%, respectively; institutions in the health system at the province, prefecture, and county levels offered 37.1%, 50.6%, and 12.3% of technical services, respectively. Conclusion In recent years, the proportion of institutions in the non-health system has increased significantly, but the proportion of institutions in the health system with radiological health qualifications is small, and the development is uneven in the numbers of institutions, technical services, and professional and technical personnel in the eastern, central, and western regions and at the province, prefecture, and county levels in China. It is necessary to further encourage and support health system institutions in strengthening capability building and applying for radiological health qualifications, and to increase construction and investment in the western region and at the district/county levels, in order to improve the overall capability and level of radiological health technical services in the country.

Triterpenoid saponins are widely used in medicine, health cares, cosmetics, food additives and agriculture because of their unique chemical properties and rich pharmacological activities. UDP-dependent glycosyltransferases (UGTs) are the key enzymes involved in triterpenoid saponin biosynthesis, and play important roles in the diversity of triterpenoid saponin structures and pharmacological activities. This review summarized the UGTs involved in plant triterpenoid saponin biosynthesis based on the sources of UGTs and the types of receptors. Moreover, the application of UGTs in heterologous biosynthesis of triterpenoid saponins based on synthetic biology was also discussed.
Glycosyltransferases/genetics* ; Plants ; Saponins/chemistry* ; Triterpenes

Both natural ginsenoside F2 and unnatural ginsenoside 3β,20S-Di-O-Glc-DM were reported to exhibit anti-tumor activity. Traditional approaches for producing them rely on direct extraction from Panax ginseng, enzymatic catalysis or chemical synthesis, all of which result in low yield and high cost. Metabolic engineering of microbes has been recognized as a green and sustainable biotechnology to produce natural and unnatural products. Hence we engineered the complete biosynthetic pathways of F2 and 3β,20S-Di-O-Glc-DM in Saccharomyces cerevisiae via the CRISPR/Cas9 system. The titers of F2 and 3β,20S-Di-O-Glc-DM were increased from 1.2 to 21.0 mg/L and from 82.0 to 346.1 mg/L at shake flask level, respectively, by multistep metabolic engineering strategies. Additionally, pharmacological evaluation showed that both F2 and 3β,20S-Di-O-Glc-DM exhibited anti-pancreatic cancer activity and the activity of 3β,20S-Di-O-Glc-DM was even better. Furthermore, the titer of 3β,20S-Di-O-Glc-DM reached 2.6 g/L by fed-batch fermentation in a 3 L bioreactor. To our knowledge, this is the first report on demonstrating the anti-pancreatic cancer activity of F2 and 3β,20S-Di-O-Glc-DM, and achieving their de novo biosynthesis by the engineered yeasts. Our work presents an alternative approach to produce F2 and 3β,20S-Di-O-Glc-DM from renewable biomass, which lays a foundation for drug research and development.

Objective:To study the genomic sequence of Coxsackievirus A8 (CV-A8) associated with hand, foot and mouth disease (HFMD) from 2013 to 2018 in China and to analyze the genetic evolution of each coding region of the full-length genome.Methods:The genome sequences of 11 CV-A8 strains isolated from patients with HFMD in different regions of China from 2013 to 2018 were determined. Sequence alignment and genetic evolution analysis were performed by Sequencher 5.0 and MEGA 7.0 software, etc.Results:Sequence alignment showed that the genome length of 11 CV-A8 strains ranged from 7 393 bp to 7 400 bp. There was no base insertion or deletion in the coding region compared with the prototype strain, but there were individual base insertion or deletion in the non-coding region. The nucleotide and amino acid similarities in the VP1 region of 11 CV-A8 strains were 78.3%-98.6% and 92.6%-99.7%, respectively, and the nucleotide and amino acid sequences identities with the CV-A8 prototype strain were 78.3%-98.2% and 92.6%-99.7%, respectively. Based on the phylogenetic analysis of VP1 region sequences, the CV-A8 can be divided into five genotypes: A, B, C, D and E. The 11 CV-A8 strains in this study belonged to genotypes C (1 strain), D (2 strains) and E (8 strains). The nucleotide and amino acid similarities of 11 CV-A8 full-length genomes were 81.3%-98.8% and 95.9%-99.5%, respectively. The phylogenetic tree of the P2 region showed that the eight E genotypes CV-A8 had the closest evolutionary distance with CV-A4, CV-A14, and CV-A16. The phylogenetic tree of the P3 region showed that the eight E genotypes CV-A8 had a close evolutionary distance with CV-A5, CV-A16, CV-A14 and CV-A4.Conclusions:The 11 CV-A8 stains in this study showed significant intra-genotype diversity in capsid region and recombinant diversity in non-capsid region which indicated that CV-A8 quasispecies were still undergoing dynamics variation. CV-A8 may become an important pathogen of HFMD and the monitoring of CV-A8 needs to be further strengthened.

Medicinal natural products derived from plants are usually of low content and difficult to extract and isolate. Moreover, these compounds are structurally complex, making it difficult to obtain them by environmental unfriendly chemical synthesis. Biosynthesis of medicinal natural products through synthetic biology is a novel, environment-friendly and sustainable approach. Taking terpenoids (ginsenosides, paclitaxel, artemisinin, tanshinones), alkaloids (vincristine and morphine), and flavonoids (breviscapine) as examples, this review summarizes the advances of the biosynthetic pathways and synthetic biology strategies of plant-derived medicinal natural products. Moreover, we introduce the key technologies and methods of synthetic biology used in the research of medicinal natural products, and provide future prospects in this area.
Biological Products ; Biosynthetic Pathways ; Plants ; Synthetic Biology ; Terpenes