Celastrol and wilforlide A are the main active triterpenoids of the traditional Chinese medicine Lei Gong Teng, which have anti-tumour, anti-inflammatory and immunosuppressive activities, and are the material basis for the clinical efficacy of Lei Gong Teng-related Chinese medicinal preparations. By analysing the biosynthetic pathway of active ingredients, optimizing genetic elements and utilizing "cell factory" to produce triterpenoids heterologously will be an effective way to obtain from Tripterygium wilfordii in the future in a "low-cost and high-efficient" manner. CYP712Ks are the first cytochrome P450s involved in the skeleton modification of friedelane-type and oleanane-type triterpenoids in T. wilfordii, and they can catalyse the generation of polpunonic acid from friedelin and 3-epi-katonic acid from β-amyrin by carboxylation at C-29 position. In this study, four multifunctional TwCYP712K1/2/3/5 were used to clarify the catalytic function and substrate selection preference using in vivo functional characterization in Saccharomyces cerevisiae. The spatial structure of the protein-substrate binding was clarified through homology modeling and molecular docking, and then the differential amino acids in the active pocket of the protein were mutated to clarify the crucial amino acids determining the catalytic function and the selection of substrate structure. A total of 63 mutant elements were constructed, and the amino acid sites affecting the carboxylation function of TwCYP712Ks were analyzed. In particular, the key amino acids affecting the substrate selectivity of TwCYP712K2 towards oleanane-type and friedelane-type triterpenoids were revealed and the TwCYP712K2^F127I and TwCYP712K2^A227T mutants would result in a reversal of the product ratio. In conclusion, four proteins of TwCYP712Ks were semi-rationally designed by homologous protein alignment and mutual mutation to elucidate multiple amino acid sites determining the catalytic function of the proteins, and a series of activity-enhancing or altering mutants were obtained, which provide abundant catalytic elements for the biosynthesis of active triterpenoids from T. wilfordii, and the mechanism of carboxylation in the C-29 position was initially elucidated.

From an aqueous extract of the Angelica sinensis root head (guitou), nine pairs of lignanoid enantiomers [(+)-/(-)-1-(+)-/(-)-9], including three pairs of new structures [(+)-/(-)-1-(+)-/(-)-3] and two pairs of chiral separated enantiomers for the first time [(+)-/(-)-4 and (+)-/(-)-5], were isolated and chirally separated by column chromatography over different types of resin, normal and reversed phase silica gels, together with HPLC techniques using reversed phase and chiral columns. Their structures were determined by spectroscopic data analysis, theoretic calculation of electronic circular dichroism (ECD) spectra, and single-crystal X-ray diffraction. The chiral separated new enantiomers named (+)-/(-)-angelignanins Q-T [(+)-/(-)-1-(+)-/(-)-4] and (+)-/(-)-daphneresinol [(+)-/(-)-5], respectively.

Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.

Aim To predict and validate the mechanism of wenshen xuanbi tang(WSXBT) in treatment of osteoporosis (OP) based on network pharmacology, molecular docking techniques and in vivo experimental techniques. Methods Network pharmacology was used to screen the key ingredients and core targets of WSXBT for the treatment of osteoporosis. Metascape database was used for gene ontology (GO) biological process enrichment analysis and kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment analysis of core targets. AutoDockTools 1. 5. 7 software was applied in molecular docking to simulate the binding activity of key active ingredients to core targets. To study the efficacy of WSXBT on rats with osteoporosis and to verify the related targets and pathways, rat models of osteoporosis were established by excising the bilateral ovaries of rats. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum OPG, PINP and RANKL content. Biomechanical tester was applied to test the biomechanics of rat femurs. Micro-CT was applied to detect the femoral bone density. Then, Western blot was employed to measure the protein expression levels of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt). Results A total of 156 active ingredients of WSXBT were screened, involving 229 potential targets, 23 core targets and 145 signaling pathways. The molecular docking results showed that five key ingredients, including quercetin, kaempferol, naringenin, isobavachin and licochalcone a, possessed good binding ability to the core targets of PIK3R1 and AKT1. The results of in vivo experiments showed that WSXBT could significantly increase bone density, improve bone tissue microstructure, enhance femur biomechanics and increase PINP expression and OPG/RANKL ratio in rats with osteoporosis. Results of WB showed that WSXBT significantly increased p-PI3K/PI3K and p-Akt/Akt ratios. Conclusions WSXBT could improve bone mineral density in postmenopausal osteoporotic rats through PI3K/ Akt signaling pathway and increasing OPG/RANKL ratio.

Objective:To explore the risk factors of coal workers' pneumoconiosis, reveal the molecular mechanism of pyroptosis in peripheral blood of coal workers' pneumoconiosis patients, and provide new strategies and potential diagnostic biomarkers for the treatment of the disease.Methods:From January 1, 2020 to December 31, 2022, workers with suspected occupational diseases who were diagnosed with coal workers' pneumoconiosis in the Third People's Hospital of Xinjiang Uygur Autonomous Region were included in the study, including 77 patients with coal workers' pneumoconiosis stage Ⅰ, 10 patients with stage Ⅱ, 6 patients with stage Ⅲ, and 49 workers with dust-free lung disease as the control group. General information of the subjects was collected, blood samples were collected for routine blood and blood biochemical results, and plasma levels of interleukin (IL) -1β and IL-18 were measured. Combined with the results of clinical examination, multi-factor ordered logistic regression analysis was carried out to evaluate the influencing factors of coal workers' pneumoconiosis. At the same time, the expression of pyroptosis related proteins in blood cells was detected to reveal the molecular mechanism of coal workers' pneumoconiosis.Results:All 142 subjects were male, with an average age of (51.65±6.31) years old and an average working age of (15.94±9.38) years. There were significant differences in smoking age ( F=4.95, P=0.003) and lunch break distribution ( H=8.84, P=0.031) among all groups. The hemoglobin content of stage Ⅰ patients was higher than that of stage Ⅱ patients, and the neutrophil percentage of stage Ⅲ patients was higher than that of the other 3 groups ( P<0.05). The levels of total bilirubin and indirect bilirubin in stage Ⅰ patients were higher than those in control group, while the erythrocyte sedimentation rate in stage Ⅱ patients was higher than that in the other 3 groups ( P<0.05). The levels of IL-18 and IL-1β in stage Ⅲ of coal workers' pneumoconiosis were higher than those in the other 3 groups ( P<0.05). Multiple logistic regression analysis showed that smoking age ( OR=1.03, 95% CI: 1.00-1.06) and IL-1β level ( OR=4.61, 95% CI: 1.59-13.32) were independent risk factors for coal workers' pneumoconiosis ( P<0.05). Compared with the control group, the expression levels of nucleotide-binding of oligomeric domain-like receptor protein 3 (NLRP3), Caspase-1, GSDMD, Caspase-4 and other proteins in stage Ⅲ of coal workers' pneumoconiosis were significantly increased ( P<0.05) . Conclusion:Smoking age is a risk factor for coal workers' pneumoconiosis, IL-1β may be a potential biomarker for the diagnosis of coal workers' pneumoconiosis, and pyroptosis may play a role in the development of peripheral inflammation of coal workers' pneumoconiosis.

Objective:To explore the risk factors of coal workers' pneumoconiosis, reveal the molecular mechanism of pyroptosis in peripheral blood of coal workers' pneumoconiosis patients, and provide new strategies and potential diagnostic biomarkers for the treatment of the disease.Methods:From January 1, 2020 to December 31, 2022, workers with suspected occupational diseases who were diagnosed with coal workers' pneumoconiosis in the Third People's Hospital of Xinjiang Uygur Autonomous Region were included in the study, including 77 patients with coal workers' pneumoconiosis stage Ⅰ, 10 patients with stage Ⅱ, 6 patients with stage Ⅲ, and 49 workers with dust-free lung disease as the control group. General information of the subjects was collected, blood samples were collected for routine blood and blood biochemical results, and plasma levels of interleukin (IL) -1β and IL-18 were measured. Combined with the results of clinical examination, multi-factor ordered logistic regression analysis was carried out to evaluate the influencing factors of coal workers' pneumoconiosis. At the same time, the expression of pyroptosis related proteins in blood cells was detected to reveal the molecular mechanism of coal workers' pneumoconiosis.Results:All 142 subjects were male, with an average age of (51.65±6.31) years old and an average working age of (15.94±9.38) years. There were significant differences in smoking age ( F=4.95, P=0.003) and lunch break distribution ( H=8.84, P=0.031) among all groups. The hemoglobin content of stage Ⅰ patients was higher than that of stage Ⅱ patients, and the neutrophil percentage of stage Ⅲ patients was higher than that of the other 3 groups ( P<0.05). The levels of total bilirubin and indirect bilirubin in stage Ⅰ patients were higher than those in control group, while the erythrocyte sedimentation rate in stage Ⅱ patients was higher than that in the other 3 groups ( P<0.05). The levels of IL-18 and IL-1β in stage Ⅲ of coal workers' pneumoconiosis were higher than those in the other 3 groups ( P<0.05). Multiple logistic regression analysis showed that smoking age ( OR=1.03, 95% CI: 1.00-1.06) and IL-1β level ( OR=4.61, 95% CI: 1.59-13.32) were independent risk factors for coal workers' pneumoconiosis ( P<0.05). Compared with the control group, the expression levels of nucleotide-binding of oligomeric domain-like receptor protein 3 (NLRP3), Caspase-1, GSDMD, Caspase-4 and other proteins in stage Ⅲ of coal workers' pneumoconiosis were significantly increased ( P<0.05) . Conclusion:Smoking age is a risk factor for coal workers' pneumoconiosis, IL-1β may be a potential biomarker for the diagnosis of coal workers' pneumoconiosis, and pyroptosis may play a role in the development of peripheral inflammation of coal workers' pneumoconiosis.

Objective:To study the therapeutic effect of cardiac rehabilitation in patients with acute myocardial infarction(AMI)after percutaneous coronary intervention(PCI)and its effect on inflammatory factors.Methods:A total of 94 AMI patients after PCI admitted in Hospital of China University of Geosciences(Wuhan)between June 2020 and August 2021 were selected and randomly divided into control group(n=47,routine therapy)and study group(n=47,individualized cardiac rehabilitation therapy based on routine therapy).Cardiopulmonary exercise indexes,blood lipid indexes,inflamma-tory factors and cardiac function indexes were compared between two groups before and 3 months after treatment.Results:Compared with control group after treatment,participants in study group had significant higher anaerobic threshold[(15.46±3.07)ml·min-1·kg-1 vs.(19.37±3.27)ml·min 1·kg-1],maximal oxygen uptake[(21.26±4.05)ml·min-1·kg-1 vs.(25.31±4.10)ml·min-1·kg-1],left ventricular ejection fraction(LVEF)[(52.20±5.75)％vs.(57.91±5.17)％],6min walking distance(6MWD)[(430.58±43.87)m vs.(481.52±44.57)m]and levels of high density lipoprotein cholesterol(HDL-C)[(1.30±0.32)mmol/L vs.(1.49±0.35)mmol/L]and interleukin(IL)-10[(5.45±0.55)pg/ml vs.(6.19±0.59)pg/ml](P＜0.01 all),and significant lower levels of triglyceride(TG)[(1.88±0.65)mmol/L vs.(1.54±0.63)mmol/L],total cholesterol(TC)[(3.49±0.54)mmol/L vs.(3.13±0.47)mmol/L],low density lipoprotein cholesterol(LDL-C)[(2.12±0.59)mmol/L vs.(1.57±0.52)mmol/L],tumor necrosis factor-α(TNF-α)[(128.34±14.5)pg/ml vs.(99.28±8.51)pg/ml],leptin(LEP)[(623.49±61.27)pg/ml vs.(483.57±47.61)pg/ml]and N terminal pro B-type natriuretic peptide(NT-proBNP)[(396.59±18.12)pg/ml vs.(302.96±17.56)pg/ml](P＜0.05 or＜0.01).Conclusion:Cardiac rehabilitation therapy can significantly im-prove the blood lipid levels,cardiac function and exercise endurance,and effectively reduce the levels of inflammatory fac-tors in AMI patients after PCI,which is an important component of secondary prevention in these patients.

The current situation of artificial intelligence(AI)was introduced when applied in the key links of cardiovascular health management such as risk prediction,early screening,clinical decision support and health consultation and education.The deficiencies of AI during the application were analyzed,and the prospects and development directions of AI in cardiovascular health management were pointed out.[Chinese Medical Equipment Journal,2024,45(2):92-96]

Objective To investigate the endoscopic ultrasonography(EUS)features of benign esophageal stenosis in children.Methods A retrospective analysis was conducted on the medical data of the children who were diagnosed with benign esophageal stenosis from February 2019 to February 2022.The clinical manifestations,EUS findings,and treatment outcome were analyzed to summarize the EUS features of benign esophageal stenosis in children.Results A total of 42 children with benign esophageal stenosis were included.Among these children,19(45% )had anastomotic stenosis after surgery for esophageal atresia,with unclear echogenic boundary of the esophageal walls and uneven thicknesses of the surrounding wall on EUS,and had 0-12 sessions of endoscopic treatment(average 2.1 sessions);5 children(12% )had corrosive esophageal stenosis and 1 child(2% )had physical esophageal stenosis,with unclear stratification of the esophageal walls on EUS,and they had 2-9 sessions of endoscopic treatment(average 5.3 sessions);1 child(2% )had patchy irregular hypoechoic areas of the esophageal walls on EUS and was diagnosed with tracheobronchial remnants with reference to pathology;16 children(38% )had unexplained esophageal stenosis and unclear stratification of the esophageal walls on EUS,among whom 6 received endoscopic treatment.During follow-up,95% (40/42)of the children had significant alleviation of the symptoms such as vomiting and dysphagia.Conclusions For benign esophageal stenosis in children,EUS can help to evaluate the degree of esophageal wall involvement in esophageal stenosis lesions,possible etiologies,and the relationship between the esophagus and the lesion and provide an important basis for selecting treatment modality and avoiding complications,thereby helping to optimize the treatment regimen.[Chinese Journal of Contemporary Pediatrics,2024,26(2):169-173]

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.