ObjectiveTo investigate the effects of excessive activation of the Specific protein 1 （Sp1）-MicroRNA-582-3p （miR-582-3p）-cyclin-dependent kinase inhibitor （p27） axis on the cell cycle and proliferation of A549 lung adenocarcinoma cells at the cellular level， thereby investigating the possible mechanisms by which Astragali Radix and Hedyotis diffusa（A-H） regulate the axis to inhibit A549 cells proliferation. MethodsLentiviral plasmid transfection technology was used to obtain four stable A549 transgenic cell lines： shRNA-Sp1+LV-miR-582-3p mimic， shRNA-Sp1+LV-mNC， shRNA-NC+LV-miR-582-3p mimic， and shRNA-NC+LV-mNC. Real-time PCR was used to detect the effect of Sp1 on miR-582-3p expression in A549 lung adenocarcinoma cells. CCK-8 and colony formation assay were used to detect the effect of Sp1 on cell proliferation through miR-582-3p， while flow cytometry was used to detect the effect of Sp1 on cell cycle via miR-582-3p. Western blot was used to detect the effect of Sp1 on cyclin in A549 cells through miR-582-3p. CCK-8 was employed to detect the effects of different concentrations （5%， 10%， 20%， 40%， 80%） of A-H on A549 cell viability， and the optimal concentration was selected for subsequent mechanism exploration. Stable transgenic strains oe-Sp1 and control oe-Vector were constructed using the above-mentioned transfection techniques. Real-time PCR was then used to investigate the effect of A-H on miR-582-3p expression in A549 cells， while Western blot was employed to detect the effect of A-H on Sp1 and p27 expression in A549 lung adenocarcinoma cells. ResultsCompared with the shRNA-NC+LV-mNC group， the expression of miR-582-3p was significantly inhibited in the shRNA-Sp1+LV-mNC group （P<0.01）. Compared with the shRNA-Sp1+LV-mNC group， the shRNA-Sp1+LV-miR-582-3p mimic group significantly reversed miR-582-3p expression （P<0.01）， indicating that Sp1 has a significant regulatory effect on miR-582-3p. Compared with the shRNA-Sp1+LV-mNC group， the shRNA-Sp1+LV-miR-582-3p mimic group significantly reversed cell proliferation （P<0.01）， suggesting that miR-582-3p can partially reverse the proliferative effect of Sp1 on A549 lung adenocarcinoma. Compared with the shRNA-Sp1+LV-mNC group， the shRNA-Sp1+LV-miR-582-3p mimic group showed a significant decrease in G₀/G₁ proportions， while the G₂/M and S phase proportions increased significantly （P<0.01）， indicating that miR-582-3p can partially reverse the effect of Sp1 on the A549 cell cycle. Compared with the shRNA-Sp1+LV-mNC group， the shRNA-Sp1+LV-miR-582-3p mimic group significantly reversed the expression of various proteins with the decrease of p27 and the increase of Cyclin D₁， CDK4， Cyclin E， CDK2， p-Rb， and E2F3 （P<0.01）， indicating that miR-582-3p can partially reverse the effect of Sp1 on the cell cycle of A549 lung adenocarcinoma. Compared with the blank group， the serum containing A-H significantly inhibited A549 cell viability in a concentration-dependent manner. Therefore， 10% A-H was selected for intervention of subsequent mechanism experiments. Compared with A-H+oe-Vector， A-H+oe-Sp1 significantly reversed the downregulation of Sp1， miR-582-3p， and the upregulation of p27 （P<0.01）. This suggests that Sp1 can partially reverse the effects of A-H on miR-582-3p and p27 levels in A549 lung adenocarcinoma cells. ConclusionOveractivation of the Sp1-miR-582-3p-p27 axis significantly promotes the proliferation of A549 lung adenocarcinoma cells， and the potential mechanism of the inhibitory effect of A-H on the proliferation of A549 cells may be related to its inhibition on the overactivation of the Sp1-miR-582-3p-p27 axis.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

At present, the C-arm structure accelerators commonly used in radiotherapy equipment are complex in operation and have potential safety hazards when realizing non-coplanar treatment. By combining with medical robotic arm technology, a spherical radiotherapy accelerator motion system is designed. The beam module is clamped by the medical robotic arm structure to achieve three-dimensional multi-angle irradiation treatment within the non-coplanar angle range. Firstly, the rotating mechanism, beam module, and MLC module of the spherical radiotherapy equipment are designed. Then, the double-plane counterweight method is used to calculate the dynamic balance of the equipment, ensuring that the beam center point does not rotate during the treatment process. Finally, the strength check and reliability analysis of the transmission component gear are conducted. The results show that the designed spherical radiotherapy accelerator motion system can meet the requirements of stable, accurate, and fast precision radiotherapy, which is conducive to improving the treatment efficiency.
Particle Accelerators/instrumentation* ; Equipment Design ; Reproducibility of Results ; Radiotherapy/instrumentation*

Clopidogrel effectively inhibits platelet aggregation in response to ADP by irreversibly binding to the platelet P2Y₁₂ receptor through its active metabolite. However, the observed discrepancies between the pharmacokinetics (PK) and pharmacodynamics (PD) of clopidogrel present substantial challenges in individualizing of antiplatelet therapy. To address these challenges, a robust liquid chromatography-tandem mass spectrometry method has been developed to facilitate the real-time assessment of platelet P2Y₁₂ receptor occupancy. This method has been validated in animal models, providing a reliable link between individual PK profiles and PD effects. Target receptor occupancy offers a comprehensive overview of interindividual variations in clopidogrel metabolism, regulation of P2Y₁₂ receptor expression, and platelet turnover. Moreover, it directly correlates with the inhibitory effect on platelet aggregation. The levels of platelet P2Y₁₂ occupancy accurately reflect the extent of clinical factors influencing the PD of clopidogrel, including dosage, drug-drug interactions (DDI), and type 2 diabetes mellitus (T2DM). As a normalized metric, platelet P2Y₁₂ occupancy not only serves potential as a diagnostic tool for personalized clopidogrel therapy but also aids in elucidating the role of the P2Y₁₂ signaling pathway in cases of abnormal on-treatment platelet reactivity.

Objective To understand the epidemiological characteristics of scrub typhus disease and to provide a scientific basis for the prevention and control of scrub typhus disease. Methods Descriptive epidemiological methods were used to analyze the population and regional distribution of scrub typhus. Seasonal characteristics were analyzed using concentration method and circular distribution method, and incidence trend was analyzed using joinpoint regression model. Results The annual incidence rate of scrub typhus was 0.95/100 000 from 2010 to 2022. The incidence rate of male was 0.77/100 000, lower than that of female 1.12/100 000 (χ²=18.89, P<0.05). The incidence rate of the 60-74 years old group was 3.38/100,000, and the total number of cases in the age group 45-74 years was 416 (74.95%). Occupational distribution was mainly among farmers, with 448 cases (80.72%). The top three regions with the highest number of reported cases (in order: Donghai County, Ganyu District, and Guannan County) reported a total of 416 cases, accounting for 74.95%. Concentration ratio was M=0.9408, and the incidence of scrub typhus disease was strictly seasonal. Circular distribution results showed a^-=-62.3728, S=20.8960. The circular distribution results indicated that the peak day was October 19th, and the peak period was between October 7 to December 19. The average annual percentage change (AAPC) of the incidence rate from 2010 to 2022 was 13.70%, 95% CI (-8.62%~41.48%), and the incidence rate showed an upward trend (t=1.15, P=0.249). Conclusion The incidence of scrub typhus disease is strictly seasonal, and the incidence rate over the years shows an upward trend. It is necessary to strengthen monitoring and take various intervention measures to reduce the risk of scrub typhus disease.

BACKGROUND:Increasing studies have shown that autophagy plays an important role in the treatment of osteoarthritis,and moderate autophagy can preserve the normal physiological function of osteoarticular chondrocytes.Traditional Chinese medicine(TCM)monomers can target and modulate autophagy to treat osteoarthritis,and their characteristics such as single components,clear efficacy,low price,and easy availability have obvious benefits in the treatment of osteoarthritis.OBJECTIVE:To review the effects of TCM monomers on the targeted regulation of autophagy in the treatment of osteoarthritis and the research progress,with a view to laying a foundation for the treatment of osteoarthritis and even other bone metabolic diseases.METHODS:Relevant literature published from January 2012 to October 2022 was retrieved in PubMed,Web of Science,CNKI,and WanFang using the keywords of"traditional Chinese medicine,Chinese herbal monomer,autophagy,osteoarthritis"in English and Chinese.Inclusion and exclusion criteria were developed,and 63 relevant articles were finally included by screening through reading the title,abstract,and full-text content.RESULTS AND CONCLUSION:TCM monomers can treat osteoarthritis by targeting autophagy to inhibit chondrocyte apoptosis,protect cartilage extracellular matrix,reduce inflammation and antagonize oxidative stress injury.Different TCM monomers can regulate autophagy in the same way,and the same TCM monomers can affect autophagy in different ways.The combination of multiple monomers and the multi-target and multi-pathway regulation of autophagy by TCM monomers remain to be explored.The regulation of autophagy by TCM monomers can provide new ideas and strategies for the prevention and treatment of osteoarthritis.Moderate regulation of autophagy by TCM monomers to keep the autophagic flux unimpeded may be the key to treating osteoarthritis.

BACKGROUND:More and more studies have shown that oxidative stress should play an important role in the treatment of osteoporosis.Oxidative stress should cause the accumulation of oxidation activity,which will damage bone-related cells.Finally,it causes the imbalance of bone resorption and bone formation,resulting in a decrease in bone volume and the destruction of the slight structure.Research in recent years has found that some natural products can regulate oxidative stress to treat osteoporosis.The characteristics of extensive sources and small side effects have obvious advantages in the treatment of osteoporosis,and the efficacy is objective. OBJECTIVE:To discuss the mechanism of natural product regulation of oxidation stress in treatment of osteoporosis,conduct a review based on the latest related research progress,provide reference and ideas for more natural products to treat osteoporosis in the future,and provide data support for the clinical application of natural compounds in the treatment of osteoporosis. METHODS:"oxidative stress,free radical,antioxidant,phytotherapy,plant extracts,medicinal plants,herbal medicine,osteoporosis,bone density,bone loss"were used as the keywords in PubMed,Web of Science,Embase,Cochrane,VIP,CBM,WanFang,and CNKI databases to search relevant articles published from January 2010 to February 2023.Inclusion and exclusion criteria were developed,and 64 relevant articles were selected by reading titles,abstracts,and full texts. RESULTS AND CONCLUSION:(1)Some natural products have antioxidant effects and can regulate osteogenic differentiation,osteoblast bone matrix mineralization,osteoclast-mediated bone resorption,proliferation,differentiation,activity,and apoptosis of bone-related cells by improving oxidative stress,thus affecting bone metabolism.(2)These natural products with antioxidant effects play a role in treating osteoporosis by improving bone remodeling balance.(3)The research on the combination of a variety of natural products to improve osteoporosis remains to be explored.(4)The use of natural products to regulate oxidative stress may become a powerful weapon for the clinical treatment of osteoporosis in the future.

Objective This study aims to investigate the pathogenesis and identify potential therapeutic targets for adolescent idiopathic scoliosis(AIS)through the utilization of bioinformatics analysis on gene chip data obtained from mesenchymal stem cells.Methods The gene chip GSE110359 was acquired from the gene expression omnibus(GEO)database to procure the gene expression profiles of mesenchymal stem cells derived from AIS and non AIS patients.Weighted gene co-expression network analysis(WGCNA)method was employed to identify the principal modules associated with adolescent idiopathic scoliosis.Furthermore,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were conducted.Additionally,immune cell infiltration analysis and protein-protein interaction(PPI)analysis were performed on 28 distinct immune cell types,leading to the identification of core genes.Results A total of eight gene co-expression modules were successfully identified.GO analysis revealed significant enrichment in various biological processes,including response to decreased oxygen levels,response to oxygen levels,ribonucleoprotein complex subunit organization,collagen-containing extracellular matrix,spliceosome snRNP complex,snRNA binding,and extracellular matrix structural components.KEGG analysis demonstrated enrichment in several pathways,such as hypoxia-inducible factor-1 signaling pathway,spliceosome,ferroptosis,fatty acid degradation,and other pathways.Furthermore,the findings pertaining to immune infiltration revealed a noteworthy decrease in the quantity of monocytes within the AIS group compared to the non AIS group(P<0.05).There was a heightened level of infiltration by activated dendritic cells in the AIS group(P<0.05).PPI analysis was conducted,resulting in the identification of angiopoietin-like 4(ANGPTL4),C-X-C motif chemokine ligand 8(CXCL8),solute carrier family 2 member 1(SLC2A1),hexokinase 2(HK2),and transferrin receptor protein(TFRC).Conclusion ANGPTL4,CXCL8,SLC2A1,HK2 and TFRC have been identified as potential biomarkers and therapeutic targets of AIS patients.Monocytes and activated dendritic cells have emerged as significant targets for immunotherapy in the context of AIS.

Objective:To compare the role and efficacy of serum Helicobacter pylori ( HP) antibody combined with pepsinogen (PG) (ABC method), serum PG combined with gastrin-17 (G-17) (new ABC method) and a new gastric cancer screening scoring system for early gastric cancer screening in healthy people. Methods:Serological examinations were performed on healthy people who underwent physical examination and gastroscopy at the Physical Examination Center of Shanghai Songjiang District Central Hospital from January 2019 to December 2021. The population were divided into low-risk population, medium-risk population and high-risk population based on the above three primary screening methods for gastric cancer. Using gastroscopy and biopsy pathology as the gold standard, the ratio of each risk stratification and the detection rate of gastric cancer of the three screening methods were calculated. Advantages and disadvantages of the three methods were evaluated.Results:A total of 3 199 people who completed physical examination and gastroscopy were included in the study. Ten cases (0.31%) of esophageal cancer were detected by endoscopy, all of whom were early esophageal cancer. Thirty-seven cases (1.16%) of gastric cancer were detected,and the detection rate of early gastric cancer was 86.49%(32/37). The three gastric cancer screening methods were used to evaluate the risk of gastric cancer. According to ABC method, there were 1 853 cases (7.92%) in the low-risk group, 1 339 cases (41.86%) in the medium-risk group, and 7 cases (0.22%) in the high-risk group. The detection rates of gastric cancer were 0.97% (18/1 853), 1.42% (19/1 339), and 0.00%, respectively. According to the new ABC method, there were 2 362 cases (73.84%) in the low-risk group, 804 cases (25.13%) in the medium-risk group, and 33 cases (1.03%) in the high-risk group. The detection rates of gastric cancer were 1.14% (27/2 362), 1.24% (10/804), and 0.00%, respectively. According to the new gastric cancer screening scoring system, there were 1 448 cases (45.26%) in the low-risk group, 1 213 cases (37.92%) in the medium-risk group and 538 cases (16.82%) in the high-risk group. The detection rates of gastric cancer were 0.28% (4/1 448), 1.32% (16/1 213) and 3.16% (17/538), respectively. The detection rate of gastric cancer in the medium- and high-risk groups in total was significantly higher than that in the low-risk group with significant difference ( χ 2=17.935, P<0.001). The ROC curve showed that the AUC of the ABC method, the new ABC method and the new gastric cancer screening scoring system were 0.546, 0.503 and 0.760, respectively. The AUC of the new gastric cancer screening scoring system was significantly higher than those of the ABC method and the new ABC method, and the differences were statistically significant ( P<0.001). Conclusion:The detection rate of gastric cancer in the medium- and high-risk groups of the new gastric cancer screening scoring system is higher than that of the low-risk group, and the missed diagnosis rate of the new gastric cancer screening scoring system is lower than those of the ABC method and the new ABC method. The screening score is of high value for early gastric cancer screening in the healthy population.