Objective: To investigate the urban and rural differences in adverse outcomes of pulmonary tuberculosis (PTB) in patients with pulmonary tuberculosis-diabetes mellitus comorbidity (PTB-DM), so as to provide insights into improving the prevention and treatment measures for PTB-DM. Methods: Patients with PTB-DM who were admitted and discharged from 14 designated tuberculosis hospitals in Hangzhou City from 2018 to 2022 were selected. Basic information, and history of diagnosis and treatment were collected through hospital information systems. The adverse outcomes of PTB were defined as endpoints, and the proportions of adverse outcomes of PTB in urban and rural patients with PTB-DM were analyzed. Factors affecting the adverse outcomes of PTB were identified using a multivariable Cox proportional hazards regression model. Results: A total of 823 patients with PTB-DM were enrolled, including 354 (43.01%) urban and 469 (56.99%) rural patients. There were 112 (13.61%) patients with adverse outcomes of PTB. The proportions of adverse outcomes of PTB in urban and rural patients were 14.41% and 13.01%, respectively, with no statistically significant difference (P>0.05). Multivariable Cox proportional hazards regression analysis identified first diagnosed in county-level hospitals or above (HR=2.107, 95%CI: 1.181-3.758) and drug resistance (HR=3.303, 95%CI: 1.653-6.600) as the risk factors for adverse outcomes of PTB in urban patients with PTB-DM, while the treatment/observed management throughout the process (HR=0.470, 95%CI: 0.274-0.803) and fixed-dose combinations throughout the process (HR=0.331, 95%CI: 0.151-0.729) as the protective factors for adverse outcomes in rural patients with PTB-DM. Conclusions There are differences in influencing factors for adverse outcomes of PTB in urban and rural patients with PTB-DM. The adverse outcomes of PTB are associated with first diagnosed hospitals and drug resistance in urban patients, and are associated with the treatment/observed management and fixed-dose combinations throughout the process in rural patients.

BACKGROUND:Steroid-induced osteonecrosis of the femoral head is a refractory disease in the field of orthopedics.There is no definitive idea to fully explain its pathogenesis.With the increased research on the active ingredients of Panax notoginseng interfering with the signaling pathways related to various diseases,the active ingredients of Panax notoginseng that treat steroid-induced necrosis of the femoral head via the regulation of relevant signaling pathways have gradually become a hot research topic. OBJECTIVE:To systematically summarize the literature on the pathological mechanism of steroid-induced osteonecrosis of the femoral head and the regulation of signaling pathways by the active ingredients of Panax notoginseng in recent years,thereby providing a reference for the follow-up study on the active ingredients of Panax notoginseng in the treatment of this disease. METHODS:CNKI,WanFang,and PubMed were searched for relevant literature with the key words of"glucocorticoid,steroid-induced osteonecrosis of the femoral head,pathological mechanism,signaling pathway,Panax notoginseng,active ingredient"in Chinese and English.Documents related to the pathological mechanism of steroid-induced osteonecrosis of the femoral head as well as related to the intervention of active ingredients of Panax notoginseng on the signaling pathway of steroid-induced osteonecrosis of the femoral head were retrieved.A total of 63 documents were finally included according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:The main ingredients of Panax notoginseng include Panax notoginseng saponins,ginsenoside,Panax notoginseng saponins,quercetin,kaempferol,etc.Panax notoginseng saponins,ginsenoside Rb1 and quercetin can promote bone repair and angiogenesis by acting on the transforming growth factor-β/bone morphogenetic protein pathway.Panax notoginseng saponins,ginsenoside CK and kaempferol can promote osteogenic differentiation and lipid metabolism by acting on the Wnt/β-catenin pathway.Panax notoginseng saponins and Panax notoginseng saponins R1/R2 act on the MAPK pathway to inhibit osteoclastogenesis and promote bone repair.Panax notoginseng saponins,ginsenoside Rb2 and quercetin can inhibit osteoclast proliferation and promote osteoblastic differentiation by acting on the RANKL/RANK/OPG pathway.Panax notoginseng saponins,quercetin and kaempferol can repair vascular injury and promote osteogenesis by acting on the hypoxia-inducible factor-1α pathway.Panax notoginseng saponins R1,quercetin combined with hydroxyapatite nanoparticles,Panax notoginseng saponins combined with polyethylene-L-lactic acid and other biomaterials have good research prospects in the treatment of steroid-induced osteonecrosis of the femoral head.The active ingredients of Panax notoginseng can regulate the signaling pathways related to steroid-induced osteonecrosis of the femoral head through various mechanisms,and play an active intervention role in the disease.However,the depth and breadth of relevant research are insufficient at present,and the future research should be based on the existing mechanism to explore the specific mechanism of Panax notoginseng regulating different pathways and the interaction between pathways,which will be beneficial to the multi-development of the active ingredients of Panax notoginseng in the treatment of steroid-induced osteonecrosis of the femoral head.

Objective: To explore the current status of knowledge, attitudes and practices (KAP) regarding tuberculosis(TB)prevention and control among high school students, and to compare differences between male and female students, so as to provide a scientific basis for targeted TB prevention and control measures in high schools. Methods: From April to May 2024, a stratified cluster random sampling method was employed to conduct an electronic questionnaire survey among 1 912 students from 10 high schools using a compiled questionnaire on KAP towards TB prevention and control. The AMOS 26.0 software was utilized to construct structural equation modeling (SEM) and compared the difference among genders. Results: The overall awareness rate of core TB knowledge among high school students in Gongshu District was 76.62%. Additionally, core knowledge about TB (6.28±1.44), prevention attitudes (6.02±1.84), and prevention practices (6.38±2.11) scores of female students were higher than those of male students (5.96±1.74, 5.59±2.21, 6.15±2.23) ( t =4.31, 4.64, 2.25, P <0.05). The SEM showed that knowledge had a strong positive impact on practices and attitudes among boys, with total effect values of 0.963 and 0.819 , respectively; while the positive influence of attitudes on practices was relatively weak, with a total effect value of 0.186. Among girls, attitudes had a positive impact on practices and knowledge, with total effect values of 0.479 and 0.222, respectively. Conclusions The pathways and strengths of influence of KAP in the SEM of TB prevention and control differ between male and female high school students. Therefore, differentiated strategies should be implemented for TB health education targeting male and female high school students.

Objective To investigate the effects of ATP-binding cassette subfamily B transporter 6 subfamily B(ABCB6)on cognitive dysfunction in Alzheimer's disease(AD)rats and its possible potential regulatory molecular mechanisms.Methods Amyloid β-protein(Aβ)was injected to construct the AD mouse model in vivo.Water maze test and Y maze test were used to evaluate the learning and memory ability and space exploration ability of rats.An in vitro AD cell model was constructed by HT22 cells and Aβ.The binding relationship between YTH domain containing 1(YTHDC1)and ABCB6 was analyzed by RNA immuniprecipitation(RIP).Quantitative real time polymerase chain reaction(qRT-PCR)was used to detect overexpression and knockdown transfection efficiency.Western blot analysis was performed to detect the expression levels of YTHDC1 and ABCB6 proteins,as well as ferroptosis related proteins[Solute Carrier Family 7 Member 11(SLC7A11),Glutathione peroxidase 4(GPX4)].Cell viability was detected with CCK-8.Malondialdehyde(MDA),Glutathione(GSH),Reactive oxygen species(ROS)levels and Fe2+content were analyzed by the assay kit.Results The ABCB6 mRNA(3.51±0.17 vs 1.02±0.01,3.45±0.21 vs 1.02±0.01)and protein(3.25±0.14 vs 1.01±0.01,3.14±0.16 vs 1.01±0.01)levels in the hippocampus of AD mice and Aβ-induced HT22 cells were up-regulated,and the differences were statistically significant(t=-46.238,-20.349;-50.468,-23.013,all P<0.001).Knocking down ABCB6 decreased the time and distance of AD mice reaching the platform,and increased the ratio of spontaneous exchange rate to the number of times of entered the new arm(t=27.007,11.264,24.414,19.901,all P<0.001).Knockdown ABCB6 promoted HT22 cell proliferation,decreased levels of MDA and Fe2+,increased GSH levels,reduced ROS generation,and promoted expression of SLC7A11 and GPX4 proteins(t=2.883～26.122,all P<0.05).YTHDC1 protein promoted its stability by binding to ABCB6 mRNA and up-regulated the expression of ABCB6 protein.Knockdown of YTHDC1 decreased ABCB6 protein level(t=18.504,P<0.001),promoted the proliferation of HT22 cells,increased GSH content,SLC7A11 and GPX4 protein levels,decreased MDA and Fe2+content,and inhibited ROS production(t=4.404～14.486,all P<0.05).Knocking down YTHDC1 could improve the learning and memory ability and spatial exploration ability of AD mice.Over-expression of ABCB6 reversed the effects of YTHDC1 knockdown on ferroptosis in HT22 cells and cognitive dysfunction in AD mice.Conclusion YTHDC1 may induce ferroptosis of neuronal cells by mediating the up-regulation of ABCB6,thus promoting cognitive dysfunction in AD mice.

AIM:To investigate the effect of plate-let(PLT)on angiogenesis in hepatocellular carcino-ma and the intervention effect of Cinobufagin(CBG).METHODS:Firstly,we screened the suitable co-incubation ratio of PLT and hepatocellular carci-noma cells,prepared conditioned medium,and de-termined the half inhibitory concentration of Cinob-ufagin;then,we set up a control group(human um-bilical vein endothelial cells(EC)+conventional me-dium),a crosstalk group(EC+CM_HP(strip culture prepared by crosstalk of HUH7 and PLT)),and an in-tervention group(EC+CM_HP+CBG).The migration,tube-formation and sprouting capacity of EC and the level of vascular endothelial growth factor(VEGF)in co-cultured supernatant were evaluated by scratch assay,tube-formation assay,budding as-say and ELISA assay.Western blot was used to de-tect the expression of VEGFR2 and p-VEGFR2,and reverse verification was performed with inhibitors.A subcutaneous transplantation tumour model of hepatocellular carcinoma in nude mice was estab-lished,with Model group,Model+CBG group and Model+Apa group.The collagen expression of the transplantation tumour was observed by Masson staining,and the expression levels of vascular endo-thelial markers CD31 and CD34 were detected by immunofluorescence.RESULTS:When PLT:HUH7=200,the activity of HUH7 was the strongest,and the crosstalk between HUH7 and PLT significantly promoted the proliferation of EC(P＜0.01).Com-pared with Control group,the migration,tube-for-mation and budding ability of Crosstalk group were enhanced,and those of Intervention group were lower than those of Crosstalk group(P＜0.01).The expression level of VEGF in the supernatant of Crosstalk group was higher than that of Control group,while that of Intervention group was lower than that of Crosstalk group(P＜0.01).The expres-sion level of p-VEGFR2 protein in Crosstalk group was significantly higher than that of Control group,but the expression level of Intervention group was lower than that of Crosstalk group(P＜0.01).Large collagen fibre deposition was seen in the Model group,and CBG intervention significantly reduced collagen fibre deposition in the transplanted tu-mour tissues.CD31 and CD34 expression was pres-ent in the hepatocellular carcinoma transplanted tumour tissues in the Model group,and CBG inter-vention significantly reduced the expression of CD31 and CD34 in the liver cancer transplanted tu-mour tissues(P＜0.01).CONCLUSION:PLT enhances angiogenesis in hepatocellular carcinoma,and CBG may inhibit its tube-forming ability via the VEGF/VEGFR2 pathway.

OBJECTIVES: This study aimed to investigate the effect of new biomimetic micro/nano surfaces on the osteoclastic differentiation of RAW264.7 macrophages by simulating natural osteons for the design of concentric circular structures and modifying graphene oxide (GO). METHODS: The groups were divided into smooth titanium surface group (SS), concentric microgrooved titanium surface group (CMS), and microgroove modified with GO group (GO-CMS). The physicochemical properties of the material surfaces were studied using scanning electron microscopy (SEM), contact-angle measurement, atomic force microscopy, X-ray photoelectron spectroscopy analysis, and Raman spectroscopy. The effect of the modified material surface on the cell biological behavior of RAW264.7 was investigated by cell-activity assay, SEM, and laser confocal microscopy. The effect on the osteoclastic differentiation of macrophages was investiga-ted by tartrate-resistant acid phosphatase (TRAP) immunofluorescence staining and quantitative real-time polymerase chain reaction (qRT-PCR) experiments. RESULTS: Macrophages were arranged in concentric circles along the microgrooves, and after modification with GO, the oxygen-containing groups on the surface of the material increased and hydrophilicity increased. Osteoclasts in the GO-CMS group were small in size and number and had the lowest TRAP expression. Although it promoted the proliferation of macrophages in the GO-CMS group, the expression of osteoclastic differentiation-related genes was lower than that in the SS group, and the difference was statistically significant (P<0.05). CONCLUSIONS Concentric circular microgrooves restricted the fusion of osteoclasts and the formation of sealing zones. Osteomimetic concentric microgrooves modified with GO inhibited the osteoclastic differentiation of RAW 264.7 macrophages.
Graphite/pharmacology* ; Titanium/pharmacology* ; Haversian System ; Macrophages ; Cell Differentiation ; Oxides/pharmacology* ; Surface Properties

The cultivation and production of cucumber are seriously affected by downy mildew caused by Pseudoperonospora cubensis. Downy mildew damages leaves, stems and inflorescences, and then reduces the yield and quality of cucumber. This review summarized the research advances in cucumber downy mildew, including pathogen detection and defense pathways, regulatory factors, mining of pathogens-resistant candidate genes, proteomic and genomic analysis, and development of QTL remarks. This review may facilitate clarifying the resistance mechanisms of cucumber to downy mildew.
Cucumis sativus/genetics* ; Oomycetes/genetics* ; Peronospora ; Plant Diseases/genetics* ; Proteomics

AIM: To explore the pharmaceutical effects of tetrahydroxy stilbene glycoside (TSG) on acute liver injury induced by acetaminophen (APAP) using method of non-targeted metabonomics. METHODS: SPF C57BL/6 mice were randomly divided into the group of APAP-induced model and the group of TSG intervention groups (n=15). After intragastric administration of TSG for 7 days, the mice were injected once by APAP via intraperitoneal injection and the livers were taken 6 hours later. RESULTS: H&E staining, MDA and SOD tests showed that the injection of APAP could cause hepatic injury, but TSG could reduce the severity of liver injury. The results of metabolite detection showed that there were significant changes in ABC transporter, choline metabolism, central carbon metabolism, galactose and alanine amino acid metabolism in TSG groups compared with APAP model group. CONCLUSION: TSG protects against acute liver injury induced by APAP, mainly by improving lipid peroxidation and disorder of energy metabolism.

Lysine acetylation is one of the major post-translational modifications and plays critical roles in regulating gene expression and protein function. Histone deacetylases (HDACs) are responsible for the removal of acetyl groups from the lysines of both histone and non-histone proteins. The RPD3 family is the most widely studied HDACs. This article summarizes the regulatory mechanisms of Arabidopsis RPD3 family in several growth and development processes, which provide a reference for studying the mechanisms of RPD3 family members in regulating plant development. Moreover, this review may provide ideas and clues for exploring the functions of other members of HDACs family.
Arabidopsis/metabolism* ; Histone Deacetylases/metabolism* ; Histones ; Plant Development/genetics*

Objective:To construct a simple, precise and personalized comprehensive nomogram for prediction the risk of multidrug-resistant tuberculosis (MDR-TB) and to evaluate its prediction value among individuals with previous tuberculosis history (PTBH).Methods:A matched case-control study (1∶2 ratios) was performed in 1 881 patients with PTBH treated in 12 designated tuberculosis hospitals in Hangzhou City between January 1, 2005 and December 31, 2019, and there were 1 719 patients in training set, and 162 in validation set. A multivariable Cox regression analysis was used to evaluate independent predictors for the incident of MDR-TB in individuals with PTBH. A comprehensive nomogram was developed based on the multivariable Cox model. The accuracy of the prediction was assessed using concordance index (C-index), calibration curve and area under the receiver operator characteristic (ROC) curve.Results:The nomogram constructed based on the multivariable Cox regression model incorporated 10 independent predictors of the risk of MDR-TB. A history of direct contact (grade 1, 0-100.0 points) ranked on the top of all risk factors, followed by duration of positive sputum culture (grade 2, 0-84.5 points), unfavorable treatment outcome (grade 3, 0-52.0 points), human immunodeficiency virus infection (grade 4, 0-48.5 points), retreated tuberculosis history (grade 5, 0-40.0 points), non-standardized treatment regimens of retreated tuberculosis (grade 6, 0-32.5 points), duration of pulmonary cavities (grade 7, 0-31.0 points), passive mode of tuberculosis case finding (grade 8, 0-25.0 points), age<60 years (grade 9, 0-17.5 points), and standard frequencies of chest X-ray examination (grade 10, 0-14.0 points). The C-indexes of this nomogram for the training and validation sets were 0.833 (95% confidence interval ( CI) 0.807-0.859) and 0.871 (95% CI 0.773-0.969), respectively, indicating that the nomogram had good fitting effect. The calibration curves for the risk of incident MDR-TB showed an optimal agreement between nomogram prediction and actual observation in the training and validation sets, respectively.The areas under ROC curve of the 1-year, 5-year, and 10-year MDR-TB risk probability of the training set were 0.904, 0.921, and 0.908, respectively, and those of the validation set were 0.954, 0.970, and 0.919, respectively. Conclusion:Through this nomogram model, clinicians could precisely predict the risk of incident MDR-TB among individuals with PTBH in the clinical practice.