Aim To investigate the effect of homocys-teine(Hcy)on the permeability of pulmonary micro-vascular endothelial cells(PMVECs)and the role and mechanism of RASAL1.Methods CBS+/-mice were fed a high methionine diet(HMD)for 16 weeks to replicate an animal model of hyperhomocysteinemia(HHcy).HE staining was used to observe the changes in lung tissue structure.qRT-PCR was used to detect the levels of RASAL1 and DNMT1 mRNA in lung tis-sue.Western blot was used to detect the expression of RASAL1,DNMT1,ZO-1,and VE cadherin proteins.Methylation specific PCR was used to detect methyla-tion in the RASAL1 promoter region.PMVECs were transfected with Ad-RASAL1 to detect the expression of ZO-1 and VE cadherin.The si-DNMT1 interference fragment was transfected into PMVECs,and the ex-pression of the RASAL1 was detected by qRT-PCR and Western blot.Results Serum Hcy level of HMD mice was significantly raised,and HE staining showed severe structural disorder in lung tissue.The expres-sion of RASAL1,ZO-1,and VE cadherin was de-creased,while the expression of DNMT1 was in-creased.The degree of methylation in the RASAL1 promoter region was raised.The expression of ZO-1 and VE cadherin increased after PMVECs were trans-fected with Ad-RASAL1.After knocking down DN-MT1,RASAL1 expression was increased.Conclusion Hcy can increase the permeability of PMVECs,and its mechanism is related to the upregulation of RASAL1 methylation level.

Aim To investigate the mechanism of Banxia Baizhu Tianma Decoction(BBTD)in interfer-ing methamphetamine(MA)addiction using network pharmacology.Methods The mechanism of BBTD intervention in MA addiction was analyzed using net-work pharmacology,and MA-dependent SH-SY5Y cell model was further constructed to observe the effects of BBTD on cell model and PI3K-Akt pathway.Results A total of 88 active ingredients and 583 potential tar-gets of BBTD were screened.KEGG analysis showed that BBTD might intervene in MA addiction through PI3K-Akt,cAMP and other pathways.The molecular docking results showed that key active ingredients ex-hibited strong binding ability with core targets of PI3K-Akt pathway.In vitro experiments showed that MA-de-pendent model cells had shorter synapses,tended to be elliptical in morphology,had blurred cell boundaries,showed typical cell damage morphology,and had high intracellular expression of cAMP(P＜0.01)and low expression of 5-HT(P＜0.05).BBTD intervention could counteract the above morphology,cAMP,and 5-HT changes,suggesting that it had therapeutic effects on MA-dependent model cells.Western blot showed that MA modeling elevated the p-PI3K/PI3K(P＜0.05)and p-Akt/Akt(P＜0.01);BBTD inter-vention decreased their relative expression.Conclu-sions Gastrodin and other active ingredients in BBTD have therapeutic effects on MA addiction,and the mechanism may be related to regulation of PI3K-Akt pathway relevant targets.

Aim To investigate the molecular mecha-nisms of the Wenyang Huazhuo Tongluo formula in in-hibiting endothelial-to-mesenchymal transition(En-doMT)of pulmonary microvascular endothelial cells and improving pulmonary microvascular injury in sys-temic sclerosis(SSc).Methods Pulmonary micro-vascular endothelial cells were cultured with serum from SSc patients to establish SSc pulmonary microvas-cular endothelial cells.A hypoxia model was estab-lished in SSc pulmonary microvascular endothelial cells using liquid paraffin sealing,and the cells were treated with the Wenyang Huazhuo Tongluo formula or HIF-1a inhibitor KC7F2.Western blot was used to detect the protein expression levels of VE-cadherin,CD31,vimen-tin,HIF-1α,Foxm1,smad3,Tie-1,and vWF.ELISA was used to measure the concentrations of E-selectin and ICAM-1 in cell culture medium.The luciferase re-porter gene system was used to detect the promoter ac-tivity of the Foxm1 gene.Results Compared to the control group,the levels of VE-cadherin,CD31,HIF-1α,Foxm1,smad3,Tie-1,and vWF significantly de-creased under hypoxic condition,while the levels of vi-mentin,E-selectin,and ICAM-1 significantly in-creased.In addition,the cell morphology exhibited a distinct"spindle-like"myoblast morphology.Treat-ment with the Wenyang Huazhuo Tongluo formula or KC7F2 reversed these changes in protein expression levels and cell morphology induced by hypoxia.Con-clusion The Wenyang Huazhuo Tongluo formula im-proves pulmonary microvascular injury in SSc by inhib-iting the HIF-1a/Foxm1/smad3 pathway-mediated En-doMT of pulmonary microvascular endothelial cells.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

To understand the distribution of ticks in the Wuwei Region,enrich tick species data,and provide a basis for the prevention of tick-borne diseases,tick were collected using flagging and tick-picking methods during the highest activity period from April to September in 2021 and 2022 in the mountainous areas of Wuwei City.The ticks were identified based on morpho-logical and molecular biological characteristics,and characteristic sequences were obtained.A systematic evolutionary tree was constructed using the neighbor-joining method in MEGA 11.0 software.In total,7 342 ticks collected in Wuwei,which be-longed to 5 species from 4 genera with in the Ixodidae family,which included Dermacentor nuttalli,Hyalomma asiaticum,Ixodes canisuga,Haemaphysalis longicornis and Haema-physalis danieli.Ticks of the same species clustered together into the same branch of an evolutionary tree.In the Wuwei Re-gion,five common tick species are found across various habi-tats,with each habitat featuring different distributions of tick species and populations.The Dermacentor nuttalli is the dom-inant tick species in this area.

Non-suicidal self-injury behavior and suicidal ideation are important risk factors for suicide attempts in patients with depression.At present,studies have found that there are obvious differences in electroencephalogram(EEG)characteristics between these two.Resting-state EEG analysis reveals that the absolute power of Gamma in specific electrode points is significantly increased in patients with depression accompanied by suicidal ideation.The Beta and Gamma activities of those with non-suicidal self-injury behavior changed.EEG microstate research shows that there are differences in microstates between those with non-suicidal self-injury behavior and those with suicidal ideation.Among them,short segments of microstate sequences have certain potential.In event-related potentials,these two show specific characteristics in components such as P3 wave and N2 wave.The amplitude of N2 wave in patients with depression accompanied by non-suicidal self-injury behavior is lower.Although there are few machine learning-related studies on EEG technology,it has shown certain application prospects.Therefore,this article will summarize the progress of EEG research related to the two,aiming to provide a basis for early prediction of suicide in depression.

HDAC(histone deacetylase)is a class of epigenetic modifying enzymes that can deacetylate proteins by altering the acetylation status of histones in the nucleus,regulating promoter activation levels,and thereby affecting downstream gene expression.However,expression changes of HDACs during endo-thelial differentiation are still unclear.This study used a three-stage method to induce human induced pluripotent stem cells(hiPSCs)to differentiate into endothelial cells,and qRT-PCR was used to detect the expression changes of class I HDAC(HDAC1,2)and class Ⅱ HDAC(HDAC4,5)genes.It was found that HDAC5 exhibits significant expression changes during endothelial differentiation.It is downreg-ulated by 90％during the mesodermal differentiation stage(P＜0.01),upregulated by 3.7-fold during the vascular precursor stage(P＜0.01),and subsequently downregulated by 70％during the late stage of endothelial differentiation(P＜0.01).Immunoblotting experiments further confirmed that HDAC5 under-goes periodic expression changes during endothelial differentiation.Mechanistic studies have shown that HDAC5 downregulation during the differentiation stage of the mesoderm is mediated by Wnt signaling.CHIR99021 treatment and overexpression of Wnt3a can activate the Wnt signaling pathway,leading to HDAC5 downregulation.Inhibiting the Wnt signaling pathway through IWP-2 promotes the recovery of HDAC5 expression.In addition,it was found that HDAC5 is mainly localized in the nucleus,and IWP-2 restores HDAC5 expression,but it remains in the cytoplasm.Further research suggests that downregu-lation of HDAC5 during mesodermal differentiation may contribute to the expression of the mesodermal marker BraT.Treatment with the HDAC inhibitor BML210 can promote early mesodermal differentiation,interfere with endothelial differentiation of vascular precursor cells,and enhance late-stage endothelial differentiation.In conclusion,HDAC5 displays a stage-specific expression during endothelial differentia-tion,and Wnt signaling activation is the main mechanism regulating the downregulation of HDAC5 during the mesoderm stage.

Objective:To investigate the effect of progression of disease within 24 months(POD24)on overall survival(OS)in patients with mantle cell lymphoma(MCL),and compare the clinical characteristics between POD24 and non-POD24 patients.Methods:A retrospective analysis was performed on 50 MCL patients with treatment indications and regular treatment who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to August 2020.According to the occurrence of POD24,the patients were grouped for prognostic evaluation and clinical characteristics comparison.Results:Univariate Cox regression analysis showed that POD24,PLT,albumin,MIPI score,ECOG PS score,LDH were the factors influencing OS in newly diagnosed MCL patients(all P＜0.05).The results of multivariate Cox regression analysis showed that POD24[HR=16.797(95％CI:3.671-76.861),P＜0.001],albumin＜40 g/L[HR=3.238(95％CI:1.095-9.572),P=0.034]and ECOG PS score≥2[HR=4.005(95％CI:1.033-15.521),P=0.045]were independent risk factors influencing OS in MCL patients.The incidence of PLT＜100 × 109/L(33.3％vs 5.9％,P=0.033)and ECOG PS score≥2(45.5％vs 5.9％,P=0.040)were significantly higher in POD24 patients than those in non-POD24 patients.Conclusion:POD24 is an independent poor prognostic factor affecting the OS of MCL patients,and the patients with PLT＜100 × 109/L and ECOG PS score ≥2 at diagnosis have a higher probability of POD24.

Objective:To investigate the effect of endothelial activation and stress index(EASIX)on the prognosis of patients with angioimmunoblastic T-cell lymphoma(AITL)and peripheral T-cell lymphoma,not otherwise specified(PTCL-NOS),and to compare the clinical characteristics of patients in the low EASIX and high EASIX groups.Methods:The clinical data of 59 newly diagnosed AITL and PTCL-NOS patients admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to September 2021 were retrospectively analyzed.The optimal cut-off value of EASIX was determined by receiver operating characteristic(ROC)curve;The chi-square test was used to analyze the correlation between EASIX and clinical features of patients with AITL and PTCL-NOS;The Kaplan-Meier survival curve was used to analyze the overall survival(OS)and progression-free survival(PFS)of the patients;Univariate and multivariate analyses were performed by using Cox proportional hazards model.Results:The optimal cut-off value of EASIX was 0.95,based on which the patients were divided into a low EASIX(＜0.95)group and a high EASIX(≥ 0.95)group.Compared with the low EASIX group,the high EASIX group had a higher proportion of patients with advanced Ann Arbor stage,higher risk according to IPI,elevated LDH,hypoproteinemia,anemia,B symptoms,extranodal involvement,and bone marrow involvement.Survival analysis showed that the OS and PFS of patients in the high EASIX group were significantly shorter than those in the lower EASIX group(P＜0.001).The multivariate analysis showed that EASIX was an independent risk factor for OS[HR=7.217(95％CI:1.959-26.587),P=0.003]and PFS[HR=2.718(95％CI:1.032-7.161),P=0.043]of PTCL patients.Conclusion:High EASIX in newly diagnosed patients with AITL and PTCL-NOS suggests a poor prognosis,and high EASIX is a risk factor affecting prognosis of the patients.

Objective: The effect on fat infiltration (FI) of paraspinal muscles in degenerative lumbar spinal diseases has been demonstrated except for spinopelvic parameters. The present study is to identify the effect of spinopelvic parameters on FI of paraspinal muscle (PSM) and psoas major muscle (PMM) in patients with degenerative lumbar spondylolisthesis. Methods: A single-center, retrospective cross-sectional study of 160 patients with degenerative lumbar spondylolisthesis (DLS) and lumbar stenosis (LSS) who had lateral full-spine x-ray and lumbar spine magnetic resonance imaging was conducted. PSM and PMM FIs were defined as the ratio of fat to its muscle cross-sectional area. The FIs were compared among patients with different pelvic tilt (PT) and pelvic incidence (PI), respectively. Results: The PSM FI correlated significantly with pelvic parameters in DLS patients, but not in LSS patients. The PSM FI in pelvic retroversion (PT > 25°) was 0.54 ± 0.13, which was significantly higher in DLS patients than in normal pelvis (0.41 ± 0.14) and pelvic anteversion (PT < 5°) (0.34 ± 0.12). The PSM FI of DLS patients with large PI ( > 60°) was 0.50 ± 0.13, which was higher than those with small ( < 45°) and normal PI (0.37 ± 0.11 and 0.36 ± 0.13). However, the PSM FI of LSS patients didn’t change significantly with PT or PI. Moreover, the PMM FI was about 0.10–0.15, which was significantly lower than the PSM FI, and changed with PT and PI in a similar way of PSM FI with much less in magnitude. Conclusion FI of the PSMs increased with greater pelvic retroversion or larger pelvic incidence in DLS patients, but not in LSS patients.