Objective To fabricate a large-diameter vascular graft with a pore size gradient structure mimicking that of natural blood vessels, using poly-L-lactic acid (PLLA) and polycaprolactone (PCL) as base materials through electrospinning and ultrasonic pore-forming techniques, and to evaluate its application potential. Methods A three-layered tubular graft was fabricated from a PCL/PLLA blend (mass ratio 6 : 4) via electrospinning, followed by an ultrasonic pore-forming process to create a gradient porosity. The resulting graft (diameter: 2 cm, length: 4 cm) was implanted into the descending thoracic aorta of an experimental pig using an end-to-end anastomosis. Graft patency and anastomotic sites were monitored by computed tomography angiography (CTA) at 1 and 6 weeks post-surgery. After 2 months, the graft was explanted for systematic evaluation of vascular regeneration and repair through gross examination, histopathology (H&E and elastic fiber staining), immunohistochemistry [for ETS-related gene (ERG), Actin, and Vimentin], and scanning electron microscopy (SEM). Results Postoperative CTA confirmed excellent graft patency at both 1 and 6 weeks, with no evidence of thrombosis or anastomotic stenosis. Gross examination of the 2-month explant revealed a smooth luminal surface covered by neotissue. Histopathological analysis demonstrated that the graft successfully induced the formation of a three-layered structure resembling a native vessel wall, comprising endothelial cells, smooth muscle cells, and fibroblasts. Immunohistochemistry further verified coverage of the luminal surface by endothelial cells (ERG-positive), along with the presence of neosmooth muscle (Actin-positive) and fibroblasts (Vimentin-positive). Endothelial cells were observed adhering to the inner surface of the artificial vessel under SEM. Conclusion The biomimetic, three-layered PLLA/PCL large-diameter vascular graft, constructed via electrospinning and ultrasonic pore-forming, exhibits excellent short-term patency and biocompatibility in a large animal model. More importantly, it demonstrates a significant potential to promote host cell infiltration and achieve in situ regeneration of a three-layered vascular wall structure, providing a promising experimental basis for the development of next-generation functional vascular substitutes.

Objective: To investigate follow-up participation situation, negative conversion, and tuberculosis incidence among boarding junior and senior high school freshmen with latent tuberculosis infection(LTBI) in Zhuhai, so as to provide a reference for better LTBI management in school settings. Methods: A prospective cohort study enrolled 413 LTBI and 27 184 non LTBI boarding junior and senior high school freshmen in Zhuhai from September to October 2023. The LTBI group underwent follow up retesting at >3-6, >6-12, >12-24, >24 months after screening. The followup content included mycobacterium tuberculosis infection testing,chest X ray examination,and questionaire survey(basic demographic information, lifestyle, history of close contact with tuberculosis, and suspected symptoms of pulmonary tuberculosis). Follow-up participation, negative conversion, and tuberculosis incidence were analyzed. Rate was compared by using the Chi-square test, and factors associated with negative conversion were assessed by multivariate Logistic regression analysis. Results: Follow-up participation rates increased initially and then declined, with rates of 25.67% within >3-6 months, 37.05% within >6-12 months, 82.02% within >12-24 months, and 52.21% after 24 months. The overall negative conversion rate was 61.03%. The differences in the conversion rate to negative of mycobacterium tuberculosis infection detection among junior and senior high school freshmen in the LTBI group by different testing methods, school types, smoking history, sleep status, and academic stress were all statistically significant( χ 2=124.96, 22.70, 4.71, 6.31, 6.08, all P <0.05). Multivariate Logistic regression analysis identified testing methods, smoking history, and sleep status as factors associated with negative conversion ( OR =1.90-21.67, all P <0.05). The cumulative incidence of tuberculosis was 726.39 per 100 000 in the LTBI group versus 14.71 per 100 000 in the non-LTBI group ( RR =49.37, 95% CI =11.08-219.87, P <0.01). Conclusions Boarding junior and senior high school freshmen with LTBI in Zhuhai have a higher risk of tuberculosis than concurrent non-LTBI students; they therefore represent a priority group for tuberculosis prevention and control. Centralized follow up is recommended to improve participation, and high specificity methods should be used in follow up retesting and maintain consistency across assessments.

The pathological changes of myocardial infarction （MI） are mainly characterized by progressive myocardial ischemic necrosis， decline in cardiac diastolic function， thinning of the ventricular wall， and enlargement of the ventricles. The clinical manifestations include myocardial ischemia， heart failure， arrhythmia， shock， and even sudden cardiac death， rendering MI one of the most perilous cardiovascular diseases. Currently， the clinical treatment for MI primarily involves interventional procedures and drug therapy. However， due to their significant side effects and high complication rates associated with these treatments， they fail to ensure a satisfactory quality of life and long-term prognosis for patients. On the other hand， traditional Chinese medicine has demonstrated remarkable potential in improving patient prognosis while reducing side effects. Research has elucidated that various signaling pathways such as nuclear transcription factor-κB （NF-κB）， adenosine 5̒-monophosphate-activated protein kinase （AMPK）， transforming growth factor-β （TGF-β）/Smads， mitogen-activated protein kinase （MAPK）， Wnt/β-catenin （β-catenin）， and phosphatidylinositol 3-kinase （PI3K）/protein kinase B（Akt） play crucial roles in regulating the occurrence and development of MI. Effectively modulating these signaling pathways through its therapeutic interventions， traditional Chinese medicine can enhance MI management by inhibiting apoptosis， providing anti-inflammatory properties， alleviating oxidative stress levels， and resisting myocardial ischemia. Due to its notable efficacy and favorable safety， it has become an area of focus in clinical practice.

Objective To investigate the effects and underlying mechanisms of down-regulating m6A demethylase fat mass and obesity-associated protein(FTO)on proplatelet formation in the MEG-01 megakaryocytic cells.Methods ①MEG-01 cells were treated with 1 nmol/L phorbol myristate acetate(PMA)(treatment group)or DMSO(control group)for 72 h.FTO expression was measured by Western blotting and RT-qPCR.② MEG-01 cells were infected with targeted FTO shRNA(knockdown group,sh-FTO)or negative control shRNA(negative control group,sh-NC)viruses.FTO knockdown group and negative control group MEG-1 cells were treated with 1 nmol/L PMA for 72 h,and the protein and mRNA expression levels of FTO were detected by Western blotting and RT-qPCR.Cell cycle,viability and apoptosis were assessed by propidium iodide(PI)DNA staining,CCK-8 assay and Annexin V-FITC/PI double staining and TUNEL staining.The expression of cleaved Caspase-3 protein was determine by Western blotting.Megakaryocyte maturation was assessed by CD41/CD61 staining.Proplatelet formation was observed under bright field and detected by CD61 immunofluorescence assay.The expression of apoptosis-related molecules(Caspase3,BAD,BAK1,BCL2 and MCL1)was detected by RT-qPCR,and the protein change of BCL2 was further verified by Western blotting.The dataset was screened out from the gene expression omnibus(GEO)database,and then analyzed with University of California,Santa Cruz(UCSC)genome browser to compare the methylation sequencing peaks on BCL2 mRNA,and m6A methylated RNA immunoprecipitation(m6A-RIP)was used to assess the m6A methylation levels of BCL2 target gene mRNAs in MEG-01 megakaryocytes.Then,the changes in the m6A methylation enrichment level of BCL2 mRNA were observed between the sh-NC group and the sh-FTO group.mRNA stability and ribosome profiling assays were performed to assess translational efficiency of target genes.Results ①PMA treatment upregulated the expression of FTO at protein(P＜0.05)and mRNA(P＜0.01)levels.② FTO shRNA resulted in reduced FTO expression at both mRNA and protein levels(P＜0.01).Compared to the negative control group,the FTO knockdown group showed more cells arrested at the G1/S phase[(60.80±1.29)%vs(72.13±1.18)%,P＜0.01],significantly reduced cell viability[(1.17±0.03)%vs(0.69±0.05)%,P＜0.01],increased Annexin V-FITC/PI positive cells[(12.87±0.83)%vs(17.45±1.58)%,P＜0.01],more TUNEL positive cells[(1.03±0.27)%vs(17.49±9.91)%,P＜0.01],enhanced protein level of cleaved Caspase-3(P＜0.01),decreased proportion of CD41/CD61 positive cells[(51.63±1.13)%vs(34.08±0.53)%,P＜0.01],and less proplatelet formation in MEG-01 megakaryocytes[(26.49±6.73)%vs(13.31±5.97)%,P＜0.01].③Compared to sh-NC group,the FTO knockdown group had significantly decreased protein and mRNA expression of anti-apoptotic molecule BCL2(P＜0.01).UCSC GEO sequencing data revealed there were m6A methylation modification sites on BCL2 mRNA,which was verified through m6A-RIP experiment in MEG-01 megakaryocytes.Compared with GAPDH mRNA,BCL2 mRNA exhibited a significantly enriched m6A signal(P＜0.01).Compared to sh-NC group,a significant increase in m6A methylation modification was observed on BCL2 mRNA.BCL2 mRNA stability was significantly decreased,and its translation efficiency significantly was decreased(P＜0.01).Conclusion m6 A demethylase FTO rgulates BCL2 mRNA stability and translation efficiency,thereby promoting proplatelet formation in MEG-01 megakaryocytes.

This paper presents a rare renal biopsy-confirmed case of enoxaparin-induced anticoagulant-related nephropathy (ARN). A 62-year-old male was admitted with microscopic hematuria, massive albuminuria, and elevated serum creatinine following postoperative right shoulder joint infection. The serum creatinine level decreased after surgical debridement and antibiotic therapy. Enoxaparin (4 000 U daily) was initiated for thromboembolism prevention. The patient developed acute kidney injury with serum creatinine 517 μmol/L accompanied by gross hematuria. Renal biopsy revealed characteristic features of ARN coexisting with infection-related glomerulonephritis. After antibiotic therapy, urinary alkalinization, hemodialysis, and glucocorticoids (prednisone acetate 30 mg daily) of therapeutic interventions, the renal function partially recovered with dialysis discontinuation. The paper reviews the relevant literature on the risk factors, clinical manifestations, pathological features, diagnosis and treatment of ARN to improve clinicians' understanding.

Chronic heart failure （CHF） is the final stage of cardiovascular diseases. It is a complex syndrome， with dyspnea and edema as the main clinical manifestations， and it is characterized by complex disease conditions， difficult cure， and high mortality. Ferroptosis， a new type of programmed cell death， is different from other types of programmed cell death. Ferroptosis is iron-dependent， accompanied by lipid peroxide accumulation and mitochondrial shrinkage， becoming a hot research topic. Studies have confirmed that ferroptosis plays a key role in the occurrence and development of CHF. The regulation of ferroptosis may become a potential target for the treatment of CHF in the future. The theory of Qi deficiency and stagnation refers to the pathological state of original Qi deficiency and abnormal transportation and distribution of Qi， blood， and body fluid， which has guiding significance for revealing the pathogenesis evolution of some chronic diseases. We believe that Qi deficiency and stagnation is a summary of the pathogenesis of ferroptosis in CHF. Deficiency of Qi （heart Qi） is the root cause of CHF， and stagnation （phlegm turbidity and blood stasis） is the branch of this disease. The two influence each other in a vicious circle to promote the development of this disease. Traditional Chinese medicine （TCM） plays an important role in the treatment of CHF， improving the prognosis and quality of life of CHF patients. This paper explores the correlation between the theory of Qi deficiency and stagnation and the mechanism of ferroptosis in CHF. Furthermore， this paper reviews the mechanism of Chinese medicines and compound prescriptions in preventing and treating CHF by regulating ferroptosis according to the principles of replenishing Qi and dredging to remove stagnation， aiming to provide new ideas and methods for the treatment of CHF with TCM.

OBJECTIVE To establish a extraction process of Changyan Heji Ⅱ(CYHJ-Ⅱ)based on UPLC-Q-TOF-MS/MS technology combined with response surface analysis,and to optimize the extraction process.METHODS The chemical components in CYHJ-Ⅱ were qualitatively analyzed by UPLC-Q-TOF-MS/MS technology,and the chemical components with good linear relation-ship in mass spectrometry response were selected as process investigation indicators;the extraction process parameters(water addition amount,extraction time and soaking time)were investigated by Box-Behnken design;the comprehensive score was obtained by princi-pal component analysis(PCA),and the optimal process was determined by the comprehensive score combined with response surface a-nalysis.RESULTS Through qualitative analysis,110 components were inferred and identified from CYHJ-Ⅱ,including 2 organic acids,82 flavonoids,13 terpenoids,and 13 alkaloids.Based on the results of qualitative analysis,48 index components with good lin-ear relationships were derived by UPLC-Q-TOF-MS/MS combined with Masshunter mass spectrometry data analysis software.PCA was performed and the comprehensive score was calculated.Response surface analysis was performed with the comprehensive score as an indicator.The optimal extraction process obtained by combining the response surface prediction results and actual production was:soaking for 45 min,8 times the amount of solvent,2 extractions,each time for 120 min.CONCLUSION This study provides a new idea for the investigation of the extraction process of traditional Chinese medicine compound prescriptions and expands a new method for the development of traditional Chinese medicine compound prescriptions.

Objective To explore the prognostic value of serum glutathione reductase(GR),superoxide dismutase(SOD),cystatin C(Cys-C),homocysteine(Hcy)and lipoprotein a[Lp(a)]levels in patients with cerebral ischemic stroke(CIS),and to provide a reference for improving the prognosis of CIS patients.Methods 126 patients with CIS admitted to the 980th Hospital of Joint Logistics Support Force from June 2022 to April 2023 were selected as the observation group,another 126 healthy individuals were selected as the control group at a ratio of 1:1.The expression levels of GR,SOD,Cys-C,Hcy and Lp(a)in the two groups were detected and compared after admission and during physical examination.The degree of neurological deficit in patients with CIS was classified into mild(NIHSS:2～4 points,n=35),moderate(NIHSS:5～15 points,n=47),moderate-severe(NIHSS:16～20 points,n=26)and severe(NIHSS:21～42 points,n=18)according to the National Institutes of Health Stroke Scale(NIHSS).The expression of serum GR,SOD,Cys-C,Hcy and Lp(a)in patients with different degrees of neurological deficit was compared,and the correlation between each indicator and the degree of neurological deficit was analyzed.The observation group received intravenous thrombolytic therapy after admission and was re-examined one day after thrombolysis.After treatment,follow-up visits were conducted for 28 days.According to the patient's condition(modified Rankin scale),patients were divided into good prognosis(n=94)and poor prognosis groups(n=32).The levels of each indicator in patients with different prognoses were compared,and the predictive value of GR,SOD,Cys-C,Hcy and Lp(a)expression for poor prognosis and early warning were analyzed.Results The expression levels of serum GR(48.54±3.07U/L)and SOD(157.17±25.47U/ml)in the observation group were lower than those in the control group(61.68±3.15U/L,203.63±18.31U/ml),while the expression levels of Cys-C(1.24±0.28mg/L),Hcy(15.21±1.62μmol/L)and Lp(a)(386.53±52.16mg/L)were higher than those in the control group(0.82±0.23mg/L,9.58±0.60μmol/L,257.83±45.34mg/L),with statistically significant differences(t=13.011～36.582,all P<0.05).As the disease progressed,the expression levels of GR and SOD gradually decreased,while the expression levels of Cys-C,Hcy and Lp(a)gradually increased,with statistically significant differences(F=14.685～197.041,all P<0.05).Spearman analysis,GR and SOD were negatively correlated with the degree of neurological deficit in patients with CIS(r=-0.814,-0.753,all P<0.05),while Cys-C,Hcy and Lp(a)were positively correlated with the degree of neurological deficit in patients with CIS(r=0.647,0.782,0.724,all P<0.05).The expression of GR and SOD in patients with good prognosis at admission and 1 day after thrombolysis was higher than that in patients with poor prognosis(t=9.109,6.338;2.934,4.358,all P<0.05),while the expression of Cys-C,Hcy and Lp(a)was lower than that in patients with poor prognosis(t=5.246,5.118,8.561;4.636,5.298,7.461,all P<0.05).The AUC(95%CI)of combined prediction of GR,SOD,Cys-C,Hcy and Lp(a)at admission was 0.898(0.832～0.945),and the AUC(95%CI)of combined prediction of GR,SOD,Cys-C,Hcy and Lp(a)at 1 day after thrombolysis was 0.931(0.871～0.968).The RR(95%CI)values caused by the expression of GR,SOD,Cys-C,Hcy and Lp(a)at 1 day after thrombolysis were 2.868(1.594～5.161),3.194(1.807～5.645),0.155(0.082～0.291),0.150(0.071～0.319)and 0.227(0.119～0.435).Conclusion Abnormal changes in the levels of GR,SOD,Cys-C,Hcy and Lp(a)are closely related to the degree of neurological deficit and prognosis in patients with CIS.Early combined detection of GR,SOD,Cys-C,Hcy and Lp(a)levels has high predictive value and early warning for evaluating the poor prognosis of patients with CIS.

Objective To analyze the risk factors for meconium-stained amniotic fluid(MSAF)in preterm infants and the clinical outcome and prognosis of preterm infants.Methods Preterm infants with gestational age＜37 weeks delivered in Zhangjiajie People's Hospital from January 2022 to December 2023 were used as the study subjects,31 cases with MSAF were in MSAF group,and 31 cases of preterm infants hospitalized during the same period without MSAF were randomly paired in the ratio of 1∶1 to select with gestational age-body mass matching as non-MSAF group.Retrospective collection and analysis of pregnancy and perinatal conditions of mothers of preterm infants in two groups,comparing the differences of related factors between two groups of children;Logistic regression analysis of risk factors related to MSAF in preterm infants;comparing the complications and clinical outcomes of preterm infants in two groups.Results A total of 387 preterm infants with gestational age＜37 weeks were collected during the study period,including 31 preterm infants with comorbid MSAF,and the prevalence of MSAF in preterm infants was 8.0％.MSAF group had a higher incidence of advanced maternal age,premature rupture of membranes＞18 hours,antepartum fever,and cholestasis during pregnancy than non-MSAF group.Logistic regression analysis suggested that combined cholestasis during pregnancy and white blood cell count ≥ 30× 109/L within 6 hours after birth increased the incidence of MSAF in preterm infants.There was no statistically significant difference in the results of postnatal umbilical artery blood gas analysis between two groups of preterm infants.The proportion of leukocyte count ≥30×109/L,ultrasensitive C-reactive protein＞0.8 mg/L,and interleukin 6＞6 pg/L in MSAF group was higher than that of non-MSAF group in the 6 hours after birth.MSAF group had a higher incidence of intrauterine infectious pneumonia,feeding intolerance,and necrotizing small bowel colitis in neonates than non-MSAF group.Conclusion Advanced maternal age,intrauterine infections,and combined intrahepatic cholestasis during pregnancy may be the major risk factors for MSAF in preterm infants.MSAF preterm infants have a higher prevalence of intrauterine infectious pneumonitis,feeding intolerance,and necrotizing small bowel colitis in newborns,as well as longer hospital stays.

Objective:To construct an evaluation system for the risk factors of PICC catheter malposition in patients with hematological diseases, providing a reference for the prevention of central venous access malposition in these patients.Methods:From July 2022, a literature review was conducted to retrieve literature published in database and website such as PubMed, Web of Science domestically and internationally related to the risk assessment system of PICC catheter malposition in hematology patients. After full-text screening and extraction, the articles were included in the system′s item pool. Through further discussions among the research group′s experts, in conjunction with evidence-based findings, the system′s consultation items were formulated. Using the Delphi expert consultation method, a standard for PICC catheter malposition risk assessment system applicable to hematology patients was ultimately formulated.Results:In this study, 25 experts were invited for consultation: 24 females and 1 male, with an average age of (48.36 ± 6.82) years. After two rounds of expert consultations and revisions, the risk factors for PICC catheter malposition in hematology patients were identified to include 4 first-level indicators: patient factors, treatment factors, catheter-related factors, and operational factors, along with 11 second-level indicators and 25 third-level indicators. The positive coefficients of the experts in the two rounds of consultations were 84% and 100%, respectively; the Kendall coordination coefficients were 0.22 and 0.55 (both P<0.05); and the expert authority coefficient was 0.93. Conclusions:The risk assessment scale for PICC catheter malposition in patients with hematological diseases has high expert recognition and good consistency, and has clinical practice and guiding value.