AIM:This study aimed to investigate the effect of ischemic post-conditioning(I-post-C)on lung ischemia-reperfusion injury(LIRI)in rats and relationship between I-post-C and zinc homeostasis.METHODS:SPF SD rats(6～8 weeks old)were randomly divided into four groups,with eight rats in each group:control group,ischemia/reper-fusion(I/R)group,I-post-C group and I-post-C+zinc ion chelator TPEN group.Inductively coupled plasma mass spec-trometry(ICP-MS)was used to measure the concentration of zinc ions in lung tissues.HE staining,lung wet/dry weight ra-tio(W/D),total lung water content(TLW),and index of quantitative assessment(IQA)of lung injury were used to detect the degree of lung tissue injury in each group.Mitochondrial membrane potential was measured using extraction and JC-1 mitochondrial membrane potential detection kits.TUNEL assay was used to detect the level of apoptosis in lung tissues.Western blot was used to detect the protein expression levels of caspase-3,solute carrier family 39 member 8(SLC39A8/ZIP8),solute carrier family 30 member 9(SLC30A9/ZNT9),and PI3K/AKT/GSK-3β in lung tissues of each group.RT-qPCR was used to detect ZIP8 and ZNT9.RESULTS:Compared to the control group,the I/R group showed significantly aggravated lung tissue injury(P<0.01),decreased zinc ion levels(P<0.01),enhanced cell apoptosis(P<0.05),re-duced mitochondrial membrane potential(P<0.01),decreased PI3K/AKT/GSK-3β phosphorylation levels(P<0.05,P<0.01),increased cleaved caspase-3/pro-caspase-3 ratio(P<0.01),and reduced ZIP8 expression(P<0.05).Compared to the I/R group,the I-post-C group exhibited alleviated injury(P<0.05 or P<0.01),increased zinc ion levels(P<0.01),reduced apoptosis(P<0.01),restored mitochondrial membrane potential(P<0.01),elevated PI3K/AKT/GSK-3β phosphorylation levels(P<0.05,P<0.01),decreased cleaved caspase-3/pro-caspase-3 ratio(P<0.05),and in-creased ZIP8 expression(P<0.05).Compared to the I-post-C group,the I-post-C+TPEN group demonstrated aggravated injury(P<0.01),decreased zinc ion levels(P<0.01),enhanced apoptosis(P<0.01),reduced mitochondrial membrane potential(P<0.05),decreased PI3K/AKT/GSK-3β phosphorylation levels(P<0.05,P<0.01),increased cleaved cas-pase-3/pro-caspase-3 ratio(P<0.05),and reduced ZIP8 expression(P<0.05).ZNT9 expression showed no significant differences among the groups(P>0.05).CONCLUSION:Ischemic postconditioning can improve LIRI by regulating zinc homeostasis,activating PI3K/AKT signaling pathway,inactivating glycogen synthase kinase 3β,inhibiting the de-cline of mitochondrial membrane potential,and antagonizing cell apoptosis in rats.

AIM:To investigate the effect and mechanism of panax notoginseng saponins(PNS)inhibiting the proliferation of pulmonary artery smooth muscle cells(PASMCs)in rats under the ef-fect of monocrotaline(MCT).METHODS:PASMCs cultured in vitro were randomly divided into the normal control(Control)group,the monocrotaline(MCT)group,the panax notoginseng saponins(PNS)group,the knockdown(M+Si ADAM10)group,the knockdown postconditioning(M+P+Si ADAM10)group,the overexpression(M+OE AD-AM10)group,and the overexpression postcondi-tioning(M+P+OE ADAM10)group.After the model was constructed,the cell viability of each group was measured using the CCK-8 assay,along with Western blot utilized to detect the expression of proliferating cell nuclear antigen(PCNA),disinteg-rin metalloproteinase 10(ADAM10),and notch ho-mology protein-3(Notch3)at the cellular neurogen-ic locus,respectively.RESULTS:Under the effect of MCT,the viability of PASMCs was significantly en-hanced(P<0.05 or P<0.01);0-400 mg/L PNS was not toxic to the viability of normal cells,and 100 mg/L PNS could significantly inhibit the MCT-in-duced viability(P<0.01).After the knockdown of ADAM10,the viability of PASMCs significantly de-clined(P<0.01),and the expression of PCNA protein was significantly decreased(P<0.05),evidently in the M+P+Si ADAM10 group.Meanwhile,the ex-pression of ADAM10 and Notch3 protein was signif-icantly decreased(P<0.05 or P<0.01),evidently in the M+P+Si ADAM10 group.After overexpression of ADAM10,the viability of PASMCs was significant-ly enhanced(P<0.01),the expression of PCNA pro-tein was significantly increased(P<0.01),the PCNA value was slightly higher(P>0.05),and the expres-sion of ADAM10 and Notch3 protein was signifi-cantly elevated(P<0.05)in the M+P+OE ADAM10 group.Additionally,PASMCs overexpressing AD-AM10 with concomitant PNS exhibited a significant decrease in the expression of PCNA protein com-pared with PASMCs knocking down ADAM10(P<0.01),and the expression of ADAM10 and Notch3 protein declined to varying degrees(P>0.05).CON-CLUSION:Panax notoginseng saponins can mitigate MCT-induced PASMCs proliferation in rats by inhib-iting the ADAM10/Notch3 signaling pathway.

AIM:To investigate the protective effect and mechanism of zinc ions on lung ischemia/reperfusion injury(LIRI)in rats.METHODS:SPF SD rats aged 6～8 weeks were divided randomly into 4 groups:control(control)group,ischemia/reperfusion(I/R)group,zinc chloride(ZnCl2)+I/R group,and PI3K inhibitor(LY294002)+ZnCl2+I/R group.Inductively coupled plasma mass spectrometry(ICP-MS)was used to measure the concentration of zinc ions in lung tissues,while the degree of lung tissue injury was assessed by HE staining,the alveolar damage index,and the lung wet/dry weight ratio.qPCR was used to detect the mRNA expression of solute carrier family 39 member 8(SLC39A8/ZIP8),with the TUNEL assay used to determine the level of apoptosis in lung tissue.The phosphorylation levels of caspase3,PI3K,AKT,GSK-3β,ZIP8,and solute carrier family 30 member 9(SLC30A9/ZNT9)were detected by Western blot,while the mitochondrial membrane potential was measured by the mitochondrial extraction kit and JC-1 mitochondrial mem-brane potential detection kit.RESULTS:Compared with the I/R group,the zinc ion level in the ZnCl2+I/R group in-creased(P<0.01),with the qPCR results showing that the expression level of ZIP8 also increased(P<0.01).The West-ern blot results demonstrated that the phosphorylation levels of PI3K/AKT/GSK-3β and cleaved caspase-3/pro were both in-creased(P<0.01 or P<0.05).In addition,the level of caspase-3 was decreased(P<0.01),the ZIP8 level was increased(P<0.05),whereas the level of ZNT9 was not significantly different(P>0.05).The mitochondrial membrane potential was increased(P<0.01)and the level of apoptosis was decreased(P<0.01).The results of HE staining,total lung water(TLW),lung index of quantitative assessment of histology(IQA),and lung tissue wet/dry weight ratio showed that the de-gree of injury was reduced significantly(P<0.05 or P<0.01).Compared with the ZnCl2+I/R group,the LY294002+Zn-Cl2+I/R group had a significant reduction in zinc ion levels(P<0.05),while qPCR showed a significant reduction in ZIP8 expression(P<0.01).Western blot showed that the phosphorylation level of PI3K/AKT/GSK-3β was decreased(P<0.01),the level of caspase-3/pro-caspase-3 was increased(P<0.01)the level of ZIP8 was decreased(P<0.05),al-though there was no significant difference in ZNT9(P>0.05).Measurements of the mitochondrial membrane potential demonstrated a significant decrease(P<0.01),while the TUNEL results showed that the level of apoptosis had increased(P<0.05).HE staining,TLW,IQA and lung tissue wet/dry weight ratio indicated that the degree of injury was aggravated significantly(P<0.05 or P<0.01).CONCLUSION:Administration of zinc chloride in rats has a protective role in lung ischemia/reperfusion injury by activating the PI3K/AKT pathway,leading to inactivation of GSK-3β,stabilization of the mitochondrial membrane potential level,and inhibition of cell apoptosis.

[Objective]To clarify the application value of nutritional scoring in patients with sepsis and explore the impact of the modified Nutritional Risk in Critically Ill(mNUTRIC)score on the in-hospital fatality of sepsis patients in the emergency intensive care unit(EICU).[Methods]A retrospective analysis was conducted on the clinical data and laboratory examination results of 436 sepsis patients treated in the EICU of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2021 to May 2024.The patients were divided into survival group(298 cases)and death group(138 cases)according to whether they died or not during hospital treatment,and then compared the two groups'data.Logistic multi-factor regression analysis was used to analyze the risk factors for in-hospital death and the ROC curve to evaluate the predictive value of each risk factor for the prognosis of sepsis patients.[Results]The death group exhibited higher Acute Physiology and Chronic Health EvaluationⅡ(APACHE Ⅱ)score,Nutritional Risk Screening 2002(NRS 2002)score,mNUTRIC score,Sequential Organ Failure Assessment(SOFA)score,Padua Prediction Score for Venous Thromboembolism,the proportions of chronic kidney failure and pneumonia patients,C-reactive protein(CRP)level,lactate concentration and neutrophil count,but lower prognostic nutritional index,cholinesterase level,cholinesterase-albumin ratio and lymphocyte count than the survival group,with statistical significance(all P<0.05).Logistic regression analysis revealed that the mNUTRIC score[OR=1.254,95%CI(1.109,1.417)],CRP[OR=1.004,95%CI(1,1.007)],and pneumonia[OR=1.82,95%CI(1.017,3.257)]were independent risk factors for in-hospital death in sepsis patients.ROC curve analysis showed that the area under the curve(AUC)of the mNUTRIC score for predicting in-hospital death in sepsis patients was 0.683[95%CI(0.623,0.742)],with a sensitivity of 83%and a specificity of 49.3%.The AUC for CRP and pneumonia were 0.602[95%CI(0.533,0.671)],and 0.582[95%CI(0.516,0.647)].[Conclusion]The mNUTRIC score is an independent predictive indicator for in-hospital death in sepsis patients in the EICU.

BACKGROUND:Early diagnosis of pulmonary fibrosis is the foundation for timely antifibrotic drug therapy.Therefore,exploring and discovering ideal biomarkers that can be effectively used for the early diagnosis of pulmonary fibrosis is crucial for the treatment of the disease.OBJECTIVE:To conduct an in-depth analysis of key autophagy-related genes involved in the process of pulmonary fibrosis by means of bioinformatics and machine learning techniques,in order to investigate whether autophagy-related core genes of pulmonary fibrosis can be used as reliable biomarkers in the assessment of the progression of pulmonary fibrosis.METHODS:Two datasets of pulmonary fibrosis,GSE24206 and GSE110147,were downloaded from the Gene Expression Omnibus(GEO)database(a public database developed and maintained by the U.S.National Center for Biotechnology Information to store and share bioinformatics data),and the gene expression matrices of these two datasets were normalized by using the"limma"package in R software.The autophagy-related genes were extracted from GeneCards database(a database created by the U.S.National Center for Biotechnology Information,which automatically integrates gene-centric data from about 200 Web sources,including genomic,transcriptomic,proteomic,genetic,clinical,and functional information).Differential gene analysis was performed on the pulmonary fibrosis dataset,and the common genes were extracted by cross-comparing the differential genes with the autophagy genes,so as to identify autophagy genes that may play a role in the process of pulmonary fibrosis.The intersecting genes were analyzed for functional enrichment and cellular immune infiltration by gene ontology and Kyoto Encyclopedia of Genes and Genomes.Core genes of pulmonary fibrosis associated with autophagy were screened by protein-protein interactions and machine learning,and core genes were subjected to the enrichment analysis.Diagnostic models were constructed from the identified core genes.Calibration curves were used to assess the predictive ability of the line graph model.An external dataset,GSE21369,was used to perform a receiver operating characteristic curve analysis to validate the expression profiles of pulmonary fibrosis genes associated with autophagy,as well as to predict Chinese herbs associated with the genes IL6 and COL1A2 via the Coremine database.Finally,human embryonic lung fibroblasts were cultured and modelled by transforming growth factor-β1 treatment,and the relative expression of genes in the model cells was verified using qRT-PCR.RESULTS AND CONCLUSION:(1)A total of 51 pulmonary fibrosis differential genes and 25 genes intersecting with autophagy genes were obtained.Gene ontology analysis showed that the 25 intersecting genes were related to extracellular matrix tissue,collagen metabolism,collagen pro-fibroblasts,and growth factor binding,etc.The results of Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that they were mainly related to the Phosphatidylinositol 3-kinase/protein kinase B signaling pathway and the signaling pathway of the extracellular matrix-receptor interactions.(2)Immunoinfiltration analysis revealed that the expression of activated memory CD4+T cells,M0 macrophages,and resting dendritic cells was significantly elevated in the pulmonary fibrosis group(P＜0.05),showing a strong correlation.(3)Two autophagy signature genes involved in the progression of pulmonary fibrosis were identified:COL1A2 and IL6.The column-line diagram model showed that the two core genes predicted the onset of pulmonary fibrosis more accurately,and the receiver operating characteristic curve analysis showed that the two characteristic genes had diagnostic significance.COL1A2 and IL6 were related to the cell-cycle pathway,mitogen-activated protein kinase signaling pathway,Janus kinase-signal transduction and activator of transcription signaling pathway and cytokine-cytokine receptor interactions.A total of 20 Chinese herbs were predicted to be related to COL1A2 and IL6 genes,and their efficacies were mainly to clear away heat and detoxify toxins and to invigorate blood and move qi.COL1A2 and IL6 were verified to be highly expressed in pulmonary fibrosis.To conclude,COL1A2 and IL6 may be potential diagnostic biomarkers for pulmonary fibrosis,but its specificity to pulmonary fibrosis needs to be further investigated.

Objective:To investigate the prevalence and influencing factors of frailty among older adults diagnosed with non-ST-segment elevation acute coronary syndrome(NSTE-ACS).Methods:We conducted a cross-sectional study involving patients aged 65 years and older with NSTE-ACS, who were admitted to the Cardiology Center and the Department of Geriatrics at Beijing Friendship Hospital, Capital Medical University, between January 2020 and November 2021.Patients were categorized into non-frail, pre-frail, and frail groups based on the FRAIL scale.We collected clinical data, including general health conditions, comorbidities, laboratory results, treatments, and comprehensive geriatric assessments.Logistic regression analysis was employed to identify the influencing factors associated with frailty and pre-frailty in older adults with NSTE-ACS.Results:A total of 528 patients with NSTE-ACS were included in the study, comprising 308 males(58.3%)and 220 females(41.7%). The age range of participants was from 65 to 90 years, with a median age of 72(68, 76)years.The prevalence of frailty among older adults with NSTE-ACS was 11.4%(60/528), while pre-frailty was observed in 51.9%(274/528), and non-frailty in 36.7%(194/528). Compared to the non-frail and pre-frail groups, patients in the frail group were older, had a higher proportion of females, exhibited a greater prevalence of chronic diseases, and presented with elevated inflammatory markers.Additionally, frail patients demonstrated poorer nutritional status and reduced functional ability(all P<0.005). Risk factors for frailty in older adults with NSTE-ACS included older age( OR=1.110, 95% CI: 1.032-1.194, P=0.005), diabetes( OR=2.489, 95% CI: 1.091-5.679, P=0.030), cerebrovascular disease ( OR=4.151, 95% CI: 1.660-10.384, P=0.002), chronic kidney disease ( OR=42.874, 95% CI: 3.957-464.513, P=0.002), and elevated white blood cell levels( OR=1.424, 95% CI: 1.125-1.802, P=0.003). Conversely, being male( OR=0.252, 95% CI: 0.105-0.604, P=0.002)was identified as a protective factor against frailty in this patient population.For pre-frail older adults with NSTE-ACS, identified risk factors included diabetes( OR=1.882, 95% CI: 1.199-2.955, P=0.006), cerebrovascular disease( OR=1.938, 95% CI: 1.176-3.195, P=0.009), and chronic kidney disease ( OR=12.137, 95% CI: 1.536-95.934, P=0.018). Similarly, being male( OR=0.601, 95% CI: 0.376-0.961, P=0.033)was also a protective factor for pre-frailty in older adults with NSTE-ACS. Conclusions:The prevalence of frailty and pre-frailty among older adults with NSTE-ACS is notably high.Common risk factors for frailty and pre-frailty in this population include female gender, diabetes, cerebrovascular disease, and chronic kidney disease.

Objective:To investigate the use of non-vitamin K antagonist oral anticoagulants(NOACs)and their associated comorbidities in patients aged 80 years and older with non-valvular atrial fibrillation(NVAF), as well as to understand the challenges faced by elderly patients receiving NOAC therapy.Methods:We retrospectively enrolled elderly patients(≥80 years old)with NVAF who were treated with NOACs at a hospital in Beijing from January 2018 to August 2023.Patients were categorized into two age groups: 80-89 years and ≥90 years.We collected baseline data, including demographic characteristics, details of atrial fibrillation, comorbidities, laboratory test results, and medication combinations, for descriptive statistical analysis and intergroup comparisons.Results:A total of 695 elderly patients with NVAF receiving NOACs were included in the study, with a median age of 84 years.Among these patients, there were 328 males(47.19%, 328/695)and 422 cases of paroxysmal atrial fibrillation(60.72%, 422/695).The age group of 80-89 years comprised 640 cases(92.09%, 640/695), while the group aged 90 years and above included 55 cases(7.91%, 55/695).The use of NOACs in patients aged 90 and older exhibited an increasing trend over the years.Inter-group comparisons indicated that the ≥90 years group had lower body mass index, longer hospital stays, increased bedridden time, poorer renal function, lower levels of albumin and hemoglobin, and higher D-dimer levels.Inappropriate dosing of DOACs occurred in 49.64%(345/695)of cases, with 90.72%(313/345)receiving doses lower than recommended.Lower-than-recommended doses were more prevalent in the ≥90 years group, while higher-than-recommended doses were more common in the 80-89 years group.Polypharmacy was noted in 61.29%(426/695)of patients.The concurrent use of antiplatelet drugs, rhythm control medications, and ventricular rate control drugs was observed in 12.52%(87/695), 19.57%(136/695), and 54.53%(379/695)of patients, respectively, with no significant differences between groups.Conclusions:Inappropriate dosing and polypharmacy are prevalent issues among elderly NVAF patients.Therefore, it is essential to enhance multidisciplinary collaboration to optimize anticoagulation treatment strategies.

Objective:To evaluate the diagnostic efficacy of B-type natriuretic peptide(BNP)combined with the Evaluation of Guidelines in Syncope Study(EGSYS)score for cardiogenic syncope(CS), and to provide evidence for rapid clinical identification of high-risk patients.Methods:We retrospectively analyzed 366 patients with syncope hospitalized in the department of cardiovascular medicine of Beijing Hospital from January 1, 2016, to December 31, 2022.Based on the international guideline diagnostic criteria, the patients were categorized into four groups: neutrally mediated reflex syncope(NMS)group, orthostatic hypotension(OH)group, cardiogenic syncope(CS)group, and syncope of unknown origin(US)group.BNP levels were measured at admission and EGSYS scores were calculated.Receiver operating characteristic(ROC)curve analysis was performed to assess the diagnostic efficacy of individual and combined indices for CS.Results:A total of 366 syncope patients were included, among which 70 patients(19.1%)were diagnosed with NMS, 25 patients(6.8%)with OH, 44 patients(12.0%)with CS, and 227 patients(62.0%)with US.Patients in the CS group had significantly higher BNP levels and EGSYS scores compared to those in the NMS, OH, and US groups(all P<0.001). The AUC of EGSYS score for diagnosing CS was 0.783(95% CI: 0.711-0.855), while the AUC of BNP level for diagnosing CS was 0.805(95% CI: 0.727-0.884). When BNP level was combined with EGSYS score, diagnostic performance was significantly improved, with the AUC increasing to 0.855(95% CI: 0.792-0.918). Conclusions:The combination of BNP and EGSYS score significantly can improve the diagnostic accuracy of cardiogenic syncope, providing a practical diagnostic strategy for the early identification of high-risk syncope patients in clinical practice.

Trichinella spiralis zinc metalloproteinase NAS-36 gene(TsNas36)is a member of the zinc metalloproteinase family found in excretory secretory products(ESP)of T.spiralis.In this study,TsNas36 gene was cloned and expressed,and its biological characteristics and temporal and spatial characteristics were identified.These results provide a theoretical and material basis for ex-ploring the biological function of TsNas36 gene.Bioinformatics analysis showed that TsNas36 was 470 amino acids(AA)in length with a molecular weight of about 54.69 kDa,no transmembrane region,and contained a signal peptide(1-20 AA),an Astacins domain(116-320 AA)and a CUB domain(355-470 AA).There were five active site residues located at amino acids 216(His),217(Glu),220(His),226(His)and 275(Tyr).The expression plasmid pET-28a(+)/TsNas36 was constructed and induced to express in E.coli BL21(DE3)to obtain the recombinant protein rTs-Nas36.The recombinant protein was used to immunize rabbits to obtain anti-rTsNas36 polyclonal antibody serum.Indirect ELISA results showed that the antibody titer reached 1∶105.qRT-PCR and Western blot results showed that the transcription levels of TsNas36 were significantly higher in newborn larvae(NBL)than in adult worm(AW)and muscle larva(ML)stages.Immunofluo-rescence results showed that TsNas36 was only localized in the epidermis of NBL.In summary,this study characterized the biological characteristics of the TsNas36 gene and found that this gene is highly period-specific and may be involved in the unique developmental process of NBL.

Objective:To analyze the clinicopathological characteristics of atypical teratoid/rhabdoid tumors (AT/RT) and the causes of pathological misdiagnosis, and summarize diagnostic strategies.Methods:A case series study was conducted.Specifically, the data of 5 misdiagnosed(misdiagnosed group) and 8 confirmed AT/RT cases(confirmed group) in the Department of Pathology of Xi′an Children′s Hospital from January 2010 to December 2018 were retrospectively analyzed.Hematoxylin-eosin and immunohistochemical staining were performed to analyze clinical features, morphology, and immune phenotypes.Rates were compared between the misdiagnosed and confirmed groups by a Fisher′s exact test.Means were compared using an independent sample t-test.Medians were compared by a Mann-Whitney U test. Results:(1)There were 4 males and 1 female in the misdiagnosed group, with a median age of 24 months.In this group, 4/5 tumors were located in the posterior cranial fossa, and 1/5 tumors were located in the spinal cord.Morphologically, rhabdoid cells were detected in 3/5 cases, and the other 2/5 cases consisted of small embryonal cells.Immunohistochemically, INI1 and BRG1 expressions were absent in 4/5 and 1/5 cases, respectively.All of them showed multiple immunephenotypes.There were 7 males and 1 female in the confirmed group, with a median age of 22 months.In the confirmed group, 4/8 tumors were located in the supratentorial region and 4/8 tumors were located in the infratentorial region.Rhabdoid cells, deficient INI1 expression and multiple immunephenotypes were observed in all 8 cases.(2)The percentage of rhabdoid cells in the misdiagnosed group was significantly lower[0.45(0, 0.46)] than that in the confirmed group[0.55(0.40, 0.85)]( Z=-2.064, P=0.039). Conclusions:The causes of misdiagnosis of AT/RT are variable sites of occurrence, diverse histomorphology, multiple phenotypes in immunohistochemistry and rare BRG1 deficiency.For high-grade rhabdoid, epithelioid, and/or embryonic small cell tumors, AT/RT should be differentiated and immunohistochemistry protocols should include INI1 and BRG1.