Aim To investigate the effect of tetrameth-ylpyrazine(TMP)on neuroinflammation after cerebral ischemia and hypoxia via mannose-binding lectin(MBL).Methods Patients diagnosed with ischaemic stroke at Shanxi Provincial People's Hospital were in-cluded in the study,and their clinicopathological data,as well as blood and urine samples,were collected with the consent of the patients and their families.Using these biological samples,differential proteins and tar-gets were identified by proteomic analysis and subse-quently verified with animal experiments.The mice were divided into the sham,dMCAO,and TMP(10,20,40 mg·kg-1)treatment groups.After seven days of drug administration,the modified neurological sever-ity score(mNSS)was used to assess the neurological function.TTC staining was used to detect the volume of cerebral infarction.Motor function was evaluated be-haviourally,and ELISA was used to detect MASP1,sC5b-9,TNF-α,IL-6,and IL-1β.Western blot was used to determine the expression of relevant proteins,such as MBL2,MASP2,and C3.Results Compared with the sham group,the dMCAO group exhibited in-creased neurological impairment,which was signifi-cantly ameliorated by TMP treatment.The expression levels of MBL2,C3 and MASP2 were elevated in the dMCAO group and were reduced following TMP treat-ment.Additionally,the dMCAO group showed elevat-ed expression of inflammatory factors IL-1 β,IL-6 and TNF-α,which were then suppressed by TMP treat-ment.Conclusion TMP inhibits the inflammatory re-sponse after ischemia and hypoxia by regulating MBL,thus attenuating brain injury.

Objective This study aims to provide theoretical support for the formulation of thyroid nodule prevention and treatment strategies in Northwest China and to investigate the characteristics of thyroid nodules and their association with metabolic indicators in this population.Methods A cross-sectional survey was conducted by retrospectively enrolling healthy individuals who underwent routine health examinations at our hospital between January 1 and December 31,2023.A total of 38 919 participants were included.The detection rate of thyroid nodules was stratified by age and sex.Univariate and multivariate binary logistic regression analyses were performed to identify risk factors for thyroid nodules.Results Among the 38 919 participants,20 395 were men(52.4%)and 18 524 were women(47.6%).The overall detection rate of thyroid nodules was 47.1%(18 317/38 919),including 40.1%(8 187/20 395)in men and 54.7%(10 130/18 524)in women.Across all age groups,women had a significantly higher detection rate than men(P<0.001).The detection rate increased with age in both sexes(χ2trend=1392.867,P<0.001 in men;χ2trend=1521.215,P<0.001 in women).Significant differences were observed between participants with and without thyroid nodules in age,body mass index(BMI),fasting blood glucose(FBG),glycated hemoglobin(HbA1c),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),triiodothyronine(T3),thyroid-stimulating hormone(TSH),and anti-thyroglobulin antibodies(TGAB),anti-thyroid microsomal antibodies,the proportion of hypertension and central obesity(all P<0.05).Multivariate binary logistic regression analysis identified female sex(OR=2.158),older age(OR=1.040),central obesity(OR=1.144),elevated FBG(OR=1.039),hypertension(OR=1.095),elevated TGAB(OR=1.008),and elevated T3(OR=1.154)as independent risk factors for thyroid nodules(all P<0.05).Conclusion Women in Northwest China are at higher risk of developing thyroid nodules.Screening and health management should be prioritized for older individuals,those with central obesity,elevated FBG,hypertension,elevated TGAB,and elevated T3 levels.

Aim To establish a lipopolysaccharide(LPS)-induced inflammatory injury model in H9c2 cardiomyocytes,and to investigate the anti-inflammato-ry effects of tanshinone ⅡA(Tan ⅡA)and its influ-ence on cuproptosis.Methods Cell viability was de-tected by CCK-8 method.The mRNA expression levels of tumor necrosis factor-alpha(TNF-α),interleukin-1 beta(IL-1β),and interleukin-6(IL-6)were meas-ured by RT-qPCR.Intracellular copper ion levels were detected via colorimetry.The protein expression levels of cuproptosis-related markers(CTR1,FDX1,DLAT,PD H α1)were determined using Western blot and im-munofluorescence techniques.Results Tan ⅡA sig-nificantly inhibited LPS-induced upregulation of in-flammatory cytokines(TNF-α,IL-1β,and IL-6)and Cu+accumulation in H9c2 cardiomyocytes.Moreover,Tan ⅡA reversed the exacerbated inflammatory re-sponse and elevated Cu+levels induced by the combi-nation of LPS and the copper ionophore Elesclomol-Cu(Ⅱ).Additionally,Tan ⅡA markedly downregulated the protein expression of CTR1,FDX1,DLAT,and PDHα1.Conclusion Tan ⅡA alleviates LPS-in-duced inflammatory injury in H9c2 cardiomyocytes by regulating intracellular Cu+levels and the expression of cuproptosis-related proteins.

Aim To investigate the effects of hydroxyl-safflor yellow A(HSYA)on the regenerative and re-pair functions of human umbilical cord mesenchymal stem cells(hUC-MSCs).Methods hUC-MSCs were mechanically isolated,and their morphology was ob-served.Cell surface marker expression was analyzed u-sing flow cytometry.Osteogenic differentiation was used to confirm the multipotency of the cells.The cells were treated with various concentrations of HSYA(0,100,200,400,600 μmol·L-1),and the optimal con-centration and duration of treatment were determined u-sing the CCK-8 assay.Cells were divided into four groups:control,100,200,and 400 μmol·L-1.The proliferative capacity of hUC-MSCs was assessed by EdU incorporation.Vascular endothelial growth factor(VEGF)and brain-derived neurotrophic factor(BD-NF)levels in the culture supernatant were measured u-sing enzyme-linked immunosorbent assays.Cell migra-tion ability was evaluated by Scratch assays.The ex-pression levels of VEGF,BDNF,and fibroblast growth factor 2(FGF2)were detected by Western blotting.Results The isolated cells exhibited characteristics consistent with stem cell surface markers and demon-strated osteogenic and adipogenic differentiation poten-tial.After 48 hours of treatment,no cytotoxicity was observed at concentrations of 100,200,and 400 μmol·L-1compared to the control group.HSYA signifi-cantly increased the number of EdU-positive cells and cell migration rate,with the most pronounced effect was achieved at 200 μmol·L-1(P＜0.01).VEGF and BDNF levels in the supernatant were elevated,with the highest expression observed at 200 μmol·L-1(P＜0.01).Similarly,the expression levels of BDNF,VEGF,and FGF2 were significantly upregulated in the HSYA groups,with the highest levels at 200 μmol·L-1(P＜0.01).Conclusion HSYA promotes the proliferation,migration and angiogenesis of hUC-MSCs,with an optimal concentration of 200 μmol·L-1.

Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38％)and primary myocardial cells(the inhibition rate was 49.7％,with P＜0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P＜0.01),decreasing the hy-drated particle size(P＜0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.

Objective To evaluate the predictive value of neutrophil/high-density lipoprotein cholesterol ratio(NHR)combined with monocyte/lymphocyte ratio(MLR)for early rebleeding after endoscopic treatment in patients with cirrhosis complicated by acute esophagogastric variceal bleeding(AEVB).Methods A total of 228 patients with cirrhosis complicated by AEVB were included in this study.According to the occurrence of early rebleeding,patients were divided into the rebleeding group(96 cases)and the non-rebleeding group(132 cases).General information and laboratory indicators of both groups were collected,and the End-Stage Liver Disease(MELD)score,Child-Turcotte-Pugh(CTP)score,Fibrosis-4(FIB-4)index,NHR,and MLR were calculated.Logistic regression analysis was used to identify the risk factors for early rebleeding in patients with cirrhosis complicated by AEVB.A nomogram model based on NHR and MLR was constructed to predict the risk of early rebleeding.The predictive performance and goodness of fit of the model were evaluated using receiver operating characteristic(ROC)curve,Hosmer-Lemeshow test,Net Reclassification Index(NRI)and Integrated Discrimination Improvement(IDI).Results Compared with the non-rebleeding group,systolic blood pressure,platelet count(PLT),albumin/globulin ratio(A/G)and low-density lipoprotein cholesterol(LDL-C)were decreased in the rebleeding group,while total bile acids(TBA),aspartate aminotransferase(AST),alanine aminotransferase(ALT),total bilirubin(TBIL),activated partial thromboplastin time(APTT),thrombin time(TT),international normalized ratio(INR),Fibrosis-4(FIB-4),NHR,MLR,MELD score and CTP score were increased(P＜0.05).NHR was positively correlated with AST,TBIL and INR(P＜0.05).MLR was negatively correlated with PLT,and positively correlated with AST,TBIL and FIB-4(P＜0.05).Logistic regression analysis results showed that prolonged TT,elevated NHR and MLR were independent risk factors for early rebleeding in patients with cirrhosis complicated by AEVB.The nomogram model based on NHR and MLR to predict early rebleeding had an area under the curve of 0.810(95%CI:0.754-0.866).The Hosmer-Lemeshow test suggested that the model fit well.IDI and NRI analyse showed that the combination of NHR and MLR had better predictive value for the early rebleeding than that of MELD score and CTP score.Conclusion NHR and MLR are effective indicators for predicting early rebleeding after endoscopic treatment in patients with cirrhosis complicated by AEVB.They are helpful in the early identification of high-risk patients and provide a reference for clinical intervention.

Aim To explore the relation between the protective effect of hyperoside(Hyp)on energy metab-olism and apoptosis in cardiomyocytes after myocardial infarction(MI)and the regulation of peroxisome pro-life rator-activated receptor α(PPARα)pathway.Methods Mouse myocardial infarction injury model was established by ligation of left anterior descending coronary artery.The mice that were successfully liga-ted were randomly divided into the following groups:MI group,Hyp(9,18 and 36 mg·kg-1)group,posi-tive fenofibrate group(120 mg·kg-1)and Hyp(36 mg·kg-1)+PPARα inhibitor GW6471 group.In addition,a sham group was set up,only threading with-out ligature.The mice were administered different kinds of drugs by gavage for seven days,once daily.ECG changes were recorded in mice 5 min before,5 min after surgery,and 1 hour after day 7 using the BL-420F biofunction system.The diagnostic ultrasound in-strument was used to examine the heart structure and function of each group of mice.The influence of myo-cardial histology was observed by hematoxylin and eo-sin (HE) staining and Sirius red(Sirius Red)stai-ning.The changes of creatine kinase isozymin-MB(CK-MB),cardiac troponin Ⅰ(cTnⅠ)and lactate de-hydrogenase(LDH)in mouse serum were assessed by ELISA kit.The expressions of PPARα signaling related proteins and apoptosis-related proteins were detected by immunofluorescence and Western blot.Results Compared with MI mice,Hyp could significantly im-prove the ECG abnormality of MI mice,increase the left ventricular ejection fraction(LVEF)and left ventricu-lar short axis shortening rate(LVFS),reduce serum cTnⅠ content,CK-MB and LDH activity,and reduce myocardial fibrosis,infarct area and cardiomyocyte ap-optosis in the MI area.Meanwhile,this research found that Hyp could activate PPARα signaling pathway and regulate apoptosis-related proteins.However,the car-dioprotective effect of hyperoside was reversed by the combination with the treatment of the PPARα signaling inhibitor,GW6471.Conclusions Hyp has an impro-ving effect on energy metabolism and apoptosis in mice after MI,and the mechanism may be related to its acti-vation of PPARα signaling pathway.

Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38％)and primary myocardial cells(the inhibition rate was 49.7％,with P＜0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P＜0.01),decreasing the hy-drated particle size(P＜0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.

Objective To compare the node strength in white matter networks between depressive disorder and bipolar depression patients,analyze structural connectivity impairments across brain regions,and assess their diagnostic utility.Methods This longitudinal study initially enrolled 91 patients with a baseline diagnosis of depressive episode.All subjects underwent diffusion tensor imaging at recruitment and white matter structural weighted networks were constructed using deterministic fiber tracking.After≥9 years of naturalistic follow-up,23 patients who maintained a diagnosis of major depressive disorder(MDD group)and 18 patients who maintained a diagnosis of bipolar disorder(BD group),while 30 demographically matched healthy controls(HC group)were included for comparison.The differences in nodal connection strength within the brain white matter networks among the three groups were compared.Furthermore,the receiver operator characteristic(ROC)curve was utilized to evaluate the diagnostic value of the differential brain regions in distinguishing between MDD and BD.Results In the left anterior cingulate gyrus,the node strength was lower in the BD than in the MDD group(3.89±0.76 vs.4.74±0.60).However,the node strength in the right caudate nucleus(4.94±1.26 vs.3.46±0.99)and right globus pallidus(1.98±0.67 vs.1.25±0.29)was higher in the BD than in the MDD group(P<0.01,FWE-corrected).The combined connectivity strengths of three brain regions—the left anterior cingulate gyrus,right caudate nucleus and right globus pallidus—were used to differentiate between MDD and BD,and an ROC curve was plotted,with an area under the curve(AUC)of 0.95(95%CI:0.91～0.99;P<0.001).The sensitivity and the specificity were 0.89 and 0.87,respectively.Conclusion The differences in node strength between patient groups may serve as a potential neuroimaging biomarker.Integration of node connectivity strengths from these differential brain regions can achieve superior discrimination accuracy.

Objective To evaluate the predictive value of neutrophil/high-density lipoprotein cholesterol ratio(NHR)combined with monocyte/lymphocyte ratio(MLR)for early rebleeding after endoscopic treatment in patients with cirrhosis complicated by acute esophagogastric variceal bleeding(AEVB).Methods A total of 228 patients with cirrhosis complicated by AEVB were included in this study.According to the occurrence of early rebleeding,patients were divided into the rebleeding group(96 cases)and the non-rebleeding group(132 cases).General information and laboratory indicators of both groups were collected,and the End-Stage Liver Disease(MELD)score,Child-Turcotte-Pugh(CTP)score,Fibrosis-4(FIB-4)index,NHR,and MLR were calculated.Logistic regression analysis was used to identify the risk factors for early rebleeding in patients with cirrhosis complicated by AEVB.A nomogram model based on NHR and MLR was constructed to predict the risk of early rebleeding.The predictive performance and goodness of fit of the model were evaluated using receiver operating characteristic(ROC)curve,Hosmer-Lemeshow test,Net Reclassification Index(NRI)and Integrated Discrimination Improvement(IDI).Results Compared with the non-rebleeding group,systolic blood pressure,platelet count(PLT),albumin/globulin ratio(A/G)and low-density lipoprotein cholesterol(LDL-C)were decreased in the rebleeding group,while total bile acids(TBA),aspartate aminotransferase(AST),alanine aminotransferase(ALT),total bilirubin(TBIL),activated partial thromboplastin time(APTT),thrombin time(TT),international normalized ratio(INR),Fibrosis-4(FIB-4),NHR,MLR,MELD score and CTP score were increased(P＜0.05).NHR was positively correlated with AST,TBIL and INR(P＜0.05).MLR was negatively correlated with PLT,and positively correlated with AST,TBIL and FIB-4(P＜0.05).Logistic regression analysis results showed that prolonged TT,elevated NHR and MLR were independent risk factors for early rebleeding in patients with cirrhosis complicated by AEVB.The nomogram model based on NHR and MLR to predict early rebleeding had an area under the curve of 0.810(95%CI:0.754-0.866).The Hosmer-Lemeshow test suggested that the model fit well.IDI and NRI analyse showed that the combination of NHR and MLR had better predictive value for the early rebleeding than that of MELD score and CTP score.Conclusion NHR and MLR are effective indicators for predicting early rebleeding after endoscopic treatment in patients with cirrhosis complicated by AEVB.They are helpful in the early identification of high-risk patients and provide a reference for clinical intervention.