Objective To explore the effect of hypoxia-inducible factor-1α(HIF-1α)inhibitor LW6 on ferroptosis in septic cardiomyopathy rats.Methods Rat septic cardiomyopathy model was prepared using cecal ligation and puncture(CLP)method.Thirty-six specific pathogen-free(SPF)6-8 weeks male SD rats were randomly divided into the sham-operated group,CLP group,CLP+solvent group,LW6 group,ferrostatin-1(Fer-1)group,and LW6+Fer-1 group.The degree of myocardial damage in each group was evaluated through hematoxylin-eosin stai-ning and detection of lactate dehydrogenase and creatine kinase content in cardiac tissue.Myocardial mitochondrial damage was observed by transmission electron microscopy.Ferroptosis level was determined by detecting iron ion concentration,reduced glutathione,malondialdehyde,and reactive oxygen species.Protein expression levels of HIF-1α,solute carrier family 7 member 11(SLC7A11),and glutathione peroxidase 4(GPX4)in cardiac tissue were detected by Western blotting.Results Compared with the CLP group and the CLP+solvent group,the LW6 group could ameliorate myocardial damage,alleviate mitochondrial damage,inhibit ferroptosis-related indicators(all P＜0.05),reduce HIF-1α protein expression levels(P＜0.05),and enhance SLC7A11 and GPX4 protein expression levels(both P＜0.05).Conclusion LW6 decreases HIF-1α expression and ferroptosis levels through the SLC7A11/GPX4 pathway,and ameliorates sepsis-induced cardiomyopathy.

Objective:To systematically review the clinical value of Golgi protein 73 (GP73) in intrahepatic cholangiocarcinoma (ICC) diagnosis.Methods:Online databases were searched by researchers on CNKI, VIP, Wanfang, PubMed, Embase, and Cochrane library. Clinical studies related to the diagnosis of ICC by GP73 value were included according to inclusion and exclusion criteria. Study data were collected, and then methodological quality was evaluated. Both RevMan 5.3 software and Meta-Disc 1.4 software were used for pooled analysis to investigate the difference of GP73 value between the ICC group and non-ICC group, as well as the diagnostic efficiency of GP73 for ICC.Results:A total of 12 studies comprising 3 723 patients (2 345 males and 1 378 females, aged 18-85 years) were included in the meta-analysis. Among these, 537 cases were definitively diagnosed as ICC, while the remaining 3 186 non-ICC cases included 600 benign liver tumors or healthy controls, 1 795 hepatocellular carcinomas (HCC), and 791 cases of liver cirrhosis. Pooled analysis of serum GP73 levels demonstrated that the ICC group exhibited higher GP73 values than the benign liver tumor/healthy control group [standardized mean difference ( SMD)=2.53, 95% CI: 1.38-3.64], exhibited lower GP73 values than the HCC group ( SMD=-1.69, 95% CI: -2.48--0.89), and both of them reached statistically significant difference (both P<0.001). No statistically significant difference was observed between the ICC and liver cirrhosis groups ( SMD=-0.33, 95% CI: -0.92-0.26, P=0.270). Regarding tissue GP73, the ICC patients showed a significantly higher rate compared to the benign liver tumor [ RR=2.31, 95% CI: 1.83-2.93, P<0.0001], whereas no significant difference was found between the ICC and HCC groups ( RR=0.83, 95% CI: 0.57-1.22, P=0.340). GP73 for ICC diagnosis yielded an area under the ROC curve of 0.87, with a sensitivity of 73% and specificity of 75%. Conclusion:GP73 demonstrates potential utility in ICC diagnosis, but its clinical application may be confounded by concurrent conditions such as liver cirrhosis, which should be identified in clinical practice.

Objective:To systematically review the clinical value of Golgi protein 73 (GP73) in intrahepatic cholangiocarcinoma (ICC) diagnosis.Methods:Online databases were searched by researchers on CNKI, VIP, Wanfang, PubMed, Embase, and Cochrane library. Clinical studies related to the diagnosis of ICC by GP73 value were included according to inclusion and exclusion criteria. Study data were collected, and then methodological quality was evaluated. Both RevMan 5.3 software and Meta-Disc 1.4 software were used for pooled analysis to investigate the difference of GP73 value between the ICC group and non-ICC group, as well as the diagnostic efficiency of GP73 for ICC.Results:A total of 12 studies comprising 3 723 patients (2 345 males and 1 378 females, aged 18-85 years) were included in the meta-analysis. Among these, 537 cases were definitively diagnosed as ICC, while the remaining 3 186 non-ICC cases included 600 benign liver tumors or healthy controls, 1 795 hepatocellular carcinomas (HCC), and 791 cases of liver cirrhosis. Pooled analysis of serum GP73 levels demonstrated that the ICC group exhibited higher GP73 values than the benign liver tumor/healthy control group [standardized mean difference ( SMD)=2.53, 95% CI: 1.38-3.64], exhibited lower GP73 values than the HCC group ( SMD=-1.69, 95% CI: -2.48--0.89), and both of them reached statistically significant difference (both P<0.001). No statistically significant difference was observed between the ICC and liver cirrhosis groups ( SMD=-0.33, 95% CI: -0.92-0.26, P=0.270). Regarding tissue GP73, the ICC patients showed a significantly higher rate compared to the benign liver tumor [ RR=2.31, 95% CI: 1.83-2.93, P<0.0001], whereas no significant difference was found between the ICC and HCC groups ( RR=0.83, 95% CI: 0.57-1.22, P=0.340). GP73 for ICC diagnosis yielded an area under the ROC curve of 0.87, with a sensitivity of 73% and specificity of 75%. Conclusion:GP73 demonstrates potential utility in ICC diagnosis, but its clinical application may be confounded by concurrent conditions such as liver cirrhosis, which should be identified in clinical practice.

Purpose Based on multimodal imaging combined with a variety of histological techniques,to visually evaluate the changes of rats brain metabolic microenvironment after cerebral hypoxia and ischemia of prematurity,and to discuss the effects of abnormal lactate metabolism in the brain on oligodendrocyte precursor cells,so as to provide a basis for the early diagnosis and treatment of premature white matter injury(PWMI).Materials and Methods A total of 36 SPF-grade healthy 3-day-old Sprague-Dawley neonatal rats were randomly assigned to the sham surgery(Sham)group and the model(PWMI)group using a random number table method,with 18 rats in each group.A neonatal rat PWMI model was established by hypoxia-ischemia method.Twenty-four hours after modeling,laser speckle imaging was used to monitor cerebral blood flow and blood oxygen changes.Multimodal imaging was used to observe the changes in brain tissue microstructure and metabolism after PWMI.HE staining was used to observe the morphological changes of nerve cells in the white matter of the brain.Enzyme-linked immunosorbent assay was used to detect the changes of lactate content and lactate dehydrogenase activity in the white matter region of the brain after PWMI in neonatal rats.PDGFR-α immunofluorescence staining was used to observe the dynamic changes of the number of oligodendrocyte precursor cells in the subependymal zone after PWMI in neonatal rats.Results Twenty-four hours after modeling,the multimodal imaging results showed that the T2WI and diffusion-weighted imaging on the injured side of the PWMI group showed high intensity,and the relative cerebral blood flow,relative oxygen saturation,relative apparent diffusion coefficient and amide proton transfer(APT)Lorentzian difference value were lower than those in the Sham group(t=29.466,23.522,59.006,54.778,10.263,all P<0.001),and the lactate content was higher than that in the Sham group(t=-7.521,P<0.001).The results of HE staining and enzyme-linked immunosorbent assay showed that the arrangement of nerve cells in the white matter area of the injured side of the brain in the PWMI group was loose and disordered.The lactate content and lactate dehydrogenase activity were higher than those in the Sham group(t=-6.079,-10.548,both P<0.001).The results of immunofluorescence staining showed that the number of PDGFR-α+cells in the subependymal zone of the damaged side of the PWMI group was higher than that of the Sham group at 24 hours after modeling,and lower than that in the Sham group at 11 days after modeling(t=-8.386,6.676,both P<0.001).The correlation analysis between the lactate content and APT Lorentzian difference value in the brain and the number of oligodendrocyte precursor cells in the brain 11 days after modeling showed that the number of oligodendrocyte precursor cells in the subependymal zone was positively correlated with the APT Lorentzian difference value(r=0.821,P=0.001 1),and negatively correlated with the lactate content in the brain(r=-0.880,P=0.000 2).Conclusion Multimodal imaging can monitor the early brain metabolism changes of PWMI in neonatal rats,especially the changes of lactate,and provide a visual basis for their early diagnosis.The level of lactate in the brain increases after cerebral hypoxia and ischemia in prematurity,and oligodendrocyte precursor cells increase transiently and then decrease,resulting in PWMI.

Purpose Based on multimodal imaging combined with a variety of histological techniques,to visually evaluate the changes of rats brain metabolic microenvironment after cerebral hypoxia and ischemia of prematurity,and to discuss the effects of abnormal lactate metabolism in the brain on oligodendrocyte precursor cells,so as to provide a basis for the early diagnosis and treatment of premature white matter injury(PWMI).Materials and Methods A total of 36 SPF-grade healthy 3-day-old Sprague-Dawley neonatal rats were randomly assigned to the sham surgery(Sham)group and the model(PWMI)group using a random number table method,with 18 rats in each group.A neonatal rat PWMI model was established by hypoxia-ischemia method.Twenty-four hours after modeling,laser speckle imaging was used to monitor cerebral blood flow and blood oxygen changes.Multimodal imaging was used to observe the changes in brain tissue microstructure and metabolism after PWMI.HE staining was used to observe the morphological changes of nerve cells in the white matter of the brain.Enzyme-linked immunosorbent assay was used to detect the changes of lactate content and lactate dehydrogenase activity in the white matter region of the brain after PWMI in neonatal rats.PDGFR-α immunofluorescence staining was used to observe the dynamic changes of the number of oligodendrocyte precursor cells in the subependymal zone after PWMI in neonatal rats.Results Twenty-four hours after modeling,the multimodal imaging results showed that the T2WI and diffusion-weighted imaging on the injured side of the PWMI group showed high intensity,and the relative cerebral blood flow,relative oxygen saturation,relative apparent diffusion coefficient and amide proton transfer(APT)Lorentzian difference value were lower than those in the Sham group(t=29.466,23.522,59.006,54.778,10.263,all P<0.001),and the lactate content was higher than that in the Sham group(t=-7.521,P<0.001).The results of HE staining and enzyme-linked immunosorbent assay showed that the arrangement of nerve cells in the white matter area of the injured side of the brain in the PWMI group was loose and disordered.The lactate content and lactate dehydrogenase activity were higher than those in the Sham group(t=-6.079,-10.548,both P<0.001).The results of immunofluorescence staining showed that the number of PDGFR-α+cells in the subependymal zone of the damaged side of the PWMI group was higher than that of the Sham group at 24 hours after modeling,and lower than that in the Sham group at 11 days after modeling(t=-8.386,6.676,both P<0.001).The correlation analysis between the lactate content and APT Lorentzian difference value in the brain and the number of oligodendrocyte precursor cells in the brain 11 days after modeling showed that the number of oligodendrocyte precursor cells in the subependymal zone was positively correlated with the APT Lorentzian difference value(r=0.821,P=0.001 1),and negatively correlated with the lactate content in the brain(r=-0.880,P=0.000 2).Conclusion Multimodal imaging can monitor the early brain metabolism changes of PWMI in neonatal rats,especially the changes of lactate,and provide a visual basis for their early diagnosis.The level of lactate in the brain increases after cerebral hypoxia and ischemia in prematurity,and oligodendrocyte precursor cells increase transiently and then decrease,resulting in PWMI.

Objective To explore the effect of hypoxia-inducible factor-1α(HIF-1α)inhibitor LW6 on ferroptosis in septic cardiomyopathy rats.Methods Rat septic cardiomyopathy model was prepared using cecal ligation and puncture(CLP)method.Thirty-six specific pathogen-free(SPF)6-8 weeks male SD rats were randomly divided into the sham-operated group,CLP group,CLP+solvent group,LW6 group,ferrostatin-1(Fer-1)group,and LW6+Fer-1 group.The degree of myocardial damage in each group was evaluated through hematoxylin-eosin stai-ning and detection of lactate dehydrogenase and creatine kinase content in cardiac tissue.Myocardial mitochondrial damage was observed by transmission electron microscopy.Ferroptosis level was determined by detecting iron ion concentration,reduced glutathione,malondialdehyde,and reactive oxygen species.Protein expression levels of HIF-1α,solute carrier family 7 member 11(SLC7A11),and glutathione peroxidase 4(GPX4)in cardiac tissue were detected by Western blotting.Results Compared with the CLP group and the CLP+solvent group,the LW6 group could ameliorate myocardial damage,alleviate mitochondrial damage,inhibit ferroptosis-related indicators(all P＜0.05),reduce HIF-1α protein expression levels(P＜0.05),and enhance SLC7A11 and GPX4 protein expression levels(both P＜0.05).Conclusion LW6 decreases HIF-1α expression and ferroptosis levels through the SLC7A11/GPX4 pathway,and ameliorates sepsis-induced cardiomyopathy.

Objective:To explore the clinical effects of flaps or myocutaneous flaps transplantation after debridement to repair the wounds with exposed titanium mesh after cranioplasty on the premise of retaining the titanium mesh.Methods:This study was a retrospective observational study. From February 2017 to October 2022, 22 patients with titanium mesh exposure after cranioplasty who met the inclusion criteria were admitted to the Department of Plastic, Aesthetic & Maxillofacial Surgery of the First Affiliated Hospital of Xi'an Jiaotong University, including 15 males and 7 females, aged from 19 to 68 years. After admission, treatments such as bacterial culture of wound exudate sample, anti-infection, and dressing change were carried out. Thorough surgical debridement was performed when the wound improved, and the wound area was 3.0 cm×2.0 cm to 11.0 cm×8.0 cm after debridement. The wound was repaired with local flaps, expanded flaps, or free latissimus dorsi myocutaneous flaps according to the size, location, severity of infection, and surrounding tissue condition of the wounds, and the areas of flaps or myocutaneous flaps were 5.5 cm×4.0 cm to 18.0 cm×15.0 cm. The donor areas of flaps were sutured directly or repaired by split-thickness skin grafts from head. The wound repair method was recorded. The survivals of flaps or myocutaneous flaps after surgery and wound healing in 2 weeks after surgery were recorded. During postoperative follow-up, recurrence of infection or titanium mesh exposure in the implanted area of titanium mesh was observed; the head shapes of patients, scar formation of the operative incision, and baldness were observed. At the last follow-up, the satisfaction of patients with the treatment effect (dividing into three levels: satisfied, basically satisfied, and dissatisfied) was evaluated. The total treatment costs of patients during their hospitalization were calculated.Results:The wounds in 11 cases were repaired with local flaps, the wounds in 5 cases were repaired with expanded flaps, and the wounds in 6 cases were repaired with free latissimus dorsi myocutaneous flaps. All flaps or myocutaneous flaps survived completely after surgery, and all wounds healed well in 2 weeks after surgery. Follow up for 6 to 48 months after operation, only one patient with local flap grafting experienced a recurrence of infection in the titanium mesh implanted area at more than one month after surgery, and the titanium mesh was removed because of ineffective treatment. Except for one patient who had a local depression in the head after removing the titanium mesh, the rest of the patients had a full head shape. Except for myocutaneous flap grafting areas in 6 cases and skin grafting area in 1 case with local flaps grafting had no hair growth, the other patients had no baldness. All the scars in surgical incision were concealed. At the last follow-up, 19 cases were satisfied with the treatment effects, 2 cases were basically satisfied, and 1 case was dissatisfied. The total treatment cost for patients in this group during hospitalization was 11 764-36 452 (22 304±6 955) yuan.Conclusions:For patients with titanium mesh exposure after cranioplasty, on the premise of adequate preoperative preparation and thorough debridement, the wound can be repaired with appropriate flaps or myocutaneous flaps according to the wound condition. The surgery can preserve all or part of the titanium mesh. The postoperative wound healing is good and the recurrence of infection or titanium mesh exposure in the titanium mesh implanted area is reduced, leading to good head shape, reduced surgical frequency, and decreased treatment costs.

Objective:To investigate and verify a novel acute graft versus host disease (aGVHD) prevention protocol in the context of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) .Methods:Patients who underwent haplo-HSCT in our center between January 2022 and December 2022 were included. All patients received reduced doses of cyclophosphamide, Rabbit anti-human tymoglobulin, ruxolitinib, methotrexate, cyclosporine, and MMF to prevent aGVHD. The transplantation outcomes, complications, and survival rate of all patients were investigated.Results:A total of 52 patients with haplo-HSCT were enrolled, 29 (55.8%) male and 23 (44.2%) female, with a median age of 28 (5-59) years. There were 25 cases of acute myeloid leukemia, 17 cases of acute lymphocyte leukemia, 6 cases of myelodysplastic syndrome, 2 cases of chronic myeloid leukemia and 2 cases of myeloproliferative neoplasms. 98.1% of patients had successful engraftment. The incidence of Ⅱ-Ⅳ aGVHD and Ⅲ-Ⅳ aGVHD was 19.2% (95% CI 8.2% -30.3% ) and 7.7% (95% CI 0.2% -15.2% ), respectively. No patients experienced severe gastrointestinal mucositis. The Epstein-Barr virus and CMV reactivation rates were 40.4% and 21.3%, respectively. 9.6% of patients relapsed during followup, with 1-year overall survival, progression-free survival, and non-relapse mortality rates of 86.5% (95% CI 76.9% -96.1% ), 78.8% (95% CI 67.4% -90.3% ) and 11.5% (95% CI 2.6% –20.5% ), respectively. Conclusion:Ruxolitinib combined with a low dose of PTCY is a safe and effective first-line aGVHD prevention strategy.

The application of Pseudomonas aeruginosa-mannose-sensitive hemagglutinin(PA-MSHA)in the field of an-titumors has been increasing.PA-MSHA has been found to promote tumor cell apoptosis,inhibit tumor cell invasion and migration,differentiation,and change drug resistance and epithelial-mesenchymal transformation(EMT)by inhibiting the EGFR pathway.Meanwhile,PA-MSHA also enhances the immune killing and inhibition of macrophages and T cells to tumor cells through toll-like receptors(TLRs).In this paper,we reviewed the reported anti-tumor mechanism and clinical application of PA-MSHA,suggesting that PA-MSHA may alter the glycosylation of EGFR and TLR proteins by acting on the regulatory process of the cellular mannosy-lation process.PA-MSHA can act on cell membrane proteins,including more receptors with high-mannosylation of signaling path-ways.Elucidating the deep relationship between PA-MSHA and mannosylation is of great significance for the mechanism research and clinical application of PA-MSHA.

In recent years, monotherapy and combination therapy with immune checkpoint inhibitors (ICIs) have achieved good efficacy in a variety of malignancies from solid tumors to lymphomas and have become a standardized and systematic treatment modality for many cancers. However, there is still a lack of studies on the safety of ICIs in hepatitis B virus (HBV)-infected patients with malignancies, and early studies have reported HBV reactivation due to ICI antitumor therapy in clinical practice. With reference to related literature, this article reviews the recent clinical trials and application of ICIs in cancer patients with chronic viral infection and clarifies the efficacy and safety of ICIs in this special population, in order to provide a reference for clinical medication.