Protein Disulfide Isomerase A2 Is Correlated with Immune Infiltrates and Is a Novel Prognostic Biomarker in Glioma Patients

Objective Protein disulfide isomerase A2(PDIA2),a member of the protein disulfide isomerase family,plays a key role in the folding of nascent proteins in the endoplasmic reticulum by forming disulfide bonds,together with enzymes such as thiol isomerase,oxidase,and reductase.This study investigated the clinical significance and potential functions of PDIA2 in glioma.Methods The expression of PDIA2 in gliomas was explored using The Cancer Genome Atlas and Gene Expression Omnibus databases.We analyzed the clinical characteristics of glioma patients and the prognostic and diagnostic value of PDIA2 expression.Kaplan-Meier and Cox regression analyses were used to examine the effect of PDIA2 expression on overall survival,progression-free interval,and disease-specific survival.Furthermore,we performed Gene Set Enrichment Analysis and immune infiltration analysis to investigate the functions of PDIA2.PDIA2 mRNA and protein expression was evaluated in cell lines and glioma tissues.Results PDIA2 was expressed at low levels in glioma patients.Kaplan-Meier survival analysis showed that glioma patients with low PDIA2 levels had a worse prognosis than those with high PDIA2 levels.Receiver operating characteristic curve analysis indicated the diagnostic and prognostic ability of PDIA2(area under the curve=0.918).Pathways associated with PD1,PI3K/AKT,cancer immunotherapy via PD1 blockade,Fceri-mediated NF-kB activation,FOXM1,and DNA repair were enriched in glioma patients with low levels of PDIA2.PDIA2 expression levels were negatively correlated with immune cell infiltrate levels.Conclusion PDIA2 levels are significantly downregulated in glioma.PDIA2 expression may be a potential biomarker for the diagnosis and prognosis of glioma patients.

Diagnosis and treatment experience of atypical hepatic cystic echinococcosis type 1 at a tertiary center in China

BACKGROUND Some hydatid cysts of cystic echinococcosis type 1(CE1)lack well-defined cyst walls or distinctive endocysts,making them difficult to differentiate from simple hepatic cysts.AIM To investigate the diagnostic methods for atypical hepatic CE1 and the clinical efficacy of laparoscopic surgeries.METHODS The clinical data of 93 patients who had a history of visiting endemic areas of CE and were diagnosed with cystic liver lesions for the first time at the People's Hospital of Xinjiang Uygur Autonomous Region(China)from January 2018 to September 2023 were retrospectively analyzed.Clinical diagnoses were made based on findings from serum immunoglobulin tests for echinococcosis,routine abdominal ultrasound,high-frequency ultrasound,abdominal computed tomography(CT)scan,and laparoscopy.Subsequent to the treatments,these patients underwent reexaminations at the outpatient clinic until October 2023.The evaluations included the diagnostic precision of diverse examinations,the efficacy of surgical approaches,and the incidence of CE recurrence.RESULTS All 93 patients were diagnosed with simple hepatic cysts by conventional abdominal ultrasound and abdominal CT scan.Among them,16 patients were preoperatively diagnosed with atypical CE1,and 77 were diagnosed with simple hepatic cysts by high-frequency ultrasound.All the 16 patients preoperatively diagnosed with atypical CE1 underwent laparoscopy,of whom 14 patients were intraoperatively confirmed to have CE1,which was consistent with the postoperative pathological diagnosis,one patient was diagnosed with a mesothelial cyst of the liver,and the other was diagnosed with a hepatic cyst combined with local infection.Among the 77 patients who were preoperatively diagnosed with simple hepatic cysts,4 received aspiration sclerotherapy of hepatic cysts,and 19 received laparoscopic fenestration.These patients were intraoperatively diagnosed with simple hepatic cysts.During the followup period,none of the 14 patients with CE1 experienced recurrence or implantation of hydatid scolices.One of the 77 patients was finally confirmed to have CE complicated with implantation to the right intercostal space.CONCLUSION Abdominal high-frequency ultrasound can detect CE1 hydatid cysts.The laparoscopic technique serves as a more effective diagnostic and therapeutic tool for CE.

Human urokinase-type plasminogen activator gene-modifiedbone marrow-derived mesenchymal stem cells attenuateliver fibrosis in rats by down-regulating the Wnt signalingpathway

AIM: To evaluate the therapeutic effects of bone marrow-derived mesenchymal stem cells(BMSCs) with human urokinase-type plasminogen activator(u PA) on liver fibrosis, and to investigate the mechanism of gene therapy.METHODS: BMSCs transfected with adenovirusmediated human urokinase plasminogen activator(Adu PA) were transplanted into rats with CCl4-induced liver fibrosis. All rats were sacrificed after 8 wk, and their serum and liver tissue were collected for biochemical, histopathologic, and molecular analyzes. The degree of liver fibrosis was assessed by hematoxylin and eosin or Masson's staining. Western blot and quantitative reverse transcription-polymerase chain reaction were used to determine protein and m RNA expression levels.RESULTS: Serum levels of alanine aminotransferase, aminotransferase, total bilirubin, hyaluronic acid, laminin, and procollagen type Ⅲ were markedly decreased, whereas the levels of serum albumin were increased by u PA gene modified BMSCs treatment. Histopathology revealed that chronic CCl4-treatment resulted in significant fibrosis while u PA gene modified BMSCs treatment significantly reversed fibrosis. By quantitatively analysing the fibrosis area of liver tissue using Masson staining in different groups of animals, we found that model animals with CCl4-induced liver fibrosis had the largest fibrotic area(16.69% ± 1.30%), while fibrotic area was significantly decreased by BMSCs treatment(12.38% ± 2.27%) and was further reduced by u PA-BMSCs treatment(8.31% ± 1.21%). Both protein and m RNA expression of β-catenin, Wnt4 and Wnt5 a was down-regulated in liver tissues following u PA gene modified BMSCs treatment when compared with the model animals.CONCLUSION: Transplantation of u PA gene modified BMSCs suppressed liver fibrosis and ameliorated liver function and may be a new approach to treating liver fibrosis. Furthermore, treatment with u PA gene modified BMSCs also resulted in a decrease in expression of molecules of the Wnt signaling pathway.

Radical resection of hepatic polycystic echinococcosis complicated with hepatocellular carcinoma: A case report

BACKGROUND Hepatic cystic echinococcosis(CE)is an infectious zoonotic parasitic disease,and the insidious onset and slow progression of hepatic CE usually contributes to delayed diagnosis and treatment.Hepatocellular carcinoma(HCC)is the fourth most common malignant tumor.Co-existence of CE and HCC is fairly rare in clinical settings and the association between the two is still not well recognized.We report a case of hepatic CE complicated with HCC which are radically resected and raise some questions worth thinking about.CASE SUMMARY A 70-year-old man presented with upper abdominal pain.On admission,laboratory data showed that,except for hepatitis B surface antigen positivity,other indicators were normal,including alpha-fetoprotein.Computed tomography of the abdomen revealed a huge polycystic lesion in left liver lobe,without reinforcement after enhanced scanning and sized about 16.9 cm×12.2 cm,which was considered a type II hydatid cyst.Multiple small solid lesions were also found adjacent to it,and thus it was highly suspected as a malignant tumor.After a multidisciplinary team discussion,the diagnosis of co-occurrence of hepatic CE and HCC was made.According to Romic classification,the case belongs to type IIb,and radical left hemi-hepatectomy was performed.Postoperative pathological examination revealed CE co-existence with welldifferentiated HCC,consistent with the preoperative diagnosis.CONCLUSION With the combination of hepatitis B and obvious extrusion by large hydatid,the HCC risk of a patient might be higher.

Successful treatment of pyoderma gangrenosum with concomitant immunoglobulin A nephropathy: A case report and review of literature

Pyoderma gangrenosum(PG)is an uncommon ulcerative cutaneous condition of an unknown etiology and is often associated with immune diseases.However,PG rarely shows visceral involvement,especially in the kidney.A 20-year-old female presented with pedal edema and skin ulceration of both lower limbs.The skin lesion began as an erythematous plaque and then became a blister.She also complained of abdominal distension and a decreasing urine volume.Laboratory data showed high proteinuria,hypoalbuminemia and hyperlipidemia.Her skin and kidney were biopsied.The pathological results indicated PG and immunoglobulin A(IgA)nephropathy.The patient was finally cured with prednisolone in combination with cyclosporine A(CsA).

Clinical characteristics and risk factors of intracranial hemorrhage after spinal surgery

BACKGROUND Intracranial hemorrhage after spinal surgery is a rare and devastating complication.AIM To investigate the economic burden,clinical characteristics,risk factors,and mechanisms of intracranial hemorrhage after spinal surgery.METHODS A retrospective cohort study was conducted from January 1,2015,to December 31,2022.Patients aged≥18 years,who had undergone spinal surgery were included.Intracranial hemorrhage patients were selected after spinal surgery during hospitalization.Based on the type of spinal surgery,patients with intracranial hemorrhage were randomly matched in a 1:5 ratio with control patients without intracranial hemorrhage.The patients'pre-,intra-,and post-operative data and clinical manifestations were recorded.RESULTS A total of 24472 patients underwent spinal surgery.Six patients(3 males and 3 females,average age 71.3 years)developed intracranial hemorrhage after posterior spinal fusion procedures,with an incidence of 0.025%(6/24472).The prevailing type of intracranial hemorrhage was cerebellar hemorrhage.Two patients had a poor clinical outcome.Based on the type of surgery,30 control patients were randomly matched in 1:5 ratio.The intracranial hemorrhage group showed significant differences compared with the control group with regard to age(71.33±7.45 years vs 58.39±8.07 years,P=0.001),previous history of cerebrovascular disease(50%vs 6.7%,P=0.024),spinal dura mater injury(50%vs 3.3%,P=0.010),hospital expenses(RMB 242119.1±87610.0 vs RMB 96290.7±32029.9,P=0.009),and discharge activity daily living score(40.00±25.88 vs 75.40±18.29,P=0.019).CONCLUSION The incidence of intracranial hemorrhage after spinal surgery was extremely low,with poor clinical outcomes.Patient age,previous stroke history,and dura mater damage were possible risk factors.It is suggested that spinal dura mater injury should be avoided during surgery in high-risk patients.

Successful robotic radical resection of hepatic echinococcosis located in posterosuperior liver segments

BACKGROUND Radical resection is an important treatment method for hepatic echinococcosis.The posterosuperior segments of the liver remain the most challenging region for laparoscopic or robotic hepatectomy.AIM To demonstrate the safety and preliminary experience of robotic radical resection of cystic and alveolar echinococcosis in posterosuperior liver segments.METHODS A retrospective analysis was conducted on the clinical data of 5 patients with a median age of 37 years(21-56 years)with cystic and alveolar echinococcosis in difficult liver lesions admitted to two centers from September to December 2019.The surgical methods included total pericystectomy,segmental hepatectomy,or hemihepatectomy.RESULTS Among the 5 patients,4 presented with cystic echinococcosis and 1 presented with alveolar echinococcosis,all of whom underwent robotic radical operation successfully without conversion to laparotomy.Total caudate lobectomy was performed in 2 cases,hepatectomy of segment Ⅶ in 1 case,total pericystectomy of segment Ⅷ in 1 case,and right hemihepatectomy in 1 case.Operation time was 225 min(175-300 min);blood loss was 100 mL(50-600 mL);and postoperative hospital stay duration was 10 d(5-19 d).The Clavien-Dindo complication grade was Ⅰ in 4 cases and Ⅱ in 1 case.No recurrence of echinococcosis was found in any patient at the 3 mo of follow-up.CONCLUSION Robotic radical surgery for cystic and selected alveolar echinococcosis in posterosuperior liver segments is safe and feasible.

Correlation of ERCC1 and GSTP1 expression in esophageal cancer tissue with platinum-based chemotherapy sensitivity as well as apoptosis and proliferation gene expression

Objective:To study the correlation of ERCC1 and GSTP1 expression in esophageal cancer tissue with platinum-based chemotherapy sensitivity as well as apoptosis and proliferation gene expression.Methods: Patients with advanced esophageal cancer who accepted PF chemotherapy in our hospital between May 2013 and October 2015 were selected, esophageal cancer tissue was collected before the chemotherapy, the patients were divided into chemotherapy sensitivity group and chemotherapy resistance group according to the effect of chemotherapy, and the expression levels of ERCC1, GSTP1 as well as apoptosis and proliferation genes in esophageal cancer tissue were detected.Results:Protein content and positive protein expression rate of ERCC1 and GSTP1 in esophageal cancer tissue of chemotherapy sensitivity group were significantly lower than those of chemotherapy resistance group, MBP1, DEC1 and PTEN protein content were significantly higher than those of chemotherapy resistance group, and PLCE1, CyclinD1 and PAR2 protein content were significantly lower than those of chemotherapy resistance group;MBP1, DEC1 and PTEN protein content in esophageal cancer tissue with positive ERCC1 and GSTP1 expression were significantly lower than those in esophageal cancer tissue with negative ERCC1 and GSTP1 expression while PLCE1, CyclinD1 and PAR2 protein content were significantly higher than those in esophageal cancer tissue with negative ERCC1 and GSTP1 expression.Conclusion:The highly expressed ERCC1 and GSTP1 in esophageal cancer tissue can decreased the cancer cell sensitivity to platinum-based chemotherapeutics, inhibit cell apoptosis and promote cell proliferation during platinum-based chemotherapy.