Objective To examine the expression pattern of apoptosis signal-regulating kinase 1(ASK1)in the intestinal tissues of patients with Crohn's disease(CD),and analyze its mechanistic impact on intestinal epithelial barrier function and inflammatory responses.Methods Ileal tissue samples from Crohn's disease patients and healthy controls were collected.ASK1 protein level was assessed by immunohistochemistry,and its relationship with the Crohn's disease activity index(CDAI)was analyzed.A mouse model of acute colitis was constructed using TNBS,and subjected to qRT-PCR,Western blotting and immunohistochemistry for ASK1 expression,and the association between ASK1 expression and the disease activity index was examined.Lentivirus transfection was employed to create stable Caco-2 cell lines with altered ASK1 expression,and the intestinal barrier integrity and inflammation were assessed by measuring transepithelial electrical resistance(TEER),FITC-dextran leakage,and IL-6,IL-1β levels.Furthermore,the effects of ASK1 expression on Krüppel-like factor 4(KLF4)levels was examined using qRT-PCR and Western blotting.Results ASK1 was highly expressed in the ileum of CD patients and positively correlated with CDAI.In a TNBS-induced mouse model of acute colitis,ASK1 expression was up-regulated and positively correlated with DAI.Inflammation-induced ASK1 overexpression weakened the Caco-2 cell intestinal barrier,whereas ASK1 knockdown strengthened it.Moreover,ASK1 had the capability to enhance the expression of inflammatory factors.Additionally,ASK1 knockdown increased KLF4 expression,while overexpression decreased it,indicating a negative correlation between ASK1 and KLF4.Conclusion ASK1 expression is notably higher in CD and positively correlates with disease activity.ASK1 can influence intestinal barrier integrity and inflammatory factor expression,possibly through its impact on KLF4 expression.

Objective To examine the expression pattern of apoptosis signal-regulating kinase 1(ASK1)in the intestinal tissues of patients with Crohn's disease(CD),and analyze its mechanistic impact on intestinal epithelial barrier function and inflammatory responses.Methods Ileal tissue samples from Crohn's disease patients and healthy controls were collected.ASK1 protein level was assessed by immunohistochemistry,and its relationship with the Crohn's disease activity index(CDAI)was analyzed.A mouse model of acute colitis was constructed using TNBS,and subjected to qRT-PCR,Western blotting and immunohistochemistry for ASK1 expression,and the association between ASK1 expression and the disease activity index was examined.Lentivirus transfection was employed to create stable Caco-2 cell lines with altered ASK1 expression,and the intestinal barrier integrity and inflammation were assessed by measuring transepithelial electrical resistance(TEER),FITC-dextran leakage,and IL-6,IL-1β levels.Furthermore,the effects of ASK1 expression on Krüppel-like factor 4(KLF4)levels was examined using qRT-PCR and Western blotting.Results ASK1 was highly expressed in the ileum of CD patients and positively correlated with CDAI.In a TNBS-induced mouse model of acute colitis,ASK1 expression was up-regulated and positively correlated with DAI.Inflammation-induced ASK1 overexpression weakened the Caco-2 cell intestinal barrier,whereas ASK1 knockdown strengthened it.Moreover,ASK1 had the capability to enhance the expression of inflammatory factors.Additionally,ASK1 knockdown increased KLF4 expression,while overexpression decreased it,indicating a negative correlation between ASK1 and KLF4.Conclusion ASK1 expression is notably higher in CD and positively correlates with disease activity.ASK1 can influence intestinal barrier integrity and inflammatory factor expression,possibly through its impact on KLF4 expression.

Objective:To assess the efficacy and safety of computed tomography (CT)-guided percutaneous cryoablation in treating malignant liver tumors located explicitly at high-risk sites.Methods:Data were collected retrospectively from patients with malignant liver tumors undergoing percutaneous cryoablation at Tianjin Medical University Cancer Hospital between January 2018 and December 2021. In all, 46 patients with malignant liver tumors at non-high-risk sites were matched 1∶1 according to the maximum tumor diameter. Technical success rate, complete ablation rate, and complications at 12 and 24 months post-surgery were evaluated. A statistical analysis of the ablation effect difference between the high-risk site and non-high-risk site groups was conducted. Univariate and multivariate logistic regression analyses were performed to identify risk factors.Results:Both groups demonstrated a 100% intraoperative technical success rate, and no major complications related to cryoablation were observed. The complete ablation rate was 82.6% (38/46) and 71.7% (33/46) in the high-risk group and 84.8% (39/46) and 73.9% (34/46) in the non-high-risk group at 12 and 24 months, respectively. There was no significant difference in complete ablation rates between the two groups ( P>0.05). Multivariate analysis identified the distance between the tumor edge and high-risk site ≤5 mm and preoperative trans-arterial chemoembolization (TACE) treatment as independent risk factors for cryoablation effect. Conclusion:CT-guided percutaneous cryoablation is a safe and effective approach for patients with malignant liver tumor at high-risk sites. Our results emphasize the importance of proper preoperative planning and intraoperative manipulation.

BACKGROUND: Cancer stem-like cells (CSCs) are a small subset of cells in tumors that exhibit self-renewal and differentiation properties. CSCs play a vital role in tumor formation, progression, relapse, and therapeutic resistance. B7-H3, an immunoregulatory protein, has many protumor functions. However, little is known about the mechanism underlying the role of B7-H3 in regulating gastric cancer (GC) stemness. Our study aimed to explore the impacts of B7-H3 on GC stemness and its underlying mechanism. METHODS: GC stemness influenced by B7-H3 was detected both in vitro and in vivo . The expression of stemness-related markers was examined by reverse transcription quantitative polymerase chain reaction, Western blotting, and flow cytometry. Sphere formation assay was used to detect the sphere-forming ability. The underlying regulatory mechanism of B7-H3 on the stemness of GC was investigated by mass spectrometry and subsequent validation experiments. The signaling pathway (Protein kinase B [Akt]/Nuclear factor erythroid 2-related factor 2 [Nrf2] pathway) of B7-H3 on the regulation of glutathione (GSH) metabolism was examined by Western blotting assay. Multi-color immunohistochemistry (mIHC) was used to detect the expression of B7-H3, cluster of differentiation 44 (CD44), and Nrf2 on human GC tissues. Student's t -test was used to compare the difference between two groups. Pearson correlation analysis was used to analyze the relationship between two molecules. The Kaplan-Meier method was used for survival analysis. RESULTS: B7-H3 knockdown suppressed the stemness of GC cells both in vitro and in vivo . Mass spectrometric analysis showed the downregulation of GSH metabolism in short hairpin B7-H3 GC cells, which was further confirmed by the experimental results. Meanwhile, stemness characteristics in B7-H3 overexpressing cells were suppressed after the inhibition of GSH metabolism. Furthermore, Western blotting suggested that B7-H3-induced activation of GSH metabolism occurred through the AKT/Nrf2 pathway, and inhibition of AKT signaling pathway could suppress not only GSH metabolism but also GC stemness. mIHC showed that B7-H3 was highly expressed in GC tissues and was positively correlated with the expression of CD44 and Nrf2. Importantly, GC patients with high expression of B7-H3, CD44, and Nrf2 had worse prognosis ( P = 0.02). CONCLUSIONS B7-H3 has a regulatory effect on GC stemness and the regulatory effect is achieved through the AKT/Nrf2/GSH pathway. Inhibiting B7-H3 expression may be a new therapeutic strategy against GC.
Humans ; Cell Line, Tumor ; Neoplasm Recurrence, Local ; NF-E2-Related Factor 2/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Stomach Neoplasms

Background: The incidence of ulcerative colitis (UC) has gradually increased in China in recent years. The pathogenesis of UC is related to the dysfunction of immune system. B7-H5 is an important immune checkpoint molecule and is significant for the regulation of immune function. Ainis: To investigate the expression and clinical significance of B7-H5 in UC. Methods: A total of 65 UC tissue specimens were collected from Jan. 2010 to Dec. 2020 at the First Affiliated Hospital of Soochow University, and 5 healthy subjects were served as controls. Immunohistoehemistry and immunofluorescence were used to detect the expression of B7-H5, and its relationship with elinieopathologieal characteristics of UC patients was analyzed. Results: Expression of B7-H5 was significantly increased in UC patients than in controls (P < 0. 001). B7-H5 expression in UC patients was positively correlated with ESR and CRP (P < 0. 01), but not related to gender, age, extent of lesion, Mayo score and UCEIS score (P > 0. 05). Conclusions; The expression of B7-H5 in UC patients is significantly increased and is correlated with ESR and CRP, and can be used as a new marker for reflecting the severity of inflammation in UC patients.

Objective To evaluate the efficacy and safety of CT-guided percutaneous argon-helium cryoablation in treating hepatic metastases from nasopharyngeal carcinoma. Methods The clinical data of 16 patients with hepatic metastases from nasopharyngeal carcinoma, who had received percutaneous argonhelium cryoablation therapy, were retrospectively analyzed. The quality of life before and after therapy, and the postoperative complications were recorded. After argon-helium cryoablation therapy, the progression-free survival (PFS), the overall survival (OS), and the one-month, 3-month, 6-month, 12-month postoperative tumor local control rates were calculated. Results In all 16 patients, no severe complications occurred and the quality of life was significantly improved after argon-helium cryoablation therapy. The one-month, 3-month, 6-month, 12-month postoperative tumor local control rates were 100％, 87.5％, 80.0％ and 58.3％respectively. The median PFS was 11 months (95％CI: 8.4-13.6 months), and the median survival time was19 months (95％CI: 9.2-28.8 months) . After argon-helium cryoablation therapy, the half-year, one-year and2-year survival rates were 93.8％, 75％ and 43.8％ respectively. Conclusion For the treatment of hepatic metastases from nasopharyngeal carcinoma, CT-guided percutaneous argon-helium cryoablation is minimally-invasive, safe and effective with reliable curative effect.

Objective: To explore the dialectical relationship between immunosuppressed cell expression and TCM inpatients with liver cancer. Methods: The clinical data of 237 HBV-related primary liver cancer patients were collectedand the differences of MDSC expression and clinical BCLC stage and intrahepatic metastasis were analyzed. Peripheralvenous blood was taken for the detection of MDSC (CD33/CDl4/HLA-DR-/low/CDllb) expression in mononuclear cells, helper T cells (Th1, Th2) and interleukin (IL-12, IL-4) ) detection. Results: There was a significant difference betweenliver stagnation and spleen deficiency syndrome (24.21％) and qi stagnation and blood stasis syndrome (5.54％) (Χ2=11.544, P ＜ 0.05) . The expression of MDSC (21.03％) was higher than that of liver-kidney yin deficiency (5.10％) in advanced hepatocellular carcinoma (＞ 5 cm) (Χ2= 8.223, P ＜ 0.005); the expression of Th2 in liver stagnation and spleendeficiency was higher than that of qi stagnation. There was a significant difference between groups in blood stasis group (t = 10.341, P ＜ 0.05) . The expression of Th2 in wet sputum was higher than that in liver and kidney yin deficiency group.There was significant difference between groups (t = 16.307, P ＜ 0.01) . The IL-4 in liver stagnation and spleendeficiency group (76.57 ± 5.01) was higher than that in qi stagnation and blood stasis group (121.70 ± 6.22); There was asignificant difference between groups (t = 21.414, P ＜ 0.05) . There was a significant difference in IL-4 (375.12 ± 5.31) inthe liver-kidney yin deficiency group compared with the group with wet phlegm (115.46 ± 4.15) (t = 12.455, P ＜ 0.05) .Conclusion: MDSC participates in tumor proliferation, invasion and metastasis by regulating Th2 and IL-4, which isclosely related to the dialectical classification of TCM.

Objective To investigate softening-hardness dissipating-binds effects of Fuzheng Huayu (reinforcing-healthy qi resolving-stasis)Tablet combined with anti-virus therapy on liver fibrosis, and relationship between these effects and regulation of pathway of miR-122-interleukin-10-reactive oxygen species(miR-122/IL-10/ROS).Methods The patients with chronic hepatitis and liver fibrosis(n=85)were chosen from Aug.2015 to Aug.2016,and then divided randomly into test group(n=45)and control group(n=40).The control group was treated with entecavir(0.5 mg/d)and monoammonium glycyrrhizinate(0.1 g/d),and test group, additionally with Fuzheng Huayu Tablet(4.5 g/d)for 48 weeks.After treatment,ISHAK fibrosis score was reviewed through routine pathology, and activities of serum superoxide dismutase(SOD)and ROS were detected by using ELISA.The expressions of miR-122 mRNA and IL-10 mRNA were detected by using RT-PCR, and content of serum inflammatory factors of liver fibrosis, including procollagen III N-terminal peptide(PCIIINP), type IV collagen(IV-C), hyaluronidase(HA)and laminin(LN),were detected by using immunoturbidimetry.Results ISHAK fibrosis score had no significant difference between 2 groups before treatment,and decreased in 2 groups after treatment,which was superior in test group to that in control group(P<0.05).The content of serum inflammatory factors of liver fibrosis all decreased in 2 groups after treatment,and the decreases of PCIIINP and HA were more significant in test group compared with control group(P <0.05).The activities of ROS and SOD had no difference in 2 groups before treatment,and ROS decreased in 2 groups after treatment.The inhibitory effect on ROS was better in test group than that in control group after treatment(P<0.05), and SOD increase was effectively relieved in test group after treatment(P <0.05).The expressions of miR-122 mRNA and IL-10 mRNA all decreased in 2 groups after treatment, which was more significant in test group compared with control group(P<0.05).Conclusion Fuzheng Huayu Tablet reduces directly the levels of collagen and HA, degrades abnormal deposition of extracellular matrix,and regulates dynamic balance of collagen,and it antagonizes effectively the genetic expressions of IL-10 and miR-122,relieves inflammatory disorders and controls progress of histology.

Recent clinical research shows that the local treatment of primary tumor can improve cancer-specific-survival and overall-survival for metastatic prostate cancer patients.Differ with lymph node metastasis,there is not enough high-level randomized controlled trial data to decide whether the prostate cancer patients with bone metastasis will be benefited from local treatment,meanwhile,it also needs to figure out the factors influencing prognosis of patients.How to efficiently combine multi local treatment with system treatment is a current research hot spot as well.

Objective To explore the influence of tranexamic acid used in different modes in total hip arthroplasty (T HA ) blood loss by control experiment .Methods 60 patients accepted total hip arthroplasty from orthopaedics in our hospital were se‐lected between March 2010 to August 2013 ,among them femoral neck fracture were 47 cases and 13 cases were osteonecrosis .aged between 45‐82 years old ,and 62 in average .All gave unilateral total hip arthroplasty .All patients were divided into three groups ,A group(contradistinction group) ,B ,C group(experiment group) .each groups include 6 men and 14 women ,no revision surgery pa‐tients .For group A ,100 mL normal saline was dripped both in half on hour before surgery and 3 hours after surgery ;For group B , tranexamic acid diluted in 100 mL normal saline according to 10 mg/kg was dripped half on hour before surgery ,100 mL normal sa‐line was dripped 3 hour after surgery ;For group C ,tranexamic acid diluted in 100 mL normal saline according to 10 mg/kg was dripped both half on hour before surgery and 3 hour after surgery .Compute and record the visible blood cell loss and hidden blood loss ,the comparative analysis was conducted to discuss the effectiveness and safety of tranexamic acid used in the two methods .Re‐sults The visible blood cell loss in each group were (196 .20 ± 44 .45)mL ,(114 .84 ± 35 .21)mL and (104 .47 ± 30 .01)mL ;hidden blood loss in each group were:(614 .50 ± 98 .41)mL ,(425 .74 ± 70 .01)mL and (337 .12 ± 52 .23)mL .Conclusion In the unilateral total hip arthroplasty ,the use of tranexamic acid can significantly reduce a significant amount of visible and hidden blood loss .Com‐pared with tranexamic acid dripped just half one hour before surgery ,dripping tranexamic acid both half one hour before surgery and 3 hour after surgery reduced more hidden blood loss ,decreased transfusion requirement ,and this does not significantly increase the risk of deep venous thrombosis .