Objective To summarize the effect of en bloc kidney transplantation (EBKT) from cardiac deceased infant donors into adult recipients and to share a new simplified EBKT technique.Methods Fourteen dual kidneys from infant donors (9 males,and 5 females) were transplanted into adult recipients (3 males,and 11 females).The donor ages ranged from 17 days to 8 months,and the recipient ages ranged from 19 years to 61 years.The recipients were categorized into 2 groups in terms of the microvascular surgical techniques.Case 1 to case 9 was given traditional techniques and case 10 to case 14 simplified techniques.In detail,the dual kidneys were recovered en bloc with the aorta and inferior vena cava.After splitting the rear wall of the donor aorta and inferior vena cava,suitable size of patches were made by cutting along the vascular openings of renal arteries and renal veins.We anastomosed the aorta patch to the external iliac artery in an end-to-side fashion.The donor inferior vena cava patch was anastomosed to the external iliac vein in an end-to-side fashion.The distal ends of ureters were implanted into the bladder separately.Results In traditional group,two cases underwent peri-operative graft loss because of renal artery thrombosis,and one patient died of pneumonia 16 days post-operation.During the follow-up period,graft loss was seen in 2 patients caused by irreversible drug-induced nephrotoxicity and donor-derived malignant tumor respectively.The mean serum creatinine level was 81.7 ± 27.4 μmol/L and eGFR level was 82.5 ± 22.2 mL/min/1.73 m2 in the other EBKT recipients at 24th week post-operation.In simplified group,no vascular complications post-operation occurred.Conclusion En bloc infant kidneys could be transplanted into adult recipients successfully with excellent graft function and survival outcome while censored perioperative patient death and surgical failure.Instead of traditional EBKT technique,simplified EBKT technique could decrease the incidence of surgical vascular complications and should be applied to more recipients.

Objective To compare the adjuvanticity of type-A,B and C CpG-ODN in mice.Methods Three types of CpG-ODN were identified through in vitro stimulation of murine splenocytes with various CpG-ODN.BALB/c mice were immunized with HBsAg,together with different types of CpG-ODN,and antigen-specific IgG.IgG1 and IgG2a titers were measured 4 weeks later by indirect ELISA.Resuits Compared with the control group.all 3 types of CpG-ODN enhanced humoral immune response to HBsAg.However,type-B and C CpG-ODN induced much higher levels of antigen-specific IgG and IgG2a than type A CpG-ODN.Type-C CpG-ODN induced a similar TH 1-biased immune response as type-B CpG-ODN,revealed by decreased IsG1 to IgG2a ratio.In contrast,although type-A CpG-ODN increased IgG titers,it did not switch the balance between TH1 and TH2 immune responses.Conclusion All 3 types of CpG-ODN can enhance the humoral immune response to vaccines,but their aaiuvanticity could be mediated through different mechanisms.

AIM:To explore the relationship between apoptosis in the lung tissues and lung ischemia/reperfusion injury,and to observe the effects of human thioredoxin (hTrx) on apoptosis in lung ischemia/reperfusion injury. METHODS:The single lung in situ ischemia/reperfusion animal model was used. Eighty four Wistar rats were randomly divided into control group (control),groups of ischemia for 1 h and reperfusion for different times (IR1h,IR3h,IR5h),and groups of IR + human thioredoxin treatment (IR1h + hTrx,IR3h + hTrx and IR5h + hTrx). Transmission electron microscope (TEM),terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and immunocytochemistry techniques were used to observe apoptosis,apoptosis signal-regulating kinase 1 (ASK1) and expression of Bcl-2 and Bax in various phases of lung ischemia/reperfusion. RESULTS:Cell apoptosis in lung tissues was significantly high,ASK1,Bcl -2 and Bax protein were upregulated in lung tissues of lung ischemia/reperfusion injury as compared to control (all P

OBJECTIVE To investigate the effect of mono-2-ethylhexyl phthalate(MEHP) on proliferation of primary neural stem cells(NSCs)of rats and NE-4C cells of mice and on the migration of NE-4C cells and the mechanism. METHODS NE-4C or NSCs were treated with MEHP 1,10,100 and 1000 μmol · L-1 for 72 h,respectively. The cytotoxicity was estimated with the cell counting kit-8 (CCK-8). Cell proliferation was analyzed by EdU assay. The mRNA expression levels of the glucocorticoid receptor(GR),signal transducer and activator of transcription 3(Stat3)and sex determining region Y (SRY)-box 2(Sox2) were detected by qRT-PCR. The protein expression levels of total GR,GRβ, Sox2,Stat3 and p-Stat3 were measured by Western blotting. RESULTS Cell viability of NE-4C cells and NSCs at MEHP 1000μmol·L-1 was significantly decreased,which was 70.3%and 40.0%of the control group, respectively. EdU assay showed that MEHP 100 μmol · L-1 decreased NE-4C cells and NSCs by 74.8%and 12.0%(P<0.05)compared with control. The effect of MEHP on the cell migration of NE-4C was evidenced by the fact that the migration was obviously reduced to (63.4±2.0)%(P<0.05)after treatment with MEHP 100μmol · L-1 for 72 h. The mRNA expression levels associated with proliferation and migration in NE-4C of GR,Stat3 and Sox2 in MEHP 100 μmol · L-1 group were down-regulated to 49.8%,26.0% and 14.0%of control(P<0.05). At MEHP 100μmol · L-1,mRNA of GR, Stat3 and Sox2 in NSCs declined to 10.0%,14.0% and 15.3% of normal control. Western blotting results revealed that protein expressions of GR,GRβ,Sox2 and p-Stat3 were remarkably inhibited by MEHP 100 μmol · L-1 in that the relative expression of NE-4C was 0.92 ± 0.17,0.87 ± 0.35,0.81 ± 0.22 and 0.62 ± 0.24(P<0.05). The corresponding protein expression in NSCs was 0.82 ± 0.20,0.56 ± 0.12,0.84 ± 0.36 and 0.53 ± 0.20(P<0.05)when the cells were treated with MEHP 100μmol · L-1 for 72 h. CONCLUSION MEHP can inhibit the proliferation and migration of NE-4C cells and NSCs possibly by decreasing Stat3 and Sox2 that are mediated by GRβ.

Objective Pulmonary fibrosis is a progressive chronic lung disease with a high incidence.Although the path of the disease has not been fully elucidated,the pathogenesis of the disease is roughly similar.Tyrosine kinases are involved in a series of signaling pathways that are critical for cell homeostasis.Substantial evidence from in vitro studies and experimental animal models suggests that tyrosine kinases play a role in promoting the development and progression of pulmonary fibrosis,and tyrosine kinase inhibitors have shown good anti-fibrosis and anti-inflammatory effect in animal models of pulmonary fibrosis.

AIM:To investigate the effect of L-arginine(L-Arg) on expression of bcl-2,bax mRNA during pulmonary ischemia and reperfusion injury(PIRI) in rabbits.METHODS: Single lung ischemia and reperfusion animal model was used in vivo.The rabbits were randomly divided into three groups: sham operated group(sham,n=12),ischemia-reperfusion group(I/R,n=12) and I/R+ L-arginine group(L-Arg,n=12).Changes of several parameters,which included apoptotic index(AI),wet to dry ratio of lung tissue weight(W/D) and index of quantitative assessment of histologic lung injury(IQA),were measured at 300 min after reperfusion in lung tissue.Meanwhile the location and expression of bcl-2,bax mRNA as well as the ratio of bcl-2 mRNA/bax mRNA were observed.The lung tissue was prepared for light microscopic and electron microscopic observation at 60,180 and 300 min after reperfusion.RESULTS: As compared with I/R group,in intima and extima of small pulmonary artery,alveoli,and bronchiole epithelia,the expression of bcl-2 mRNA and the ratio of bcl-2 mRNA/bax mRNA were increased,and the expression of bax mRNA was decreased in L-Arg treatment group.The values of AI,W/D and IQA showed significantly lower than that in I/R group at 180 minutes after reperfusion in lung tissue(P

Objective: To explore the prognostic value of the international prognostic index (IPI), the national comprehensive cancer network IPI(NCCN-IPI)and the age-adjusted IPI (aa-IPI) in diffuse large B cell lymphoma. Methods: A total of 311 patients with de novo diffuse large B-cell lymphoma (DLBCL) diagnosed from 2003 to 2012 in Nanfang hospital were included. All patients were divided into CHOP (cyclophosphamide, vincristine, doxorubicin, and prednisone) and R-CHOP (rituximab, CHOP) groups. Survival analysis was compared among IPI, NCCN-IPI and aa-IPI models. Discrimination of three different prognostic models was assessed using the Harrell’s C statistic. Results: A total of 311 patients were analyzed. Among them, 128 patients were treated with CHOP regimen and other 183 patients were treated with R-CHOP regimen. In CHOP groups, both NCCN-IPI (5-year OS: 59.7% vs 26.8%, P<0.001) and aa-IPI (5-year OS: 71.0% vs 25.0%, P<0.001) showed better risk stratification for low-intermediate and high-intermediate group than the IPI (5-year OS: 47.6% vs 36.6%, P=0.003). However, in the patients treated with R-CHOP, NCCN-IPI showed better risk stratification in low, low-intermediate, high-intermediate groups (5-year OS: 96.0% vs 83.0% vs 66.5%, P=0.009). According to the Harrell’s C statistic, C-index of IPI, NCCN-IPI and aa-IPI for overall survival (OS) were 0.546, 0.667, 0.698 in CHOP group and 0.611,0.654, 0.695 in R-CHOP group respectively. In patients younger than 60 years old, C-index of IPI, NCCN-IPI and aa-IPI for OS were 0.534, 0.675, 0.698 in CHOP group and 0.584, 0.648, 0.695 in R-CHOP respectively. Conclusion The NCCN-IPI is more powerful than IPI and aa-IPI in DLBCL patients receiving R-CHOP. aa-IPI is a preferable model in predicting prognosis than IPI and NCCN-IPI in anthracycline-based chemotherapy without rituximab.

Myeloid differentiation factor 88 (MYD88) is a key linker in the Toll-like receptor (TLR) signaling pathway, which plays an important role in the progression of the tumour. Recent studies have shown that the activating mutation of MYD88 L265P has been identified in about of 90% lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia and about of 40% diffuse large B-cell lymphoma and other subtypes of B-cell proliferative neoplasms. Different types of B-cell proliferative neoplasms have their own histology, immunohistochemistry and clinical characteristics, thus, mutation rates of MYD88 L265P are different. This review discusses the latest progress of MYD88 L265P mutation in B-cell proliferative neoplasms.

Macrophages are important cells of the immune system. Tumor-associated macrophages are enriched macrophages near tumor cells or tissues. Their role is mainly to promote the construction of tumor inflammatory microenvironment and inhibit tumor immune response. Cell co-culture system is a symbiotic culture system formed by mimicking the internal environment of the body in vitro. The co-culture condition is relatively consistent with the environment in vivo, enabling better information exchange and material exchange between cells, which is a supplement to the monolayer cell culture and animal experiments. Tumor-associated macrophages and tumor cells co-exist in the tumor microenvironment. Thus, constructing a co-culture system for tumor-associated macrophages and tumor cells would be conducive to studying the antitumor effect of tumor-associated macrophages and developing new immunotherapy drugs. The co-culture system would provide a new direction for treating malignant tumors. This article mainly reviewed the co-culture patterns of macrophages and the antitumor effects of different phenotypes of macrophages, and highlighted the importance of using immunotherapy to treat malignant tumors in the tumor microenvironment.

Objective:To explore the relationship between gene polymorphisms of integral protein alpha-4 ( ITGA4) and intercellular adhesion molecule-1 ( ICAM-1) and the risk of ulcerative colitis (UC), and to analyze the effects of ITGA4 and ICAM-1 gene variations on the clinical response of vedolizumab (VDZ) treatment in UC patients at week-14. Methods:From January 1, 2010 to January 31, 2023, at Department of Gastroenterology of the Second Affiliated Hospital of Wenzhou Medical University, a total of 500 UC patients (UC group) and 529 gender- and age-matched healthy controls (healthy control group) were collected. The 500 UC patients were divided into mildly active stage (264 cases) and moderately to severely active stage (236 cases); distal colitis (299 cases), extensive colitis (201 cases); of the 500 UC patients, 120 cases received VDZ treatment, and 78 cases achieved clinical response and the remaining 42 cases had no response at week-14. Chi-square test and unconditional logistic regressionmodel were used to analyze the difference in gene polymorphisms of ITGA4 rs6740847, rs7562325 and ICAM-1 rs5498 gene polymorphisms between UC group and healthy control group, between patients of mildly active stage and patients of moderately to severely active stage, between patients with distal colitis and patients with extensive colitis, between patients with clinical response and patients without response through dominant, recessive, and allelic gene models. Results:The results of dominant gene model analysis showed that, the frequency of the variant allele G and the variant genotype AG+ GG of ITGA4 rs6740847 of UC group were lower than those of healthy control group (28.60% vs. 33.18%, 48.00%vs. 56.15%), the frequency of variant allele T and variant genotype CT+ TT of ITGA4 rs7562325 of UC group were higher than those of healthy control group (37.30% vs.31.57%, 62.20% vs. 54.63%), and the differences were statistically significant( χ2=5.04, 6.83, 7.49 and 6.06, P=0.025, 0.009, 0.006 and 0.014); the frequency of variant allele G and variant genotype AG+ GG of ITGA4 rs6740847 of patients with moderate to severe active UC were lower than those of patients with mild active UC (25.42% vs. 31.44%, 43.22% vs. 52.27%), while the frequency of variant allele T and variant genotype CT+ TT of ITGA4 rs7562325 were both higher than those of mild active UC (40.89% vs. 34.09%, 66.95% vs. 57.96%), and the differences were statistically significant( χ2=4.42, 4.09, 4.93 and 4.29, P=0.036, 0.043, 0.026 and 0.038); the frequency of variant allele G and variant genotype AG+ GG of ITGA4 rs6740847, the variant allele T of ITGA4 rs7562325, and the variant allele G and variant genotype AG+ GG of ICAM-1 rs5498 of patients with extensive colitis UC were lower than those of patients with distal colitis UC (24.38% vs. 31.44%, 39.80% vs. 53.51%, 33.58% vs.39.80%, 19.65% vs.26.09%, 35.82% vs. 45.82%), and the differences were statistically significant( χ2=5.87, 9.05, 3.97, 5.54 and 4.94, P=0.015, 0.003, 0.046, 0.019 and 0.026); the frequency of variant allele G and variant genotype AG+ GG of ITGA4 rs6740847 of patients with clinical response were higher than those of patients without response (34.62% vs.21.43%, 61.54% vs. 33.33%), and the differences were statistically significant( χ2=4.52 and 8.70, P=0.039 and 0.001). The results of recessive gene model analysis showed that, the frequency of variant genotype TT of ITGA4 rs7562325 of UC group was higher than that of healthy control group (12.40% vs.8.51%), and the difference was statistically significant ( χ2=4.18, P=0.041); the frequency of variant allele G and variant genotype GG of ICAM-1 rs5498 of patients with moderate to severe active UC were higher than those of patients with mild active UC (27.33% vs. 20.08%, 8.47% vs. 2.27%), and the differences were statistically significant( χ2=7.30 and 9.72, P=0.007 and 0.002); the frequency of variant allele T and variant genotype TT of ITGA4 rs7562325 of patients with clinical response were lower than those of patients without response (32.05% vs. 45.24%, 10.26% vs. 23.81%), and the differences were statistically significant( χ2=4.09 and 3.93, P=0.043 and 0.047). Conclusions:The variation of ITGA4 rs6740847 gene may reduce the risk and disease activity of UC, and may increase the clinical response to VDZ treatment in UC patients. However, the variation of ITGA4 rs7562325 gene may increase the risk and disease activity of UC, and may reduce the clinical response to VDZ treatment in UC patients. The variation of ICAM-1 rs5498 gene may worsen the disease activity of UC. In addition, the variations of ITGA4 rs6740847, rs7562325 and ICAM-1 rs5498 gene may all reduce the risk of extensive colitis.