Objective To investigate the role of sufentanil on intestinal ischemia-reperfusion model of liver cell apoptosis and bel-2/Bax expression,and the opioid receptor-mediated effects in the process.Methods Seventy two healthy adult Wistar rats,weight 200-250 g,either male or female,were randomly divided into 9 groups(n=8),sham operation group(S),ischemia-reperfusion group(IR),sufentanil treated group (SPC),three kinds of opioid receptor antagonist,NTD(δ receptor antagonist,),nor-BNI(κ receptor antagonist),CTOP(μ receptor antagonist)in the intervention groups(NTD + SPC,nor-BNI + SPC,CTOP + SPC),three kinds of opioid receptor antagonist control groups(NTD,nor-BNI,CTOP).by clamping the superior mesenteric artery production model of intestinal ischemia-reperfusion injury,after the end of the experiment,immediately take the left lobe of liver specimens.Immunohistochemical detection of bcl-2/Bax protein expression,terminal transferase labeling(TUNEL)assay of liver cell apoptosis index(AI).Results Compared with IR group,SPC Group bcl-2 expression increased(0.277±0.014 vs 0.230±0.013)(P＜0.05),bcl-2/Bax ratio increased(1.375±0.113 vs 0.819±0.102)(P＜0.05),Bax down regulation(0.202±0.013 vs 0.283±0.025)(P＜0.05),liver cell AI reduced(6.491±1.191vs10.094±1.051)(P＜0.05).Compared with the SPC group,NTD + SPC group,nor-BNI +SPC group,CTOP+SPC group bcl-2 expression decreased(F=59.698,P＜0.05),bcl-2/Bas ratio decreased(F=40.349,P＜0.05),Bax expression was elevated(F=53.765,P＜0.05),liver cells AI elevated(F=76.728,P＜0.05).Conclusion Sufentanil pretreatment inhibit rat intestinal ischemia-reperfusion liver cell apoptosis.δ,κ,μthree kinds of opioid receptor mediate the protective effect of sufentanil,and the effects are equal.

ObjectiveTo evaluate the effect of sufentanil preconditioning on acute lung injury induced by intestinal ischemia-reperfusion (I/R) in rats and the role of opioid receptors.MethodsForty-eight male Wistar rats weighing 200-250 g were randomly divided into 6 groups ( n =8 each):sham operation group (group S) ; I/R group; sufentanil preconditioning group (group SPC) ; COTP (μ receptor antagonist) + SPC group; NTD (δ receptor antagonist) + SPC group and nor-BNI (κ receptor antagonist) + SPC group.Intestinal I/R was produced by occlusion of the superior mesenteric artery for 45 min followed by 2 h reperfusion in groups I/R,SPC,COTP +SPC,NTD + SPC and nor-BNI + SPC.Sufentanil 10 μg/kg was injected intravenously at 10 min before ischemia in groups SPC,COTP + SPC,NTD + SPC and nor-BNI + SPC.COTP 1 mg/kg and NTD 5 mg/kg were injected intravenously at 10 min before sufentanil injection in groups COTP + SPC and NTD + SPC respectively,while nor-BNI 5 mg/kg was injected intravenously at 15 min before sufentanil administration in group nor-BNI + SPC.The animals were sacrificed at 2 h of reperfusion,the intestinal tissue was removed for microscopic examination and intestinal damage was assessed and scored according to Chiu.Left lung tissue was also removed for microscopic examination (1 =normal,4 =severely injured).The apoptosis in lung cells was detected using TUNEL and apoptosis index (AI) was calculated.The expression of Bcl-2 and Bax proteins in lung tissues was detected using immuno-histochemistry and Bcl-2/Bax ratio was calculated.ResultsCompared with group S,Chiu's score,lung injury score and AI were significantly increased,expression of Bcl-2 and Bax proteins was up-regulated,Bcl-2/Bax ratio was significantly decreased in the other groups ( P ＜ 0.01 ).Compared with group I/R,Chiu' s score,lung injury score and AI were significantly decreased,Bcl-2 protein expression was up-regulated,Bax protein expression was downregulated,and Bcl-2/Bax ratio was significantly increased in group SPC (P ＜ 0.01 ).Compared with group SPC,Chiu's score,lung injury score and AI were significantly increased,Bcl-2 protein expression was down-regulated,Bax protein expression was up-regulated,and Bcl-2/Bax ratio was significantly decreased in groups COTP + SPC,NTD + SPC and nor-BNI + SPC ( P ＜ 0.01 ).ConclusionSufentanil preconditioning can attenuate lung injury induced by intestinal I/R by activation of opioid receptors in rats.

Objective To describe the distributions of FCGR polymorphisms in human immunodeficiency virus (HIV)-uninfected patients with cryptococcosis,and to investigate the association of FCGR polymorphisms with the susceptibility to cryptococcosis.Methods The distributions of the four functional polymorphisms,including FCGR2A 131H/R,FCGR3A 158F/V,FCGR3B NA1/NA2,and FCGR2B 232I/T were compared between 198 cryptococcosis patients and 190 healthy controls.The polymorphisms distribution patterns were also compared between patients with central nervous system (CNS) infection and those without CNS infection.Genotyping of eight single nucleotide polymorphism (SNP) in FCGR were performed by multiplex SNaPshot technology using DNA extracted from blood samples.The comparison between patients and controls was performed by chi square test or Fisher exact test.Results Compared to healthy controls,the frequency of FCGR2B 232I/I increased (65％ vs 53％,x2 =4.27,P=0.039,OR=1.652,95％CI:1.02-2.67) and that of FCGR2B 232I/T decreased (27％ vs 40％,x2 =5.77,P=0.016.OR=0.542,95％CI:0.33-0.90) in patients with cryptococcal meningitis.Among immunocompetent patients,the frequency of FCGR2B 232I/I was also over-presented (69％ vs 53％,x2=4.53,P =0.033,OR=1.958,95％CI:1.05-3.66) and the FCGR2B 232I/T genotype was also less frequently observed (24％ vs 40％,x2=5.14,P=0.023,OR=0.467,95％CI:0.24-0.91) compared to healthy controls.There were 117 cases with CNS infection and 81 non-CNS infection cases.The genotype of FCGR2A 131R/Rwas over-presented (19％ vs 6％,x2 =6.48,P=0.011,OR=3.52,95％CI:1.27-9.73) and the FCGR2B 232I/T genotype was under-presented (27 ％ vs 46 ％,x2 =7.56,P =0.006,OR=0.431,95％CI:0.24-0.79) in patients with CNS infection compared with those without CNS infection.Furthermore,the frequency of FCGR2B 232I/I genotypes increased (69％ vs47％,x2 =5.47,P=0.019,OR=2.479,95％CI:1.15-5.34) and the frequency of FCGR2B 232I/T decreased (24％ vs 51％,x2 =8.66,P=0.003,OR=0.307,95％CI:0.14-0.68) in immunocompetent patients with CNS infection compared with those without CNS infection.Conclusions FCGR2A 131H/R and FCGR2B 232I/T are associated with the susceptibility to cryptococcal CNS infection,which suggests that FcγRⅡA and FcγRⅡB may contribute to the pathogenesis of cryptococcosis.

Objective To investigate the association between genetic polymorphisms of Dectin-2 and pulmonary cryptococcosis.Methods A total of 134 non-human immunodeficiency virus (HIV)patients with pulmonary cryptococcosis and 464 healthy controls were included in this case control study.The peripheral leucocyte DNA was extracted and genotyping was performed by multiplex SNaPshot technology.The single nucleotide polymorphism (SNP)of rs11045418 located at 5′-flanking locus of Dectin-2 gene was genotyped.Patients without predisposing conditions were compared independently.The differences of gene polymorphism distributions compared between pulmonary patients and healthy control, and between patients without predisposing conditions and healthy control.All data were analyzed withχ2 tests.Results Among the total 134 patients,82 patients had no predisposing factors.Thirty two patients met the proven diagnosis criteria and 102 patients were probable pulmonary cryptococcosis.According to the site of infection, 72 patients had local infection in lungs and 62 patients had disseminated cryptococcosis.Three samples failed in genotyping,one of which was a patient without predisposing factor.Compared with the control group,there was a trend of increasing proportion of heterozygote rs11045418 CT in the 131 pulmonary cryptococcosis patients (59% vs 50%,P =0.069,OR=1.44,95%CI :0.97-2.13),and the heterozygote was significantly increased in 81 patients without predisposing conditions(64% vs 50%,P =0.017,OR= 1 .82,95 %CI :1 .11 -2.95 ).No significant difference of genotype distribution was found between the local and disseminated infection patients.Conclusion Our study shows that rs11045418 CT heterozygote in Dectin-2 is associated with the susceptibility of pulmonary cyrptococcosis among non-HIV-infected Chinese patients,which indicated that the change of Dectin-2 receptor may play a role in the pathogenesis of pulmonary cyrptococcosis.

Objective To determine the results of treatment combining all-trans-retinoic acid(ATRA)in childhood acute promyelocytic leukemia(APL).Methods 22 children with newly diagnosed APL received induction therapy with ATRA followed by 3 courses of consolidation chemotherapy:daunorubicin,idarubicin,homoharringtonine or aclacinomycin plus cytosine arabinoside.A maintenance therapy was then administered with ATRA and these reigems for 36 months.Results Early deaths from diffuse intravazcular clotting and intracranial hemorrhage occurred in two patients.The other children achieved a complete remission(CR).By June 2007,the estimated disease-free survival rates at 1,3 and 5 years were 100%,93.3% and 84.7%;respectively.The side effects of ATRA were xerosis eutis and xerocheilia,headaches,nausea and vomiting,hepatic function lesion and ATRA syndrome.Conclusion Remission induction therapy with ATRA is effective and safe for newly diagnosed childhood APL.The maintenance therapy combined chemotherapy with ATRA can improve the long-term effects of APL patients.The main causes of death in APL children is diffuse intravascular clotting and intracranial hemorrhage.The side effects of ATRA can be tolerated.

Objective To observe the clinical safety and efficacy of foscarnet prophylaxis and pre-emptive therapy for cytomegalovirus (CMV) infection in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods Ninety-six patients undergoing allo-HSCT from October 2014 to December 2016 were retrospectively analyzed. Plasma CMV-DNA was monitored with real-time quantitative polymerase chain reaction (RQ-PCR) from beginning to 180 days after transplantation. Foscarnet was used not only for prophylaxis but also for first-line pre-emptive therapy when plasma CMV-DNA turned to positive. Foscarnet was given 60 mg·kg-1·d-1 and 120 mg·kg-1·d-1 respectively in prevention and pre-emptive therapy. Incidences of CMV infection and CMV disease were observed, influencing factors on CMV in faction and the efficacy and safety of foscarnet prophylaxis were analyzed, and survival of patients treated by all-HSCT was evaluated. Results Of the total 96 patients, 42 cases (43.8%) had CMV infection with the median time of 42 days after allo-HSCT. CMV-DNA became negative in 36 patients (85.7%, 36/42) after pre-emptive therapy. Six patients (14.3 %, 6/42) developed CMV disease, including 5 patients with CMV negative and 1 patient died for CMV pneumonia. Haploidentical donor and grade Ⅱ-Ⅳacute graft versus host disease (GVHD) were the risk factors for CMV reactivation (χ2 = 3.834, P< 0.05; χ2 = 16.807, P< 0.001). The side effects of foscarnet prophylaxis were mild without hematologic toxicities. 12 patients (28.6 %) died in 42 patients with CMV infection, and 6 patients (11.1 %) died in 54 patients without CMV infection. The difference of survival rates between both groups was not statistically significant. Conclusion Foscarnet is an effective agent for prophylaxis and pre-emptive therapy in CMV infection after allo-HSCT with mild adverse reactions, especially for patients following with hematopoietic recovering.

Objective To compare the effects of CalliSpheres drug-eluting beads transcatheter arterial chemoembolization(DEB-TACE)and conventional TACE(c-TACE)on liver fibrosis and liver function in the treatment of primary hepatocellular carcinoma(HCC).Methods A total of 40 patients diagnosed with HCC at Xuzhou Municipal Cancer Hospital of China between October 2020 and October 2022 were enrolled in this study.According to therapeutic scheme,the patients were divided into DEB-TACE group(n=20)and c-TACE group(n=20).The preoperative,and postoperative 5-day and one-month hyaluronidase(HA),type Ⅲ procollagen peptide(P Ⅲ NP),type Ⅳ collagen(CⅣ)and laminin(LN),alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil),albumin(Alb),and prothrombin time(PT)were compared between the two groups.Results The technical success rate was 100％in both groups,and tumor staining completely disappeared immediately after TACE in all patients.The postoperative 5-day levels of HA,LN,P Ⅲ NP,and CⅣ in both groups were remarkably higher than the preoperative ones(P＜0.05).One month after TACE,HA level in the DEB-TACE group was prominently higher than its preoperative value(P＜0.05);HA and LN levels in the c-TACE group were obviously higher than their preoperative values(P＜0.05);and the HA and LN levels in c-TACE group were significantly higher than those in DEB-TACE group(P＜0.05).Five days after TACE,in the DEB-TACE group the AST and PT levels were higher than their preoperative values while the Alb level was lower than its preoperative value(P＜0.05);in the c-TACE group the ALT,AST,TBiL and PT were higher than their preoperative values while the Alb level was lower than its preoperative value(P＜0.05);the ALT and AST levels in the c-TACE group were strikingly higher than those in the DEB-TACE group while Alb level was strikingly lower than that in the DEB-TACE group(P＜0.05).Conclusion Both CalliSpheres DEB-TACE and c-TACE can aggravate liver fibrosis and cause liver function damage.However,the degree of liver fibrosis and liver function damage caused by CalliSpheres DEB-TACE is less than that caused by c-TACE.(J Intervent Radiol,2024,33:259-263)

Objective:To investigate the expressions and correlation of bcl-2, programmed death-1 (PD-1) and programmed death ligand-1(PD-L1) in diffuse large B-cell lymphoma (DLBCL) tissue specimens, and the relationship between chemotherapy efficacy and prognosis of DLBCL patients.Methods:The expressions of bcl-2, PD-1 and PD-L1 in 82 patients with DLBCL who were admitted to Chenzhou First People's Hospital of Hunan Province from May 2011 to April 2014 were detected by using immunohistochemistry, and the correlation of the expressions of bcl-2, PD-1 and PD-L1 with clinicopathological characteristics and prognosis was analyzed.Results:The positive rate of bcl-2, PD-L1 and PD-1 in cancer tissues of DLBCL patients was 53.7% (44/82), 56.1% (46/82) and 32.9% (27/82), respectively. There was a correlation between bcl-2 and PD-L1 expression ( r = 0.306, P = 0.005). Bcl-2 was highly expressed in patients with international prognosis index (IPI) score 3-4 points, non-germinal center B-cell-like (non-GCB) subtype and B symptoms (all P < 0.05); PD-1 was highly expressed in patients with IPI score 3-4 points ( P < 0.05); PD-L1 was highly expressed in patients with IPI score 3-4 points, tumor stage Ⅲ-Ⅳ, B symptoms, ≥60 years old, and non-GCB (all P < 0.05). The overall survival (OS) and progression-free survival (PFS) in bcl-2-negative group were better than those in the bcl-2-positive group, and the differences were statistically significant (both P < 0.05); OS and PFS in PD-L1-negative group were better than those in PD-L1-positive group, and the differences were statistically significant(both P < 0.01). There were no statistical differences in OS and PFS between PD-1-positive group and PD-1-negative group (both P > 0.05). OS and PFS in bcl-2 and PD-L1 co-expression group were worse than those in both negative or any negative group (all P < 0.01), and PFS in bcl-2 and PD-1 co-expression group was worse than those in both negative or any negative group ( P = 0.044). Cox multivariate analysis showed IPI score 3-4 points and B symptoms were the independent influencing factors of OS in DLBCL patients (both P < 0.01); IPI score 3-4 points, B symptoms and PD-L1-positive were the independent influencing factors of poor PFS in DLBCL patients (all P < 0.05). Conclusion:The positive expressions of bcl-2 and PD-L1 are the independent factors for the poor prognosis of DLBCL patients, which may become new targets for the treatment of DLBCL.

Objective:To analyze the electrocardiographic characteristics of patients with chronic pulmonary artery stenosis (PAS), and to explore their relationship with disease severity indicators.Methods:The study was a retrospective case-series analysis. Patients with chronic PAS admitted to Gansu Provincial Hospital from January 2018 to July 2021 were enrolled. The clinical data and the results of electrocardiography, transthoracic echocardiography, right cardiac catheterization, N-terminal B-type natriuretic peptide (NT-proBNP) measurement and 6-min walking distance test of patients were analyzed. The linear regression model or logistic regression model was used to analyze the relationship between electrocardiographic characteristics and the disease severity in patients with chronic PAS.Results:Sixty-three patients aged (62.1±9.7) years including 43 females (68.3%) were enrolled in the study. Among them, 62 patients (98.4%) had (R 1+S Ⅲ)-(S Ⅰ+R Ⅲ)<1.5 mV, and no patients had V 5lead R: S ratio to V 1 lead R: S<0.04 and V 6 lead R: S ratio<0.4. There were 55 patients (87.3%), with flat or inverted T-waves in V 1, and 10 patients (15.9%) with flat or inverted T-waves in all precordial leads (V 1-V 6). There were 18 patients (28.6%) with flat or inverted T-waves in inferior leads (Ⅱ, Ⅲ, aVF). Multiple liner regression analysis showed that Max R V1, 2+Max S I, aVL-S V1 combined with the number of flat or inverted T-waves in limb leads was independently correlated with atrial area ( R2=0.290, P=0.002); R V1+S V5 was independently correlated with right ventricular area ( R2=0.257, P=0.001); R peak V 1 combined with the number of flat or inverted T waves in precordial leads was independently correlated with tricuspid annular plane systolic excursion ( R2=0.407, P<0.001); (R 1+S Ⅲ)-(S Ⅰ+R Ⅲ) combined with the number of flat or inverted T waves in precordial leads was independently correlated with NT-proBNP ( R2=0.504, P<0.001); Max R V1, 2+Max S I, aVL-S V1 were independently correlated with right atrial pressure ( R2=0.803, P=0.036); (R 1+S Ⅲ)-(S Ⅰ+R Ⅲ) were independently correlated with mean pulmonary artery pressure ( R2=0.302, P<0.001); R aVRcombined with the number of flat or inverted T-waves in precordial leads was independently correlated with cardiac index ( R2=0.173, P=0.003); (R 1+S Ⅲ)-(S Ⅰ+R Ⅲ) was independently correlated with pulmonary vascular resistance ( R2=0.173, P=0.002); R peak V 1 combined with the number of flat or inverted T-waves in precordial leads was independently correlated with mixed vein oxygen saturation ( R2=0.302, P<0.001). Conclusion:The vast majority of patients with chronic PAS have (R 1+S Ⅲ)-(S Ⅰ+R Ⅲ)<1.5 mV and flat or inverted T-wave in V 1 lead, and some characteristic electrocardiographic manifestations are correlated with indicators of disease severity.