The effects and molecular mechanisms of vitamin D3 on airway inflammation and oxidative stress response in a mouse model of bronchial asthma / 安徽医科大学学报

Objective @#To investigate the role and related molecular mechanisms of vitamin D3 ( VitD3 ) in airway inflammation and oxidative stress response in bronchial asthma mice．@*Methods @#Twenty-eight female C57BL/6 mice were randomly divided into a control group ( Ctrl) and a model group．The model group mice were sensitized using ovalbumin ( OVA) to establish an asthma model，and were further divided into an asthma (Asthma) group， VitD3 treatment (Asthma + VitD3 ) group，and Forkhead Box O1 (FOXO1) inhibitor AS1842856 treatment (Asth- ma + AS) group．Lung resistance (LR) changes were measured in each group of mice．Enzyme-linked immunosor- bent assay (ELISA) was used to detect the levels of tumor necrosis factor-alpha (TNF-α) ，interleukin ( IL) -1 β , and IL-18 in bronchoalveolar lavage fluid ( BALF) ．Western blot was used to determine the expression levels of FOXO1，NOD-like receptor pyrin domain containing 3 (NLRP3) ，Caspase-1，and apoptosis-associated speck-like protein (ASC) in lung tissue. @*Results @#ompared to the Ctrl group mice，LR increased in the Asthma group mice (P＜0. 01) ．Compared to the Asthma group，LR decreased in the Asthma + VitD3 and Asthma + AS group mice (P＜0. 05) ，with no significant difference in LR change between Asthma + VitD3 and Asthma + AS group mice. Compared to the Ctrl group，TNF-α , IL-1 β , and IL-18 levels in BALF，as well as NLRP3，Caspase-1，and ASC protein expression levels in lung tissue，increased in the Asthma，Asthma + VitD3 ，and Asthma + AS group mice (P＜0. 05) ．Compared to the Asthma group，the Asthma + VitD3 and Asthma + AS group mice showed decreased levels of the mentioned inflammatory factors in BALF and reduced protein expression of NLRP3，FOXO1，Caspase- 1，and ASC in lung tissue (P＜0. 05) ．Compared to the Asthma + VitD3 group，the Asthma + AS group showed in- creased FOXO1 protein expression (P ＜0. 05) ，with no statistically significant differences in the other measured indicators．@*Conclusion @#VitD3 can alleviate asthma symptoms induced by OVA in mice，improve the degree of air- way inflammation，and reduce oxidative stress levels．The mechanism may be related to the downregulation of the FOXO1/ NLRP3 axis.

Inhibition of miR-20a by pterostilbene facilitates prostate cancer cells killed by NK cells via up-regulation of NKG2D ligands and TGF-ß1down-regulation.

Natural killer (NK) cells play a potent role in antitumor immunity via spontaneously eliminating tumor directly. However, some tumors such as prostate cancer constantly escape this immune response by down-regulating cell surface molecule recognition and/or secreting immune impressive cytokines. Here, we found pterostilbene, a natural agent with potent anticancer activity, could enhance expression of major histocompatibility complex class I chain-related proteins A and B (MICA/B) on prostate cancer cells surface, which are ligands of the natural killer group 2 member D (NKG2D) expressed by NK cells, and inhibit TGF-ß1 secretion by prostate cancer cells. Further, we discovered that these effects were caused by inhibition of miR-20a in prostate cancer cells by pterostilbene. MiR-20a could target the 3' untranslated region (UTR) of MICA/B, resulting in their expression down-regulation. Inhibition of TGF-ß1 function by its specific antibody attenuated its impairment to NKG2D on NK cells. Finally, we observed that pterostilbene-treated prostate cancer cells were more easily to be killed by NK cells. Taken together, our findings demonstrated inhibition of miR-20a by pterostilbene in prostate cancer cells could increase MICA/B expression and decrease TGF-ß1 secretion, which enhanced NK cell-mediated cytotoxicity againt prostate cancer cells, suggesting a potential approach for increasing anti-prostate cancer immune.

Biomechanical Evaluation of Oblique Lateral Interbody Fusion Combined with Different Internal Fixation Methods for Treating Degenerative Lumbar Scoliosis:A Finite Element Analysis / 医用生物力学

Objective To verify the biomechanical stability of oblique lateral interbody fusion ( OLIF) combinedwith different fixation methods for treating degenerative lumbar scoliosis (DLS) by three-dimensional (3D) finite element analysis. Methods The L1-S1 3D finite element DLS model ( Model 1) was established, and then the OLIF (L2-5) at 3 contiguous levels of fusion and its combination with different internal fixation methods were simulated, namely, stand-alone OLIF model ( Model 2), vertebral screw fixation model ( Model 3), unilateral pedicle screw fixation model (Model 4) and bilateral pedicle screw fixation model (Model 5) were established,respectively. Under upright, flexion, extension, lateral bending and axial rotation states, range of motion (ROM) of fusion segments, as well as cage stress, internal fixation stress, and stress distribution were recorded and analyzed. Results Under six motion states, the overall ROM of fusion segments in Models 2-5 was smaller than that of Model 1. Compared with Model 1, the overall ROM reduction of Model 3 and Model 4 was larger than that of Model 2 and smaller than that of Model 5. Under flexion and extension, the overall ROM reduction of Model 4 and Model 5 was basically equal. Under left and right lateral bending, the overall ROM reduction of Model 3 and Model 5 was basically equal. Under all motion states, the peak stress of Model 3 and Model 4 fusion cage was larger than that of Model 5 and smaller than that of Model 2. The peak stresses of L2-3, L3-4 and L4-5 fusion cages in Model 3 increased by 5. 52% , 10. 96% and 7. 99% respectively compared with Model 5 under left lateral bending, and the peak stresses of L2-3, L3-4 and L4-5 fusion cages in Model 4 increased by 8. 70% , 7. 00% and 6. 99% respectively under flexion. Under all motion states, the peak stress of screw rod in Model 5 was smaller than that of Model 3 and Model 4, and the peak stresses of screw rod in Models 3-5 were the smallest in upright state. Conclusions The OLIF with unilateral pedicle screw fixation or vertebral screw fixation can provide favorable biomechanical stability of the fusion segment. The results provide some references for clinical application of OLIF technology in the treatment of DLS.

4-1BB antibody enhances cytotoxic activity of natural killer cells against prostate cancer cells via NKG2D agonist combined with IL-27.

Aims: To enhance the cytotoxicity of natural killer (NK) cells against prostate cancer cells via NKG2D agonist, with 4-1BB antibody and IL-27 combination. Materials & methods: FACS was used to detect degranulation and cell surface receptors in NK cells isolated from healthy donors. Cytokine concentrations were measured using ELISA. NK-cell cytotoxicity was analyzed using Cell Counting Kit-8. Results: NKG2D agonist, 4-1BB antibody and IL-27 combination treatment improved the activating receptor expression and IFN-γ and TNF-α secretion but decreased the suppressive receptor CD158a expression and IL-10 secretion in NK cells. The combined treatment enhanced NK-cell cytotoxicity against both PC3 and DU145 cells with concurrent enhanced STAT3 activation. Conclusion: 4-1BB antibody and IL-27 improved NKG2D agonist function in NK cells against prostate cancer cells.

Thoughts on professional postgraduate training strategy for urology / 中华医学教育探索杂志

Education of professional postgraduate medical students is an important way for the cultivation of high-level medical and health talents in China.This article discusses the current status and problems in the training of professional postgraduate medical students,with thoughts on how to train qualified professional postgraduate medical students majoring in urology in the context of the expansion of enrollment scale.This article also puts forward the following detailed suggestions:pay attention to the quality of students and formulate corresponding training strategies;continuously improve the teaching level of postgraduate tutors and teachers and attach importance to the quality of teaching;improve the rotation and assessment system for postgraduates;actively apply new training methods.

Prostaglandin E2 Inhibits Prostate Cancer Progression by Countervailing Tumor Microenvironment-Induced Impairment of Dendritic Cell Migration through LXRα/CCR7 Pathway.

Migration and homing of dendritic cells (DCs) to lymphoid organs are quite crucial for T cell-induced immune response against tumor. However, tumor microenvironment can make some tumor cells escape immune response by impairing DC migration. Prostaglandin E2 (PGE2) plays important roles in initiating and terminating inflammatory responses. In this study, we investigated whether PGE2 could inhibit murine prostate cancer progression by countervailing tumor microenvironment-induced impairment of dendritic cell migration. We found that murine prostate cancer cell line RM-1-conditioned medium impaired chemotactic movement of marrow-derived DCs and splenic cDCs toward CC chemokine receptor-7 (CCR7) ligand CCL19 in vitro and migration to draining lymph gland in vivo. Meanwhile, it also induced LXRα activation and CCR7 inhibition on maturing DCs. However, the treatment of PGE2 rescued this impairment of DC migration with upregulation of CCR7 and inhibition of LXRα. Further, it was observed that PGE2 also increased MMP9 expression and activated Notch1 signaling on DCs. In RM-1-bearing mouse model, PGE2 treatment was identified to inhibit tumor growth and induce more tumor-infiltrating T cells and CD11c dendritic cells in tumor sites. Therefore, our findings may demonstrate a new perspective for therapeutic interventions on prostate cancer immunoescape.

Synthesis of a novel long-circulating dual-receptor targeting and dual-modal molecular probe：an in-vitro study / 中华放射学杂志

Objective To explore a novel long-circulating dual-receptor targeting and dual-modal molecular probe and investigate its physicochemical properties and targeting effect on breast cancer cells in vitro. Methods Dual-receptor targeting and dual-modal molecular probe RGD@BBN-lipo(QDs)-SPIO was synthesized in the following steps: long-circulating liposome was prepared by film dispersion method;water-soluble superparamagnetic iron oxide (SPIO) nanoparticles and Quantum dots (QDs) were loaded in the hydrophilic and hydrophobic layer of liposome, respectively;RGD and BBN polypeptides were coupled on the former functional magnetic/fluorescent liposomes. Stability of the probe in different physiological solutions was investigated. Transmission electron microscopy (TEM) and particle size analyzer were used to measure nanoparticle sizes and the Zeta potential. Characterization of RGD and BBN was investigated through 1H-NMR and elemental analysis. The MRI T2 relaxivities (1/T2) of RGD@BBN-lipo(QDs)-SPIO was measured through T2 map scanning on 3.0 T MR system. HUV-EC-C cells were used for assessment of cells viability by MTS assay. Prussian blue staining and fluorescence imaging were carried out to determine the targeted breast cellular uptake of RGD@BBN-lipo(QDs)-SPIO nanoparticles. Results The targeting magnetic/fluorescent dual-model molecular probes appeared spherical or para-spherical,with a mean diameter of(118.2±3.9)nm,Zeta potential of (-24.78±1.68) mV,MR T2 magnetic relaxation rate of 0.498 1× 106 M-1 · s-1.RGD and BBN polypeptides were successfully coupled on the former functionally magnetic/fluorescent liposomes with the bind rates of 33.05%and 45.06%, respectively. There was low cytotoxity of the molecular probe on human umbilical vein endothelical cells(HUV-EC-C)by MTS study. Prussian blue staining and fluorescence imaging studies showed that the RGD@BBN-lipo(QDs)-SPIO nanoparticles could target any αvβ3 or gastrin releasing peptide receptor overexpression breast cancer. Conclusions RGD@BBN-lipo(QDs)-SPIO is a novel long-circulating dual-receptor targeting and dual-modal molecular probe and has excellent physicochemical properties and stability, high T2 relaxivities and strong targeting effect on cancer cells and has laid a solid foundation for early diagnosis of breast cancer.

TMP combined with salvia miltiorrhiza delays the progression of chronic allograft nephropathy in rats / 中华器官移植杂志

Objective To investigate the effects of ligustrazine (TMP) combined with salvia miltiorrhiza on the progression of chronic allograft nephropathy (CAN) in rats and the action mechanism.Methods Fischer 344 rats and Lewis rats were used as renal transplant recipients and donors for ortlotopic kidney transplantation. The CAN model was established.By using random number table,the kidney transplant recipients were divided into five groups:cyclosporine A (CsA) group (A),TMP + CsA group (B),Salvia + CsA group (C),TMP + Salvia + CsA group (D) and blank control group (E,receiving no treatment).At 2nd,4th,6th,8th and 12th week after operation,5 mice in each group were sacrificed,and the transplanted kidney was removed for examination of renal histopathological changes. The immunohistochemistry was used to detect the expression of transforming growth factor β1 (TGF-β1) in the renal allograts,and by using fluorescent quantitative polymerase chain reaction,TGF-β1 mRNA expression in the renal allograts assayed.Results In blank control group,the survival time was no more than two weeks.In group A,the CAN pathological changes occurred at 4th week postoperation,those in group B and group C occurred later than in group A,and latest in group D with mild pathological lesions.In all groups after operation,Banff scores showed an upward trend,and at the same time point,those in group A were significantly higher than groups B,C and D ( P＜0.05 and P＜0.01 ).and those in group D was significantly lower than in group B and group C (P＜0.05),but no significant difference was found between group B and group C (P＞0.05).With time over,the TGF-β1 expression intensity showed an increasing trend.At the same time point,TGF-β1 expression intensity in group A was strongest among groups A,B,C and D (P＜0.05 and P＜0.01 ),and that in group D was significantly lower than in group B and group C (P＜0.05),but no significant difference was found between group B and group C (P＞00.05).The changes of TGF-β1mRNA expression pattem in each group showed the same trends as TGF-β1 protein expression.Conclusion TMP or salvia miltiorrhiza can delay the progression of CAN in kidney transplant rats by down-regulating the TGF-β1 expression,and the combined use of them exerts synergic effects.

Impact of intravenous immunoglobulin to penal reactive antibody levels in highly sensitized adult patients waiting for renal transplantation / 中国组织工程研究

BACKGROUND: Many methods can reduce panel reactive antibody (PRA) levels in highly sensitized adult patients waiting for renal transplantation. Desensitisation with plasmapheresis or immunoabsorption is commonly used. Howevel the adverse effects limit their applications. OBJECTIVE: To investigate the effect of pretreatment of intravenous immunoglobulin (IVIG) on PRA levels in highly sensitized adult patients waiting for renal transplantation. DESIGN, TIME AND SETTING: Case analysis, self-contrast of 57 patients waiting for renal transplantation from Ren Transplantation Center. First Affiliated Hospital of Chongqing Medical University between January 2003 and Novembem 2006. PARTICIPANTS: Fifty-seven adult patients, who were highly sensitized to the human leucocyte antigen (HLA), agcd 21 to 65 years. were selected. The average baselines of PRA levels of patients were(46.7±29.5)%. METHODS: All patients received IVIG pretreatments at a dose of 5 g/d for 2 weeks. as one course of treatment. A weel later. some of them received additional 2 weeks iniection of IVIG. The PRA levels of patients were measured before and just after the IVIG treatments. MAIN OUTCOME MEASURES: PRA levels. RESULTS: It was significantly decreased below the non-sensitive level(＜10%)in 48 candidates(84.2%),and partially decreased in 6 ones(10.6%),however, was not changed in 3 ones(5.2%).The total effective rate was 94.8%.Thereafter.each candidate received a cadaveric renal graft. The preoperative complement-dependent cytotoxicity of each candidate was blow 10%. Furthermore. no hyperacute rejection was observed in all 57 recipients. Only two recipients experienced acute reiection, however, that was successfully conversed by methylprednisolone and FK506 treatments. CONCLUSION: Pretreatment of IVIG is a promising and effective option for lower allosensitization and can improve transplantation in highly sensitized candidates with end-stage renal diseases.

Efficacy of Early Use of Rapamycin for Patients after Renal Transplantation and the Complications / 中国药房

OBJECTIVE:To evaluate the efficacy and safety of early use of rapamycin in renal transplant recipients.METHODS:A total of 58 patients undergoing renal transplantation(with kidneys came from corpses)were assigned to receive cyclosporine A(CsA)plus rapamycin(RPM)and prednisone(trial group,n=28)or CsA plus mycophenolate(MMF)and prednisone(control group,n=30).The clinical efficacy at 6 months after renal transplantation,the complications and the adverse drug reactions of the two groups were observed,meanwhile,biochemical indicators including serum blood lipid level and hepatic and renal functions were monitored to analyze the effects of two immunosuppressive schemes on acute rejection of the transplanted kidneys and the survival rates of patients/kidneys.RESULTS:The transplanted kidneys in both group all survived with function.There was no significant difference between the two groups in the incidence of acute rejection(4/28(14.3%)for trial group vs.5/30(16.7%)for control group).The abnormal serum lipid level,infection of incisional wound,diarrhea and hypoleukemia were noted in 11 cases(39.3%),4 cases(14.3%),3 cases(10.7%)and 1 case(3.6%)for the trial group vs.3 cases(10.0%),2 cases(6.7%),8 cases(26.7%)and 5 cases(16.7%)for the control group.CONCLUSION:The early use of triple immunosuppressive therapy(CsA + RPM+ Pred)showed more potent immunosuppressive efficacy but fewer acute rejections as compared the control group(CsA + MMF + Pred).The main side effects of the trial group(CsA +RPM+ Pred)manifested as increased serum lipid level and infection of incisional wound,however,the incidences of diarrhea and hypoleukemia were significantly lower than in the control group.

Multimedia Teaching in the Clinical Practice of Urology / 中华医学教育探索杂志

The clinical practice is a bridge between theoretical learning and clinic practice.The learning interests of medical students can be enhanced and the teaching effects be improved by using multimedia teaching in the clinical practice of urology.

Diagnosis and treatment of herpes zuster in renal transplant recipients / 重庆医科大学学报

Objective:To evaluate the methods of diagnosis and treatment of Herpes Zoster(HZ)in renal transplant recipients.Methods:Diagnosis and treatment of 23 cases of varicella-zoster virus(VZV) infaction in renal transplant recipients were reviewed.Results:Herpes Zoster usually occurred1~2 years after renal transplantation.It could be diagnosed by symptom and physical examination.The dose of CsA and other immunosuppressants were adjusted according to the concentration of CsA after diagnosis.It was effective to use acyclovir(1200mg/d) in 15 patients and to use ganciclovir(500 mg/d)in other 8 patients.Antibiotics were used in all patients to avoid bacterial infection.The total effective rate 100%(23/23).Conclusion:VZV was a common disease after renal was transplantation.Early diagnosis,prompt treatment and rational adjustment of the immunosuppressant were essentia1.Both acyclovir and ganciclovir are effective for the treatment of HZ.

Impact of preemptive cytomegalovirus infection on renal transplantation / 第三军医大学学报

Objective To investigate the effect of preemptive cytomegalovirus infection(CMV) on acute rejection (AR) and assess the value of preemptive prophylactic antivirus therapy. Methods Retrospective study of 116 transplant recipients from September 2001 to February 2005 was made. The CMV infection was diagnosed by CMV-PP65 antigen tests. According to the result of CMV-PP65 antigen, 116 transplant recipients were divided into preemptive CMV infected group and non-infected group. The preemptive CMV infected recipients were subdivided into valacyclovir-treated group and non-valacyclovir-treated group. The impact of preemptive cytomegalovirus infection on acute rejection was analyzed. At the same time, CMV-PP65 antigen in 35 healthy subjects was detected. Results Seventy-four recipients had preemptive CMV infection, and the infection rate of renal transplant recipients was higher than healthy subjects (63.8% vs 14.3%, P

Management for late complications after transurethral resection of the prostate / 第三军医大学学报

Objective To analyze the causes and management of the late complications after transurethral resection of the prostate (TURP) for benign prostatic hyperplasia. Methods The clinical data of 102 patients who were hospitalized for the late complications after TURP were analyzed retrospectively. Results The causes of readmission were residual prostatic hyperplasia for 32 patients (31.37%),bladder neck restriction for 22 patients (21.57%),urethral stricture for 18 patients (17.65%),hematuria for 15 patients (14.71%),epididymitis for 6 patients (5.88%),urinary tract infection for 4 patients (3.92%),carcinoma of prostate for 3 patients (2.94%),and neuropathic bladder dysfunction for 2 patients (1.96%). All patients were satisfied with their therapeutic efficacy after different treatments. Conclusion The main complications after TURP include residual prostatic hyperplasia,bladder neck restriction,urethral stricture and hematuria. Best therapeutic approach should be chosen according to different causes of the late complications after TURP.

Assessment of perioperative psychological distress in patients undergoing renal transplantation / 重庆医科大学学报

Objective: To assessment of preoperative psychological distress in patients undergoing renal transplantation.Methods: A total of 73 renal transplantation patients were prospectively surveyed preoperatively using the 18-item Brief Symptom Inventory,a validated instrument that measures the psychological domains of general distress,anxiety and depression.Preoperative and 1 week postoperative distress scores were evaluated with respect to age,sex,marital status,economic status,serums creatinine.Results: The preoperative prevalence of psychological distress in patients of renal transplantation was 56.1%(41/73) and it remained somewhat increased at 35.6%(26/73) approximately 1 weeks after operation.In the entire group there was a statistically significant decrease in anxiety(3.5?3.1 vs 5.7?4.6,P400 umol/L.There was a statistically significant increase in anxiety from receiving one's own health services to public health services(4.4?4.1 vs 3.8?3.7,P