Objective:To introduce a programmed death-1 (PD-1) inhibitor nivolumab used as a new antitumor agent. Methods:According to the literatures, the action mechanism of nivolumab and the clinical trial results on the main indications approved or being investigated in phase III trials were reviewed and evaluated. Results:Nivolumab could restore the antitumor activity of T cells through binding with PD-1 and consequently blocking its interaction with the key ligands of PD-L1 and PD-L2. Several completed and ongoing clinical trials showed that nivolumab used alone or combined with chemotherapy or CTLA-4 inhibitor ipilimumab exhibited better effica-cy when compared with current clinical used chemotherapy drugs in the treatment of melanoma, non-small cell lung cancer and renal cell carcinoma. Nivolumab was well tolerated during the treatment with such main grade 3-4 adverse events as immune-mediated pneu-monia, abnormal liver functions and fatigue. Conclusion:Through its anti-tumor immune response, nivolumab can improve the clinical efficacy in the treatment of various tumors including melanoma, non-small cell lung cancer and renal cell carcinoma.

Objective:To explore the effects of necroptosis specific inhibitor-1 (Nec-1) on brain injury in rats after cardiac arrest and its mechanism.Methods:A total of 24 Sprague-Dawley (SD) rats were divided into Sham group, model group and Nec-1 group ( n = 8 per group) according to random number table method. In the Sham group, only general surgical procedures were underdone without inducing cardiac arrest. In the model group, the rats were subjected to asphyxial cardiac arrest followed by cardiopulmonary resuscitation (CPR) at 6 minutes after cardiac arrest. In the Nec-1 group, Nec-1 of 1 mg/kg was administered after cardiac arrest, and CPR was performed at 6 minutes after cardiac arrest. At 72 hours after CPR, neurological deficit scores (NDS) were assessed, serum S100B levels were measured by enzyme linked immunosorbent assay (ELISA), receptor-interacting protein 3 (RIP3) expression in cerebral cortex and hippocampus was observed under immunofluorescence and positive rate was calculated, and the levels of RIP3 protein expression in brain were analyzed by Western blotting. Results:At 72 hours after CPR, the rats in the model group showed obvious necroptosis and injury in brain. Compared with the Sham group, the NDS scores in the model group were significantly decreased [57.0 (52.7, 60.0) vs. 80.0 (80.0, 80.0), P < 0.05], the serum S100B was significantly increased (ng/L: 44.9±4.5 vs. 18.6±1.5, P < 0.05), the percentages of RIP3 positive cells in cerebral cortex and hippocampus were significantly elevated [cerebral cortex: (31.7±4.8)% vs. (11.6±3.2)%, hippocampus: (28.4±0.8)% vs. (10.9±0.6)%, both P < 0.05], and the levels of RIP3 protein expression in brain were significantly increased [RIP3 protein (RIP3/GAPDH): 0.708 (0.642, 0.722) vs. 0.408 (0.253, 0.504), P < 0.05]. After Nec-1 intervention, necroptosis and injury in brain were obviously improved. Compared with the model group, the NDS scores at 72 hours after CPR in the Nec-1 group were significantly increased [70.5 (68.5, 71.7) vs. 57.0 (52.7, 60.0), P < 0.05), the serum S100B was significantly decreased (ng/L: 31.9±2.7 vs. 44.9±4.5, P < 0.05), the percentages of RIP3 positive cells in cerebral cortex and hippocampus were significantly lowered [cerebral cortex: (23.7±4.1)% vs. (31.7±4.8)%, hippocampus: (20.4±0.4)% vs. (28.4±0.8)%, both P < 0.05], and the levels of RIP3 protein expression in brain were significantly declined [RIP3 protein (RIP3/GAPDH): 0.437 (0.379, 0.507) vs. 0.708 (0.642, 0.722), P < 0.05]. Conclusion:Nec-1 attenuated necroptosis of brain cells by inhibiting the expression of RIP3 protein, so as to reduce brain injury after cardiac arrest in rats.

Objective To explore the effects of tumor necrosis factor-α induced protein 6 (TSG-6) on acute kidney injury (AKI) following paraquat poisoning in rats.Methods Twenty-four male Sprague-Dawley (SD) rats were randomly divided into sham group (n=8),model group (n=8) and TSG-6-treated group (n=8) using a randomized number table.Rats were given an injection of 50 mg/kg of paraquat intraperitoneally (total volume was equalled to sterile normal saline) in model and TSG-6-treated groups.Rats in sham group were given 2 mg/kg of sterile saline.Mter 1 hour of paraquat administration,rats were treated with 30 μg of recombinant human TSG-6 intraperitoneally in TSG-6-treated group.After 6 hours of paraquat administration,serum was collected to assess renal function,then rats were sacrificed and renal tissues were immediately harvested.AKI score was evaluated by renal histopathology and gene expression of pro-inflammatory cytokines including interleukins (IL-1β and IL-6) and tumor necrosis factor-α (TNF-α) in kidney was assayed with real-time reverse transcription-polymerase chain reaction (RT-PCR).Results Compared with sham group,blood urea nitrogen (BUN),creatinine (Cr) and AKI score were significandy increased in model group [BUN (mmoUL):22.64 ±2.36 vs.7.09 ±0.65,t=6.986,P=0.000; Cr (μmol/L):177.28 ± 18.67 vs.60.32 ± 3.11,t=7.134,P=0.000; AKI score:9.14 ± 0.28 vs.0.30 ± 0.23,t=9.013,P=0.000].Moreover,the mRNA expressions of IL-1β,IL-6 and TNF-α were significantly elevated in model group (IL-1β mRNA:3.23 ± 0.28 vs.1.00 ±0.07,t=5.874,P=0.000; IL-6 mRNA:4.16 ±0.37 vs.1.00 ±0.08,t=7.125,P=0.000; TNF-α mRNA:3.85 ±0.31 vs.1.00 ±0.10,t=6.342,P=0.000).However,serum BUN,Cr,AKI score and the mRNA expressions of IL-1β,IL-6 and TNF-α in TSG-6-treated group were significantly lower than those in model group [BUN (mmol/L):14.07 ± 5.23 vs.22.64 ± 2.36,t=2.533,P=0.026; Cr (μmol/L):112.76 ± 14.81 vs.177.28 ± 18.67,t=2.778,P=0.016; AKI score:5.35 ±0.19 vs.9.14 ±0.28,t=2.885,P=0.013; IL-1β mRNA:2.26 ± 0.19 vs.3.23 ±0.28,t=2.457,P=0.023; IL-6 mRNA:2.92 ±0.29 vs.4.16 ±0.37,t=2.975,P=0.011; TNF-α mRNA:2.58 ± 0.23 vs.3.85 ± 0.31,t=2.564,P=0.019].Conclusion TSG-6 attenuates AKI following paraquat poisoning by suppressing inflammatory response.

BACKGROUND: As a main gene engineering vector, adeno-associated virus (AAV) is characterized by its extensive host cells, lasting and stable expression and less immune response to hosts, and is applied widely. But AAV is a kind of defective virus, and need incasing cells to supply E1 protein. As important and special AAV incasing cells, AAV-293 cells can produce E1 in trans. But AAV-293 cells are delicated and cultivated difficultly, and the biological character is easy to be changed. Therefore, it is necessary to establish a culture method of AAV-293 cells to meet the need of gene engineering.OBJECTIVE: To establish a culture method of AAV-293 cells in vitro.DESIGN: An opening study.SETTING: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.MATERIALS: AAV-293 cells line was provided by Stratagene Corporation; high-carbohydrate OMEM (H-DMEM) powder by Gibco Company; there plasmids in AAV Helper-Free by Stratagene Company.METHODS: This experiment was carried out in the neurology laboratory of Tongji Hospital in Wuhan during the period from October 2006 to April 2007. AAV-293 cells were resuscitated and cultivated with H-DMEM growth medium in vitro, and were passaged and stored in liquid nitrogen when the cells monolayer confluence reached 50%. At the same time, their growing state was observed by inverted microscope, and their growth curve was noted. According to whether AAV-293 cells could give out green fluorescence or not (observed by fluorescence inverted microscope) after they were cotransfected with the there AAV system plasmids and infected with AAV supernatant, their biological character of packing AAV was assessed.MAIN OUTCOME MEASURES: ① Morphological observation of AAV-293 cells; ② the growth curve; ③ the package of AAV.RESULTS: ① AAV-293 cells observed by fluorescence inverted microscope were growing adhesively well with irregular polygons, light endochylemas and ambiguous nuclei appearances. ②The growth curve showed that the growing adaptive phase was the first day after AAV-293 cells were passaged, the actively growing phase was from the second day to the fifth day, and the growing platform phase was after the sixth day. ③ AAV-293 cells with green fluorescence observed by fluorescence inverted microscope, and cotransfection of the there AAV system plasmids was successful. AAV-293 cells gave out green fluorescence after infected with AAV supernatant, and AAV package succeeded.CONCLUSION: The culture method established by the authors in the experiment is simple and useful, and the cultured AAV-293 cells remain a good function of AAV package.

Objective: To compare regeneration of motor fibers with that of sensory fibers by end to side neurorrhaphy and compare the effect of end to side neurorrhaphy with that of end to end neurorrhaphy. Methods: 20 SD rats were randomly divided into two groups: group A and group B. In group A, the right peroneal nerve was sectioned and the distal end was sutured laterally to the tibial nerve; in group B, the right peroneal nerve was sectioned and sutured with end to end neurorrhaphy. All left sides of two groups were used as control. Retrograde transportation of HRP was observed after 28 weeks. Results: The labelled neurons were also found in the anterior horn of the spinal cord and the spinal ganglia. Conclusion: The regenerative nerve fibers had motor fibers as well as sensory fibers by end to side neurorrhaphy. The effect of end to side neurorrhaphy is not as good as that of end to end neurorrhaphy. [

Objective To compare the myocardial protective effects of post-treatment with sevoflurane and isoflurane on myocardial ischemia-reperfusion injury(MIRI) in adult rats.Methods Twenty-four adult male SD rats were divided into four groups (n =6) by using the random number table,control group (C),isehemia-reperfusion group (R),sevoflurane post-treatment (S) and isoflurane post-treatment group(I).The Langendorff isolated heart perfusion model was established.The heart rate(HR),left ventricular end-diastolic pressure(LLVEDP),left ventricular developed pressure(LVDP),maximum rate of rise of left ventricular pressure(LV+-dp/dtmax),and maximum rate of decrease of left ventricular pressure(LV-dp/dtmax) were recorded at the end of equilibrium perfusion,and at 30,90 min of reperfusion,respectively.At the end of infusion,1 mm3.of apical myocardial tissue was removed for observing mitochondrial structure under electron microscopy and scoring.The myocardial infarct size(MIS) in the remaining heart tissue was measured by TTC staining.Results Compared with the R group,the S and I groups showed improved cardiac function indicators,decreased MIS,and reduced mitochondrial damage after reperfusion(P＜0.05).Compared with the S group,the I group showed worse heart function,increased MIS,and more severe mitochondrial damage after reperfusion(P＜0.05).Conclusion Post-treatment with sevoflurane and isoflurane has a protective effect on MIRI in adult rats.Post-treatment with sevoflurane has a better cardioprotective effect than that with isoflurane.

Objective To study the X-ray findings of post-traumatic osteolysis and to improve the knowledge of that disease.Methods X-ray features of 7 cases of post-traumatic osteolysis confirmed by clinical findings and pathology were reviewed retrospectively.There were 5 females and 2 males.from 9-56 years(mean 34 years)of age.Three patients had traffic accidents and 4 had trauma unrelated to traffic accidents.Osteolysis occurred from 3 to 18 months after trauma(1 case at 18 months,2 cases at 10 months,2 cases at 6 months and 2 cases at 3 months).Results There were 2 pubis fractures,1 distal tibiofibular shaft fracture,1 femoral neck fracture,1 humeral upper end commiuuted fracture,1 shoulder joint dislocation.and 1 soft tissue swelling around the wrist.The X-ray findings are:3 massive osteolysis,3 plaque flake osteolysis and 1 cystic osteolysis.There were no hardening of bony edge at the site of osteolysis in all 7 cases,clear margin in 5 cases and ill-defined margin in 2 cases,no residual bone in osteolytic area in 4 cases and residual bone in octeolytic area in 3 cases,no periosteal reaction and thickerning of bony cortex in osteolytic area in all 7 Cascs,bone repair in 2 cases and no bone repair in 5 cases.Histopathological findings showed:extensive capillary hyperplasia and fibrous tissue hyperplasia;hyperemia and swelling of synvium,proliferation of granulation tissue,osteonecrosis,increased osteoclast activity,some inflammatory cells,no evidence of neoplastic cells in the involved area.Conclusions Posttraumatic osteolysis is closely related to trauma.X-ray findings include massive osteolysis,plaque-like osteolysis,and irregular cystic changes.Early dignosis may be a challenging task.

Objective To analyze the clinical and pathological features of collecting duct carcinoma (CDC) of the kidney. Methods 11 patients with CDC were analyzed,among which 6 were males and 5 were females.Their age ranged from 22 to 67 years old with a mean age of 55.4 cases were found by routine health examination,4 cases were presented with gross hematuria and 3 cases had flank or abdomen pain.The CT scan showed an unclear boundary mass in kidney,with tumor sizes from 2.1 to 8.5 cm ( mean 5.6 cm).Only medullary involvement was present on CT in 3 cases,Medullary and cortical involvement in 5 cases,Medullary and pelvic involvement in 2 cases,and all involvement in 1 case.Infiltrative lesion has expanded kidney but maintains reniform contour.Contrast-enhanced CT scan showed lesion mild to moderate enhancement compared with surrounding parenchyma. Results Radical nephrectomy was performed in 8 cases and palliative nephrectomy in 3 cases.All patients were finally diagnosed by pathology.Grossly,the tumor is often appears gray or white.In HE staining,tumor showed prominent tubular or tubulaopapillary structures with desmoplasia and inflammatory reaction.Occasionally,some tumor cells take on a hobnail appearance.Immunohistochemical examination showed UEA-1 positive in all cases,EMA positive in 9 cases,PNA positive in 8 cases,and HMW-CK positive in 7 cases.Only 2 patients showed positive CD10.7 patients died within 6 to 47 months (mean 12.5 months),2 survived with tumor free for 9 months and 8 years respectively,one lost of follow-up,and one patient with distant metastasis is receiving postoperative chemotherapy. Conclusions Collecting duct carcinoma of the kidney is a rare histological type of renal cell carcinoma,whose final diagnosis depends on histopathological examination.Rapid progression,highly malignant,poor prognosis are the characteristics of this disease.

Through various common domestic and foreign electronic sphygmomanometers to test blood pressure, we find that when measuring high blood pressure or low blood pressure, there is a mismatch between the maximum inflation pressure and the blood pressure measurement, which often results in repeatedly inflating and deflating as well as the problem of high inflation pressure. In order to solve these problems and find a suitable maximum inflation pressure, two intelligent pneumatic solutions based on identifying of pulse wave are suggested and 700 groups of blood pressure experiments are done, then the two solutions are verified by experiments. The experiment proved that these solutions proposed have good stability and accuracy, they can solve the problems appeared in measuring blood pressure effectively, at the same time, the second solution that estimate the maximum inflation pressure during inflation is considered as the best one.
Blood Pressure ; Blood Pressure Determination ; instrumentation ; Heart Rate ; Humans ; Hypertension ; Sphygmomanometers

Objective To summarize the clinical experie nce in the diagnosis and treatment of cystolithiasis complicated by squamous cel l carcinoma (SCC) of the bladder. Methods Retrospective analysis was performed in 28 patients (19 men and 9 women) with cystolithiasis c omplicated by SCC of the bladder.Their age ranged from 26 to 68 years with a mea n of 33 years.The disease course of cystolithiasis ranged from 2 to 18 years wit h a mean of 4.5 years. Among the 24 cases who underwent urine cytology,atypical cells were found in 19 cases.KUB showed solitary stone of the bladder in 5 case and multiple stones in 23.Space-occupying lesions were noted in 11 cases on IVU ,in 17 cases on B-ultrasonography and CT scan.Cystoscopy was performed in 28 ca ses, and tumors were found in 21 cases.The size of the tumors ranged from 1.2 cm ?1.5 cm to 2.2 cm?5.0 cm. Partial cystectomy was performed in 21 cases, includ ing ureterocysto-transplantation in 6 cases.Radical cystectomy was performed in 7 cases. Results Pathology revealed SCC of the bladder in all 28 cases,including G_1 in 11 cases,G_2 in 12 cases,G_3 in 5 cases;T_1 in 11 cases,T_2 in 12 cases,T_3 in 5 cases. Twenty-two patients were followe d up for 1 to 8 years with a mean of 3 years. The 1- and 5-year survival rates were 63.6% (14/22) and 16.7% (3/18),respectively. Conclusions Cystolithiasis is the main cause of SCC of the bladder. Early diagnosis a nd surgical treatment is very important for such patients.