0.05),only RE increased significantly in 2 minutes after injection(P

Recent clinical studies have found that there are still a large number of patients who do not respond to immune checkpoint inhibitors (ICIs). Improving immunotherapy response in ccRCC patients is an urgent clinical need. Targeting different components of the tumor immune microenvironment becomes a breakthrough point for overcoming the immunotherapy resistance and optimizing therapeutic strategies in advanced ccRCC. Several novel immunotherapeutic strategies are currently under clinical investigation, including targeting other co-inhibitory and co-stimulatory molecules, modified cytokine therapies, small-molecule immunomodulators, targeting immune metabolism, and cancer vaccines, each of which target different immunomodulatory pathways in the tumor immune microenvironment for the treatment of ccRCC. In this paper, we provide an overview of the current challenges faced by immunotherapy for advanced ccRCC and review novel immunotherapy strategies based on the tumor immune microenvironment.

Objective To discuss the principles of surgical treatment of closed spinal cord injury. Methods The treatment and outcome of a series of 210 patients with closed spinal cord injury admitted to our department from Jan, 1990 to Jan, 2003 were retrospectively analyzed. Results Of the 210 patients, 113 cases (53.8%) were classified as grade A, 49 cases (23.3%) as grade B, 37 cases (17.6%) as grade C, and 11 cases (5.2%) as grade D, respectively, according to Frankel's classification. After treatment and followed-up for 3 months to 10 years, 42 cases (20.0%) were re-classified as grade A, 15 cases (7.1%) as grade B, 45 cases (21.4%) as grade C, 61 cases (29.0%) as grade D, and 47 cases (22.4%) as grade E. Conclusion Surgical treatment for a patient with closed spinal cord injury depends on findings of examination of the nervous system, tomographic examination of the spinal cord, indications for decompression of the spinal cord, stabilization of the spine, early ambulation and rehabilitation. Principles of the treatment of closed spinal cord injury include early treatment, decompression of the spinal cord with operation, reduction and fixation, prevention of complications, and rehabilitation.

Objective To study the effective methods of diagnosis and microsurgical treatment for tumors in spinal canal. Methods The diagnosis, treatment, and prognosis of 192 patients with spinal tumors admitted to our department ( from Jan,1992 to Dec,2002) were retrospectively analyzed. Results All the patients in this group underwent operative treatment. Total removal of tumor was achieved in 162 cases (84.4%), subtotal removal of tumor in 18 cases (9.4%), and removal a large portion of tumor with decompression in 12 cases (6.3%). Postoperatively, 163 patients (84.9%) were cured, the neurological symptoms were apparently improved in 27 patients (14.1% ), and unchanged in 2 patients (1.0%). No operative death occurred. Conclusion Early diagnosis and treatment of spinal tumor are important measures to improve prognosis. Imaging and microsurgery play a key role in the diagnosis and treatment of spinal tumors.

Objective To investigate the expressions and clinical significance of the tumor supressor gene phosphatase and tensin homlog deleted on chromosome ten protein(PTEN) and oncogene phosphoserine/threonine protein kinase B(phospho-serine/threonine protein kinase Akt/PKB,pAkt) in hepatocellular carcinoma(HCC).Method The expressions of PTEN and pAkt in 65 cases of HCC and their pericarcinomatous tissues were detected by immunohistochemical staining with S-P method.Results The positive expression rate of PTEN in HCC was significantly lower than that in pericarcinomatous liver tissues,and the positive rate of pAkt was significantly higher than that in pericarcinomatous liver tissues(all P

To investigate the expressions and significance of the tumor suppressor gene phosphatase and tensin homlog deleted on chromosome ten protein (PTEN) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC), and to analyze the relationship between their expressions and the tumor's invasion and their pericarcinomatous tissues, the correlation of their expressions with the tumor's clinicopathological characteristics and invasion potential were studied. Our study showed that the expression level of PTEN in HCC was remarkably lower than that in pericarcinomatous liver tissues, while the expressions of both VEGF and MVD were higher than that in pericarcinomatous liver tissues. Correlation analysis revealed that the expression of PTEN was negatively related to the progression of the pathological differentiation and invasion of tumor, whereas the expressions of VEGF and MVD were positively related. Moreover, there was a negative relationship between the expression of PTEN and the expressions of VEGF and MVD, and a positive one between VEGF and MVD. The expressions of PTEN and VEGF may reveal the degree of differentiation and the invasive potential of HCC tissues. The mechanism by which the lack of PTEN expression probably induces abnormal hyperexpression of VEGF may play an important role in the invasion and metastasis of HCC.

Aim To explore the change of mGluR1α and mGluR5 expression in brain CA1 region after infrasonic action, and the role of antagonist MCPG in rats. Methods 160 SD rats were divided randomly into infrasonic damage group and MCPG therapy group. The two groups were subdivided into control group and 1-time, 7-time and 14-time groups respectively. Rats were exposed to 8Hz, 130dB infrasound two hours each time. Expression of mGluR1α and mGluR5 were detected by immunohistochemical staining and in situ hybridization methods. The morphological changes of neurons after MCPG therapy were observed under microscopes. Results Comparing with the control group, the number and the A value of mGluR1α and mGluR5 positive cells changed after one infrasonic action(P∨ 0.05); and the expression of mGluR1α and mGluR5 in the 7-time group were most obvious(P∨ 0.01); in the 14-time group, they recovered already to normal level. Morphological study confirmed that MCPG protected neurons from infrasonic damage. Conclusion Change of mGluR1α and mGluR5 activity can mediate exciting neurotoxicity after infrasonic action, and it is one of the major factors relative to neurons injury, MCPG had an protective effect on brain damage caused by infrasound.

Objective: To explore the role of integrin ?v?6 in proliferation and apoptosis of gastric cancer AGS cells. Methods: Gastric cancer AGS cells were treated with ?v?6 monoclonal antibody 10D5 or the negative control mouse immunogloblins IgG2a. Cell viability was measured by MTT assay, cell apoptosis was detected by FCM, and caspase-3 activity was examined by Western blot. Results: Compared with the control and IgG2a group, the apoptotic rate and caspase-3 activity of AGS cells treated with 10D5 increased, meanwhile cells survival rate decreased. There were significant differences of the indexes between the 10D5 group and the other two groups (P0.05). Conclusion: Integrin ?v?6 plays an important role in the proliferation and apoptosis of gastric cancer AGS cells.

Objective To investigate clinical result of hepatectomy and porta-enterostomy in the treatment of Bismuth type Ⅳ hilar cholangiocarcinoma.Methods Nine patients with Bismuth type Ⅳ hilar cholangiocarcinoma underwent accurate hilar resection(portal parecnchyma resection including about Ⅰ cm of the hilar part of the segments 5 and 4b and caudate lobe beyond the tumor),and the biliary drainage was reconstructed by Roux-en-Y portal parecnchyma-jejunum lpop anastomosis.None of the biliary radicals had to be ligated and all of them were drained into thus constructed"biliary pool".Results Hilar resection was successfully performed in all cases,and there was no postoperative mortality.Aspartate transaminase and alanine transaminase and serum bilirubin decreased evidently four weeks later.Three patients presented postoperative complications.One patient developed a transient anastomotic leakage,while one patient developed self-limiting hemobilia,wound infection occurred in one patient.All three patients were treated conservatively and recovered.The mean Karnofsky performance score was 86,with which they could carry on normal activity with minor symptoms of disease.Two patient died after 9 months and 17 months of extensive metastasis and intrahepatic metastasis respectively.The remaining seven patients are alive by a mean followup of 24.9 months after surgery without any signs of recurrence.Conclusions With accurate hilar resection and portal parecnchyma-to-enterostomy,the patients considerably benefit from the preservation of liver parenchyma and patent biliary drainage and radical resection.So the Hew technique prolongs the survival time and enhances the quality of life of the patients.

Objective To summarize the experiences in the diagnosis and treatment of the hepatic hereditary hemorrhagic telangiectasia (HHHT).Methods The clinical data of 15 HHHT patients who were admitted to the Qilu Hospital,People's Hospital of Mengyin,People's Hospital of Liaocheng,Henan Provincial People's Hospital,the Second Hospital of Hebei Medical University,First Affiliated Hospital of Zhejiang University were retrospectively analyzed.The clinical manifestation,features of imaging and laboratory examination were summarized,and the diagnosis,treatment and prognosis of the disease were investigated.Results HHHT patients had nonspecific symptoms in the early stage,and some patients presented with right upper quadrant discomfort,shortness of breath,anemia and liver bruit.The condition of HHHT patients could be worsened by liver cirrhosis or portal hypertension rapidly.The results of color doppler ultrasound and computed tomography showed intrahepatic telangiectasia,arteriovenous fistula and hepatic artery aneurysm in the 15 patients.Digital subtraction angiography was not clear enough for 2 HHHT patients with more than 1 enlarged hepatic arteries,but computed tomographic angiography was feasible.According to the degree and stages of the HHHT,all the 15 patients were divided into asymptomatic HHHT,simple HHHT and complex HHHT.Among the 6 patients who underwent surgical treatment,5 received ligation or banding of the enlarged hepatic arteries with subsequent disappearance of symptoms.Three patients received interventional treatment,and the treatment for 1 patient with complex HHHT was failed,and the patient died 30 months after medical treatment.Six patients were treated by conservative treatment,2 patients of them had no symptoms at the beginning,then they suffered from hepatic dysfunction and ascites at 21 and 35 months,respectively,and 1 of them died 6 months later.Four patients received medical treatment,and the results of color doppler ultrasound and computed tomography showed the pathological changes were aggravated gradually.Conclusions Telangiectasia,intrahepatic arteriovenous fistula and hepatic artery aneurysm are the main imaging characteristics of HHHT,and imaging diagnosis has significant value in the diagnosis of HHHT.HHHT is a progressive disease,early,active and individualized treatment is beneficial to the patients.The outcome of ligation or banding of the hepatic arteries is satisfactory.