[Association of hyperuricemia-induced renal damage with sirtuin 1 and endothelial nitric oxide synthase in rats].

Objective: To investigate the association of hyperuricemia-induced renal damage with sirtuin 1 (SIRT1) and endothelial nitric oxide synthase (eNOS) in rats. Methods: Using the random number table method, 32 Sprague-Dawley rats were randomly divided into 4 groups: control group, model A group (the model was generated using oxonic acid potassium salt alone), model B group (hyperuricemia model was generated using oxonic acid potassium salt combined with uric acid) and resveratrol group, with 8 rats in each group. The experiment lasted 12 weeks. Serum uric acid and cystatin C levels were monitored regularly. In week 12, serum creatinine and urea nitrogen levels were measured, and the kidneys were extracted. The expression of SIRT1 and eNOS in renal tissues was measured and determined by immunohistochemistry, quantitative reverse-transcription polymerase chain reaction (RT-qPCR) and western blotting. Immunohistochemistry of alpha-smooth muscle actin combined with Masson staining was employed to evaluate the degree of renal fibrosis, and pathological changes were observed based on hematoxylin and eosin staining. Results: In week 12, the uric acid levels in both the model A and model B groups were higher than those in the control group [(316±43) µmol/L, (297±40) µmol/L vs (118±44) µmol/L, both P<0.05]. The levels of cystatin C in the model A, model B, and resveratrol groups were all higher than those in the control group [(156±20) ng/ml, (143±29) ng/ml, (128±26) ng/ml vs (62±18) ng/ml, all P<0.05]. Creatinine levels were higher in the model A and model B groups than those in the control group [(68.5±10.3) µmol/L, (64.5±13.9) µmol/L vs (43.2±10.6) µmol/L, both P<0.05]. The levels of uric acid, cystatin C and creatinine in the resveratrol group were lower than those in the model A group (all P<0.05). Immunohistochemistry, RT-qPCR, and Western blotting for renal SIRT1 and eNOS showed that the expression in the model A and model B groups was inhibited, while the expression in the resveratrol group was not significantly inhibited, compared with that in the control group. Microscopically, obvious abnormalities were not found in the renal tissue of the control group. Renal inflammatory cell aggregation and edema occurred, and interstitial fibrosis was obvious in both the model A and model B groups, while these lesions in the resveratrol group were significantly improved. Conclusions: Hyperuricemia may cause renal injury by inhibiting the expression of SIRT1 and eNOS.

[Immune-related pneumonitis caused by programmed death-1 inhibitor Pembrolizumab: a case report and literature review].

Objective: To investigate the risk factors, clinical manifestations, radiological features, diagnosis, treatment and prognosis of immune-related pneumonitis caused by programmed death-1(PD-1)/PD-L1 inhibitors. Methods: The clinical data of immune-related pneumonitis caused by PD-1 inhibitor Pembrolizumab in a patient with advanced esophageal carcinoma admitted to the 307(th) Hospital of Chinese People's Liberation Army was retrospectively analyzed and the related literatures were reviewed. We searched Medline database using the keywords"PD-1 inhibitor","PD-L1 inhibitor","Pembrolizumab","Nivolumab","Atezolizumab"combined with"Pneumonitis"by Mar 31, 2017. Results: The patient was a 60-year-old male presented with progression disease after surgery, local radiation and couples of chemotherapy for his esophageal carcinoma. Then pembrolizumab, a kind of PD-l inhibitors, was given intravenously every 3 weeks with the average dosage 3 mg per kg. After six cycles of pembrolizumab, the patient began to have fever, cough and dyspnea, which aggravated gradually. Chest CT showed diffuse ground glass opacity, exudation and consolidation in both lungs and little pleural effusion in the right side. Cellular interstitial pneumonitis was confirmed by pathological examination. The patient's symptoms were alleviated after enough steroids and chest CT showed pulmonary infiltration was also absorbed. But the pneumonitis reoccurred twice after stopping or tapering steroids quickly and could also be controlled by using steroids again. Now the patient was still given steroids treatment and the primary esophageal cancer remained stable. 14 articles were retrieved and 88 cases of immune-related pneumonitis caused by PD-1/PD-L1 inhibitors were reported. Among these 89 cases with immune-related pneumonitis, both male and female could attack and the median age was 67 years old. Most cases were grade 1 or 2. The common clinical manifestations were dyspnea, cough, fever and other immune-related damages. And about 20% patients had no symptoms. Ground glass opacities, reticular opacities, consolidation and centrilobular nodules were the common radiological features. The commonest histologic pattern of pneumonitis associated with anti-PD-1/PD-L1 therapy on lung biopsy was organizing pneumonia. Adequate steroid and tapering slowly is the standard treatment. Immunosuppressive agents could be added in some serious cases. The prognosis was relatively good. Most patients were alleviated but few patients died of progression disease or infections during treatment. Conclusions: Immune-related pneumonitis associated with PD-l/PD-L1 inhibitor should be aware of; early detection, early treatment, and the prognosis could be better.