Objective To investigate the effects of exosomes (Exo) derived from high glucose-stimulated glomerular mesangial cells (GMC) on the kidneys of C57BL/6 mice and the intervention mechanism of Tongluo Yishen Formula (TLYSF). Methods The rat GMC were divided into a normal glucose group (NG, with 5.6 mmol/L glucose) and a high glucose group (HG, with 30 mmol/L glucose). After 24 hours of culture, the supernatant was collected, and exosomes were extracted using the ultracentrifugation method. The exosomes were then identified by transmission electron microscopy and Western blot analysis. Male C57BL/6 mice were divided into three groups: NO-Exo group, NG-Exo group, and HG-Exo group. These groups were respectively administered tail vein injections of PBS buffer, exosomes derived from GMC cultured in normal glucose, and exosomes derived from GMC cultured in high glucose, three times a week for a total of 8 weeks. After 8 weeks, the mice in the HG-Exo group were randomly divided into three subgroups: the HG-Exo group [gavaged with saline], the HG-Exo+TLYSF group [gavaged with TLYSF at 34.32 g/(kg.d)], and the HG-Exo + VAL group [gavaged with valsartan suspension at 10.4 mg/(kg.d)], and the intervention lasted for 4 weeks. Urinary microalbumin (mALb), urinary N-acetyl-β-D-aminoglucosidase (NAG), glycated hemoglobin (HbA1c), serum creatinine (Scr) and urea nitrogen (BUN) were detected. Transmission electron microscopy was used to observe the ultrastructure of renal tissues. TUNEL was used to detect the DNA damage of renal tissue cells. Immunofluorescence was used to detect the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) and wilms tumor 1(WT-1). RT-PCR was used to detect the mRNA levels of NLRP3, cysteinyl aspartate-specific proteinase 1 (caspase-1), interleukin-1 beta (IL-1β), miR-200c-3p and miR-148a-3p. Western Blot was employed to detect the protein expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1 and IL-1β. Results Compared with the NG-Exo group, mice in the HG-Exo group exhibited significantly increased levels of mALb, urinary NAG, Scr and BUN. Transmission electron microscopy revealed ruptured podocyte membranes and swollen mitochondria. The positive rate of cells stained by the TUNEL increased, with elevated optical density of NLRP3 and decreased optical density of WT-1. Additionally, there was a significant increase in the level of NLRP3, caspase-1, IL-1β mRNA, as well as miR-200c-3p and miR-148a-3p. The protein expression of NLRP3, ASC, caspase-1, and IL-1β also increased. Compared with HG-Exo group, mice in the HG-Exo+TLYSF group showed decreased levels of mALb, urinary NAG, Scr, and BUN. The podocyte membranes were relatively intact, and mitochondrial damage was alleviated. The positive rate of cells stained by the TUNEL decreased, along with a reduction in the optical density of NLRP3 and an increase in the optical density of WT-1. Furthermore, the mRNA expression levels of NLRP3, caspase-1, IL-1β, miR-200c-3p, and miR-148a-3p were all downregulated to varying degrees. The protein expression levels of NLRP3, ASC, caspase-1, and IL-1β also decreased. Conclusion Exosomes derived from GMC stimulated by high glucose can damage the kidneys of mice and induce podocyte pyroptosis. TLYSF may ameliorate podocyte pyroptosis by downregulating the expression of exosomal miR-200c-3p and miR-148a-3p and inhibiting the activation of the NLRP3/ASC/caspase-1 pathway.
Animals ; Exosomes/ultrastructure* ; Glucose/pharmacology* ; Male ; Podocytes/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Mice, Inbred C57BL ; Mice ; Mesangial Cells/metabolism* ; Pyroptosis/drug effects* ; Rats ; MicroRNAs/genetics*

Objective To summary the pathological and clinical characteristics,treatments and prognosis of malignant renal perivascular epithelioid cell tumor (PEComa).Methods Between August 2013 and June 2017,8 cases of malignant renal PEComa were analysed respectively.Of all the patients,there were 4 males and 4 females,aged 27-65 years with the average of 46.3 years old.Three cases were detected in routine examination occasionally,three cases complained of intermittent back pain with fever,one presented with swollen and painful right hand and right foot,and one case presented with hematuria.CT or MRI examinations indicated the malignant lesions before the surgery.Clinical staging was performed with 2 cases of T1N0M0,1 case of T1 N0M1,2 cases of T2N0M0,1 case of T3M0M0,and 2 cases of T4N0M1.Three cases underwent radical nephrectomy,1 case underwent radical nephrectomy plus renal artery embolization,2 cases underwent partial nephrectomy,and 2 cases underwent nephrectomy plus inferior vena cava tumor thrombectomy.One case was treated with ifosfamide plus epirubicin after operation due to multiple distant metastases and 1 case was treated with oxaliplatin before the sugery because of excessive tumor diameter.None of the rest received any adjuvant therapy.Results Postoperative histopathological examination showed multiple nodules in reddish gray and yellow color,with soft texture and partial incomplete capsule.Microscopically,there were large atypical cell components,some of which were spindle shaped,with disordered cell arrangement,some of which were associated with a large amount of necrotic tissue,and abundant light eosinophil cytoplasm.Tissue components can be found thick-wall blood vessels,smooth muscle-like cells,and adipose tissue.Immunohistochemistry showed 4 cases were positive of HMB-45,4 of Melan-A,7 of SAM.Seven cases were negative of CK,6 of S-100 75％ (6/8) and Ki67 (10％-70％).Two cases died of multiple metastases (lung,bone,liver),1 case survived with tumor recurrence,with a follow-up from 14 to 60 months (mean 29 months).Conclusions Primary malignant renal PEComa is rare in practice with relative large diameter.The diagnosis depends on pathological findings,and radical nephrectomy is the first choice of treatment.It is easy to recur and metastasize after the operation.

Non-small cell lung cancer (NSCLC) accounts for 85% of total cases of lung cancer, which has the highest incidence and mor-tality in China. Most patients with lung cancer present with advanced stage disease at the time of diagnosis. With the limited develop-ment of cytotoxic chemotherapy for NSCLC therapy, median overall survival in patients receiving platinum-based doublet chemothera-py has been less than one year in several trials. To date, anti-angiogenesis agents combined with chemotherapy, small molecule tyro-sine kinase inhibitors (TKI) and immune checkpoint inhibitors were commonly applied in NSCLC instead of purely chemotherapy, which makes a great breakthrough in NSCLC therapy. This review summarizes and discusses the application of anti-angiogenic therapy in ad-vanced NSCLC.

Objective To discuss the pathological and clinical characteristics,treatments and prognosis of schwannoma of the kidney.Methods Two cases of schwannoma of the kidney in our hospital were reviewed with clinicopathological data and their follow-up.The related literatures were reviewed.The first case was a male patient,28 years old,complained about paroxysmal abdominal pain with nausea over 2 weeks.The physical exam found a 10 cm,qualitative hard,poor activity,tenderness mass in kidney region.MRI preoperative diagnosis was right renal cell carcinoma with renal vein and inferior vena cava tumor thrombus formation.The second patient,female,53 years old,the mass on upper right kidney was found occasionally.It was diagnosed as adrenal pheochromocytoma before operation,laparoscopic resection of right renal hilum mass and right partial adrenectomy plus right nephrectomy were performed.There was no tumor recurrence in the follow-up.Results The abdominal aortography and double renal arteriography were done and right renal artery embolization and inferior vena cava filter were allocated.Then right radical nephrectomy and inferior vena cava tumor thrombus removal were carried out on the first patient.The first malignant and the second benign renal schwannoma patient showed significant difference in pathological presentations.Their immunohistochemistry also showed great diversity.Malignant renal schwannoma was significantly stained by Ki-67 ＞ 40％,S-100 was negative.Ki-67 in benign neurilemmomas was about 2％,and S-100 in benign renal schwannoma was positive.Conclusions Schwannoma of the kidney is rare with a favorable prognosis.The golden standard of diagnosis is pathology.Surgical resection has become the first choice for treatment.Recurrence and malignant transformation would happen after the surgery so that all the patients should be followed up.