AIM: Niflumic acid (NFA) is known as a kind of inhibitor of calcium-activated chloride channel. The inhibition and mechanism of NFA on the proliferation of airway smooth muscle cells (ASMCs) were investigated. METHODS: Using [ 3H]-TdR incorporation method, we examined the effect of NFA (at concentration of 10 and 50 ?mol/L) on the proliferation of primarily ASMCs from BALB/c mouse. With confocal laser scanning microscope the [Ca 2+ ]i in ASMCs exposed to histamine was observed, and the opposed effects of NFA and nifedipine on histamine were also checked. Finally the effect of NFA on expression of MAPK in ASMCs was examined by indirect immunofluorescent assay. RESULTS: Compared with control group, the proliferation of NFA group was reduced markedly with dependent concentration. Histamine significantly improved the [Ca 2+ ]i in ASMCs, but NFA and nifedipine showed the inhibition on the effect of histamine. NFA reduced the level of MAPK expression in ASMCs. CONCLUSION: It is demonstrated that NFA inhibits the proliferation of ASMCs by reducing [Ca 2+ ]i and the expression level of MAPK. [

Objective:To evaluate the risk factors of hypoalbuminemia (serum albumin <35 g/L) in the maintenance hemodialysis (MHD) patients.Methods:From January 2011 to December 2018, 915 patients (≥18 years) who underwent MHD programs from 12 hospitals in south China were enrolled in a retrospective analysis. Univariate and multivariate Logistic regression analysis was applied to evaluate the risk factors of hypoalbuminemia in the MHD patients.Results:The MHD patients had poor albumin level in general, with hypoalbuminemia accounting for about 20.55% (188/915). Compared with the patients with normal albumin level, the patients with hypoalbuminemia had older age (61.46 years vs. 55.85 years, P<0.01), the greater incidence of diabetes [29.79%(56/188) vs. 19.39%(141/727), P = 0.002] and the lower application in high flux dialysis [42.55%(80/188) vs. 57.36%(417/727), P<0.01], while the gender, duration of dialysis, dialysis frequencies and the incidence of hepatitis showed no significant difference between 2 groups. In linear correlation analysis, albumin and hemoglobin level were positively correlated ( r = 0.213, P<0.01). In Spearmen correlation analysis, albumin was negatively correlated with age, hypersensitive C reactive protein (hsCRP), alkaline phosphatase, and diabetes ( r = -0.232, -0.176, -0.153 and -0.132; P<0.01); and it was positively correlated with the Kt/V and the application in high flux dialysis ( r = 0.151 and 0.124, P<0.01). The multivariate Logistic regression analysis showed that age, diabetes, alkaline phosphatase and hsCRP were the independent risk factors of hypoalbuminemia, while the application of high flux dialysis and hemoglobin were the independent protection factors. Conclusions:The patients undergoing a MHD program have poor albumin level. Diabetes is the independent risk factor of hypoalbuminemia of MHD patients, and the practice of high flux dialysis may reduce the hypoalbuminemia.

Objective To compared hemostatic effect of agkistrodon haemocoagulase and other hemostatic agents in hepatectomy,and observe clinical safety.Methods From November 2014 to February 2016,122 patients undergoing hepatectomy of the department of hepatobiliary surgery in the hospital,according to the inclusion and exclusion criteria,were randomly divided into three groups,which was group A-haemocoagulase agkistrodon for injection,group B-ferdelance haemocoagulase for injection and group Cdesmopressin acetate injection.After drug administration,according to the clinical research plan,the indexes for therapeutic effectsbleeding time of wound,bleeding volume of wound,postoperative drainage volume for 24 h,preoperative and postoperative safety indices-Routine blood test,clotting function,liver and kidney function were compared among the three groups.Results The general data of the 3 groups were comparable.The bleeding time of wound,bleeding volume of wound,postoperative drainage volume for 24 h showed no significant difference(P＞0.05).Routine blood test,coagulation function,liver and kidney function,pre-admi nistration and post-administration administration of the group on the third day between and within groups were compared and showed no significant difference(P＞0.05).ECG and lower extremity ultrasound examination showed no abnormality in each group.No adverse events happened in the cases of groups for the clinical study.Conclusion Hemostatic effects of haemocoagulase agkistrodon for injection and other hemostatic drugs were similar in hepatectomy.No sinificant adverse effects on postoperative routine blood,coagulation function,liver and kidney function,with good efficacy and safety,being worthy of using widely worth in hepatectomy.

Objective:To evaluate the safety and efficacy of endoscopic cryoablation (ECA) in patients with upper tract urothelial carcinoma (UTUC).Methods:The clinical data of 9 patients with UTUC treated with ECA from April 2018 to September 2019 were retrospectively analyzed. Patients consisted of 3 males and 6 females, with median age of 76 years old (ranging from 50 to 88 years old). Among the patients, 6 cases had tumors of ureter, 1 case had tumor of renal pelvis and 2 cases had tumors of renal pelvis combined with ureter. Of the 9 patients, two had bilateral UTUC, six were presented with single lesion, three were presented with multiple lesion. The size of tumors were (1.53±0.91)cm. The tumors of all cases were localized (≤stage T 2), and there was no carcinoma or suspicious lymph node/distant metastasis. All patients enrolled in this study had strong will to choose kidney-sparing therapy. Biopsy, resection of intraluminal lesion with laser and cryoablation under ureteroscopy or percutaneous nephroscopy was performed under general aneasthesia.Ureteroscopy was performed 3 months after cryoablation. Perioperative complications and follow-up results were recorded and assessed. Results:Cryoablation was successfully performed in patients under ureteroscopy (n=8) or nephroscopy (n=1). The median cryoablation time was 6 (ranging from 4-16) minutes. The median follow-up was 16 months (ranging from 4-24 months). No tumor recurrence was observed at primary sites during follow-up. Two patients with multiple lesions were observed denovo ureteral neoplasms outside the primary sites 3 months and 6 months after cryoablation and treated with second cryoablation. One case died due to cardiovascular events 4 months after surgery. One patient underwent ureteral stricture during follow-up and received ureteroscopic balloon dilatation. No recurrent stricture was found in this case during the subsequent follow-up of 16 months. The other 5 cases showed no recurrence or complications like stricture during follow-up.Conclusions:ECA could probably be a promising treatment for localized UTUC. No recurrence in primary site and low incidence of ureteral stricture was observed during follow-up. The efficacy and safety of ECA need to be verified with large sample study.

Background and purpose: Sorafenib hepatocellular carcinoma assessment randomized protocol (SHARP) and sorafenib in patients in Asia-Pacific region with hepatocellular carcinoma (ORIENTAL) had indicated that multi-kinase inhibitor sorafenib could prolong overall survival (OS) and time to progression (TTP) as well as improve progress free survival (PFS) in patients with advanced stage hepatocellular carcinoma. Drug-related adverse events in the course of treatment restricted its clinical application to a certain degree. This study was aimed to summerize the adverse events as well as the management of sorafenib in our clinic. Methods: Twenty-five cases clinically diagnosed as advanced hepatocellular carcinoma were enrolled from January 2008 to October 2009. All the patients who received sorafenib treatment met inclusion criteria as followed: (1) Progression of disease after trans-hepatic arterial chemoembolization therapy; (2) Extensive portal vein cancerous thrombus formation; (3) Portal zone or retroperitoneal lymph node metastasis or multiple remote metastasis, such as lung or bone; (4) Diffused poor blood supply to tumor; (5) Inform consent was obtained. All adverse events with different grade were observed during the beginning 12 weeks, and clinical treatment were carried out relatively. Results: Total of 25 cases were enrolled. Nine patients died of the disease, 3 of them died during the first 12 weeks, 3 patients abandoned sorafenib treatment, among them 2 died before the finish of 12 weeks treatment and 1 patient discontinued 5 months after the sorafenib treatment. Twenty cases finally assigned. Number of patients encountered drug-related adverse events were: HFSR (hand-foot-skin-reaction) 4(4/20), diarrhea 4(4/20), alopecia 5(5/20), rasb 4(4/20), fatigue 8(8/20), leukopenia and Thrombocytopenia 4(4/20), elevated blood pressure 1(1/20) and abdominal pain 1(1/20). After clinical management, 20 patients' sorafenib treatment were eventually not affected by adverse events. Conclusion: Sorafenib was well-tolerated and is a safe option of treatment for patients with advanced hepatocellular carcinoma.

Objective To study the role of Med19 in bladder cancer by analyzing the effects of lentivirus-mediated suppression of Med19 expression on T24 bladder cancer cells in vitro.Methods The lentivirus vectors containing a small hairpin RNA (shRNA) to target Med19 were constructed.After T24 bladder cancer cells were infected,real-time PCR and Western-blotting were used to study the Med19 expressions in the CON group (non-infected cells),the NC group (Lv-NC-infected cells) and the KD group (Lv-shMed19-infected cells).The influence of Med19 on the proliferation of bladder cancer cells were assessed using MTT,BrdU,colony formation assay and tumorigenicity experiment in mice.Cell cycle was analyzed with flow cytometry assay.Results Med19 relative mRNA level (0.35 ± 0.03) and Med19 protein expressing in the KD group were significantly inhibited (P ＜ 0.05).The KD group displayed an increased proportion of cells (77.50 ± 0.29)％ in the G0/G1 phase compared with the CON group (69.81 ± 0.81)％and NC group (67.53 ± 0.67) ％ (P ＜ 0.05).Compared with the CON group and the NC group,the KD group displayed a significant cell proliferation defect by MTT and BrdU assay and the number of colonies (91.33 ± 6.11) was significant decreased (P ＜ 0.05).On the day 24,the tumor volume (596.64 ± 485.36) mm3 and weight (0.57 ± 0.44) g of the KD group mice were decreased after inoculation into nude mice (P ＜ 0.05).Specific lentivirus-mediated knockdown of Med19 significantly impacted the cell cycle and proliferation of bladder cancer cells.Infected T24 cells nearly lost their tumorigenicity when being inoculated into nude mice.Conclusion Our results provide new evidence of an important role for Med19 in the development of bladder cancer,suggesting that lentiviruses delivering shRNA against Med19 may be a promising tool for bladder cancer therapy.

Sesamin, a lipid-soluble lignin originally isolated from sesame seeds, which induces cancer cell apoptosis and autophagy. In the present study, has been reported that sesamin induces apoptosis via several pathways in human lung cancer cells. However, whether mitophagy is involved in sesamin induced lung cancer cell apotosis remains unclear. This study, the anticancer activity of sesamin in lung cancer was studied by reactive oxygen species (ROS) and mitophagy. A549 cells were treated with sesamin, and cell viability, migration ability, and cell cycle were assessed using the CCK8 assay, scratch-wound test, and flow cytometry, respectively. ROS levels, mitochondrial membrane potential, and apoptosis were examined by flow cytometric detection of DCFH-DA fluorescence and by using JC-1 and TUNEL assays. The results indicated that sesamin treatment inhibited the cell viability and migration ability of A549 cells and induced G0/G1 phase arrest. Furthermore, sesamin induced an increase in ROS levels, a reduction in mitochondrial membrane potential, and apoptosis accompanied by an increase in cleaved caspase-3 and cleaved caspase-9. Additionally, sesamin triggered mitophagy and increased the expression of PINK1 and translocation of Parkin from the cytoplasm to the mitochondria. However, the antioxidant N-acetyl-L-cysteine clearly reduced the oxidative stress and mitophagy induced by sesamin. Furthermore, we found that cyclosporine A (an inhibitor of mitophagy) decreased the inhibitory effect of sesamin on A549 cell viability. Collectively, our data indicate that sesamin exerts lethal effects on lung cancer cells through the induction of ROS-mediated mitophagy and mitochondrial apoptosis.

Sesamin, a lipid-soluble lignin originally isolated from sesame seeds, which induces cancer cell apoptosis and autophagy. In the present study, has been reported that sesamin induces apoptosis via several pathways in human lung cancer cells. However, whether mitophagy is involved in sesamin induced lung cancer cell apotosis remains unclear. This study, the anticancer activity of sesamin in lung cancer was studied by reactive oxygen species (ROS) and mitophagy. A549 cells were treated with sesamin, and cell viability, migration ability, and cell cycle were assessed using the CCK8 assay, scratch-wound test, and flow cytometry, respectively. ROS levels, mitochondrial membrane potential, and apoptosis were examined by flow cytometric detection of DCFH-DA fluorescence and by using JC-1 and TUNEL assays. The results indicated that sesamin treatment inhibited the cell viability and migration ability of A549 cells and induced G0/G1 phase arrest. Furthermore, sesamin induced an increase in ROS levels, a reduction in mitochondrial membrane potential, and apoptosis accompanied by an increase in cleaved caspase-3 and cleaved caspase-9. Additionally, sesamin triggered mitophagy and increased the expression of PINK1 and translocation of Parkin from the cytoplasm to the mitochondria. However, the antioxidant N-acetyl-L-cysteine clearly reduced the oxidative stress and mitophagy induced by sesamin. Furthermore, we found that cyclosporine A (an inhibitor of mitophagy) decreased the inhibitory effect of sesamin on A549 cell viability. Collectively, our data indicate that sesamin exerts lethal effects on lung cancer cells through the induction of ROS-mediated mitophagy and mitochondrial apoptosis.

Objective:To study the safety and efficacy of a treatment protocol using immune checkpoint inhibitors (ICIs) and antiangiogenic targeted drugs (AATDs) in converting 41 patients with initially unresectable to resectable hepatocellular carcinoma (HCC).Methods:The data of 41 patients with initially unresectable HCC treated with immunotherapy combined with targeted therapy from December 2018 to April 2021 in Chinese PLA General Hospital were analysed. There were 34 males and 7 females, aged (51.8±10.7) years. The clinical characteristics, conversion to resectable HCC, adverse drug reactions, surgical data and postoperative complications were analysed. Patients were followed-up by outpatients clinics or telephone calls.Results:There were 5 patients with Chinese Liver Cancer Staging (CNLC)-Ⅰb, 4 with CNLC-Ⅱ, 28 with CNLC-Ⅲa and 4 with CNLC-Ⅲb before the treatment protocol. Among them, 28 patients had portal vein tumor thrombosis (PVTT) and 4 had retroperitoneal lymph node metastases. All patients had a mean tumor diameter of (9.16±4.43) cm before and (6.49±4.69) cm after the treatment protocol. The latter was based on the last assessment before hepatectomy. The efficacy of the treatment protocol in converting unresectable to resectable HCC was assessed by the modified Response Evaluation Criteria in Solid Tumors after 3-15 cycles (median dose cycles, 5) of protocal therapy: 15 patients achieved a complete response; 15 patients achieved a partial response; 6 patients had a stable disease, and 5 patients had a progressive disease. 21 patients (51.2%) experienced adverse reactions associated with drug treatment, which resolved with symptomatic treatment or brief discontinuation of the therapy. All patients underwent successful hepatectomy. Postoperative complications of grade Ⅱ or higher occurred in 9 patients (22.0%). The cumulative overall survival rates at 6 months, 1 year and 2 years from diagnosis were 100.0%, 92.6% and 64.7% respectively. The cumulative overall survival rates at 6 months, 1 year and 2 years after surgery were 95.1%, 74.7% and 60.8%, and the recurrence-free survival rates at 6 months, 1 year and 2 years after surgery were 87.8%, 56.7% and 48.6%, respectively.Conclusions:This study provided preliminary evidences that surgical resection after immunotherapy combined with targeted therapy in patients with initially unresectable HCC was safe and efficacious.

Background: Feline panleukopenia virus (FPV) is a widespread and highly infectious pathogen in cats with a high mortality rate. Although Yanji has a developed cat breeding industry, the variation of FPV locally is still unclear. Objectives: This study aimed to isolate and investigate the epidemiology of FPV in Yanji between 2021 and 2022. Methods: A strain of FPV was isolated from F81 cells. Cats suspected of FPV infection (n = 80) between 2021 and 2022 from Yanji were enrolled in this study. The capsid protein 2 (VP2) of FPV was amplified. It was cloned into the pMD-19T vector and transformed into a competent Escherichia coli strain. The positive colonies were analyzed via VP2 Sanger sequencing. A phylogenetic analysis based on a VP2 coding sequence was performed to identify the genetic relationships between the strains. Results: An FPV strain named YBYJ-1 was successfully isolated. The virus diameter was approximately 20–24 nm, 50% tissue culture infectious dose = 1 × 10 −4.94 /mL, which caused cytopathic effect in F81 cells. The epidemiological survey from 2021 to 2022 showed that 27 of the 80 samples were FPV-positive. Additionally, three strains positive for CPV-2c were unexpectedly found. Phylogenetic analysis showed that most of the 27 FPV strains belonged to the same group, and no mutations were found in the critical amino acids. Conclusions A local FPV strain named YBYJ-1 was successfully isolated. There was no critical mutation in FPV in Yanji, but some cases with CPV-2c infected cats were identified.