Radiation resistance of the lung adenocarcinoma is related to the AKT-Onzin-POU5F1 axis.

Non-small cell lung carcinoma is the predominant type of lung cancer, and shows an easily developable tolerance to radiotherapy. Cancer stem cells are suggested to be involved in the resistance against therapies. Onzin might be accumulated during the process tumor overcoming the radiation stress. To address the relationship between Onzin, stemness and radiation resistance, we treated the lung cancer tumor bearing mice with radiaotherapy and observed the differences between radiation sensitive (RS) and resistant (RR) tumors. Immunohistochemistry and HE staining were used to observe Onzin and POU5F1 expression in tumor tissues. Quantitative realtime-PCR and Western blot were applied for Onzin and POU5F1 in tumors and cells. In-vitro cellular viability was assessed by CCK8 methods for tumor derived cells. The stably transfected A549 cell lines overexpressing Onzin were generated through lentivirus transfection. After radiotherapy, those RR adenocarcinoma tumors and cells derived from them showed an increased Onzin expression. Further, RR cells were found upregulated stemness, indicated by increased sphericity and proliferation, as well as POU5F1 expression. Next, we overexpressed Onzin in the A549 cells and found an elevated POU5F1 expression, increased proliferation, and enhanced sphericity. Moreover, this could be suppressed by the AKT inhibitor MK-2260. In vivo, the A549 cells overexpressing Onzin showed not only higher tumor formation capability and growth, but also a significant resistance to radiation. Taken together, RR tumors have upregulated Onzin and POU5F1 expression. Ectopic expression of Onzin promotes the POU5F1 expression as well as stemness functions, and confers adenocarcinomas the resistance to radiotherapy.

Standard versus extended pancreaticoduodenectomy in treating adenocarcinoma of the head of the pancreas.

OBJECTIVES: To compare the postoperative complications and survival of standard pancreatoduodenectomy (SPD) and extended pancreatoduodenectomy (EPD) in patients with resectable adenocarcinoma of the head of the pancreas. METHODS: Between January 1994 and December 2011, 165 patients with biopsy-proven adenocarcinoma of the pancreatic head were treated in West China Hospital, among whom 93 underwent SPD and 72 had EPD. Complications and survival after the surgery were analyzed retrospectively. RESULTS: The median operation time of the EPD group was longer compared with the SPD group (375 minutes vs.310 minutes, P<0.01), the volume of blood transfusion was larger (700 mL vs.400 mL, P<0.05), while the median hospital stay (13.5 days vs.12 days, P=0.79) and the total complication rates were comparable (34.7% vs.32.4%, P=0.93). The total recurrence rates of the SPD and EPD groups were not significantly different (52.7% vs. 43.1%, P=0.83). No significant differences were found between the SPD and EPD groups in 1-year (81.7% vs. 86.1%), 3-year (38.7% vs. 43.1%), 5-year (16.7% vs. 19.4%), and median survivals (19.8 months vs. 23.2 months, P= 0.52). CONCLUSION: The postoperative complications and survival donot differ significantly between SPD and EPD.

Central pancreatectomy for benign or borderline lesions of the pancreatic neck: a single centre experience and literature review.

BACKGROUND/AIMS: To investigate the effectiveness and safety of central pancreatectomy. METHODOLOGY: We retrospectively studied 44 cases that underwent central pancreatectomy (CP), 55 patients who underwent distal pancreatectomy (DP), and 62 patients who underwent pancreatoduodenectomy (PD) for their benign or borderline pancreatic lesions; as well as the different management styles for pancreatic stumps in CP. RESULTS: The duration of surgery and length of hospital stay were shorter in the CP group than that of PD group, and blood loss was also less in CP group. There were no differences between the CP and DP groups in duration of surgery, length of hospital stay, and blood loss. The incidence of common surgical complications was higher in the PD group. There were more pancreatic fistulas (grade B/C) in CP and PD groups compared to that of the DP group. New onset or worsening of diabetes occurred only in the CP and PD groups at 4.8% and 10.9%, respectively. A pancreaticogastrostomy for distal pancreatic stumps reduced the incidence of pancreatic fistula (p=0.038). Duct-to-mucosa anastomosis had less pancreatic fistula than invagination anastomosis (p=0.017). There was no difference in incidence of pancreatic fistula between pancreaticojejunostomy and oversewing of proximal pancreatic stumps (p=0.601). CONCLUSIONS: CP is an available and safe operation for benign or borderline lesions located in the pancreatic neck. A pancreaticogastrostomy for distal pancreatic stumps or duct-to-mucosa anastomosis may reduce the risk of pancreatic fistula.

Effect of recombinant human growth hormone and interferon gamma on hepatic collagen synthesis and proliferation of hepatic stellate cells in cirrhotic rats.

BACKGROUND: Fibrosis plays a key role in the development of liver cirrhosis. In this study, we investigated the effect of growth hormone and interferon gamma on hepatic collagen synthesis and the proliferation of hepatic stellate cells in a cirrhotic rat model. METHODS: Cirrhosis was induced in rats using carbon tetrachloride. Rats were simultaneously treated with daily subcutaneous injections of recombinant human growth hormone or interferon gamma combined with recombinant human growth hormone. The control group was given saline. The relative content of type I and type IV collagen was assessed by indirect immunofluorescence analysis. Activated hepatic stellate cells were prepared from cirrhotic rats. The 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) method was used to assess the effects of recombinant human growth hormone and interferon gamma on these cells in vitro. RESULTS: Both qualitative and quantitative analysis showed that type I and type IV collagen secretion increased with time after recombinant human growth hormone administration and was significantly higher than control and recombinant human growth hormone combined with interferon gamma administration. In vitro, recombinant human growth hormone significantly stimulated hepatic stellate cell proliferation in a concentration-dependent manner (10(-3)-10(-1) mg/100 µL), and interferon gamma (10(-2)-10(-1) µg/100 µL) significantly inhibited their growth compared to the control group. Interferon gamma combined with recombinant human growth hormone eliminated this growth-promoting effect to a certain degree in a concentration-dependent manner (10(-1) µg/100 µL, P<0.05, 10(-2)-10(-3) µg/100 µL, P>0.05) and a time-dependent manner (P<0.05). CONCLUSIONS: Recombinant human growth hormone increased collagen secretion in cirrhotic rats in vivo and promoted the proliferation of hepatic stellate cells from cirrhotic rats in vitro. It is possible that concurrent interferon gamma therapy can offset these side-effects of recombinant human growth hormone.

Multi-Omic Analysis in a Metabolic Syndrome Porcine Model Implicates Arachidonic Acid Metabolism Disorder as a Risk Factor for Atherosclerosis.

Background: The diet-induced gut microbiota dysbiosis has been suggested as a major risk factor for atherothrombosis, however, the detailed mechanism linking these conditions is yet to be fully understood. Methods: We established a long-term excessive-energy diet-induced metabolic syndrome (MetS) inbred Wuzhishan minipig model, which is characterized by its genetic stability, small size, and human-like physiology. The metabolic parameters, atherosclerotic lesions, gut microbiome, and host transcriptome were analyzed. Metabolomics profiling revealed a linkage between gut microbiota and atherothrombosis. Results: We showed that white atheromatous plaque was clearly visible on abdominal aorta in the MetS model. Furthermore, using metagenome and metatranscriptome sequencing, we discovered that the long-term excessive energy intake altered the local intestinal microbiota composition and transcriptional profile, which was most dramatically illustrated by the reduced abundance of SCFAs-producing bacteria including Bacteroides, Lachnospiraceae, and Ruminococcaceae in the MetS model. Liver and abdominal aorta transcriptomes in the MetS model indicate that the diet-induced gut microbiota dysbiosis activated host chronic inflammatory responses and significantly upregulated the expression of genes related to arachidonic acid-dependent signaling pathways. Notably, metabolomics profiling further revealed an intimate linkage between arachidonic acid metabolism and atherothrombosis in the host-gut microbial metabolism axis. Conclusions: These findings provide new insights into the relationship between atherothrombosis and regulation of gut microbiota via host metabolomes and will be of potential value for the treatment of cardiovascular diseases in MetS.

[Diagnosis and surgical interventions for the chronic obstructive pancreatitis due to the inflammatory lesions at the opening of the pancreatic duct].

OBJECTIVE: To explore the diagnostic methods and reasonable surgical interventions for the chronic obstructive pancreatitis due to the inflammatory lesions at the opening of the pancreatic duct. METHODS: From January 2002 to November 2010 the data of 28 patients who were diagnosed as the chronic obstructive pancreatitis (COP) was retrospectively reviewed. Out of the 28 patients, it was analyzed that the clinical manifestations, diagnostic methods, surgical finding and surgical interventions of the 13 patients who were diagnosed as COP due to the inflammatory lesions at the opening of the pancreatic duct in the exploratory operation accompanying recurrent acute abdominal pain with increased serum amylase and lipase, dilation of entire pancreatic duct on imaging before surgery. The conditions included pain recrudescence, quality of life, pancreatic changes on imaging and the serum amylase and lipase after surgery were recorded. RESULTS: All the 13 patients had clinical manifestations of COP. However, 12 patients had different manifestations on imaging from those chronic pancreatitis imaging due to tumors at the duodenal papilla, ampulla or inner pancreatic duct. Via exploratory operation and magnetic resonance cholangiopancreatography (MRCP), there were short pancreaticobiliary common channel or pancreas divisum existing in most patients. There was no acute abdominal pain with the increased serum amylase and lipase in the 12 patients who receiving the transduodenal mastoid, ampulla and pancreatic ductal opening incision and plasty, the paramastoideus incision and plasty in the visit. CONCLUSIONS: The imaging character of COP due to the inflammatory lesions at the opening of the pancreatic duct is the dilation of the pancreatic duct without the chronic obstruction in the bile duct. The patients with short pancreaticobiliary common channel or pancreas divisum easily suffer COP due to the stenosis of the pancreatic ductal opening caused by the duodenal mastoiditis or paramastoiditis. The local plasty surgery to correct the stenosis at the pancreatic ductal opening and improve the drainage of the pancreatic duct is an easy and effective management.

Clinical efficacy of low dose recombinant tissue-type plasminogen activator for the treatment of acute intermediate-risk pulmonary embolism.

OBJECTIVES: To investigate the efficacy and safety of initial thrombolysis by recombinant tissue-type plasminogen activator (rt-PA) in compared with anticoagulant therapy in patients with acute intermediate-risk pulmonary embolism (PE).  Methods: Sixty-six patients with acute intermediate-risk PE were randomly assigned to receive rt-PA or LMWH between June 2014 and June 2017 in our department. We obtained information regarding the difference in the right ventricle/left ventricle (RV/LV) ratio, pulmonary artery systolic pressure (PASP), clinical symptoms improvement, PE-related mortality, hemodynamic decompensation, recurrent PE, and major and minor bleeding.  Results: In the rt-PA group, the mean PASP was reduced from 52.0±12.2 at baseline to 34.8±9.4 (p less than 0.001) and the mean RV/LV ratio was reduced from 1.26±0.22 at baseline to 0.96±0.18 (p less than 0.001) at 24 hours. In the LMWH group, the mean PASP was 53.4±12.8 at baseline and 48.5±11.9 at 24 hours (p=0.11), and the mean RV/LV ratio was 1.22±0.19 at baseline and 1.17±0.21 at 24 hours (p=0.31). In comparison with the LMWH group, there was a significant reduction in PASP and an improvement in the symptom severity in the rt-PA group. At 90 days, there was no difference in mortality, recurrent venous thromboembolism and major bleeding as a safety outcome, but increased minor bleeding and decreased hemodynamic decompensation occurred in the rt-PA group. Conclusions: In patients with acute intermediate-risk PE, low dose thrombolytic therapy is considered safe and effective, it can be recommended as an alternative option in clinical treatment.

Effectiveness and safety of diagnostic flexi-rigid thoracoscopy in differentiating exudative pleural effusion of unknown etiology: a retrospective study of 215 patients.

BACKGROUND: The aim of this study was to evaluate the effectiveness and safety of diagnostic flexi-rigid thoracoscopy in differentiating exudative pleural effusion of unknown etiology. METHODS: A total of 215 patients with undiagnosed exudative pleural effusion were consecutively recruited between January 2011 and February 2013. Thoracoscopy was carried out under local anesthesia, and multisite pleural biopsies were performed using a flexi-rigid thoracoscope. The tolerance of the patients, surgical complications and postoperative pathological diagnosis rate were used to evaluate the effectiveness and safety of the thoracoscopy procedures. RESULTS: All patients, Karnofsky performance status (KPS) >70, could tolerate both the thoracoscopic surgery and pleural biopsy; there were no severe complications. Thoracoscopic findings included pleural hyperaemia, fibrinous adhesion, nodular bulge and fester. The pathological biopsy confirmed diagnoses of malignant tumor (97 cases), tuberculous pleuritis (91 cases), tuberculous empyema (one case), pulmonary schistosomiasis (one case) and unknown etiology (25 cases). The total diagnosis rate was 88.4%. Subcutaneous emphysema occurred in ten cases and fever in six cases, all of which recovered completely with conservative treatment. CONCLUSIONS: Flexi-rigid thoracoscopy had a high diagnosis rate, differentiating exudative pleural effusion of unknown etiology with satisfactory effectiveness and safety. There was high degree of relationship between thoracoscopic appearance and primary disease or tumor classification.

Pancreatic panniculitis associated with acinar cell carcinoma of the pancreas: a case report.

Pancreatic panniculitis is a rare type of disorder associated with pancreatic diseases. We describe here a case of 54-year-old man who was admitted to the Department of Dermatology with the diagnosis of erythema nodosum. The patient presented with a 9-month history of painful erythematous nodules on the extremities, joint pain and swelling, and weight loss. A highly elevated level of pancreatic lipase was found on the laboratory examinations. The biopsy specimens from the skin lesions showed subcutaneous fat necrosis. Abdominal computed tomography (CT) revealed a large mass with central necrosis in the body and tail of the pancreas. Distal pancreatectomy, splenectomy and partial transverse colectomy were successfully performed on day 17 of the hospitalization. The histopathologic findings supported the diagnosis of acinar cell carcinoma of the pancreas (ACCP). Postoperatively, the level of serum lipase returned to normal, and the skin lesions and joint manifestations gradually regressed. However, the swelling did not significantly resolve in the left knee. In view of the non-specific clinical presentation of this disease, clinicians should be alert and have a high index of suspicion for pancreatic panniculitis.

Coexistence of pancreatic carcinoma and pancreatic tuberculosis: case report.

Pancreatic tuberculosis (TB) is extremely rare and mimics pancreatic carcinoma both clinically and radiologically. This paper discusses the occurrence of 2 heterogeneous masses located in the head and tail of the pancreas in an adult male. In this patient, laparotomy was performed because of the high suspicion of pancreatic carcinoma. Intraoperative fine needle aspiration biopsy revealed the coexistence of pancreatic carcinoma with pancreatic TB, and a combined resection of the distal pancreas and spleen was successfully performed. Following surgery, the patient received standard chemotherapy for TB. At 7-month follow-up, computed tomography showed resolution of the mass in the pancreatic head. Clinicians must maintain a high index of suspicion for pancreatic TB in patients with pancreatic masses. The coexistence of malignancy and TB should be considered when patients present with multiple pancreatic masses.

Cordyceps sinensis extract suppresses hypoxia-induced proliferation of rat pulmonary artery smooth muscle cells.

OBJECTIVE: To investigate the effects of a Chinese herb Cordyceps sinensis (C. sinensis) extract on hypoxia-induced proliferation and the underlying mechanisms involved. METHODS: This prospective study was carried out at the Central Laboratory of Yichang Central People's Hospital, Yichang, China from March 2008 to April 2010. The C. sinensis was extracted from the Chinese herb C. sinensis using aqueous alcohol extraction techniques. Forty healthy adult male Sprague Dawley rats were used in the study. The proliferation of pulmonary artery smooth muscle cells (PASMCs) was measured using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell viability was determined by trypan blue exclusion. Cell cycles were analyzed using FACSort flow cytometric analysis. The expression of proliferating cell nuclear antigen (PCNA), c-jun, and c-fos in rat PASMCs was determined by immunohistochemistry. RESULTS: We found an increased proliferation of PASMCs and increased expression of transcription factors, c-jun and c-fos in PASMCs cultured under hypoxic conditions. The C. sinensis extract significantly inhibited hypoxia-induced cell proliferation in a dose-dependent manner. In addition, C. sinensis extract also significantly inhibited the expression of PCNA, c-jun, and c-fos in these PASMCs. CONCLUSION: Our results indicated that C. sinensis extract inhibits hypoxia-induced proliferation of rat PASMCs, probably by suppressing the expression of PCNA, c-fos, c-jun, and decreasing the percentage of cells in synthesis phase, second gap phase, and mitotic phase in cell cycle (S+G2/M) phase. Our results therefore, provided novel evidence that C. sinensis extract may be used as a therapeutic reagent in the treatment of hypoxic pulmonary hypertension.