Objective　To summarize the methods of diagnosis and operation of carcinoma of the extrahepatic bile ducts. Methods　The clinical data of 100 cases of carcinoma of the extrahepatic bile ducts which were treated in our hospital from 1972 to 1999 were retrospectively analysed. In this series, there were 68 cases of the cancer located in the upper portion of exlrahepatic duct(proximal cancer), 12 in midder portion(midder cancer), 18 in lower portion(distal cancer), and 2 in whole bile duct. Results　The initial symptom was upper abdominal discomfort or vague pain, abdominal distension, weakness, weight loss and progressive jaundice. BUS, CT and MRI were scatheless. If the intrahepatic bile duct dilatation or extrahepatic cholestatic jaundice were revealed, PTC(13 cases in this series) or ERCP(42 cases in this series) were to further determine the location of tumor. According to the position and type of the tumor, the different operations were selected. Twenty-five cases(36.8%) of the proximal cancer were resected, including 15 cases of type Ⅰ treated with localresection or “skeletonization” resection, 9 cases of type Ⅱ treated with resection of the tumor and caudate lobe, 1 case of type Ⅲb treated with resection of the tumor, caudate lobe and left hepatic trisegmentectomy. Nine cases(75%) of midder cancer were resected. After resected the proximal and midder cancer, bile duct reconstruction by Roux-en-Y hepaticojejunostomy was performed on all the cases. Fourteen cases(77.8%) of distal cancer were treated by pancreatoduodenectomy. The total resection rate in this series was 48%. Of the cancer resected cases, 35 were followed up, the five-year survival rate was 58%. 32 of the 52 cases without cancer resection were followed up, and all of them died one to one and half year after operation. Conclusions　BUS, CT and MRI are the first selective methods for early diagnosis of the carcinomas of extrahepatic bile duct. If needed, PTC or ERCP should be done because of these methods have more accurate diagnostic value. Surgical resection of the tumor is the only likelihood for effective treatment.

Objective : To explore the predictive value of oxygenation index ( P/F) for clinical outcomes in adult community acquired pneumonia (CAP) patients . Methods : 493 patients with CAP eligible for inclusion were extracted from AHCCDM , and were divided into survival group ( n = 405 ) and death group ( n = 88) according to whether they survived at discharge ; multivariate Logistic regression analysis was used to identify independent risk factors associated with hospitalization death in CAP patients ; the trend of changes in oxygenation index (P/F) and hospital mortality risk was evaluated using a restricted cubic spline ( RCS) curve . Results : Multivariate Logistic regression analysis found that independent risk factors affecting hospitalization death in CAP patients included acute and chronic health scores (Apache II score)( OR = 1 . 11 , 95% CI : 1 . 07 - 1 . 15 , P = 0. 02) , P/F ( OR = 1 . 70 ,95% CI : 1 . 03 - 2. 82 , P = 0. 04) , and hemoglobin (Hb) and HCO3- concentration P > 0. 05 , which were not statistically significant; restrictive cubic spline regression analysis found that there was a non⁃linear response relation ship between P/F and hospital mortality (non⁃linear test P < 0. 001) , and a P/F of 250 mmHg was the cutoff point for the hospital mortality association analysis . P/F < 250 mmHg , for every 1 mmHg increased in P/F , the risk of in⁃hospital mortality was reduced by 1% , HR : 0. 99 (0. 99 - 1 . 00) , P < 0. 001 . P/F > 250 mmHg , there was no association between CAP patients and in⁃hospital mortality , HR : 1 . 00 ( 1 . 00 - 1 . 01) , P < 0. 001 , indicating that other factors played a dominant role . Conclusion A significantly reduced P/F has a high predictive value for mortality in patients with community⁃acquired pneumonia .

Objective To observe neuroprotective effects of Ca2+/calmodulin-dependent kinase Ⅱ(CaMKⅡ)γ and CaMkⅡ δ against acute neuronal ischemic reperfusion injury in mice and explore the underlying mechanism.Methods Primary cultures of brain neurons isolated from fetal mice(gestational age of 18 days)were transfected with two specific siRNAs(si-CAMK2G and si-CAMK2D)or a control sequence(si-NT).After the transfection,the cells were exposed to oxygen-glucose deprivation/reperfusion(OGD/R)conditions for 1 h followed by routine culture.The expressions of phosphatidylinositol-3-kinase/extracellular signal-regulated kinase(PI3K/Akt/Erk)signaling pathway components in the neurons were detected using immunoblotting.The expressions of the PI3K/Akt/Erk signaling pathway proteins were also detected in the brain tissues of mice receiving middle cerebral artery occlusion(MCAO)or sham operation.Results The neuronal cells transfected with si-CAMK2G showed significantly lower survival rates than those with si-NT transfection at 12,24,48,and 72 h after OGD/R(P<0.01),and si-CAMK2G transfection inhibited OGD/R-induced upregulation of CaMKⅡγ expression.Compared to si-NT,transfection with si-CAMK2G and si-CAMK2D both significantly inhibited the expressions of PI3K/Akt/Erk signaling pathway components(P<0.01).In the mouse models of MCAO,the expressions of CaMKⅡδ and CaMKⅡγ were significantly increased in the brain,where activation of the PI3K/Akt/Erk signaling pathway was detected.The expression levels of CaMKⅡδ,CaMKⅡγ,Erk,phosphorylated Erk,Akt,and phosphorylated Akt were all significantly higher in MCAO mice than in the sham-operated mice at 24,48,72,and 96 h after reperfusion(P<0.05).Conclusion The neuroprotective effects of CaMKⅡδ and CaMKⅡγ against acute neuronal ischemic reperfusion injury are mediated probably by the PI3K/Akt/Erk pathway.

Objective To observe neuroprotective effects of Ca2+/calmodulin-dependent kinase Ⅱ(CaMKⅡ)γ and CaMkⅡ δ against acute neuronal ischemic reperfusion injury in mice and explore the underlying mechanism.Methods Primary cultures of brain neurons isolated from fetal mice(gestational age of 18 days)were transfected with two specific siRNAs(si-CAMK2G and si-CAMK2D)or a control sequence(si-NT).After the transfection,the cells were exposed to oxygen-glucose deprivation/reperfusion(OGD/R)conditions for 1 h followed by routine culture.The expressions of phosphatidylinositol-3-kinase/extracellular signal-regulated kinase(PI3K/Akt/Erk)signaling pathway components in the neurons were detected using immunoblotting.The expressions of the PI3K/Akt/Erk signaling pathway proteins were also detected in the brain tissues of mice receiving middle cerebral artery occlusion(MCAO)or sham operation.Results The neuronal cells transfected with si-CAMK2G showed significantly lower survival rates than those with si-NT transfection at 12,24,48,and 72 h after OGD/R(P<0.01),and si-CAMK2G transfection inhibited OGD/R-induced upregulation of CaMKⅡγ expression.Compared to si-NT,transfection with si-CAMK2G and si-CAMK2D both significantly inhibited the expressions of PI3K/Akt/Erk signaling pathway components(P<0.01).In the mouse models of MCAO,the expressions of CaMKⅡδ and CaMKⅡγ were significantly increased in the brain,where activation of the PI3K/Akt/Erk signaling pathway was detected.The expression levels of CaMKⅡδ,CaMKⅡγ,Erk,phosphorylated Erk,Akt,and phosphorylated Akt were all significantly higher in MCAO mice than in the sham-operated mice at 24,48,72,and 96 h after reperfusion(P<0.05).Conclusion The neuroprotective effects of CaMKⅡδ and CaMKⅡγ against acute neuronal ischemic reperfusion injury are mediated probably by the PI3K/Akt/Erk pathway.

ObjectiveTo investigate the expression level of lysophosphatidyllecithin acyltransferase 4 （LPCAT4） in pancreatic cancer and its effect on the proliferation of pancreatic cancer cells. MethodsIn this study， the differentially expressed genes of patients with KRAS mutant and wild-type pancreatic cancer were analyzed by online database LinkedOmics. The LPCAT4 expression in pancreatic cancer tissues was analyzed online by the University of Alabama at Birmingham Cancer Data Analysis （UALCAN）， Sangerbox and gene expression profile interaction analysis 2 （GEPIA2）. Kaplan-Meier Plotter database was used to explore the correlation between LPCAT4 and the prognosis of patients with pancreatic cancer. The expression of LPCAT4 in human pancreatic cancer cells were detected by quantitative real-time PCR and Western blot analysis. LPCAT4 was knocked down in the high-expressing SW1990 cell line and overexpressed in the low-expressing MIA PaCa-2 cell line. The effects of LPCAT4 expression on cell proliferation were assessed using CCK-8 and EdU assays. STRING and GEPIA2 databases were used to obtain LPCAT4 binding and coexpressed genes in tumors， which were then analyzed by GO and KEGG. ResultsAnalysis of the LinkedOmics online database revealed a significant upregulation of LPCAT4 in patients with KRAS mutant pancreatic cancer compared to patients with KRAS wild-type pancreatic cancer. The online analysis of GEPIA2， UALCAN and Sangerbox 3.0 showed that the expression of LPCAT4 was higher in pancreatic cancer than in normal tissues. Analysis of the Kaplan-Meier Plotter database revealed that high LPCAT4 expression was associated with poorer prognosis in pancreatic cancer patients.Western blot and qPCR results showed that expression of LPCAT4 in pancreatic cancer cell lines was significantly higher than in normal pancreatic ductal epithelial cells. Knockdown of LPCAT4 in SW1990 cells inhibited proliferation， while overexpression in MIA PaCa-2 cells promoted proliferation. Enrichment analysis indicated that LPCAT4 was closely related to sulfur metabolism. ConclusionsLPCAT4 is highly expressed in pancreatic cancer and is associated with poor prognosis of patients. It plays a significant regulatory role in the proliferation of pancreatic cancer cells， with its expression level closely correlated with cell proliferation capacity. These findings reveal the critical role of LPCAT4 in the malignant progression of pancreatic cancer and provide important evidence for its potential as a therapeutic target.