Objective To investigate the effects of NVP-BEZ235 on proliferation and apoptosis of human cholangiocarcinoma(CCA) cell QBC939 in vitro and to reveal the antineoplastic mechanisms of NVP-BEZ235.Methods Human CCA cell line QBC939 was used in this study.Cell apoptosis by NVP-BEZ235 was analyzed using the flow cytometry.Cell growth inhibition by NVP-BEZ235 for 24h 48h 72h by MTT assay.The antineoplastic mechanisms of NVP-BEZ235 for 48h were assessed by western blotting for PARP、Bcl-2、Akt、p-Akt、c-FLIPL and Mcl-1 assay in QBC939 cell.Results NVP-BEZ235 treatment inhibited the proliferation and induced apoptosis of human CCA cell QBC939,which appeared time-dependent and concentration-dependent effects.NVP-BEZ235 reduced protein levels of Mcl-1、c-FLIPL and Bcl-2 and downregulate protein level of p-Akt significantly.Conclusion NVP-BEZ235 inhibited the phosphorylation of Akt.NVP-BEZ235 downregulated Bcl-2、c-FLIPL、Mcl-1 protein level via PI3K/AKT signaling pathway to induce apoptosis and inhibit the proliferation of human CCA cell QBC939.

Objective To explore the effectiveness of early enteral nutrition (EN) support and growth hormone (GH) treatment in critically ill patients.Methods Seventy critically ill patients were randomly divided into early EN support group and early EN support plus GH treatment group.The nutrition intakes were isonitrogenic and isocalorie in these two groups.Body weight,blood biochemistry,nutritional statues,and lactulose/mannitol levels were measured or analyzed before and after nutrition support.Immunologic functions were analyzed after ten days.Nitrogen balance was measured daily.Results The changes of body weight,albumin level,and transferrin level were more obvious in the EN + GH group than those in the EN group without significant difference (P ＞0.05).The changes of prealbumin and fibronectin in the EN + GH group were significantly higher than those in the EN group (P ＜ 0.05).The level of IgA in the EN + GH group was significantly lower than that in the EN group,while the levels of CD4 and NK in the EN + GH group was significandy higher than those in the EN group (P ＜0.05).The gut barrier function in the EN + GH group was superior to that in the EN group during nutrition support (P ＜0.05).Nitrogen balance was positive in the EN + GH group and negative in the EN group (P ＜ 0.05).Conclusions Early EN can improve the nutritional status and reduce complications in critically ill patients.GH treatment may strengthen the immune function and remarkably decrease the disability and mortality in critically ill patients.

Objective:To investigate the effect of pulmonary vascular dysfunction in the prognosis of patients with acute lung injury (ALI).Methods:Patients with ALI who underwent pulmonary artery catheterization in the department of critical care medicine of Wuhan NO.1 Hospital from June 2017 to June 2019 were enrolled. The general information, clinical and hemodynamic indexes [central venous pressure (CVP), pulmonary artery wedge pressure (PAWP), pulmonary artery systolic pressure (sPAP), pulmonary artery diastolic pressure (dPAP), mean pulmonary artery pressure (mPAP), cardiac index (CI)], acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, arterial blood gas parameters [pH, partial pressure of oxygen (PO 2), partial pressure of carbon dioxide (PCO 2), oxygenation index (PaO 2/FiO 2)], whether there was shock or not; ventilator parameters [platform pressure (Plat), positive end-expiratory pressure (PEEP)], etc. were recorded. Pulmonary artery oxygen saturation, pulmonary vascular function indexes [transpulmonary potential gradient (TPG) and pulmonary vascular resistance index (PVRi)] were calculated. The relationship between TPG, PVRi and mechanical ventilation time, the length of intensive care unit (ICU) stay, cardiovascular days and 60-day mortality were analyzed in patients with different prognosis of 60-day and whether the TPG increased (≥12 mmHg was defined as elevated TPG, 1 mmHg = 0.133 kPa). Results:A total of 65 patients were included in the study, including 30 males and 35 females; aged (48.9±15.2) years old. Forty-eight cases survived in 60-days, 17 died, and the 60-day mortality was 26.2%. At the baseline, there were no significant differences in cardiopulmonary function measurements, such as CVP, sPAP, dPAP, PAWP, CI, etc. between the two groups of patients with different prognosis. The APACHEⅡ score, shock ratio, TPG and PVRi of the death group were significant higher than those of the survival group [APACHEⅡ: 34±9 vs. 28±11, shock: 52.9% vs. 25.0%, TPG (mmHg): 16.2±1.9 vs. 14.6±2.1, PVRi (kPa·s·L -1): 31.8±4.2 vs. 29.7±3.5, all P < 0.05]. The 60-day mortality of 47 patients with TPG ≥ 12 mmHg was significantly higher than that of 18 patients with TPG < 12 mmHg (34.0% vs. 5.6%), and the mechanical ventilation time and the length of ICU stay were also significantly longer (days: 17±9 vs. 11±8, 16±5 vs. 12±5), and the cardiovascular days also increased significantly (days: 23±7 vs. 18±6), and the differences were statistically significant (all P < 0.05). Pearson correlation analysis showed that PVRi was significantly correlated with mechanical ventilation time, the length of ICU stay and cardiovascular days ( r1 = 0.317, P1 = 0.030; r2 = 0.277, P2 = 0.005; r3 = 0.285, P3 = 0.002). In the individual multivariate Logistic regression model, the highest PVRi was an independent risk factor for the 60-day mortality [odds ratio ( OR) = 30.5, 95% confidence interval was 20.4-43.1, P = 0.023]. Conclusion:Pulmonary vascular dysfunction is common in ALI patients and is independently associated with adverse outcomes.

ObjectiveTo investigate related factors for stone recurrence after endoscopic minimally invasive gallbladder-preserving cholecystolithotomy, and to establish a nomogram model for predicting the risk of stone recurrence after surgery based on independent risk factors. MethodsA retrospective analysis was performed for the clinical data of 144 patients with gallstones who underwent endoscopic minimally invasive gallbladder-preserving cholecystolithotomy in Qinghai University Affiliated Hospital from January 2012 to January 2018, and according to postoperative stone recurrence, the patients were divided into non-recurrence group and recurrence group. The chi-square test was used for comparison of categorical data between two groups. LASSO and logistic regression analyses were used to analyze independent risk factors for postoperative stone recurrence, and the corresponding nomogram prediction model was plotted according to regression coefficient. The calibration curve was plotted to evaluate the reliability of the predictive nomogram; Harrell consistency index was used to quantify the discriminatory performance of the predictive nomogram; the receiver operating characteristic (ROC) curve was used to evaluate the sensitivity, specificity, and area under the ROC curve (AUC) of this predictive nomogram. ResultsAll 144 patients underwent successful endoscopic minimally invasive gallbladder-preserving cholecystolithotomy, among whom 14 patients (9.7%) experienced stone recurrence after surgery. The multivariate analysis showed that family history (odds ratio ［OR］= 3.245, 95% confidence interval ［CI］: 0.752-13567, P=0.104), regular diet (OR=3.752, 95% CI: 1.067-14.141, P=0.041), stone homogeneity (OR=5.871, 95% CI: 1636-25.390, P=0.010), and medication compliance (OR=0.225, 95% CI: 0.057-0.799, P=0.024) were independent risk factors for recurrence. The nomogram model had an index of concordance (C-index) of 0.835 (95% CI: 0.732-0.938) in the modeling sample and 0.7925 in the verification sample, suggesting that the nomogram model in this study had good accuracy and discrimination. The predictive nomogram had an AUC of 0.835, suggesting that this nomogram had a relatively high predictive value. ConclusionFamily history, regular diet, stone homogeneity, and medication compliance are independent risk factors for stone recurrence after endoscopic minimally invasive gallbladder-preserving cholecystolithotomy, and the nomogram constructed based on these independent risk factors may help to predict the risk of postoperative stone recurrence.

Objective:To analyze the clinical features, differential diagnosis, treatment and prognosis of complex lymphatic malformations.Methods:The clinical data of patients with complex lymphatic malformation were retrospectively analyzed from April 2010 to April 2022 in the Multidisciplinary Outpatient Department of the Vascular Disease Team of West China Hospital, Sichuan University. All patients were diagnosed with complex lymphatic malformation after consultation with multidisciplinary experts in pediatric surgery, radiology, plastic surgery, pathology, rehabilitation and other departments. The clinical manifestations, blood routine, coagulation function, magnetic resonance imaging and treatment methods of the patients were analyzed. According to the follow-up and disease results, the patients were divided into improvement, stability, progress and death.Results:A total of 18 patients with complex lymphatic malformations were included in the study, including 6 males and 12 females. The age of first diagnosis ranged from 1 month to 29 years old, and the median age was 2.5 years old. Patients were followed up and treated for 0.4 to 12.0 years, with an average follow-up of 3.5 years. Ten patients had pleural and pericardial effusion; 15 patients had visceral involvement which showed multifocal changes in imaging examinations; 9 cases were accompanied by bone destruction, which in Gorham-Stout disease patients broke through the cortex while in generalized lymphatic anomalies it did not; 14 patients had various degrees of coagulation abnormalities, of which 8 patients with severe coagulation dysfunction were all diagnosed as kaposiform lymphangiomatosis. Of the 18 patients, one kaposiform lymphangiomatosis patient died; six patients progressed; eight patients were stable; and three patients improved.Conclusion:The clinical characteristics of patients with complex lymphatic malformations are systemic, diverse and complex. The clinical symptoms of patients with diffuse lymphatic malformation accompanied by involvement of bone and multiple internal organs, chest and abdominal effusion, and coagulation dysfunction should be considered as complex lymphatic malformation. However, due to overlapping clinical characteristics of each subtypes, it is difficult to distinguish patients with complex lymphatic malformation, and the curative effect and prognosis are poor. Precision targeted drugs are the future research direction for the treatment of such diseases.

Objective:To analyze the clinical features, differential diagnosis, treatment and prognosis of complex lymphatic malformations.Methods:The clinical data of patients with complex lymphatic malformation were retrospectively analyzed from April 2010 to April 2022 in the Multidisciplinary Outpatient Department of the Vascular Disease Team of West China Hospital, Sichuan University. All patients were diagnosed with complex lymphatic malformation after consultation with multidisciplinary experts in pediatric surgery, radiology, plastic surgery, pathology, rehabilitation and other departments. The clinical manifestations, blood routine, coagulation function, magnetic resonance imaging and treatment methods of the patients were analyzed. According to the follow-up and disease results, the patients were divided into improvement, stability, progress and death.Results:A total of 18 patients with complex lymphatic malformations were included in the study, including 6 males and 12 females. The age of first diagnosis ranged from 1 month to 29 years old, and the median age was 2.5 years old. Patients were followed up and treated for 0.4 to 12.0 years, with an average follow-up of 3.5 years. Ten patients had pleural and pericardial effusion; 15 patients had visceral involvement which showed multifocal changes in imaging examinations; 9 cases were accompanied by bone destruction, which in Gorham-Stout disease patients broke through the cortex while in generalized lymphatic anomalies it did not; 14 patients had various degrees of coagulation abnormalities, of which 8 patients with severe coagulation dysfunction were all diagnosed as kaposiform lymphangiomatosis. Of the 18 patients, one kaposiform lymphangiomatosis patient died; six patients progressed; eight patients were stable; and three patients improved.Conclusion:The clinical characteristics of patients with complex lymphatic malformations are systemic, diverse and complex. The clinical symptoms of patients with diffuse lymphatic malformation accompanied by involvement of bone and multiple internal organs, chest and abdominal effusion, and coagulation dysfunction should be considered as complex lymphatic malformation. However, due to overlapping clinical characteristics of each subtypes, it is difficult to distinguish patients with complex lymphatic malformation, and the curative effect and prognosis are poor. Precision targeted drugs are the future research direction for the treatment of such diseases.

ObjectiveTo investigate the correlation between systemic immune-inflammation index (SII) and prognosis in patients with hepatic alveolar echinococcosis. MethodsA retrospective analysis was performed for the clinical data of 242 patients who were admitted to Department of Hepatopancreatobiliary Surgery, Qinghai University Affiliated Hospital, from January 2015 to December 2018 and underwent surgery for hepatic alveolar echinococcosis, and SII was calculated. The chi-square test was used for comparison of categorical data between two groups, and a Spearman correlation analysis was performed. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value of SII; the Kaplan-Meier method was used to plot survival curves and analyze overall survival time in the two groups, and the log-rank test was used for comparison of survival rates between the two groups; univariate and multivariate Cox regression analyses were used to identify the influencing factors for the prognosis of patients with hepatic alveolar echinococcosis. ResultsThe Spearman correlation analysis showed that SII was positively correlated with the postoperative fatality rate of patients with hepatic alveolar echinococcosis (r=0.267, P＜0.001). The ROC curve showed that the optimal cut-off value of SII before surgery was 758.92, and based on this, 242 patients with hepatic alveolar echinococcosis were divided into low SII (SII ≤758.92) group with 126 patients and high SII (SII ＞758.92) group with 116 patients. The low SII group had 1-, 3-, and 5-year survival rates of 98.20%, 88.47%, and 6610%, respectively, and the high SII group had 1-, 3-, and 5-year survival rates of 90.80%, 53.05%, and 27.40%, respectively. The low SII group had a cumulative survival rate of ＞50% and a mean survival time of 55.584 months (95% confidence interval［CI］: 53550-57.617), while the high SII group had a cumulative survival rate of ＜50%, a mean survival time of 39.384 months (95% CI: 35.070-43.698), and a median survival time of 43 months (95% CI: 34.694-51.306). The low SII group had a significantly better survival rate than the high SII group, and there was a significant difference in overall survival rate between the two groups (χ2=46.979, P＜005). The univariate analysis showed that SII ＞758.92 (hazard ratio ［HR］=5.907, 95% CI: 3.386-10.306, P=0.001) was an influencing factor for the overall survival time of patients with hepatic alveolar echinococcosis, and the multivariate Cox regression analysis showed that preoperative peripheral blood SII (HR=3.507, 95% CI: 1.911-6.435, P=0.001) was an independent risk factor for the overall survival rate of patients with hepatic alveolar echinococcosis. ConclusionPreoperative SII level is clearly correlated with the prognosis of patients with hepatic alveolar echinococcosis and can thus be used as a clinical indicator to evaluate the prognosis of patients. The higher the peripheral blood SII before surgery, the worse the prognosis of patients.

Objective:To preliminarily assess the clinical value of sirolimus combined with prednisone in the treatment of Kaposiform hemangioendothelioma (KHE) complicated by Kasabach-Merritt phenomenon (KMP) .Methods:A retrospective study was conducted. General clinical data and relevant data on efficacy and adverse reactions were collected from 36 patients with KHE complicated by KMP, who received oral sirolimus combined with prednisone in Department of Pediatric Surgery, West China Hospital, Sichuan University from January 2011 to January 2018.Results:Among the 36 patients with KHE complicated by KMP, the male-to-female ratio was 1∶0.8; their average age was 15.0 months (range, 4.0 - 60.0 months) , and the average age of onset was 6.3 months (range, 0.8 - 48.0 months) ; 32 (88.9%) patients were diagnosed with mixed KHE, and 4 (11.1%) with deep KHE; the tumor size ranged from 2.5 cm × 4.0 cm to 20.0 cm × 24.0 cm. During the combined treatment, the average duration of prednisone administration was 6.4 weeks (range, 5.0 - 9.0 weeks) , and that of sirolimus administration was 19.3 months (range, 13.0 - 27.0 months) . After 1-5 weeks of combined treatment, platelet counts and fibrinogen levels of the 36 patients gradually returned to normal. After short-term prednisone combined with long-term sirolimus treatment, the average disease severity score decreased from 4.0 before treatment to 2.4 at 6 months and 1.6 at 12 months. After 12 months of the combined treatment, tumors mostly regressed in 32 (88.9%) patients, partially regressed in 3 (8.3%) , showed no obvious change in 1 (2.8%) . During the treatment, common adverse reactions included gastrointestinal discomfort and oral ulcers, no patient discontinued the treatment due to severe adverse reactions, and no drug toxicity-related death occurred.Conclusion:Sirolimus combined with prednisone is effective and safe for the treatment of KHE complicated by KMP.

Objective:To investigate the similarities and differences in clinical manifestations, lesion features, treatment options and prognosis in patients with kaposiform hemangioendothelioma (KHE) and tufted angioma (TA).Methods:The clinical data of KHE patients and TA patients diagnosed and treated in West China Hospital of Sichuan University from August 2016 to June 2020 were retrospectively analyzed. The similarities and differences in gender, the age of onset, clinical features, complications, histopathology, imaging manifestations, treatment and prognosis of the two diseases were compared. The χ2 test or Fisher’s exact test were used to analyze the qualitative data. The Mann-Whitney U test was used to analyze the quantitative data of the two groups that did not conform to the normal distribution. P<0.05 was considered to be statistically significant. Results:A total of 217 patients were included, including 183 patients with KHE and 34 patients with TA. There was no significant difference between KHE and TA in male to female ratio ( χ2=0.44, P=0.510), the age of onset ( U=2 757.00, Z=-1.09, P=0.278) and the sites of lesion ( χ2=3.64, P=0.162). The mixed type of KHE was the most common, reaching 63.39% (116/183), while the superficial type of TA was the most common, reaching 88.24% (30/34). The lesion diameter of KHE patients was 6.30(4.40, 9.70) cm, which was larger than that of TA patients 2.95(2.05, 4.03) cm, and the difference was statistically significant ( U=967.50, Z=-6.38, P<0.001). KHE is more likely to involve skeletal muscle, and cause thrombocytopenia and severe fibrinogenopenia. KHE mainly involved the dermis, subcutaneous tissue and even deep muscles, and manifested as an infiltrative mass. Magnetic resonance imaging (MRI) showed mass diffuse with high signal on T 2 phase. TA was often a superficial lesion that only involved the subcutaneous fat layer and was lumpy. MRI showed that the high signal was confined to the subcutaneous fat layer. The total effective rate of KHE [KHE(85.79%) vs. TA(91.18%)] and the total effective rate of drug therapy [KHE(85.32%) vs. TA(95.65%)] were lower than those of TA. Conclusions:Compared with TA, KHE has a larger tumor diameter, higher invasiveness, higher risk of complications. In addition, treatment plan was more complicated and treatment response rate was lower in patients with KHE compared with those in patients with TA.

Objective:To investigate the similarities and differences in clinical manifestations, lesion features, treatment options and prognosis in patients with kaposiform hemangioendothelioma (KHE) and tufted angioma (TA).Methods:The clinical data of KHE patients and TA patients diagnosed and treated in West China Hospital of Sichuan University from August 2016 to June 2020 were retrospectively analyzed. The similarities and differences in gender, the age of onset, clinical features, complications, histopathology, imaging manifestations, treatment and prognosis of the two diseases were compared. The χ2 test or Fisher’s exact test were used to analyze the qualitative data. The Mann-Whitney U test was used to analyze the quantitative data of the two groups that did not conform to the normal distribution. P<0.05 was considered to be statistically significant. Results:A total of 217 patients were included, including 183 patients with KHE and 34 patients with TA. There was no significant difference between KHE and TA in male to female ratio ( χ2=0.44, P=0.510), the age of onset ( U=2 757.00, Z=-1.09, P=0.278) and the sites of lesion ( χ2=3.64, P=0.162). The mixed type of KHE was the most common, reaching 63.39% (116/183), while the superficial type of TA was the most common, reaching 88.24% (30/34). The lesion diameter of KHE patients was 6.30(4.40, 9.70) cm, which was larger than that of TA patients 2.95(2.05, 4.03) cm, and the difference was statistically significant ( U=967.50, Z=-6.38, P<0.001). KHE is more likely to involve skeletal muscle, and cause thrombocytopenia and severe fibrinogenopenia. KHE mainly involved the dermis, subcutaneous tissue and even deep muscles, and manifested as an infiltrative mass. Magnetic resonance imaging (MRI) showed mass diffuse with high signal on T 2 phase. TA was often a superficial lesion that only involved the subcutaneous fat layer and was lumpy. MRI showed that the high signal was confined to the subcutaneous fat layer. The total effective rate of KHE [KHE(85.79%) vs. TA(91.18%)] and the total effective rate of drug therapy [KHE(85.32%) vs. TA(95.65%)] were lower than those of TA. Conclusions:Compared with TA, KHE has a larger tumor diameter, higher invasiveness, higher risk of complications. In addition, treatment plan was more complicated and treatment response rate was lower in patients with KHE compared with those in patients with TA.