Objective:To explore the clinical and pathological features and survival outcomes of patients with early-onset intrahepatic cholangiocarcinoma (EOICC).Methods:This is a multicenter, retrospective cohort study. Data of 1 160 intrahepatic cholangiocarcinoma patients undergoing radical resection in 14 tertiary Grade A hospitals in China from January 2010 to November 2021 were retrospectively collected. The cohort included 632 males and 528 females, aged( M (IQR)) 61 (14) years (range: 22 to 93 years). ICC aged ≤50 years at the time of diagnosis was defined as EOICC and >50 years as late-onset intrahepatic cholangiocarcinoma (LOICC). Of these, there were 247 cases in the EOICC group and 913 cases in the LOICC. The clinical and pathological characteristics of both groups were analyzed and compared using the independent sample t-test, Mann-Whitney U test or Kaplan-Meier method. Univariate and multivariate Cox regression models for patient outcomes were constructed and forest graphed. Results:Compared with the patients in the LOICC group, patients in the EOICC group had lower carcinoembryonic antigen levels (2.5(4.0) μg/L vs. 3.1(5.2)μg/L, U=124 899, P=0.009) and CA19-9 level (63.4(524.7)U/ml vs. 77.9(611.3)U/ml, U=120 320, P=0.013), higher levels of ALT (29(35)U/L vs. 24(26)U/L, U=101 214, P=0.013), a lower score of the Eastern US Cooperative Oncology Group (0 score patients: 54.7% vs. 44.1%, χ2=12.472, P=0.014), higher TNM stage ( χ2=11.807, P=0.038), and proportion of lymph node dissection (62.3% vs. 54.1%, χ2=5.355, P=0.021). Patients in the two groups in sex, first diagnosis symptoms, intrahepatic bile duct stone history, nail protein, albumin, total bilirubin, transaminase, liver function Child-Pugh grade, T stage, stage, N stage, preoperative laparoscopic exploration proportion, tumor diameter, vascular invasion proportion, differentiation, margin, intraoperative bleeding, postoperative complications, postoperative hospital days were no statistical significance (all P>0.05). Patients in the EOICC group had better outcomes than the LOICC group (median survival time: 29.7 months vs. 25.0 months, 3-year overall survival: 45.1% vs. 37.8%, P=0.027). Conclusion:EOICC patients are better than LOICC patients in carcinoembryonic antigen, CA19-9, ALT, physical strength status and TNM stage, and the long-term prognosis is also better than LOICC patients.

Objective:To explore the clinical and pathological features and survival outcomes of patients with early-onset intrahepatic cholangiocarcinoma (EOICC).Methods:This is a multicenter, retrospective cohort study. Data of 1 160 intrahepatic cholangiocarcinoma patients undergoing radical resection in 14 tertiary Grade A hospitals in China from January 2010 to November 2021 were retrospectively collected. The cohort included 632 males and 528 females, aged( M (IQR)) 61 (14) years (range: 22 to 93 years). ICC aged ≤50 years at the time of diagnosis was defined as EOICC and >50 years as late-onset intrahepatic cholangiocarcinoma (LOICC). Of these, there were 247 cases in the EOICC group and 913 cases in the LOICC. The clinical and pathological characteristics of both groups were analyzed and compared using the independent sample t-test, Mann-Whitney U test or Kaplan-Meier method. Univariate and multivariate Cox regression models for patient outcomes were constructed and forest graphed. Results:Compared with the patients in the LOICC group, patients in the EOICC group had lower carcinoembryonic antigen levels (2.5(4.0) μg/L vs. 3.1(5.2)μg/L, U=124 899, P=0.009) and CA19-9 level (63.4(524.7)U/ml vs. 77.9(611.3)U/ml, U=120 320, P=0.013), higher levels of ALT (29(35)U/L vs. 24(26)U/L, U=101 214, P=0.013), a lower score of the Eastern US Cooperative Oncology Group (0 score patients: 54.7% vs. 44.1%, χ2=12.472, P=0.014), higher TNM stage ( χ2=11.807, P=0.038), and proportion of lymph node dissection (62.3% vs. 54.1%, χ2=5.355, P=0.021). Patients in the two groups in sex, first diagnosis symptoms, intrahepatic bile duct stone history, nail protein, albumin, total bilirubin, transaminase, liver function Child-Pugh grade, T stage, stage, N stage, preoperative laparoscopic exploration proportion, tumor diameter, vascular invasion proportion, differentiation, margin, intraoperative bleeding, postoperative complications, postoperative hospital days were no statistical significance (all P>0.05). Patients in the EOICC group had better outcomes than the LOICC group (median survival time: 29.7 months vs. 25.0 months, 3-year overall survival: 45.1% vs. 37.8%, P=0.027). Conclusion:EOICC patients are better than LOICC patients in carcinoembryonic antigen, CA19-9, ALT, physical strength status and TNM stage, and the long-term prognosis is also better than LOICC patients.

Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

Objective: To validation and optimization the indicator system of risk assessment for mechanical cuts. Methods: The risk assessment index system of mechanical cutting injury established earlier was used to assess the risk of mechanical cutting injury in 40 cases of mechanical cutting injury registered from January 2015 to December 2017 and 40 similar positions without accidents in the same period. The multiple stepwise regression analysis was used to screen the indicator system, and to adjust the weight coefficient of each index. The total coincidence rate and Kappa value were compared between before and after optimization respectively. Results: The new index system has 3 first-class indicators, 10 second-class indicators and 14 three-class indicators, fewer than the old index system which has 3 first-class indicators, 10 second-class indicators, 34 three-class indicators. There three indicators have revamped in the first-class. The total of coincidence rates of the new and old indicator systems were 67.50% and 90.00%, the difference was statistically significant (P<0.01). The Kappa value were 0.35 and 0.80, respectively. Conclusion The evaluation results with new indicator systems is more consistent with the actual hazard detection the the old indicator systems, and scientific, reasonable and practical, and the indicator system of risk assessment for mechanical cuts can be used for the risk assessment of mechanical cutting injuries.

Objective To investigate the effects of low dose of gamma knife irradiation on the expression of N-methyl-D-aspartate (NMDA) receptor subunits in cortex and hippocampus of epileptic rats. Methods The rats were randomly divided into 4 groups: control group, GK group, pentylenetetrazole (PTZ) group and GK+ PTZ group. The rats were injected intraperitoneally with PTZ to establish the epileptic models. Gamma knife irradiation was performed on bilateral frontal cortex of rats at a peripheral dose of 15Gy. After irradiation, the changes of the seizure and behaviors were observed and recorded. The rats were killed on the 12th week after irradiation, Immunohistochemstry and western blotting were used to detect the relative expression levels of NMDAR subunits (NR1, NR2A, and NR2B) in the cortex and hippocampus. Results There were no epileptic seizures in the control group and the GK group. Compared with the PTZ group, the epileptic seizures of rats in the GK+PTZ group were significantly reduced after low dose gamma knife irradiation (P<0.05). Compared with control group, the protein expression levels of NR1, NR2A and NR2B in the PTZ group increased significantly in the cortex and hippocampus, and so were the positive neurons and their average absorbance value (P<0.05). Compared with PTZ group, the protein expression levels of NR1, NR2A and NR2B of the GK+PTZ group decreased remarkably in the cortex and hippocampus (P<0.05). Protein expression levels of NR1, NR2A and NR2B were not significantly different between control group and GK group (P＞0.05). Conclusion Epileptic rats exhibited an increase in the protein expression levels of NR1, NR2A and NR2B in the cortex and hippocampus while low dose of gamma knife irradiation can decrease expression levels of NMDA receptor subunits in the cortex and hippocampus of epileptic rats, which might represent a possible mechanism underlying the therapeutic effects of gamma knife irradiation on epileptic seizure.

OBJECTIVE:To study the effect and its mechanism of carvedilol on leptin-induced activation and proliferation of LX2 human hepatic stellate cells(HSC-LX2). METHODS:HSC-LX2 with logarithmic growth periods were divided into blank con-trol group,leptin-stimulated group and carvedilol low-concentration,medium-concentration,high-concentration groups(5,10,20μmol/L). Except for the blank control group,other groups were added 0.1 g/L leptin and corresponding concentration of carvedilol. After 24 h,MTT method was used to detect the optical density(OD)value of cells and calculate the proliferation rate. Flow cytom-etry was used to detect the cell cycle and apoptosis. Real-time fluorescence quantitative polymerase chain reaction method was used to detect the α-smooth muscle actin (α-SMA),matrix metalloproteinase inhibition factor 1 (TIMP-1),leptin,leptin receptor mRNA expressions. Western blot method was used to detect phosphorylated Janus kinase 2(p-JAK2),phosphorylated signal trans-duction and transcriptional activator 3 (p-STAT3) protein expressions. RESULTS:Compared with blank control group,OD value of cell was increased in leptin-stimulated group;apoptotic rate was decreased;cells of G0/G1 were decreased;α-SMA,TIMP-1, leptin,leptin receptor mRNA expressions and p-JAK2,p-STAT3 protein expressions were increased (P<0.05). Compared with leptin-stimulated group,OD values of cells were decreased in carvedilol concentration groups;apoptotic rate was increased,and the cells were mainly blocked in G0/G1 phase;α-SMA,TIMP-1,leptin,leptin receptor mRNA expressions and p-JAK2,p-STAT3 protein expressions were decreased(P<0.05)and was concentration-depended(P<0.05). CONCLUSIONS:Carvedilol can inhibit the activation and proliferation of leptin-induced HSC-LX2,promote its apoptosis. The mechanism may associate with down-regulat-ing leptin,leptin receptor gene expression and blocking JAK2/STAT3 signal pathway activation by leptin in cells.

Objective To investigate non-invasive and safe methods for positioning and assessing the functional areas of epilepsy patients secondary to cerebral hemisphere atrophy to reduce postoperative dysfunction.Methods Eight epilepsy patients with cerebral hemisphere atrophy,admitted to our hospital from March 2006 to April 2009,were chosen in our study; magnetoencephalography (MEG) and magnetic resonance diffusion tensor imaging (DTI) were combined to locate the functional areas and assess the functional compensation of these patients.Different surgical methods were adopted according to different results of the patients.All patients were followed up for 12-46 months,averaged 21.6 months.Results MEG could clearly position the cortical sensory,motor,language and visual functional areas of 5 patients,and the other 3 could only be conformed functional areas without clear boundary resulting from their bad cooperation.DTI successfully showed the shape of functional area cortical fibers,which helped the surgery in deciding the extent of resection.Modified hemispherectomy was performed in two patients,multi-lobe resection in five,and temporal lobe resection and hemisphere incision in one; muscles in the contralateral limb of surgery appeared short-term myodynamia weakness and recovery was achieved after rehabilitation exercise.No epileptic seizure was noted in all the patients,enjoying Engle Ⅰ grading.Conclusion Combination of MEG and DTI is a safe,noninvasive method for locating functional areas,could provide security protection for surgical treatment of patients with epilepsy secondary to cerebral hemisphere atrophy.

Objective To investigate the combination application of the intracranial buried electrode and electrical stimulation techniques in excising the epileptogenic zone in the central zone.Methods Seven patients with epileptogenic zone located close to or in the central zone of brain were recruited in the present study.The lone term ECoG monitoring and electrical stimulation of the codex were performed to identify the epileptogenic zone and the central zone of the brain after patients received intracranial electrode implants.The epileptogenic zone was excised with maximum preservation of the cen-tral zone.The patients were follow-up for 6 to 12 months,the outcomes were evaluated based on the Engel's scale and the Karnofsky(KPS)score.Results Seven patients did not experience any seizures and their Engei's and KPS scores were markedly improve after operation.Conclusions Intracranial buried electrodes and cortical electrical stimulation can guide the resection of epileptogenic zone in the central zone.Patients have no seizure and no serious dysfunction after operation and their quality of life was improved markedly.