[Clinical characteristics of epileptic seizure in neurofibromatosis type 1 in 15 cases].

Objective: To summarize the clinical characteristics of epileptic seizure associated with neurofibromatosis type 1 (NF1). Methods: From January 2017 to July 2023 at Children's Hospital Capital Institute of Pediatrics, medical records of patients with both NF1 and epileptic seizure were reviewed in this case series study. The clinical characteristics, treatment and prognosis were analyzed retrospectively. Results: A total of 15 patients(12 boys and 3 girls) were collected. Café-au-lait macules were observed in all 15 patients. There were 6 patients with neurodevelopmental disorders and the main manifestations were intellectual disability or developmental delay. The age at the first epileptic seizure was 2.5 (1.2, 5.5) years. There were various seizure types, including generalized tonic-clonic seizures in 8 patients, focal motor seizures in 6 patients, epileptic spasm in 4 patients, tonic seizures in 1 patient, absence in 1 patient, generalized myoclonic seizure in 1 patient and focal to bilateral tonic-clonic seizure in 1 patient. Among 14 patients whose brain magnetic resonance imaging results were available, there were abnormal signals in corpus callosum, basal ganglia, thalamus or cerebellum in 6 patients, dilated ventricles of different degrees in 3 patients, blurred gray and white matter boundary in 2 patients, agenesis of corpus callosum in 1 patient and no obvious abnormalities in the other patients. Among 13 epilepsy patients, 8 were seizure-free with 1 or 2 antiseizure medications(ASM), 1 with drug resistant epilepsy was seizure-free after left temporal lobectomy, and the other 4 patients who have received 2 to 9 ASM had persistent seizures. One patient with complex febrile convulsion achieved seizure freedom after oral administration of diazepam on demand. One patient had only 1 unprovoked epileptic seizure and did not have another seizure without taking any ASM. Conclusions: The first epileptic seizure in NF1 patients usually occurs in infancy and early childhood, with the main seizure type of generalized tonic-clonic seizure and focal motor seizure. Some patients have intellectual disability or developmental delay. Most epilepsy patients achieve seizure freedom with ASM.

[A case of intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures caused by PHF21A gene variation and review of literature].

Objective: To discuss the clinical and genetic features of intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures (IDDBCS). Methods: The clinical and genetic records of a patient who was diagnosed with IDDBCS caused by PHF21A gene variation at Children's Hospital Capital Institute of Pediatrics in 2021 were collected retrospectively. Using " PHF21A gene" as the keyword, relevant articles were searched at CNKI, Wanfang Data and PubMed from establishment of databases to February 2023. Clinical and genetic features of IDDBCS were summarized in the combination of this case. Results: An 8 months of age boy showed overgrowth (height, weight and head circumference were all higher than the 97th percentile of children of the same age and sex) and language and motor developmental delay after birth, and gradually showed autism-like symptoms like stereotyped behavior and poor eye contact. At 8 months of age, he began to show epileptic seizures, which were in the form of a series of spastic seizures with no reaction to adrenocorticotropic hormone but a good response to vigabatrin. Physical examination showed special craniofacial appearances including a prominent high forehead, sparse eyebrows, broad nasal bridge, and downturned mouth with a tent-shaped upper lip. The patient also manifested hypotonia. Whole exome sequencing showed a de novo heterogeneous variant, PHF21A (NM_001101802.1): c.54+1G>A, and IDDBCS was diagnosed. A total of 6 articles (all English articles) were collected, involving this case and other 14 patients of IDDBCS caused by PHF21A gene variation. Clinical manifestations were intellectual disability or developmental delay (15 patients), craniofacial anomalies (15 patients), behavioral abnormalities (12 patients), seizures (9 patients), and overgrowth (8 patients). The main pathogenic variations were frameshift variations (8 patients). Conclusions: IDDBCS should be considered when patients show nervous developmental abnormalities, craniofacial anomalies, seizures and overgrowth. PHF21A gene variation detection helps to make a definite diagnosis.

[Comparison of the efficacy of irreversible electroporation and conversional resection for locally advanced pancreatic cancer].

Objective: To compare the short-term and long-term prognosis of irreversible electroporation(IRE) and conversional resection for locally advanced pancreatic cancer(LAPC). Methods: The clinical and pathological data of 98 LAPC patients who underwent IRE or conversional resection at the Department of Pancreatobiliary Surgery,Sun Yat-sen University Cancer Center from August 2015 to December 2020 were retrospectively collected and analyzed.The study comprised of 53 males and 45 females, with age(M(IQR)) of 57.5(13.5)years old(range:20 to 87 years old). Fifty-three patients received IRE treatment(IRE group) and 45 patients received surgical resection(resection group). The differences of clinical and pathological data between both groups were not significant(all P<0.05). The Mann-Whitney U test was used for quantitative data and the χ2 test was used for categorical data.Survival was analyzed using Kaplan-Meier method and compared using Log-rank test. Results: The operation time and intraoperative blood loss were 5.0(2.4)hours and 50(100) ml in the IRE group,respectively,which were significantly less than those of resection group(7.0(3.3)hours and 400(200)ml,both P<0.05).The hospital stay and hospitalization cost were 9.0(3.0)days and 79 154 (83 738) yuan in the IRE group,respectively,which were also significantly less than those in the resection group(16.0(8.5)days and 109 557(37 795)yuan,both P<0.05).The complication rate of IRE group was significantly lower than that of the resection group(18.8% vs. 55.6%,χ2=14.270,P<0.01).The median overall survival(OS) time of IRE group was 28.9 months(95%CI:23.2 to 34.6 months),with the 1-,2-,and 3-year OS rates of 91.6%,61.7%,and 24.6%,respectively.The median survival of OS of resection group was 27.1 months(95%CI:20.9 to 33.3 months),with the 1-,2-,and 3-year OS rates of 81.8%,53.9%,and 30.3%,respectively.There was no significant difference in OS between the two groups(χ2=0.900,P=0.760).The median progression free survival(PFS) time of IRE group was 18.0 months(95%CI:14.7 to 21.3 months),with the 1-,2-,and 3-year PFS rates of 68.3%,29.7%,and 9.9%,respectively.The median survival of PFS of resection group was 11.1 months(95%CI:6.1 to 16.2 months),with the 1-,2-,and 3-year PFS rates of 45.2%,21.9%,and 14.6%,respectively.There was no significant difference in PFS between the two groups(χ2=1.850,P=0.170). Conclusion: IRE can achieve similar survival for LAPC and may has less complications compared to those with conversion resection.

[Predictive value of prognostic inflammatory and tumor score in intrahepatic cholangiocarcinoma].

Objective: To compare and analyze the predictive value of different inflammatory factors and tumor markers in intrahepatic cholangiocarcinoma and to develop a new and effective preoperative prognostic scoring system. Methods: 102 and 72 cases with intrahepatic cholangiocarcinoma who underwent radical surgery in Tianjin Medical University Cancer Institute and Hospital and the Affiliated Hospital of Weifang Medical University were selected as the experimental group and the validation group, respectively. Clinicopathological and follow-up data were collected. Cox proportional-hazards model was used to analyze the predictive value of different prognostic markers. The relationship between prognostic markers and clinicopathological data was analyzed by rank sum test, χ2 or Fisher's exact test. Results: Among the direct inflammatory factors, tumor markers and combined inflammatory factors, prognostic inflammatory index (PII), carbohydrate antigen (CA) 19-9 and systemic inflammation score (SIS) were the most significant predictive factors for postoperative survival outcomes in patients with intrahepatic cholangiocarcinoma. The prognostic inflammatory and tumor score (PITS) was proposed as a new prognostic scoring system for intrahepatic cholangiocarcinoma. PII and CA19-9 were included into the scoring criteria for prognostic stratification of patients. PITS was an independent predictor of tumor-free survival and overall survival in patients with intrahepatic cholangiocarcinoma. Patients with high-grade PITS had later tumor grade and higher frequency of vascular invasion. Conclusion: PITS is highly effective prognostic scoring system for patients with intrahepatic cholangiocarcinoma. In addition, PITS is recommended for preoperative prognostic stratification in patients with intrahepatic cholangiocarcinoma.

Evaluating the Effectiveness of Digital Content Marketing Under Mixed Reality Training Platform on the Online Purchase Intention.

The purpose of this research is to investigate the effectiveness of Digital Content Marketing (DCM) on a Mixed Reality (MR) training platform environment with the consideration of online purchase intention (OPI) through social media. E-commerce today encounters several common issues that cause customers to have reservations to purchase online. With the absence of physical contact points, customers often perceive more risks when making purchase decisions. Furthermore, online retailers often find it hard to engage customers and develop long-term relationships. In this research, a Structural Equation Model (SEM) is proposed to examine the efficacy of DCM from both immediate and long-term OPI. The results examine whether adopting DCM on an MR training platform environment through social media brings positive results in OPI. Empirical research was carried out through online questionnaires collected in 2021 and 2022. A total of 374 questionnaires were qualified for data analysis in this study, conducted with IBM SPSS and AMOS. The results imply that DCM is critical to stimulating both immediate and long-term OPI. The immediate OPI is positively affected by increasing perceived value through MR in DCM. Regarding the long-term OPI, increased customer engagement with DCM under MR environment can cultivate brand trust and significantly affect the long-term OPI.

[Impact of co-infection of streptococcus pneumoniae and pneumococcal vaccination on the clinical outcomes of coronavirus disease 19].

Coronavirus disease 19 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has spread all over the world. Streptococcus pneumoniae as a common pathogen of community-acquired pneumonia shares similar high-risk susceptible populations with COVID-19. Streptococcus pneumoniae co-infection is a key risk factor for severe COVID-19 and death. Pneumococcal vaccination has a beneficial impact on reducing the incidence and mortality of COVID-19. The vaccination rate of streptococcus pneumoniae is still low in China. Streptococcus pneumoniae vaccination may be one of effective strategies in the management of COVID-19 for high-risk population such as the elderly and those who have underlying chronic diseases.

[Induction of hepatocellular carcinoma in B6C3 (F1) mice chronicly exposed to trichloroethylene with enhanced acetylation of histone H2AK9ac and SET expression in the liver tissue].

Objective: To establish an animal model of trichloroethylene (TCE) -induced liver cancer following chronic exposure and to understand the changes in SET expression and histone acetylation, potentially serving as a molecular mechanism for TCE-induced hepatocarcinogenesis. Methods: B6C3 mice at 6 weeks were treated with TCE at a series of doses (500, 1000 and 2000 mg/kg) by gastric gavage, with corn oil used as the negative control and carbon tetrachloride (CCl(4)) as the positive control. The serum and liver were sampled for the determination of biochemical indexes and pathological examination after 56 weeks of chemical exposure. Western blot was used to determine the levels of SET, H2AK9ac and HDAC1 expression. Results: The overall survival rate of the mice in various groups was 90.4% (141/156) , with no statistical difference between groups (P>0.05) . Compared with the negative control, the organ coefficient for the liver in the high dose TCE group and the positive control group were significantly increased (P<0.05) . The levels of ALT, AST, LDH and BUN in the all the three TCE groups and the positive control were significantly higher than those in the negative control (P<0.01) . CREA levels in the 1000 and 2000 mg/kg TCE groups were significantly higher than those in the negative control (P<0.05) . Statistical increases in the incidence of hepatocellular carcinoma and the activities of ALT and AST in various doses of TCE-exposed mice as compared with the control were observed (P<0.01) , in a dose-dependent manner. In the 1000 and 2000 mg/kg of TCE treated mice, levels of SET and H2AK9ac were increased (P<0.05) , while HDAC1 was decreased (P<0.05) , Compared to the tissue adjacent to liver cancer, in the 1000 and 2000 mg/kg TCE groups, the levels of SET were increased (P<0.05) , while HDAC1 was decreased (P<0.05) , and H2AK9ac increased in the 2000 mg/kg group. Conclusion: The hepatocellular carcinoma mouse model induced by chronic exposure to trichloroethylene was successfully established, with enhanced SET protein expression and H2AK9ac in the hepatic tissue.

[Combining intraoperative ultrasound-guided irreversible electroporation with chemotherapy for treating locally advanced pancreatic cancer: a clinical report of 64 cases].

Objective: To examine the safety and clinical efficacy of ultrasound-guided irreversible electroporation (IRE) using the open surgery approach, after induction chemotherapy, in the treatment of locally advanced pancreatic cancer (LAPC) . Methods: The data of 64 LAPC patients who underwent ultrasound-guided IRE using the open surgery approach after induction chemotherapy at Department of Pancreatobiliary Surgery, Sun Yat-sen University Cancer Center from August 2015 to March 2019 were retrospectively analyzed. The study comprised of 30 males and 34 females, with median age of 58.5 years old (range: 34 to 87 years old) , were included in this study.The tumor was located in the pancreatic head and body/tail in 30 and 34 patients, respectively.The largest recorded tumor size was 6.1 cm (≤4.0 cm: n=35; >4.0 cm: n=29) .To create an electric field around the tumor, Two to six probes were parallelly inserted into each patient's tumor, based on the size of the tumor, at a distance of 2 cm apart through the transverse mesocolon in a caudal-to-cranial direction.According to the numerical sequence of patients undergoing ultrasound-guided IRE, the first 15 cases and following 49 patients were categorized as the primary and secondary treatment group, respectively.T text or χ(2) test was analyzed to the data between two groups.The study endpoints were overall survival (OS) and progression free survival (PFS) , which were investigated using Kaplan-Meier method, and their differences were compared using log-rank test. Results: The overall length of hospital stay was (8.9±2.7) days (range: 5 to 20 days) . Four patients were lost to follow-up.The study follow-up rate was 93.8%, with a median follow-up time of 29.3 months (range: 13.5 to 55.7 months) .The median OS and PFS of the entire cohort was 24.6 months (95% CI: 22.0 to 27.3 months) and 12.0 months (95%CI: 8.8 to 15.2 months) , respectively.One month after IRE, abdominal pain was significantly relieved in 95.3% of the patients (t=-28.55, P<0.01) .The rate of complications in the entire cohort was 20.3% and all were classified as grade B.Of them, pancreatic fistula, incisional infection, and upper gastrointestinal hemorrhage were observed in 7, 4, and 2 cases, respectively.The rate of complications for patients in the primary and secondary treatment groups were significantly different (10/15 vs. 6.1%) , respectively (χ(2)=26.01, P<0.01) .Further, two deaths were observed after IRE in the primary treatment group, while none was observed in the secondary treatment group. Conclusions: Ultrasound-guided IRE using the open surgery approach after induction chemotherapy is found to be safe and effective in treating patients with LAPC.However, these findings should be validated in prospective randomized trials before wide clinical application.

[Safety analysis of 12 241 infants inoculated in three sites of diphtheria, tetanus, acellular pertussis and haemophilus influenzae type b combined vaccine in Chaoyang District of Beijing].

Objective: To observe the adverse reactions of Diphtheria, Tetanus, Acellular Pertussis and Haemophilus Influenzae Type b Combined Vaccine conjugate vaccine at the anterolateral thigh muscle, upper arm deltoid muscle and upper gluteal region. Methods: A total of 12 241 infants who were voluntarily vaccinated DTaP-Hib from April 2015 to April 2019 in Beijing were selected for the study. DTaP-Hib vaccine is recommended for 3, 4, 5 months of age for basic immunization and 18 to 24 months of age to strengthen immunization. Subjects were divided into the groups of lateral thigh muscle, the upper arm deltoid and upper gluteal region according to the actual inoculation sites. Adverse reactions were collected within 30 minutes and 7 days after each does of vaccination at different sites and compared between three groups. The incidence of adverse reactions at the three different inoculation sites was compared by Chi-square test. Results: A total of 12 241 infants and toddlers received combined DTaP-Hib and 35 027 doses of DTaP-Hib were investigated. The number and of lateral thigh muscles, upper arm deltoids and gluteal muscles were 3 461 infants and 11 129 doses, 2 659 infants and 7 957 doses, 6 121 infants and 15 941 doses respectively. A total of 2 489 adverse reactions occurred. The incidence of adverse reactions was 7.11%. The incidence of adverse reactions in deltoid muscle of upper arm was 9.69%（771 doses）, which was higher than that in gluteal muscle (7.58%, 1 211 doses) and anterolateral muscle of thigh (4.56%, 507 doses). The incidence of mild, moderate and severe adverse reactions in the upper arm deltoid group were higher than those in the other two groups. The incidence rates were 4.85% (386 doses), 3.77% (300 doses) and 1.07% (85 doses) respectively. The differences between groups were statistically significant（P<0.001）. The total adverse reactions of the three doses of basic immunization and the fourth dose of enhanced immunization had the same trend in different parts. The incidence of adverse reactions was in the order of the upper arm deltoid injection, upper gluteal injection and lateral thigh muscle injection from high to low. The differences were statistically significant (P<0.001). Conclusion: The incidence of adverse reactions of DTaP-Hib vaccination in three different sites was low, which confirmed that the DTaP-Hib vaccination got expected safety regardless of the sites of inoculation. The lateral femoral muscle group had the lowest incidence of adverse reactions, hence it should be preferred as the inoculation site of DTaP-Hib vaccination.

[Analysis of the relationship between the number of lymph nodes examined and prognosis for curatively resected gallbladder carcinoma: a multi-institutional study].

Objective: To examine the role of the number of lymph nodes examined(NLNE) on the prognosis of patients with curatively resected gallbladder carcinoma(GBC). Methods: The clinicopathological data and prognosis of 401 patients with GBC who underwent radical surgery from six institutions of China from January 2013 to December 2017 were analyzed retrospectively. There were 153 males(38.2%) and 248 females(61.8%), with age of (62.0±10.5) years (range: 30-88 years). Fifty-three patients(22.2%) were accompanied by jaundice. All patients underwent radical resection+regional lymphadenectomy.R0 or R1 resection was confirmed by postoperative pathological examination.The different cut-off values of NLNE were determined by the X-tile software, the optimal cut-off values were identified by analyzing the relationship between different cut-off values of NLNE with survival rate. Kaplan-Meier method was used for survival analysis. Univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model. Results: Among the 401 patients enrolled, 135 cases (33.6%) had lymphatic metastasis, of which 98 cases were in N1 stage(24.4%) and 37 cases were in N2 stage(9.2%).A total of 2 794 NLNE were retrieved, with a median count of 6 (5).The median positive lymph nodes count was 0 (1), and the median positive lymph nodes ratio was 0 (IQR, 0-0.2). Since the 12 and 15 were determined as the cut-off values by X-tile, all patients were divided into three groups of 1-11, 12-15 and ≥16.The 3-year survival rate of the three groups was 45.2%, 74.5%, 12.0% respectively, with statistically significant difference between three groups (χ(2)=10.94, P<0.01). The results of multivariate analysis showed that NLNE was an independent prognostic factor for overall survival (P<0.05). Further analysis was performed specifically for subgroup of T stages. For T1b patients, the prognosis of the NLNE with 1-7 group was significantly better than that of the ≥8 group(χ(2)=4.610, P<0.05). For T2 patients, the prognosis of the TLNE ≥7 group was significantly better than that of 1 -6 group (χ(2)=4.287, P<0.05). For T3 and T4 patients, the prognosis of the TLNE with 12 - 15 group was significantly better than that of 1 -11 group (χ(2)=5.007, P<0.01) and ≥16 group (χ(2)=10.158, P<0.01). Conclusions: The NLNE is an independent factor affecting the prognosis of patients with GBC.For patients with stage T1b,8 lymph nodes should be retrieved; for patients with stage T2,extensive dissection of more than 6 lymph nodes can significantly improve the prognosis.For advanced patients (stages T3 and T4), extensive dissection with 12-15 lymph nodes is recommended. However, it fails to get more survival benefits by dissecting more than 16 lymph nodes.

[Association between fruit consumption and stroke in adults in Qingdao: a prospective study].

Objective: To understand the fruit consumption of adults of Qingdao and examine the association between fruit consumption and stroke. Methods: We analyzed baseline data and stroke incidence of the participants who were aged 30-79 years and had been enrolled into the China Kadoorie Biobank (CKB) study from Qingdao city. Cox proportional hazards regression model was conducted to estimate the association of fruit consumption with risk of stroke. Results: A total of 35 509 participants were investgated in the baseline survey. Ratio of male to female was 1∶1.27, and the average age was (50.3±10.2) years. Respondents with higher frequency of fruit consumption were younger, more women, with higher education level and higher income (P<0.05). A total of 1 011 new cases of stroke were observed, with a stroke incidence of 387.63/100 000 person-years. Multivariate Cox regression analysis showed that fruit consumption had a protective effect on stroke incidence. Compared to the respondents who never consumed fruit, respondents who consumed fruit more than 4 days per week had a 44% lower risk of stroke incidence (HR=0.56, 95%CI: 0.50-0.62, P<0.05), and the risk reduced by 46% (HR=0.54, 95%CI: 0.46-0.64, P<0.05) and 42% (HR=0.58, 95%CI: 0.52-0.69, P<0.05) in male and female, respectively. Further adjustment for WC, BMI, SBP and random blood glucose did not change the association. Conclusion: Increasing fruit consumption can effectively decrease the risk of stroke. People should increase fruit consumption advisably to set up reasonable and healthy dietary habits.

Inhibitory effect of TGF-ß gene modified human amniotic mesenchymal stem cells on rejection after xenotransplantation of peripheral nerves.

OBJECTIVE: To explore the inhibitory effect of transforming growth factor-beta (TGF-ß) gene modified human amniotic mesenchymal stem cells on rejection after xenotransplantation of peripheral nerves. MATERIALS AND METHODS: In this study, 6 placentas collected in our hospital were selected as the source of human amniotic mesenchymal stem cells. A total of 60 C57BL/6 experimental mice (mouse sciatic nerves were removed before the experiment) were taken as research objects. Mice were randomly divided into experimental group 1, experimental group 2 and experimental group 3 (xenogenous peripheral nerves were introduced to all experimental groups), and a control group (autologous peripheral nerves were introduced). Among them, TGF-ß gene modified (overexpression) human amniotic mesenchymal stem cells were introduced to experimental group 1; TGF-ß gene modified (inhibition) human amniotic mesenchymal stem cells were introduced to experimental group 2; normal human amniotic mesenchymal stem cells were introduced to experimental group 3; and autologous sciatic nerves were introduced to control group. The messenger ribonucleic acid (mRNA) and protein expressions of the TGF-ß in different human amniotic mesenchymal stem cells were detected by quantitative polymerase chain reaction (qPCR) and Western blotting, respectively. Mouse sciatic nerve function in each group after 2 weeks of procedures was detected via the CatWalk system. Expression level of interleukin-22 (IL-22) in the peripheral tissues of transplanted nerves and blood was detected using immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Its mRNA level was examined via fluorescence quantitative PCR. RESULTS: TGF-ß1 was highly expressed in mice of experimental group 1, but lowly expressed in experimental group 2 relative to that of experimental group 3 (p<0.05). CatWalk test results revealed that the main indexes in experimental group 1 were superior to those in other groups, while the main indexes in experimental group 2 were inferior to those in other groups. According to immunohistochemistry and ELISA results, there were significant differences in the expression level of IL-22 in mice of different treatment groups (p<0.05). IL-22 level was the lowest in control group [(5.05±0.15) pg/mL], followed by that in experimental group 1 [(6.52±0.24) pg/mL], and it was the highest in experimental group 2 [(9.47±0.31) pg/mL]. CONCLUSIONS: Human amniotic mesenchymal stem cells overexpressing TGF-ß can inhibit rejection after xenotransplantation of peripheral nerves.

[Pilot study of the relationship between clinical classification of gallbladder cancer and prognosis: a retrospective multicenter clinical study].

Objectives: To propose a novel clinical classification system of gallbladder cancer, and to investigate the differences of clinicopathological characteristics and prognosis based on patients who underwent radical resection with different types of gallbladder cancer. Methods: The clinical data of 1 059 patients with gallbladder cancer underwent radical resection in 12 institutions in China from January 2013 to December 2017 were retrospectively collected and analyzed.There were 389 males and 670 females, aged (62.0±10.5)years(range:22-88 years).According to the location of tumor and the mode of invasion,the tumors were divided into peritoneal type, hepatic type, hepatic hilum type and mixed type, the surgical procedures were divided into regional radical resection and extended radical resection.The correlation between different types and T stage, N stage, vascular invasion, neural invasion, median survival time and surgical procedures were analyzed.Rates were compared by χ(2) test, survival analysis was carried by Kaplan-Meier and Log-rank test. Results: Regional radical resection was performed in 940 cases,including 81 cases in T1 stage,859 cases in T2-T4 stage,119 cases underwent extended radical resection;R0 resection was achieved in 990 cases(93.5%).The overall median survival time was 28 months.There were 81 patients in Tis-T1 stage and 978 patients in T2-T4 stage.The classification of gallbladder cancer in patients with T2-T4 stage: 345 cases(35.3%)of peritoneal type, 331 cases(33.8%) of hepatic type, 122 cases(12.5%) of hepatic hilum type and 180 cases(18.4%) of mixed type.T stage(χ(2)=288.60,P<0.01),N stage(χ(2)=68.10, P<0.01), vascular invasion(χ(2)=128.70, P<0.01)and neural invasion(χ(2)=54.30, P<0.01)were significantly correlated with the classification.The median survival time of peritoneal type,hepatic type,hepatic hilum type and mixed type was 48 months,21 months,16 months and 11 months,respectively(χ(2)=80.60,P<0.01).There was no significant difference in median survival time between regional radical resection and extended radical resection in the peritoneal type,hepatic type,hepatic hilum type and mixed type(all P>0.05). Conclusion: With application of new clinical classification, different types of gallbladder cancer are proved to be correlated with TNM stage, malignant biological behavior and prognosis, which will facilitate us in preoperative evaluation,surgical planning and prognosis evaluation.

[Genotype-phenotype correlation in patients with alternating hemiplegia of childhood].

Objective: To explore the correlation between ATP1A3 genotype and phenotype in children with alternating hemiplegia of childhood (AHC). Methods: This was a retrospective study. The clinical data and peripheral blood DNA of AHC patients were collected in Peking University First Hospital from August 2005 to December 2017. ATP1A3 gene mutations were screened by Sanger sequencing or next generation sequencing (NGS). AHC patients were divided into difference groups according to different hotspot mutations. SPSS 23.0 was used to analyze the correlation between genotype and phenotype. Variance analysis was used to compare the measurement data between groups. Chi square test was used to compare the categorical data between groups. Kruskal-Wallis test was used to compare the unidirectional ordered data between groups. Least-significant difference(LSD) was used to compare the data between two groups. Results: A total of 119 AHC patients were recruited, including 68 males and 51 females. The onset age of 113 (95.0%) patients was within 18 months. There were 119 cases (100.0%) with hemiplegic seizures, 109 cases (91.6%) with abnormal eyeball movements, 104 cases (87.4%) with dystonia, 31 cases (26.1%) with autonomic neurological symptoms, 31 cases (26.1%) with epileptic seizures and 117 cases (98.3%) with long-term developmental delay. In 113 patients (95.0%) with ATP1A3 gene mutations, 111 were de novo mutation and 2 were genetic mutations. A total of 39 mutation types were found, including 37 missense mutations and 2 deletion mutations. Seventeen of them were novel mutations. The three hotspot mutations were D801N (n=34, 30.1%), E815K (n=20, 17.7%) and G947R (n=13, 11.5%). The age of onset of D801N and E815K were earlier than G947R ((3.1±2.1)and (2.3±2.3)vs.(6.4±7.7) months, P=0.004 and 0.003). The age of first hemiplegic events of D801N and E815K were earlier than G947R((6.4±3.1) and (6.8±3.3) vs. (11.4±10.1) months, P=0.004 and 0.016). More patients with E815K mutations presented epilepsy than those with D801N (P=0.003) and G947R (P=0.001). More patients with E815K mutations presented greater motor and intellectual disability than the patients with D801N (P=0.001) and G947R mutations (P=0.001). Conclusions: ATP1A3 gene is the main causative gene of AHC. Three hotspot mutations, D801N, E815K and G947R, were found. Hotspot mutation E815K is associated with the most severe phenotype, which presented an earlier age at the time of the first paroxysmal manifestation and first hemiplegic event, severer developmental delay and a greater proportion of epilepsy.

[The survival prediction model of advanced gallbladder cancer based on Bayesian network: a multi-institutional study].

Objective: To investigate the clinical value of Bayesian network in predicting survival of patients with advanced gallbladder cancer(GBC)who underwent curative intent surgery. Methods: The clinical data of patients with advanced GBC who underwent curative intent surgery in 9 institutions from January 2010 to December 2015 were analyzed retrospectively.A median survival time model based on a tree augmented naïve Bayes algorithm was established by Bayesia Lab software.The survival time, number of metastatic lymph nodes(NMLN), T stage, pathological grade, margin, jaundice, liver invasion, age, sex and tumor morphology were included in this model.Confusion matrix, the receiver operating characteristic curve and area under the curve were used to evaluate the accuracy of the model.A priori statistical analysis of these 10 variables and a posterior analysis(survival time as the target variable, the remaining factors as the attribute variables)was performed.The importance rankings of each variable was calculated with the polymorphic Birnbaum importance calculation based on the posterior analysis results.The survival probability forecast table was constructed based on the top 4 prognosis factors. The survival curve was drawn by the Kaplan-Meier method, and differences in survival curves were compared using the Log-rank test. Results: A total of 316 patients were enrolled, including 109 males and 207 females.The ratio of male to female was 1.0∶1.9, the age was (62.0±10.8)years.There was 298 cases(94.3%) R0 resection and 18 cases(5.7%) R1 resection.T staging: 287 cases(90.8%) T3 and 29 cases(9.2%) T4.The median survival time(MST) was 23.77 months, and the 1, 3, 5-year survival rates were 67.4%, 40.8%, 32.0%, respectively.For the Bayesian model, the number of correctly predicted cases was 121(≤23.77 months) and 115(>23.77 months) respectively, leading to a 74.86% accuracy of this model.The prior probability of survival time was 0.503 2(≤23.77 months) and 0.496 8(>23.77 months), the importance ranking showed that NMLN(0.366 6), margin(0.350 1), T stage(0.319 2) and pathological grade(0.258 9) were the top 4 prognosis factors influencing the postoperative MST.These four factors were taken as observation variables to get the probability of patients in different survival periods.Basing on these results, a survival prediction score system including NMLN, margin, T stage and pathological grade was designed, the median survival time(month) of 4-9 points were 66.8, 42.4, 26.0, 9.0, 7.5 and 2.3, respectively, there was a statistically significant difference in the different points(P<0.01). Conclusions: The survival prediction model of GBC based on Bayesian network has high accuracy.NMLN, margin, T staging and pathological grade are the top 4 risk factors affecting the survival of patients with advanced GBC who underwent curative resection.The survival prediction score system based on these four factors could be used to predict the survival and to guide the decision making of patients with advanced GBC.

[A multicenter retrospective study for the prognosis of T1b stage gallbladder carcinoma underwent different surgical procedure].

Objective: To explore the prognosis of patients with T1b stage gallbladder carcinoma underwent different surgical procedure. Methods: The clinicopathological data of 97 patients with T1b stage gallbladder carcinoma came from 8 clinical centers from January 2010 to December 2016 and 794 patients who were admitted to the SEER database of USA from January 1973 to December 2014 were analyzed.There were 891 patients including 254 males and 637 females (1.0∶2.5) with age of (69.5±12.0)years. There were 380 patients who were less than 70 years old, 511 patients who were more than 70 years old. And there were 213 patients with the diameter of tumor less than 20 mm, 270 patients with the diameter of tumor more than 20 mm, 408 patients were unclear. There were 196 patients with well differentiation, 407 patients with moderately differentiation, 173 patients with poorly differentiation, 8 patients with undifferentiated, 107 patients were unclear. In the 891 patients with T1b stage gallbladder carcinoma, there were 562 cases accepted the simple cholecystectomy, 231 cases with simple cholecystectomy plus lymphadenectomy, and 98 cases with radical cholecystectomy. The time of follow-up were until June 2017. χ(2) test was used to analyze the enumeration data, rank-sum test was used to analyze the measurement data, the analyses of prognostic factors were used Cox proportional hazards model, the survival analysis was performed using Kaplan-Meier method. Results: The results of Cox proportional hazards model indicated, age, differentiation, surgical procedure were the risk factors of prognostic(1.929(1.594-2.336), P<0.01; 1.842(1.404-2.416), P<0.01; 1.216(0.962-1.538), P<0.01). The results of Kaplan Meier test indicated, the overall survival of T1b stage gallbladder carcinoma were (85.5±3.8)months, the overall survival of patients with simple cholecystectomy were (71.3±4.4)months, the overall survival of patients with cholecystectomy plus lymphadenectomy were(87.6±5.8)months, and the overall survival of patients with radical cholecystectomy were(101.7±9.3)months. The overall survival of patients with cholecystectomy plus lymphadenectomy and radical cholecystectomy were more than simple cholecystectomy(P<0.05). There were 329 patients with Lymph nodes examined in and after operations(231 patients with cholecystectomy plus lymphadenectomy, 98 patients with radical cholecystectomy). There were 265 patients with negative lymph node metastasis, the overall survival were(98.3±4.2)months. There were 64 patients with positive lymph node metastasis, the overall survival were(75.5±3.1)months. The overall survival of 38 patients with cholecystectomy plus lymphadenectomy were(62.7±2.6) months, and 26 patients with radical cholecystectomy were (82.2±3.7)months. The overall survival of patients with radical cholecystectomy were more than cholecystectomy plus lymphadenectomy(P<0.05). Conclusions: The T1b stage gallbladder carcinoma patients with cholecystectomy plus lymphadenectomy or radical cholecystectomy has improved the prognosis comparing with simple cholecystectomy, significantly. When lymph node metastasis occurs, radical cholecystectomy has improved the prognosis comparing with cholecystectomy plus lymphadenectomy.

Jujube leaf green tea extracts inhibits hepatocellular carcinoma cells by activating AMPK.

Here we evaluated the anti-hepatocellular carcinoma activity by the Jujube leaf green tea extracts (JLGTE). We showed that JLGTE exerted anti-proliferative, cytotoxic and pro-apoptotic activities against HepG2 and primary human hepatocellular carcinoma cells. It was however non-cytotoxic to the normal hepatocytes. JLGTE activated AMP-activated protein kinase (AMPK) signaling, which was required for its cytotoxicity against hepatocellular carcinoma cells. Silence of AMPKα1, via targeted short hairpin RNAs or CRISPR-Cas9 genome editing, inhibited JLGTE-induced AMPK activation and HepG2 cell apoptosis. Further, in-activation of AMPK by a dominant negative AMPKα1 (T172A) also alleviated JLGTE's cytotoxicity against HepG2 cells. On the other hand, forced-activation of AMPK by introduction of a constitutively-active AMPKα1 (T172D) mimicked JLGTE's actions and led to HepG2 cell apoptosis. These results suggest that JLGTE inhibits human hepatocellular carcinoma cells possibly via activating AMPK.