[Activation of HIF-1α/ACLY signaling axis promotes progression of clear cell renal cell carcinoma with VHL inactivation mutation].

Objective: To explore the potential pathogenesis of clear cell renal cell carcinoma (ccRCC) based on the HIF-1α/ACLY signaling pathway, as well as to provide new ideas for the treatment of ccRCC. Methods: Seventy-eight ccRCC cases diagnosed at the First Affiliated Hospital of Soochow University, Suzhou, China were collected. The VHL mutation was examined using exon sequencing. The expression of HIF-1α/ACLY in VHL-mutated ccRCC was evaluated using immunohistochemical staining and further validated in VHL-mutated ccRCC cell lines (786-O, A498, UM-RC-2, SNU-333, and Caki-2) using Western blot. The mRNA and protein levels of ACLY were detected using real-time quantitative PCR and Western blot after overexpression or interference with HIF-1α in ccRCC cell lines. HeLa cells were treated with CoCl2 and hypoxia (1%O2) to activate HIF-1α and then subject to the detection of the ACLY mRNA and protein levels. The potential molecular mechanism of HIF-1α-induced ACLY activation was explored through JASPAR database combined with chromatin immunoprecipitation assay (ChIP) and luciferase reporter gene assay. The effect of HIF-1α/ACLY regulation axis on lipid accumulation was detected using BODIPY staining and other cell biological techniques. The expression of ACLY was compared between patients with ccRCC and those with benign lesions, and the feasibility of ACLY as a prognostic indicator for ccRCC was explored through survival analysis. Results: Exon sequencing revealed that 55 (70.5%) of the 78 ccRCC patients harbored a VHL inactivation mutation, and HIF-1α expression was associated with ACLY protein levels. The protein levels of ACLY and HIF-1α in ccRCC cell lines carrying VHL mutation were also correlated to various degrees. Overexpression of HIF-1α in A498 cells increased the mRNA and protein levels of ACLY, and knockdown of HIF-1α in Caki-2 cells inhibited the mRNA and protein levels of ACLY (P<0.001 for all). CoCl2 and hypoxia treatment significantly increased the mRNA and protein levels of ACLY by activating HIF-1α (P<0.001 for all). The quantification of transcriptional activity of luciferase reporter gene and ChIP-qPCR results suggested that HIF-1α could directly bind to ACLY promoter region to transcriptionally activate ACLY expression and increase ACLY protein level (P<0.001 for all). The results of BODIPY staining suggested that the content of free fatty acids in cell lines was associated with the levels of HIF-1α and ACLY. The depletion of HIF-1α could effectively reduce the accumulation of lipid in cells, while the overexpression of ACLY could reverse this process. At the same time, cell function experiments showed that the proliferation rate of ccRCC cells with HIF-1α knockdown was significantly decreased, and overexpression of ACLY could restore proliferation of these tumor cells (P<0.001). Survival analysis further showed that compared with the ccRCC patients with low ACLY expression, the ccRCC patients with high ACLY expression had a poorer prognosis and a shorter median survival (P<0.001). Conclusions: VHL mutation-mediated HIF-1α overexpression in ccRCC promotes lipid synthesis and tumor progression by activating ACLY. Targeting the HIF-1α/ACLY signaling axis may provide a theoretical basis for the clinical diagnosis and treatment of ccRCC.

[Value of autocrine motility factors in the prediction of the disease progression of PBC- associated hepatocellular carcinoma].

Objective: To clarify the value of autocrine motility factor (ATX) in predicting the disease progression of primary biliary cholangitis (PBC)-associated hepatocellular carcinoma (HCC). Methods: A prospective cohort of 179 newly diagnosed autoimmune liver disease (PBC) patients admitted to the Department of Hepatology at the Fifth Medical Center of the People's Liberation Army General Hospital from January 2016 to January 2018 was selected. All PBC patients received ursodeoxycholic acid (UDCA) treatment and were followed up.The endpoint of the follow-up was the occurrence of primary liver cancer. The relationship between ATX and the clinical characteristics of patients and its significance in predicting disease progression and HCC were analyzed. Results: The peripheral blood ATX level was significantly higher in PBC patients than that of alcoholic cirrhosis (t = 3.278, P = 0.001) and healthy controls (t = 6.594, P < 0.001), but there was no significant difference in ATX levels compared with patients with non-PBC- associated HCC (t = -0.240, P = 0.811). The expression of ATX in liver tissue of PBC patients was significantly higher than that of healthy individuals (Z = -3.633, P < 0.001) and patients with alcoholic cirrhosis (Z = -3.283, P < 0.001), while the expression of ATX in the advanced stage was significantly higher than that in early-stage PBC patients (Z = -2.018, P = 0.034). There was a significant difference in baseline ATX levels between PBC patients without HCC and PBC patients with HCC (228.451 ± 124.093 ng/ml vs. 301.583 ± 100.512 ng/ml, t = 2.339, P = 0.021). Multivariate logistic regression analysis showed that ATX was an independent predictor of PBC progression to HCC (OR = 1.245, 95%CI 1.097-1.413). The baseline peripheral blood ATX level in predicting AUROC of PBC-associated HCC was 0.714, 95%CI 0.597-0.857 and the sensitivity and specificity were 84.6%, and 59.0%, respectively. The optimal cutoff value for predicting serum ATX levels in the occurrence of HCC was 235.254 ng/ml. Conclusion: Patients with PBC have significantly higher levels of ATX expression in their peripheral blood and liver tissue, which can be utilized to assess treatment effectiveness and predict disease progression.

[Preparation and in vitro evaluation of FDM 3D printed theophylline tablets with personalized dosage].

OBJECTIVE: To explore the feasibility of preparing different doses of tablets for personalized treatment by fused deposition modeling (FDM) 3D printing technology, and to evaluate the in vitro quality of the FDM 3D printed tablets. METHODS: Three different sizes of hollow tablets were prepared by fused deposition modeling 3D printing technology with polyvinyl alcohol (PVA) filaments. Theophylline was chosen as the model drug. In the study, 20 mg, 50 mg and 100 mg of theophylline was filled into the cavity of the tablets, respectively. The microscopic morphology of the tablets was observed by scanning electron microscopy (SEM). The weight variation of the tablets was investigated by weighing method. The hardness of the tablets was measured by tablet hardness tester. The contents of the drugs in the tablets were determined by ultraviolet and visible spectrophotometry (UV-Vis), and the dissolution apparatus was used to assay the in vitro drug release of the tablets. RESULTS: The prepared FDM 3D printed tablets were all in good shape without printing defects. And there was no leakage phenomenon. The diameter and thickness of the tablets were consistent with the design. The layers were tightly connected, and the fine structure of the formulation could be clearly observed without printing defects by scanning electron microscopy. The average weight of the three sizes of tablets was (150.5±2.3) mg, (293.6±2.6) mg and (456.2±5.6) mg, respectively. The weight variation of the three sizes of tablets were boss less than 5%, which met the requirements; The hardness of the tablets all exceeded 200 N; The contents of theophylline in the three tablets were 98.0%, 97.2% and 97.9% of the dosage (20 mg, 50 mg and 100 mg), and the relative standard deviation (RSD) was 1.06%, 1.15% and 0.63% respectively; The time for 80% drug released from the three dosage of tablets was within 30 min. CONCLUSION: Three different dosages of theophylline tablets were successfully prepared by FDM 3D printing technology in this study. The exploration may bring beneficial for the preparation of personalized dose preparations. We expect that with the development of 3D printing technology, FDM 3D printed personalized tablets can be used in the clinic as soon as possible to provide personalized treatment for patients.

[Multicenter retrospective study of 38 cases with fumarate hydratase deficiency uterine leiomyoma].

Objective: To investigate the clinicopathological features of fumarate hydratase (FH) deficiency uterine leiomyoma. Methods: The data of 38 patients with FH deficiency uterine leiomyoma were screened and analyzed. The expressions of FH, S-(2-succino)-cysteine (2SC), desmin, p16, p53, CD10 and cell proliferation associated nuclear antigen (Ki-67) proteins were detected by immunohistochemistry, and their clinicopathological features were analyzed retrospectively. Results: (1) Clinical features: the median age of the patients was (42.5±7.4) years old. Twenty-one cases (55%) of them were myomas found in physical examination, and the median maximum diameter of the tumor was 6.0 cm (range: 5.0-7.5 cm); myomectomy was performed in 23 cases (61%), total hysterectomy with or without bilateral appendages in 15 cases (39%); laparoscopic surgery in 27 cases (71%), open surgery in 11 cases (29%); none of the patients had renal cell carcinoma. (2) Histological features: atypical nuclear cells were distributed locally or diffusely, eosinophilic nucleoli and intranuclear inclusion bodies could be seen, glass like globules could be seen in the cytoplasm, nuclear division was 0-4/10 high power field (HPF), and antler like blood vessels and pulmonary edema-like changes could be seen in the stroma. Among 38 patients with FH deficiency uterine leiomyoma, FH was negative in 37 cases (97%), and positive in 1 case (3%); 2SC, desmin, p16, p53, CD10 and Ki-67 showed focal positive expression in 38 cases (100%), including 35 cases (92%) with Ki-67 index<10% and 3 cases (8%) with Ki-67 index ≥10%. (3) Follow-up: 4 cases (11%) recurred, and there was no death. There were significant differences in age, family history, distribution of atypical nuclei and mitosis number between recurrent group and non-recurrent group (all P<0.05). Conclusions: FH deficiency uterine leiomyoma is a rare tumor, which needs pathological examination,immunohistochemical examination and clinical history. Patients younger than 43 years old, with family history, histologically atypical diffuse nuclear distribution and mitotic number ≥3/10 HPF should be alert to the risk of recurrence.

[Relationship between parental reproductive age and the risk of overweight and obesity in offspring].

Objective: To explore the role of parental reproductive age on the risk of overweight and obesity in offspring. Methods: The participants were derived from physical examination data of students aged 6-18 years in seven provinces in China, and questionnaire survey was used to collect demographic characteristics and lifestyle information of the students and their parents. A total of 41 567 children with complete data were included. According to the restricted cubic spline curve, maternal reproductive age was divided into three categories, 14-23, 24-28, and 29-38 years, and paternal reproductive age was divided into 14-23, 24-30, and 31-42 years. Multivariate logistic regression model was used to analyze the association between parental reproductive age and parental nutritional status and the risk of overweight and obesity in offspring. Results: The mean age of 41 567 children was (10.6±3.2) years, and the mean paternal and maternal age were (27.9±4.4) years and (25.8±4.0) years, respectively. The detection rate of overweight and obesity was 23.4%. After adjusting factors of children diet and behaviors, the OR(95%CI)of offspring overweight and obesity in groups of fathers aged 24-30 years and mothers aged 24-28 years was 1.11 (1.04-1.18) and 1.16 (1.08-1.24), respectively. When none parents were overweight and obese, the difference of obesity risk was not statistically significant. When both parents were overweight and obese, the OR(95%CI)of offspring overweight and obesity in groups of fathers aged 24-30 years and mothers aged 14-28 years old was 1.27 (1.00-1.62) and 1.33 (1.07-1.65) respectively. Conclusion: Parental reproductive age and parental overweight and obesity status may both increase the risk of overweight and obesity in offspring, with a significant interaction effect.

[Epidemiological characteristics of infectious diseases of group A, B and C among Chinese students' population].

OBJECTIVE: To analyze the secular trend, ranking change, age- and regional- characteristics of leading infectious diseases among Chinese students population aged 6 to 22 years from 2008 to 2017. METHODS: Data were drawn from the national surveillance from 2008 to 2017, and the participants were students aged from 6 to 22 years who were diagnosed with notifiable infectious diseases. A total of 40 infectious diseases were classified into three groups based on national notifiable infectious diseases classification of A, B and C. The morbidity and mortality rates from infectious diseases were calculated using the numbers of students published by the ministry of education as the denominator. The age- and province-specific infectious diseases with the highest incidence were selected as the leading infectious diseases for analysis. RESULTS: From 2008 to 2017, the incidence rate, the number of cases and the number of deaths of infectious diseases among the boys aged 6-22 years in China were higher than that of the girls, and the overall trend was downward during the study period. The incidence rates in the boys and girls decreased from 2008 to 2015 with decrease of 43.4% and 40.1%, respectively. However, by 2017, the increase rate rebounded with the increases of 47.1% and 53.8%. The rebound trend was mainly caused by the increase of group C of infectious diseases. During the past decade, the top leading three diseases of groups A and B of infectious diseases were viral hepatitis, tuberculosis and dysentery in 2018, respectively, which changed to tuberculosis, scarlet fever and viral hepatitis in 2017. The top leading three infectious diseases in terms of mortality were rabies, tuberculosis, and human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) in 2008, which were transformed into HIV/AIDS, rabies, and tuberculosis in 2017. There was no significantly obvious change in the incidence and mortality order of group C of infectious diseases during the decade. In the analysis of age groups and regions, the leading infectious diseases in groups A and B transferred from viral hepatitis to scarlet fever and tuberculosis, while in group C, mumps and infectious diarrhoea almost always dominated the leading infectious diseases. But in recent years, influenza and hand-foot-and-mouth disease increased significantly in the eastern region. CONCLUSION: During the past decade, China has got remarkable achievements in the prevention and control of children infectious disease. However, the change patterns and characteristics of notifiable infectious diseases among children and adolescents show the urgent need for prevention and control of respiratory tract infectious diseases, HIV/AIDS and other sexually transmitted diseases as well as new emerging infectious diseases in China in the future. This study provides important basis for policy making of Chinese national school-based infectious disease prevention and control mechanism.

[Renal mucinous tubular and spindle cell carcinoma: clinicopathological and whole exome sequencing analyses].

Objective: To explore the clinicopathological characteristics, immunophenotype, diagnosis and differential diagnosis of renal mucinous tubular and spindle cell carcinoma (MTSCC), and to explore the all-exon mutations, microsatellite stability and tumor mutational burden (TMB) in MTSCC cases. Methods: The data of 5 patients with MTSCC that were submitted to the Department of Pathology, First Affiliated Hospital of Soochow University, China from January 2008 to May 2020, were reviewed and analyzed. The whole exome sequencing (WES) was conducted in all patients, while 3 of them were subject to the analyses of microsatellite stability and TMB. Results: Among the 5 patients, 3 were males and 2 were females. They were 37-76 years old. The maximum diameter of the tumor was 3.5-6.0 cm. The borders of the tumors were well defined. Microscopically, MTSCC was characterized by tubular structure, spindle cell and mucinous stroma, and the nuclear grade of tumor cells was overall low. The average follow-up was 15 months, and no recurrence or metastasis was found. Immunohistochemistry showed that all 5 cases were positive for broad-spectrum cytokeratin (CKpan), cytokeratin (CK)7, CK19, vimentin, PAX8, and P504s (varying expression levels), and the Ki-67 positive index was low. The WES of 5 cases showed that NF2 and PTPN14 exhibited higher mutation rates, which were 3/5 and 2/5, respectively. The microsatellite stability analysis indicated that the 3 cases were all microsatellite stable, and the TMB analysis showed that the TMB of the 3 cases were all <9 mut/Mb. Conclusions: MTSCC is a unique, low-grade pleomorphic kidney tumor. The WES analyses suggest that NF2 and PTPN14 have a higher mutation rate, indicating that the occurrence and development of MTSCC may be closely related to the Hippo pathway. The analysis of microsatellite stability indicates that there is no significant relationship between microsatellite stability and MTSCC, and the TMB analysis suggests that MTSCC patients may not benefit from immunotherapy.

[Immune pathogenesis of primary biliary cholangitis].

Primary biliary cholangitis (PBC) is an autoimmune liver disease, mainly characterized by chronic progressive cholestasis. The root cause of PBC is the loss of immune tolerance to autoantigen E2 subunit of pyruvate dehydrogenase (PDC-E2). The unique immunobiological characteristics of intrahepatic bile duct epithelial cells make it an active participant in the pathogenesis of PBC. In recent years, the detection rate of PBC has been increasing year by year, but the clinical situation of ursodeoxycholic acid monotherapy has not changed. Therefore, an in-depth understanding of the immune pathogenesis of PBC will help clinicians better prevent and treat diseases.

Horner Syndrome Caused by Internal Jugular Vein Catheterization.

THE RISK FACTORS, clinical manifestation, and preventive measures of Horner syndrome (HS) caused by internal jugular vein (IJV) catheterization were explored. Electronic databases were searched to identify all case reports of HS caused by IJV catheterization. Two authors independently extracted literature characteristics, IJV catheterization method, clinical manifestations, and prognosis data. Twenty case reports (22 patients in total) were included, 18 of which were written in English and the other 2 in Chinese. Patients were between 19 months to 65 years old, and clinical manifestations included ptosis (n = 22), miosis (n = 21), anhidrosis (n = 8), enophthalmos (n = 3), and hoarseness (n = 1). Onset of HS manifestation ranged from a few hours to 19 days after the procedure. Eight patients with ptosis, 6 patients with miosis, and 1 patient with hoarseness recovered during follow-up. Of the 22 patients, 8 underwent more than 1 attempt of IJV catheterization. Six patients experienced accidental carotid artery puncture or hematoma formation during or after IJV catheterization. Ultrasound guidance was applied in 4 patients and anatomic landmark technique was used in the other 18 patients. The left IJV was catheterized in 3 patients, and the right IJV was catheterized in 19 patients. Repeated attempts of puncture, anatomic landmark technique, accidental carotid artery puncture, or hematoma formation may increase the possibility of HS. Ptosis and miosis are the most common manifestations of HS caused by IJV catheterization.

[Application of molecular analysis in differential diagnosis of ovarian adult granulosa cell tumors].

Objective: To investigate the application value of molecular detection in the differential diagnosis of ovarian adult granulosa cell tumors (AGCT) by analyzing FOXL2, AKT1 and DICER1 mutations in these tumors. Methods: A total of 48 cases of ovarian sex cord-stromal tumor (SCST) were selected from July 2012 to June 2019 in Beijing Obstetrics and Gynecology Hospital, including 21 adult granulosa cell tumors (AGCT), 15 fibromas/fibrothecomas, 8 Sertoli-Leydig cell tumors (SLCT) and 4 other types of ovarian SCST. Genomic DNA was extracted from the formalin-fixed paraffin-embedded tissue sections. Polymerase chain reaction amplification for FOXL2, AKT1 and DICER1 genes was performed, followed by sequencing using capillary electrophoresis. Fisher exact test was used to compare the prevalence difference of FOXL2, AKT1 and DICER1 mutations among the groups. P<0.05 was considered significant. Results: Eighteen of the 21 (85.7%) AGCT harbored FOXL2 mutation. Compared with other SCST (13.0%, 3 of 23; including fibromas/fibrothecomas and SLCT), FOXL2 mutation was significantly higher in AGCT (P<0.001). In addition, FOXL2 mutation was also detected in one fibrothecoma, two SLCT and two gynandroblastomas. DICER1 mutation was identified in four of eight SLCT, and these cases were moderately to poorly differentiated. FOXL2 mutation was found in one SLCT with DICER1 mutation. There was no DICER1 mutation in other ovarian SCST. No AKT1 mutation was detected in all the patients. Conclusions: FOXL2 mutation is a highly specific biomarker for adult AGCT and may be helpful to resolve problematic cases. Diagnosis should also be taken into consideration of the clinical and histological features as FOXL2 mutation is also found in other SCST. The detection of DICER1 mutation is helpful for the differential diagnosis of ovarian SLCT. Synchronous DICER1 and FOXL2 mutation in the SLCT has been observed, and its significance needs to be further studied.

Analysis of Driver-Passenger Relationship and Restoration of Accident Process Based on 3D Laser Scanning Technology.

ABSTRACT: Objective To discuss the application of 3D laser scanner and computer technology in restoration of the accident scene and reconstruction of the accident process, as well as identification of the driver-passenger relationship. Methods The scene of a traffic accident, the accident vehicle and the vehicle of the same type as accident vehicle were scanned using 3D laser scanner. The accident scene, traces and accident vehicle were integrated using computer technology to restore the accident scene, and the accident process was reconstructed and analyzed by combining the characteristics of the body injuries. Results By restoring the accident scene and reconstructing the accident process with 3D laser scanner, it was determined that Wu was in the driving seat at the time of the accident. Conclusion It is more objective and scientific to use 3D laser scanning technology to restore the accident scene, reconstruct the accident process and analyze the moving track of the driver and passengers in the vehicle. It will help to improve the accuracy of forensic identification of road traffic accidents.

Strong anisotropic nodal lines in the TiBe family.

Using first-principles calculations and k·p model analysis, we find that Dirac nodal lines (DNLs) exist in low energy band structures of real materials of the body-centered cubic TiBe family. The nodal lines are protected by mirror reflection symmetries of the systems. The anisotropic electronic state interaction around the Fermi level produces a strong anisotropic quasi-square shape nodal line in the systems. Moreover, all the systems demonstrate drumhead surface states spanning a large energy window showing their potential in terms of high temperature superconductivity. The slight gap induced by spin-orbit coupling (SOC) indicates that materials of the TiBe family are promising candidates for future experimental studies on nontrivial topological semimetals.

[Comparison between hybrid surgery and transabdominal preperitoneal surgery in treatment of irreducible inguinal hernia: A case-control study].

Objective: To compare the effects between hybrid surgery and transabdominal preperitoneal surgery in treatment of irreducible inguinal hernia. Methods: A total of 60 patients who underwent laparoscopic inguinal hernia repair between June 2011 and December 2017 were included in the study. Patients were divided into two group: hybrid surgery group (observation group, n=30) and transabdominal preperitoneal group (control group, n=30). The operation time, intraoperative bleeding, hospital stay, hospital cost and complications were analyzed. Results: The operative time of observation group and control group was 45 (35-65) minutes and 50(35-70) minutes, respectively. Intraoperative blood loss of two groups was 10(5-15) ml and 5(2-10) ml. The length of postoperative hospital stay was 2(1-4) days and 2(1-3) days in the two groups, respectively. And the hospitalization cost of two groups was 9 646 (9 066-11 560) yuan and 9 494(8 989-10 660) yuan, respectively. The intraoperative complications occurred in 4 cases in control group, including 1 case of vas deferens injury, 2 cases of spermatic vessel injury and 1 case of inferior epigastric artery injury. No intraoperative complications occurred in observation group. Perioperative complications in observation group and control group included dysuria (6.7% vs 10.0%), scrotum hematoma (3.4% vs 0%), wound pain (46.7% vs 6.7%) and fever (16.7% vs 20.0%). Twelve months of follow-up was completed in all the patients, and no recurrence or infections occurred in the two groups. The incidence of seroma in observation group and control group was 26.7%, 33.3%, respectively. One case of foreign body sensation and one case of chronic pain occurred in control group. The incidence of perioperative wound pain in patients undergoing hybrid surgery was higher than those undergoing transabdominal preperitoneal surgery (P<0.05), but no statistical differences were observed for other variables between the two groups (all P>0.05). Conclusion: Hybrid surgery is safe and feasible for the treatment of irreducible inguinal hernia. Though with a higher incidence of postoperative acute pain, it may have advantages of avoiding injuries of the vas deferens and spermatic vessels.

[Combined anluohuaxianwan and entecavir treatment significantly improve the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection].

Objective: To explore the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection who received entecavir alone or in combination with anluohuaxianwan for 78 weeks. Methods: Patients with chronic HBV infection were randomly treated with entecavir alone or in combination with anluohuaxian for 78 weeks. Ishak fibrosis score was used for blind interpretation of liver biopsy specimens. The improvement in liver fibrosis condition before and after the treatment was compared. Student's t test and non-parametric test (Mann-Whitney U-Test and Kruskal-Wallis test) were used to analyze the measurement data. The categorical variables were analyzed by Chi-square test method and Spearman's rank correlation coefficient was used to test bivariate associations. Results: Liver fibrosis improvement rate after 78 weeks of treatment was 36.53% (80/219) and the progression rate was 23.29% (51/219). The improvement of liver fibrosis was associated to the degree of baseline fibrosis and treatment methods (P < 0.05). The improvement rate of hepatic fibrosis in patients treated with anluohuaxianwan combined with entecavir at baseline F < 3 (54.74%, 52/95) was significantly higher than that in patients treated only with entecavir (33.33%, 16/48), P = 0.016 and the progression rate of hepatic fibrosis (13.68%, 13/95) was lower than that in patients treated alone (18.75%, 9/48), P = 0.466. In patients with baseline F < 3, the proportion of patients with improved and stable liver fibrosis in the combined treatment group (68.1%, 32/47) was higher than that in the treatment group alone (51.7%, 15/29). Conclusion: Combined anluohuaxianwan and entecavir treatment can significantly improve the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection. Furthermore, it has the tendency to improve the stability rate and reduce the rate of progression of liver fibrosis.

[Helical tomotherapy using simultaneously integrated boost and simultaneous integrated protection technique for unresectable biliary tract cancer].

Objective: To evaluate the safety and efficacy of helical tomotherapy using simultaneously integrated boost and simultaneous integrated protection technique in the treatment of unresectable biliary tract cancers. Methods: The data of 23 patients with unresectable biliary tract cancer who received tomotherapy-based hypofractionated radiotherapy at Comprehensive Cancer Centre of Drum Tower Hospital,the Affiliated Drum Tower Clinical College of Nanjing Medical University between February 2015 and October 2017 were analyzed. There were 10 males and 13 females, aged from 40 to 85 years(median:58 years). Pathological type included intrahepatic cholangiocarcinomas(n=11), gallbladder cancers(n=6),extrahepatic cholangiocarcinomas(n=6). The irradiated sites covered primary tumors and areas of local invasion,including metastatic lymph nodes which were confined to the abdominal or retroperitoneal space. Dose escalation was achieved using simultaneously integrated boost(SIB) technique, and simultaneous integrated protection(SIP)technique was used to protect gastrointestinal tracts and other adjacent organs. Cox regression modal and Kaplan-Meier analysis were used to analyze the associations between patients' characteristics and overall survival(OS). Results: The median total radiation dose was 54 Gy(range: 28-72 Gy)and median biologically effective dose(BED)was 74.4 Gy(range: 37.8-115.2 Gy).The median planning target volume(PTV)was 445.79 cm(3)(range:126.02-950.12 cm(3)). Based on the various PTV,patients received 2.4-6.0 Gy/fraction with 8-28 fractions. The local control rate was 65.2% and the median OS was 11.3 months(range:2.1-31.9 months).The most common cause of death was out-field failure and only 3 patients died of in-field failures. The longest survival was 31.9 months. BED≥70 Gy significantly improved OS,compared to BED<70 Gy(16.8 months vs.5.1 months)(HR=0.146, 95%CI:0.028-0.762, P=0.022). No patients developed grade ≥4 toxicities. Conclusions: Helical tomotherapy-based hypofractionated radiotherapy is effective and well tolerated for patients with unresectable biliary tract cancer. The dose escalation with higher BED could improve the survival for such patients.

[Association between the blood pressure status and nutritional status among Chinese students aged 7-18 years in 2014: based on the national blood pressure reference for Chinese children and adolescents].

OBJECTIVE: To analyze the epidemic situation of blood pressure (BP) status and its association with nutritional status among Chinese children and adolescents aged 7-18 years old in 2014, and to provide important scientific basis for the control of students' hypertension. METHODS: All the subjects aged 7 to 18 years in both genders were sampled from 2014 Chinese national surveys on students' constitution and health. BP status was evaluated according to Chinese national gender-, age- and height-specific references, including hypertension (HTN), elevated hypertension (elevated HTN), isolated systolic HTN (SHTN), isolated diastolic HTN (DHTN) and mix HTN. Their nutritional status was evaluated using the international obesity task force (IOTF) definition, including thinness (severe thinness and moderate thinness), normal, overweight and obesity (severe obesity and moderate obesity). The Logistics method was used to analyze the association between BP status and nutritional status. The population attributable risk (PAR%) of overweight and obesity for BP status was calculated. RESULTS: The prevalence of HTN and elevated HTN among the Chinese children and adolescents aged 7-18 years in 2014 was 14.9% and 9.2%, respectively. And the prevalence of isolated SHTN, isolated DHTN and mix HTN was 3.1%, 8.8% and 3.0%, respectively. The prevalence estimates for HTN differed the greatest for the boys, those in rural, those with high age, those in the East, and those with high BMI. The highest prevalence of HTN was detected in those with severe obesity with 44.2% and 38.8% in the boys and girls respectively, which was 2.8-fold and 3.7-fold than those with normal groups. The negative association was detected between HTN and thinness, but the positive association with overweight and obesity. The PAR% of HTN due to overweight and obesity was 16.2%, and the expected prevalence of HTN was 12.5% if controlling for overweight and obesity. Higher PAR% of isolated SHTN and mix HTN due to overweight and obesity was detected in the Chinese children and adolescents with proportions of 28.7% and 35.1%. CONCLUSION: The prevalence of HTN among the Chinese children and adolescents aged 7-18 years was still high, whose components mainly focused on isolated DHTN. Overweight and obesity can increase the risk of HTN in children and adolescents significantly, especially for isolated SHTN and mix HTN. Controlling for overweight and obesity can decrease the risk of HTN among Chinese national children and adolescents largely, which can play an important role in preventing the occurrence of chronic disease in adults.

[Effects of sodium arsenite exposure on activation and extracellular matrix secretion of human hepatic stellate cells].

Objective: To explore the effects of sodium arsenite (NaAsO(2)) exposure on the activation and extracellular matrix secretion of human hepatic stellate cells, and to provide a theoretical basis for the mechanism study of arsenic induced hepatic fibrosis. Methods: Different doses of NaAsO(2) (0.0, 0.1, 1.0, 10.0, 50.0, 100.0 µmol/L) were exposed to human hepatic stellate cell line (Lx-2) for 24, 48 and 72 huors. CCK-8 assay was used to measure cell viability and IC(50) of NaAsO(2) on Lx-2 was then calculated; According to IC(50) results, 0.000, 1.875, 3.750, 7.500, and 15.000 µmol/L of NaAsO(2) were exposed to Lx-2 cells for 24 hours, besides, 7.500 µmol/L of NaAsO(2) was exposed to Lx-2 cells for 0, 12, 24, 48, and 72 hours, then collected cells and culture supernatant; HSC activation-related protein, including α-smooth muscle actin (α-SMA), and transforming growth factor-ß1 (TGF-ß1) expression levels were detected by Western blot analysis, the main extracellular matrix including laminin (LN) , hyaluronic acid (HA), collagen Ⅳ (COL-Ⅳ) and procollagen Ⅲ(P Ⅲ NP) secretion level was detected by Elisa assay. Results: CCK-8 assay showed that the cell viability of Lx-2 cells were increased obviously at low doses (≤1.0 µmol/L) of arsenic exposure, especially at 48 and 72 h. In contrast, with the increasing doses of arsenic exposure, the survival rate of Lx-2 cell was decreased gradually, and the survival rate of the high-dose (50, 100 µmol/L) arsenic exposure group at 24, 48 and 72 h were significantly lower than 0.0 µmol/L group, P<0.05. The IC(50) of NaAsO(2) on Lx-2 cells at 24, 48, 72 h were calculated as 72.75, 48.19 and 29.95 µmol/L, respectively; The expression levels of HSC activation-related protein showed that, after treated with 1.875, 3.750, 7.500, 15.000 µmol/L NaAsO(2) for 24 h, α-SMA and TGF-ß1 protein level were higher than 0.000 µmol/L group. The increased expression of α-SMA and TGF-ß1 protein were most significant in 7.500 µmol/L NaAsO(2) group (P<0.05). In addition, the expression levels of α-SMA and TGF-ß1 also showed a time-dependent increasing in Lx-2 cells after treated with 7.500 µmol/L NaAsO(2) for 0, 12, 24, 48 and 72 h; Elisa assay showed that after treated with 1.875, 3.750, 7.500, 15.000 µmol/L NaAsO(2) for 24 h, the secretion levels of HA, LN, COL-Ⅳ and PⅢNP were obvious higher than 0.000 µmol/L group (P<0.05). Moreover, the secretion levels of HA, LN, COL-Ⅳ and P Ⅲ NP also showed a time-dependent increased manner in Lx-2 cells after exposed to 7.500 µmol/L NaAsO(2) for 0, 12, 24, 48 and 72 h (P<0.05). Conclusion: NaAsO(2) exposure to Lx-2 cells can upregulate the expression level of HSC activation-related proteins, induce its further activation, then increase ECM secretion level.

[The association between the malnutrition and blood pressure in Chinese Han students aged 7-18 years in 2014].

Objective: This study aimed to explore the association between malnutrition and the level of blood pressure (BP) as well as elevated BP (EBP) in Han students aged 7 to 18 years in China. Methods: 170 037 subjects with normal nutritional status and malnutrition were enrolled in this study from 2014 Chinese National Surveys on Students' Constitution and Health with a multi-stage stratified cluster random sampling framework covering 31 provinces, autonomous regions and municipalities after the exclusion of 44 317 overweight and obese students. According to the standard of "Screening Standard for Malnutrition of School-age Children and Adolescents" (WS/T456-2014), the nutritional status of children were classified into two categories, normal nutritional status and malnutrition containing stunting, mild wasting and moderate severe wasting. The level of BP and prevalence of EBP were compared between students with normal nutritional status and malnutrition. The multivariate logistic regression model was used to analyze the association between malnutrition and EBP. Results: The levels of systolic BP (SBP) and diastolic BP (DBP) in Chinese Han students aged 7-18 years who were non-overweight and non-obesity status were (103.4±12.3) and (64.7±9.5) mmHg (1 mmHg=0.133 kPa), respectively. The prevalence of EBP, systolic EBP and diastolic EBP in Chinese Han malnourished students (N=21 012) were 3.1% (n=649), 1.5% (n=324) and 2.1% (n=445), respectively, which was significantly lower than those (N=148 320) with normal nutritional status (4.5% (n=6 707), 2.6% (n=3 872) and 2.7% (n=3 959)), and the corresponding differences were statistically significant (P<0.05). The OR (95%CI) between malnutrition and EBP was 0.68 (0.62-0.73), which were 0.65 (0.58-0.72) and 0.68 (0.60-0.77) for boys and girls. The OR (95%CI) between EBP and stunting as well as mild wasting and moderate severe wasting were 0.69 (0.62-0.77), 0.63 (0.55-0.72) and 0.79 (0.60-1.05), respectively. Conclusion: The level of BP and prevalence of EBP in Chinese Han students with malnutrition were lower than those with normal nutritional status. The negative correlation existed between malnutrition and EBP in Chinese Han students aged 7 to 18 years.

[Analysis on prevalence of physical fitness and related influencing factors among Chinese Han students aged 13-18 years in 2014].

Objective: To analyze the prevalence of physical fitness among Chinese Han students aged 13-18 years in 2014, and explore related influencing factors. Methods: This study recruited 106 881 Han students aged 13-18 years who had taken physical fitness test from Chinese National Survey on Students' Constitution and Health in 2014. After the exclusion of 1 047 students without complete records of physical fitness test, 105 834 students were included in the final analysis. According to the National Student Physical Health Standard modified in 2014, seven indicators including body mass index, vital capacity, 50-m run, sit-and-reach, standing broad jump, pull-ups/curl-ups and endurance run were tested to calculate the total score of students' physical fitness. Students with score ≥60 were regarded as qualified students. Multivariate non-conditional logistic regression model was used to analyze influencing factors of physical fitness. Results: Among Chinese Han students aged 13-18 years, the total score was 70.1±10.7 and the qualified rate was 83.9% (n=88 813). Boys (83.5% (44 197/52 910)) had a lower qualified rate of physical fitness than girls (84.3% (44 616/52 924)) (P<0.001), and 13-15 age group (86.5% (46 255/53 465)) was higher than the 16-18 age group (81.3% (42 558/52 369)) (P<0.001). Except for 16-18-year-old boys from central region, normal body mass index, eastern region, good socioeconomic status, enough PE class, exercise time ≥1 h/d, homework time ≥2 h/d, TV time <1 h/d were all related to high qualified rates of physical fitness (P<0.05). Conclusion: Chinese Han students aged 13-18 years were in good physical condition. The qualified rates of physical fitness were significantly different by gender and age groups. Nutritional status, region, socioeconomic status, PE class, exercise time per day, homework time per day, and TV time per day were related factors of physical fitness.

[The epidemiological characteristics and related factors of dyslipidemia among children and adolescents aged 6-17 years from 7 provinces in China, 2012].

Objective: To investigate the prevalence and related factors of dyslipidemia among children and adolescents aged 6-17 years in 7 provinces in China. Methods: Using the method of stratified cluster random sampling, 93 primary and secondary schools were selected from Guangdong, Hunan, Liaoning provinces, Shanghai, Chongqing, Tianjin municipalities and Ningxia Hui Autonomous Region in China, 2012. A total of 16 434 students aged 6-17 years old with completed physical and lipid profiles parameters were selected into this study from above 93 primary and secondary schools. Dyslipidemia was determined by the definition of Expert Advice on Prevention and Treatment of Dyslipidemia in Children and Adolescents in 2009. Logistic regression model was used to explore the factors related to dyslipidemia. Results: The prevalence of elevated total cholesterol, elevated triglyceride, elevated low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol, and dyslipidemia was 5.4% (887 cases), 15.7% (2 578 cases), 3.0% (492 cases), 13.5% (2 221 cases) and 28.5% (4 679 cases) among children and adolescents aged 6-17 years, respectively. Sugary drinks intake ≥once per week (OR=1.14; 95%CI: 1.05-1.24), sedentary time >10 hours per day (OR=1.14, 95%CI: 1.01-1.28), overweight (OR=1.50, 95%CI: 1.33-1.70), and obesity (OR=2.62, 95%CI: 2.31-2.96) were significantly associated with the prevalence of dyslipidemia. Conclusion: The prevalence of dyslipidemia was high among children and adolescents aged 6-17 in 7 provinces in China, 2012. Sugary drinks intake ≥once per week, sedentary time >10 hours per day, overweight and obesity might be the risk factors of dyslipidemia among children and adolescents.