[A real-world study on the features of postpartum hepatitis flares in pregnant women with chronic HBV infection].

Objective: To analyze the clinical features of postpartum hepatitis flares in pregnant women with hepatitis B virus (HBV) infection. Methods: A retrospective study was conducted. Patients who met the enrollment criteria were included. Liver function and HBV virology tests were collected from pregnant women with chronic HBV infection at delivery, 6, 24, 36, and 48 weeks after delivery through the hospital information and test system. Additionally, antiviral therapy types and drug withdrawal times were collected. Statistical analysis was performed on all the resulting data. Results: A total of 533 pregnant women who met the inclusion criteria were included, with all patients aged (29.5±3.7) years old. A total of 408 cases received antiviral drugs during pregnancy to interrupt mother-to-child transmission. There was no significant difference in the levels of alanine aminotransferase (ALT, z = -1.981, P = 0.048), aspartate aminotransferase (AST, z = -3.956, P < 0.001), HBV load (z = -15.292, P < 0.001), and HBeAg (z = -4.77, P < 0.001) at delivery in patients who received medication and those who did not. All patients ALT, AST, total bilirubin, direct bilirubin, and albumin showed an upward trend within six weeks after delivery. A total of 231 cases developed hepatitis within 48 weeks after delivery. Among them, 173 cases first showed ALT abnormalities within six weeks postpartum. Conclusion: Hepatitis flare incidence peaked six weeks after delivery or six weeks after drug withdrawal in pregnant women with chronic HBV infection.

[Construction and validation of a nomogram model of early related factors for hepatic insufficiency after hemihepatectomy].

Objectives: To investigate the early related factors for hepatic insufficiency after hemihepatectomy and to construct and validate a nomogram model. Methods: This was a retrospective cohort study.There were 207 patients with liver tumor who underwent hemihepatectomy in the Department of Hepatobiliary Surgery,Cancer Hospital,Chinese Academy of Medical Sciences from October 2016 to December 2022. Using the random number method,patients were randomly divided into a model group(n=166) and a validation group(n=41) according to an 4︰1 ratio. There were 118 males and 48 females in the modeling group,with an age (M(IQR)) of 59.0(13.3) years (range: 22.0 to 81.0 years),42 patients in the group with postoperative liver insufficiency and 124 patients in the group without postoperative liver insufficiency. There were 32 males and 9 females in the validation group, with an age of 54.0(19.0) years (rang: 25.0~81.0 years). The first results of the peripheral blood test of patients within 24 hours after surgery were collected,and the independent related factors for incomplete postoperative liver function were determined by multivariate Logistic regression analysis,and related factors of postoperative incomplete liver function were screened by best subset selection. A nomogram model of the risk of postoperative hepatic insufficiency after hemihepatectomy was constructed using R software,followed by internal and external validation of the model. Results: Multivariate logistic regression analysis showed that elevated D-dimer level and decreased antithrombin Ⅲ (AT-Ⅲ) activity within 24 hours after surgery were independent related factors for the development of postoperative hepatic insufficiency in hemihepatectomized patients. The results of the best subset selection showed that ALT,D-dimer, and AT-Ⅲ activity levels within 24 hours postoperatively were the most relevant factors for postoperative hepatic insufficiency. The R software was applied to build a nomogram prediction model based on the above three indicators in the model set,and the receiver operating characteristic(ROC) curve of the model showed an area under the curve of 0.803 and the calibration curve showed a U-index of -0.012 for the model(P=0.977). The results of the clinical decision analysis and the clinical impact curve indicated that the model had good clinical utility. The internal validation results of the Bootstrap method suggested that the model had reasonable consistency. The area under the ROC curve of the validation group model was 0.806,suggesting that the model had a good generalization prediction ability. Conclusions: The levels of ALT,D-dimer,and AT-Ⅲ activity within 24 hours after hemihepatectomy are valuable indicators for predicting liver insufficiency after hemihepatectomy. The nomogram model is reliable and can be used as an indicator for close postoperative monitoring.

[Effect of postoperative adjuvant chemotherapy on prognosis of patients with intrahepatic cholangiocarcinoma:a multicenter retrospective study].

Objectives: To examine the influence of adjuvant chemotherapy after radical resection on the survival of patients with intrahepatic cholangiocarcinoma(ICC) and to identify patients who may benefit from it. Methods: The clinical and pathological data of 654 patients with ICC diagnosed by postoperative pathology from December 2011 to December 2017 at 13 hospitals in China were collected retrospectively. According to the inclusion and exclusion criteria,455 patients were included in this study,including 69 patients (15.2%) who received adjuvant chemotherapy and 386 patients (84.8%) who did not receive adjuvant chemotherapy. There were 278 males and 177 females,with age of 59 (16) years (M(IQR))(range:23 to 88 years). Propensity score matching (PSM) method was used to balance the difference between adjuvant chemotherapy group and non-adjuvant chemotherapy group. Kaplan-Meier method was used to plot the survival curve,the Log-rank test was used to compare the difference of overall survival(OS) and recurrence free survival(RFS)between the two groups. Univariate analysis was used to determine prognostic factors for OS. Multivariate Cox proportional hazards models were then performed for prognostic factors with P<0.10 to identify potential independent risk factors. The study population were stratified by included study variables and the AJCC staging system,and a subgroup analysis was performed using the Kaplan-Meier method to explore the potential benefit subgroup population of adjuvant chemotherapy. Results: After 1∶1 PSM matching,69 patients were obtained in each group. There was no significant difference in baseline data between the two groups (all P>0.05). After PSM,Cox multivariate analysis showed that lymph node metastasis (HR=3.06,95%CI:1.52 to 6.16,P=0.039),width of resection margin (HR=0.56,95%CI:0.32 to 0.99,P=0.044) and adjuvant chemotherapy (HR=0.51,95%CI:0.29 to 0.91,P=0.022) were independent prognostic factors for OS. Kaplan-Meier analysis showed that the median OS time of adjuvant chemotherapy group was significantly longer than that of non-adjuvant chemotherapy group (P<0.05). There was no significant difference in RFS time between the adjuvant chemotherapy group and the non-adjuvant chemotherapy group (P>0.05). Subgroup analysis showed that,the OS of female patients,without HBV infection,carcinoembryonic antigen<9.6 µg/L,CA19-9≥200 U/ml,intraoperative bleeding<400 ml,tumor diameter>5 cm,microvascular invasion negative,without lymph node metastasis,and AJCC stage Ⅲ patients could benefit from adjuvant chemotherapy (all P<0.05). Conclusion: Adjuvant chemotherapy can prolong the OS of patients with ICC after radical resection,and patients with tumor diameter>5 cm,without lymph node metastasis,AJCC stage Ⅲ,and microvascular invasion negative are more likely to benefit from adjuvant chemotherapy.

[Status and related factors on the drinking behavior among primary and secondary students in China rural middle and western regions in 2019].

Objective: To analyze the daily drinking behavior and related factors of primary and middle school students in the Nutrition Improvement Program for Rural Compulsory Education Students (NIPRCES) pilot regions. Methods: Multi-stage stratified random cluster sampling method was used to select one to three national pilot counties in 22 provinces in central and western China where the NIPRCES was implemented in 2019. According to different feeding patterns, two primary schools and two middle schools were selected as key monitoring schools. One or two classes were selected from grade 3 to grade 9. The student questionnaire was used to collect the basic information and daily drinking behavior. Taking whether the drinking water ≥5 cups every day as the dependent variable, multivariate logistic regression model was used to analyze the related factors of drinking behavior among students. Results: A total of 27 374 students were included. On average, primary and middle school students in the regions where NIPRCES was implemented had 3.9 cups of water every day. Logistic regression model showed that boys (OR=1.230, P<0.001), primary school students (OR=1.379, P<0.001), father worked outside the home (OR=1.169, P<0.001), both parents worked outside the home (OR=1.228, P<0.001), non-resident students (OR=1.142, P<0.001), the school in the village (OR=1.638, P<0.001) or township (OR=1.358, P<0.001), school feeding (OR=1.252, P<0.001), the school building with flush toilets (OR=1.384, P<0.001) and the central regions (OR=1.300, P<0.001) students were more likely to drink ≥5 cups water every day. Conclusion: The water consumption of primary and middle school students in the pilot regions of NIPRCES is low, and their drinking behaviors are affected by many factors.

[Status and influencing factors on the leftover school meals among students the Nutrition Improvement Program for Rural Compulsory Education Students in 2019].

Objective: To analyze the situation and influencing factors of school meals leftover among primary and secondary school students in the area of the Nutrition Improvement Program for Rural Compulsory Education Students, improve the quality of school meals, develop healthy dietary behavior, and reduce food waste. Methods: In 2019, among the 50 monitoring counties that implemented the Compulsory Education Student Nutrition Improvement Program, two primary schools and two junior schools were randomly selected according to different food supply patterns.This study randomly selected one or two classes from grade 3 to grade 9. Basic information and school meals of 26 778 students were collected by using a student questionnaire. Multivariate logistic regression was used to analyze the influencing factors of leftovers rate. Results: 54.93% (14 709) of students wasted school meals, in which the highest rate was the staple food, with the main reason as "not in favor". 11.87% (1 743) of the students wasted school meals 6-7 days a week, with 54.20% (7 957) of students wasted but in less amount. The leftover rate of staple food was the highest (29.78%), followed by vegetables and meat. The main reason of leftovers was that they didn't like this kind of food (33.52%). The rate of school meal waste was higher for girls (OR=1.19,95%CI:1.13-1.25), junior high school students (OR=1.17, 95%CI: 1.11-1.25), resident students (OR=1.06, 95%CI: 1.00-1.12), lower economic level (OR=1.06, 95%CI: 1.00-1.12), parents working outside their houses (OR=1.22, 95%CI: 1.13-1.30), health education classes (OR=1.70, 95%CI: 1.40-2.06), company-based meals (OR=1.89, 95%CI: 1.71-2.07) and school meals were not as good as home food(OR=1.89, 95%CI: 1.78-2.00)(P<0.05). Conclusions: It is common for poor rural primary and middle school students in central and western China to waste school meals, and the reasons were affected by many factors. Reducing food waste requires the joint efforts of individuals, families, schools and society.

[Comparison of follow-up treatment regimens for colorectal cancer liver metastases without objective response to neoadjuvant chemotherapy: direct surgery or surgery after second-line chemotherapy].

Objective: To compare the effect of direct surgery or surgery after second-line chemotherapy for colorectal cancer patients with liver metastases who did not achieve objective remission after neoadjuvant chemotherapy. Methods: A retrospective case cohort study was used. The clinical and pathological data of 107 patients with colorectal cancer liver metastases who did not achieve objective response to neoadjuvant chemotherapy at Department of Hepatobiliary Surgery,Cancer Hospital,Chinese Academy of Medical Sciences from December 2008 to December 2016 were retrospectively collected. There were 71 males and 36 females, median age was 57 years (range: 28 to 79 years). According to the different treatment regimens after neoadjuvant chemotherapy,107 cases were divided into a direct surgery group (direct group,n=65) and an operation after receiving second-line chemotherapy group (second-line group,n=42). The propensity score matching(PSM) of the Logistic regression model was used to match the bilobar distribution of liver metastases and the number of first-line chemotherapy cycles in the two groups of patients. The caliper value was set to 0.10 and the matching ratio was 1∶2. T test, Mann-Whitney U test, χ2 test or Fisher's exat test was used to analyzed the data between the tuo groups, respectively. Survival analysis design was used to investigate the difference in prognosis between the two groups of patients. Results: The follow-up time(M(IQR)) was 56.3(34.3) months (range: 2.1 to 95.0 months),and all patients were followed up. After PSM,there were 28 cases in the direct group and 42 cases in the second-line group, there were no significant differences in whether R0 resection was feasible,blood loss,blood transfusion,postoperative complications and postoperative hospital stay between the two groups (all P>0.05). The 1,3,and 5-year progression-free survival(PFS) rates of the direct group were 40.0%,16.5%,and 11.0%,and the 1,3,and 5-year overall survival(OS) rates were 98.5%,61.2%,and 41.4%,respectively, the second-line group 1,3,5 years PFS rates were 35.7%,14.3%,14.3%,1,3,5-year OS rate were 95.2%,55.1%,44.4%,respectively. The median PFS time of the direct group and the second-line group was 8.5 months and 7.5 months,respectively,and the difference was not statistically significant (P=0.826). The median OS time of the direct group and the second-line group were 33.8 months and 46.9 months,respectively. The difference was not statistically significant(P=0.646).The median PFS time of the direct group and second-line chemotherapy complete remission and partial remission group(CR/PR group) was 10.2 months and 9.1 months,respectively,and the difference was not statistically significant(P=0.669). The median OS time of the direct group and the second-line CR/PR group was 51.0 months and 46.9 months,respectively,and the difference was not statistically significant(P=0.427). The results of survival analysis suggested that major liver resection was an independent prognosis factor for PFS (HR=1.809,95%CI: 1.067 to 3.067,P=0.028) and OS(HR=2.751,95%CI: 1.317 to 5.747,P=0.007). Second-line chemotherapy was not an independent prognostic factor for PFS (HR=0.945, 95%CI:0.570 to 1.567,P=0.828) and OS (HR=0.866,95%CI: 0.468 to 1.602,P=0.646). Conclusions: There is no significant difference in the short-term outcome and long-term prognosis between direct surgery patients and second-line chemotherapy followed by surgery. Second-line chemotherapy is not an independent prognostic factor for colorectal cancer liver metastases patients who fail to achieve objective response after neoadjuvant chemotherapy.

[Stereotactic body radiation therapy for patients with lung and liver oligometastases from colorectal cancer: a phase â ¡ trial].

Objective: To explore the safety and effectiveness of stereotactic body radiation therapy (SBRT) for oligometastases from colorectal cancer (CRC). Methods: This is a prospective, single-arm phase Ⅱ trial. Patients who had histologically proven CRC, 1 to 5 detectable liver or lung metastatic lesions with maximum diameter of any metastases ≤5 cm were eligible. SBRT was delivered to all lesions. The primary endpoint was 3-year local control (LC). The secondary endpoints were treatment-related acute toxicities of grade 3 and above, 1-year and 3-year overall survival (OS) and progression free survival (PFS). Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: Petients from 2016 to 2019 who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Forty-eight patients with 60 lesions were enrolled, including 37 liver lesions and 23 lung lesions. Forty-six patients had 1 or 2 lesions, with median diameter of 1.3 cm, the median biologically effective dose (BED(10)) was 100.0 Gy. The median follow-up was 19.5 months for all lesions. Twenty-five lesions developed local failure, the median local progression free survival was 15 months. The 1-year LC, OS and PFS was 70.2% (95% CI, 63.7%~76.7%), 89.0% (95% CI, 84.3%~93.7%) and 40.4% (95%CI, 33.0%~47.8%). The univariate analysis revealed that planning target volume (PTV) and total dose were independent prognostic factors of LC (P<0.05). For liver and lung lesions, the 1-year LC, OS and PFS was 58.7% and 89.4% (P=0.015), 89.3% and 86.5% (P=0.732), 30.5% and 65.6% (P=0.024), respectively. No patients developed acute toxicity of grade 3 and above. Conclusion: SBRT is safe and effective treatment method for oligometastases from CRC under precise respiratory motion management and robust quality assurance.

[Pay attention to standardized treatment of hepatocellular carcinoma].

Hepatocellular carcinoma is a serious disease that threatens the health of Chinese people. At present,various treatments for hepatocellular carcinoma have their own advantages and disadvantages,which are suitable for its specific individual patient. This article makes a brief review about the importance of standardized treatment for hepatocellular carcinoma. Meanwhile,it should be noticed that standardized staging system is the prerequisite for making a reasonable treatment plan,standardized pathological diagnosis is the basis of comprehensive treatment,standardized treatment is the key to the efficacy,and the multidisciplinary team is the organizational basis for standardized treatment.

[Analysis of genetic characteristics in two Chinese children of type â ¡ Waardenburg syndrome].

Objective: To screen and analyze the mutations of MITF gene in two children of type Ⅱ Waardenburg syndrome (WS2) from different families in Yunnan,China,and to explore the possible molecular pathogenesis. Methods: With informed consent, medical history collection, physical examinations, audiological evaluation, and high resolution computer tomography (HRCT) scan of temporal bone were performed on the two WS2 probands and their family members. Genomic DNA was extracted from peripheral blood of all individuals. The coding regions including all exons, part of introns and promoters of MITF, PAX3, SOX10, SNAI2, END3, ENDRB, and KITLG genes were sequenced by high-throughput sequencing. According to the results of high-throughput sequencing, pathogenic mutations detected in the probands and their parents were verified by Sanger sequencing. Results: The proband 1 carried c.641_643delGAA mutation in the 7th exon of MITF gene, which was a frame-shift mutation resulting in an amino acid change of p.214delR. It was a de novo mutation as the parents of proband 1 showed no variation on this site. The proband 2 carried heterozygous loss of the large fragment ranging from exon 1 to exon 9 of MITF gene, which defected the function of MITF protein. Conclusion: Genetic examinations provide important evidence for diagnosis of Waardenburg syndrome. Heterozygous mutation c.641_643delGAA and heterozygous loss of the large fragment ranging from exon 1 to exon 9 of MITF gene might be the molecular pathogenesis of the two WS2 probands in this study.

[A comparative study of total laparoscopic and laparoscopic-assisted simultaneous resection for colorectal cancer liver metastasis].

Objective: To compare the safety and outcome between total laparoscopic and laparoscopy-assisted synchronous resection for colorectal cancer patients with liver metastases. Methods: The data of patients who underwent total laparoscopic or laparoscopy-assisted simultaneous resection of primary colorectal cancer and liver metastases in our hospital between December 2008 and December 2016 were collected and analyzed. The total laparoscopic surgery patients were matched 1∶2 to the laparoscopy-assisted surgery patients based on the propensity score. 22 patients were classified in the total laparoscopic group and 44 patients were classified in the laparoscopy-assisted group. The intraoperative conditions and postoperative outcomes of the two groups were compared. Results: There was no difference in the preoperative baseline data between the two groups (P>0.05). The median operative time were 317.50 and 267.50 minutes in the total laparoscopic group and the laparoscopy-assisted group, respectively, and the median intraoperative blood loss were 100 and 200 ml, both with no statistically significant differences (P>0.05). There were 1 case of intraoperative blood transfusion in the total laparoscopic group and 5 cases in the laparoscopy-assisted group, with no statistically significant difference (P=0.650). The median postoperative hospital stay in the two groups were 11.0 and 10.0 days, the median postoperative defecation time were 4.0 and 4.0 days and postoperative complication rates were 13.6% and 20.5%, and none of these differences were statistically significant (P>0.05). However, no Clavien-DindoⅡ level and above complications occurred in total laparoscopic group. The median disease-free survival (DFS) were 15.0 and 15.7 months in the total laparoscopic group and the laparoscopy-assisted group, the overall survival (OS) were 25.9 and 37.6 months, respectively, with no statistically significant differences (P>0.05). Conclusion: Laparoscopy-assisted approaches are similar, so the appropriate approach should be chosen according to the clinical condition and surgeon's experience.

[Trend analysis of age of diagnosis for liver cancer in cancer registry areas of China, 2000-2014].

Objective: To investigate trends of mean age of diagnosis for liver cancer during 2000 to 2014, which may provide basic information for making feasible cancer prevention strategies. Methods: Based on the continuous cancer incidence data from 22 cancer registries of China between 1 January 2000 and 31 December 2014, the incidence by birth-cohort (year of birth between 1925 and 1994) and age specific incidence rates were calculated. The incidence of different age groups were also calculated. World Segi's population was used for age standardization. The liner regression model was applied to analyze the changing trend of mean age of diagnosis. Results: In 2014, the incidence rate for population with 80 years older and above was 108.21 per 100 000, whereas the rate for population at 30-39 years old was 5.09 per 100 000. But the mean age of diagnosis for liver cancer showed an increasing trend from 2000 to 2014. For male, it had increased from 58.80 to 62.35 (t=18.70, P<0.001) . For female, it had increased from 64.02 to 68.99 (t=20.50, P<0.001) . After age standardization, the mean age of diagnosis still showed increasing trend. Meanwhile, the proportion of liver cancer in people above 70 years old was 25.05% in 2014, which was higher than that in 2000 (22.49%). Conclusion: The mean age of liver cancer incidence was increasing during 2000-2014.

[Correlation between postoperative neutrophil to lymphocyte ratio and recurrence and prognosis of hepatocellular carcinoma after radical liver resection].

Objective: To investigate the correlation between postoperative peripheral blood neutrophil to lymphocyte ratio (NLR) and recurrence and prognosis of patients with hepatocellular carcinoma (HCC). Methods: The clinicopathological and follow-up data of 344 patients with HCC who underwent radical liver resection from May 2010 to April 2014 were analyzed retrospectively. Results: Of the 344 patients, 104 had early recurrence and 84 had late recurrence. Receiver operating characteristic (ROC) curve analysis showed that the NLR predicted area under the curve (AUC) of early recurrence was 0.622 (P<0.001), the optimal cut-off value was 2.41. The AUC of late recurrence was 0.634 (P=0.001), the optimal cut-off value was 2.15. Cox multivariate analysis showed the serum concentration of hepatitis B surface antigen (HR=2.508, 95% CI: 1.311-4.798), microvascular invasion (HR=2.422, 95% CI: 1.239-4.734), Milan criteria (HR=2.373, 95% CI: 1.427-3.948) and postoperative NLR (HR=2.285, 95% CI: 1.379-3.788) were independent risk factors of early recurrence after HCC resection. Postoperative NLR (HR=2.927, 95% CI: 1.630-5.255), liver cirrhosis (HR=2.531, 95% CI: 1.291-4.962) and serum concentration of albumin (HR=2.257, 95% CI: 1.251-4.073) were independent risk factors of late recurrence after HCC resection. The median recurrence-free survival (RFS) of the 344 patients was 45.0 months, and the median overall survival (OS) was 63.2 months. ROC curve analysis showed that the postoperative NLR predicted 5-year survival AUC was 0.689 (P<0.05), with an optimal cutoff of 2.29. Cox multivariate analysis showed microvascular invasion (HR=2.247, 95% CI: 1.534-3.291), postoperative NLR (HR=2.217, 95% CI: 1.653-2.974), and liver cirrhosis (HR=1.685, 95% CI: 1.168-2.431), Milan criteria (HR=1.679, 95% CI: 1.238-2.277), serum concentration of hepatitis B surface antigen (HR=1.623, 95% CI: 1.102-2.392), serum concentration of albumin (HR=1.43, 95% CI: 1.066-1.918) were independent factors of RFS after HCC resection, while microvascular invasion (HR=3.862, 95% CI: 2.407-6.197), Barcelona staging (HR=2.864, 95% CI: 1.600-5.125), postoperative NLR (HR=2.688, 95% CI: 1.782-4.055), liver cirrhosis (HR=2.039, 95% CI: 1.184-3.514), serum concentration of albumin (HR=1.81, 95% CI: 1.204-2.720) were independent factors of OS. Conclusions: For HCC patients who receive radical liver resection, postoperative NLR ≥2.29 implicates poor prognosis. Moreover, postoperative NLR ≥2.41 suggests early recurrence, while NLR ≥2.15 suggests late recurrence.

[A new prognostic score system of hepatocellular carcinoma following hepatectomy].

Objective: To establish a new scoring system based on the clinicopathological features of hepatocellular carcinoma (HCC) to predict prognosis of patients who received hepatectomy. Methods: A total of 845 HCC patients who underwent hepatectomy from 1999 to 2010 at Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. 21 common clinical factors were selected in this analysis. Among these factors, the cut-off values of alpha-fetoprotein (AFP), alkaline phosphatase (ALP) and intraoperative blood loss were evaluated by using a receiver operating characteristic (ROC) curve analysis.The Kaplan-Meier method and Cox regression model were used to evaluate the independent risk factors associated with the prognosis of HCC patients after hepatectomy. HCC postoperatively prognostic scoring system was established according to the minimum weighted method of these independent risk factors, and divided the patients into 3 risk groups, including low-risk, intermediate-risk and high-risk group. The relapse-free survival (RFS) and overall survival (OS) were compared among these groups. Results: The univariate analysis showed that clinical symptoms, preoperative α-fetoprotein (AFP) level, serum alkaline phosphatase (ALP) level, tumor size, tumor number, abdominal lymph node metastasis, macrovascular invasion or tumor thrombus, extrahepatic invasion or serosa perforation, the severity of hepatic cirrhosis, intraoperative blood loss, the liver operative method, pathological tumor thrombus, intraoperative blood transfusion, perioperative blood transfusion were significantly associated with median RFS of these HCC patients (P<0.05). Alternatively, clinical symptoms, preoperative AFP level, serum ALP level, tumor size, tumor number, abdominal lymph node metastasis, macrovascular invasion or tumor thrombus, extrahepatic invasion or serosa perforation, the severity of hepatic cirrhosis, intraoperative blood loss, the liver operative method, pathological lymphocyte invasion, pathological tumor thrombus, intraoperative blood transfusion, perioperative blood transfusion were significantly associated with the median OS of these HCC patients (P<0.05). The multivariate analysis showed that AFP ≥20 ng/ml, clinical symptoms, tumor diameter ≥5 cm, multiple tumors, macrovascular invasion or tumor thrombus, extrahepatic invasion or serosa perforation, moderate and severe liver cirrhosis, non- anatomic resection were the independent risk factors of RFS and OS (P<0.05). The independent risk factor of RFS was intraoperative bleeding loss ≥325 ml (P<0.05); The independent risk factors of OS were abdominal lymph node metastasis and pathological tumors thrombus (P<0.05). The respective weight of 11 independent factors was used to establish the scoring system (scores range from 0 to 26). In the score system, 0 to 5 points were defined as the low-risk group (286 cases), 6 to 12 points were determined as the intermediate-risk group (503 cases), more than 13 points were classified as the high-risk group (56 cases). The median RFS of the low-risk, intermediate-risk and high-risk group were 80, 27 and 6 months, respectively. The differences were statistically significant (P<0.001). The median OS of the three groups were 134, 51 and 15 months, respectively, and the differences were statistically significant (P<0.001). Conclusion: This new score system provides effective prediction of postoperative prognosis for HCC patients.

[Effect of different anesthetic techniques on the prognosis of hepatocellular carcinoma after hepatectomy].

Objective: To investigate the influence of different anesthetic techniques on the prognosis of hepatocellular carcinoma (HCC)after hepatectomy. Methods: A total of 185 consecutive patients with HCC confirmed underwent surgery in Cancer Hospital, Chinese Academy of Medical Sciences were recruited from January 2006 to January 2008. The patients were assessed as American Society of Anesthesiologists (ASA)Ⅰ-Ⅲ, with body mass index (BMI) (22.8±4.6)kg/m(2). There were 169 males, with an average age of 56 years old and 16 females, with an average age of 53 years old. According to the different anesthesia methods, 185 patients were divided into two groups: total intravenous anesthesia group (TIVA) (n=53) and intravenous-inhalation combined anesthesia group (n=132). Postoperative pain and adverse reactions were compared in recent follow-up, prognosis were compared in long-term follow-up. Results: Recent follow-up showed that the NRS scores 2 hours after operation in TIVA group was 2.0 (0-2.0), whereas those in intravenous-inhalation combined anesthesia group was 3.0 (1.0-3.0). The pain in TIVA groups was significantly lower than that in intravenous-inhalation combined anesthesia group (Z=-3.261, P=0.001). But for 24 hours after operation, the NRS scores in these two groups were 3.0 (2.0-5.0) and 3.0 (3.0-4.0), respectively. There was no significant difference in the two groups (Z=-0.035, P=0.972). In addition, there was no significant difference between the two groups in the incidence of sedation, nausea/vomiting, restlessness and other adverse reactions (all P>0.05). Long-term follow-up indicated that anesthetic techniques have no correlation with HCC prognosis in Kaplan-Meier analysis and Cox's regression analysis. Conclusion: There is no significant effect of two anesthesia methods on the long-term prognosis of HCC.

[Prognostic analysis of colorectal liver metastases treated by surgery combined with intraoperative radiofrequency ablation].

Objective: To investigate the clinical value of intraoperative radiofrequency ablation (RFA) in the treatment of colorectal liver metastasis (CLM). Methods: A retrospectively analysis of 187 patients with CLM who underwent liver resection with or without RFA from January 2009 to August 2016 in Department of Hepatobiliary Surgery, Cancer Hospital, Chinese Academy of Medical Sciences was performed. According to whether RFA was used intraoperatively, patients were divided into resection only group and combined treatment group. The clinical and pathological characteristics of the two groups were compared to explore factors influencing survival and recurrence. Imbalance of background characteristics between the two groups was further overcome by propensity score matching method (PSM). Results: The number of liver metastases (267), simultaneous liver metastases (100%), bilobar involvement (73.3%) and preoperative chemotherapy (93.3%) rates were significantly higher in the combined treatment group than those in the resection only group(471, 74.7%, 42.0% and 63.1%)(all P<0.05). In the combined treatment group, median overall survival (OS) was 25.7 months; and 3-year and 5-year OS were 47.9% and 28.8%, respectively. In the resection only group, the median survival time was 46.9 months; and 3-year and 5-year OS rate was 59.1% and 42.4%, respectively (χ(2)=4.579, P=0.034). Median disease-free survival (DFS) was 5.4 months in the combined treatment group, and 10.1 months in the resection only group (χ(2)=5.399, P=0.023). In multivariate analysis, intraoperative RFA was not an independent prognostic factor for OS and DFS (HR=0.98, 95%CI: 0.47-2.08, P=0.965; HR=1.21, 95%CI: 0.71-2.07, P=0.465). After PSM, the median OS of the resection only and the combined treatment groups were 30.2 and 25.7 months (χ(2)=0.876, P=0.350). The median DFS in the two groups was 5.3 and 4.2 months, respectively (χ(2)=0.199, P=0.650). Conclusion: In patients with similar tumor burden, liver resection combined with intraoperative RFA for unresectable CLM can achieve long-term outcomes similar to hepatectomy alone for resectable CLM.

The WNT/ß-catenin signaling pathway may be involved in granulosa cell apoptosis from patients with PCOS in North China.

INTRODUCTION: Investigate the expressions of WNTs in granulosa cells of PCOS in North China, and explore the possible mechanism. MATERIAL AND METHODS: Patients with PCOS (n=40) and controls without PCOS (n=20) were enrolled into the study. The levels of serum sex hormone were detected by chemiluminescent enzyme immunoassay. RT-qPCR was used to measure mRNA levels of WNT family members (WNT1, WNT3, WNT4, WNT5, sFRP4 and sFRP5). The levels of Bax and Bcl-2 were measured by enzyme-linked immunosorbent assay. RESULTS: The levels of PROG, TES and LH/FSH had difference (p<0.05) on third day of menstrual cycle between PCOS and control groups. After injection of HCG, the levels of LH, E2 and PROG had significant difference (p<0.05). The PCOS group had higher transcript levels of WNT1, WNT3 and WNT4 (p<0.05), compared to controls. The level of secreted frizzled-related protein (sFRP4) was lower level in PCOS patients (p<0.05). In addition, we found a significant reduction of the ß-catenin as well as the downstream targets (survivin and BMP4) (p<0.05). The level of Bax was significantly higher in PCOS group than in the control group (p<0.05). Above all, the WNT/ß-catenin signaling pathway might be involved into granulosa cell apoptosis, which may provide a strategy for clinical treatment.

Treatment of silicosis with hepatocyte growth factor-modified autologous bone marrow stromal cells: a non-randomized study with follow-up.

Pulmonary silicosis is an irreversible and untreatable disease that is characterized by interstitial lesions and perpetual fibrosis in the lungs. This study was performed to determine whether mesenchymal stem cells (MSCs) and hepatocyte growth factor (HGF) could exhibit therapeutic effects on human silicosis. This non-randomized uncontrolled trial comprised four patients with pulmonary silicosis who had developed lung fibrosis and received autologous bone marrow MSCs previously transfected by a vector containing human HGF cDNA (MSCs/HGF). MSCs/HGF were intravenously administered weekly for three consecutive weeks at a dose of 2 x 10(6) cells/kg. Pulmonary function, high kilo-voltage chest X-ray radiography, computed tomography (CT) scan, and peripheral blood lymphocyte subset and serum IgG concentrations were evaluated after cell therapy. The treatment was found to be generally safe. Symptoms such as cough and chest distress gradually ameliorated at six months post-therapy, accompanied by the significant improvement of pulmonary function. The ratios of the peripheral CD4- and CD8- positive cell concentrations were increased (P < 0.05). Furthermore, the serum IgG levels in these patients were decreased and reached the normal range (P < 0.05). CT scans showed partial absorption of the nodular and reticulonodular lesions in the lungs during follow-up of at least 12 months. The effectiveness of this novel regimen observed in these patients suggests that a placebo-controlled clinical trial needs to be developed. This study carries trial registration No. NCT01977131 (ClinicalTrials.gov).

Allopolyploidization is not so simple: evidence from the origin of the tribe Cyprinini (Teleostei: Cypriniformes).

The identification of allopolyploidization events benefits from molecular dating and divergence assessments of progenitor genomes. Information on gene duplications only, either orthologs or paralogs, provides incomplete information. Analyses of mitochondrial DNA yield insights into matrilineal history, which may differ from patrilineal evolution. Two important food and pet fishes, the common carp (Cyprinus carpio) and goldfish (Carassius sp.), appear to have experienced allotetraploidization sometime from 12 to 20 million years ago (Ma). However, much work is necessary to detail the initial polyploidization event. Herein, we use this group of fishes as a model system to investigate competing scenarios for allopolyploidization. We analyze both the nuclear genes encoding growth hormone (GH), recombination activating protein 1 (RAG1) and HOXA2B gene, and the maternal heredited 12 concatenated mitochondrial protein-coding gene in 19 species of cyprinids and use two species in Balitoridae as outgroup taxa. Our analyses clarify the phylogenetic position of the paternal and maternal ancestors for the common carp and goldfish. The estimation of matrilineal divergence (10.71-12.42 Ma) is significantly younger than the dates of the parental ancestor divergedthat obtained by nuclear genes (16.62-19.64 Ma). Analyses of both genomes date the allopolyploidization event of the common ancestor of Cy. carpio and Ca sp. to about 10.71-12.42 Ma, which is most likely represented by maternal divergent time. The divergence of the two copies of the nuclear genes which was more ancient than the maternal markers might have been included the divergence of the progenitors' genome divergence when the allopolyploidization event occurred. Thus, the scenarios of allopolyploidzation for this group of fish can be suggested as the following: the matrilineal common ancestor of species in tribe Cyprinini might have doubled its genome by mating with a paternal ancestor in the subfamily Cyprininae, which was a sister-group that diverged around 4.20-8.93 Ma. Our work provides new evidence for the divergence dates of allopolyploidization within the Cyprinini, and documents the necessity of considering both matrilineal and patrilineal histories when investigating allopolyploidization.

Tempo and mode of recurrent polyploidization in the Carassius auratus species complex (Cypriniformes, Cyprinidae).

Polyploidization is an evolutionarily rare but important mechanism in both plants and animals because it increases genetic diversity. Goldfish of the Carassius auratus species complex can be tetraploids, hexaploids and octaploids. Polyploidization events have occurred repeatedly in goldfish, yet the extent of this phenomenon and its phyletic history are poorly understood. We explore the origin, tempo and frequency of polyploidization in Chinese and Japanese goldfish using both mitochondrial (mtDNA) and nuclear DNA sequences from up to 1202 individuals including the outgroup taxon, Cyprinus carpio. Analyses of de novo nuclear gene data resolve two clusters of alleles and the pattern supports the prior hypothesis of an ancient allotetraploidization for Carassius. Alleles shared by tetraploid and hexaploid individuals indicate recent autoploidizations within the C. auratus complex. Sympatric tetraploids and hexaploids share mtDNA haplotypes and these frequently occur independently within six well-supported lineages and sublineages on a small spatial scale. Gene flow estimates (Fst values) indicate that hexaploids differ only slightly from sympatric tetraploids, if at all. In contrast, allopatric populations of tetraploids and hexaploids differ from one another to a far greater extent. Gene flow between sampled localities appears to be limited. Coalescence-based time estimations for hexaploids reveal that the oldest lineage within any sampled locality is around one million years old, which is very young. Sympatric, recurrent autoploidization occurs in all sampled populations of the C. auratus complex. Goldfish experience polyploidization events more frequently than any other vertebrate.