Objective:To analyze the impact of lymph node dissection on textbook outcomes (TO) and the prognosis of intrahepatic cholangiocarcinoma (ICC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 376 ICC patients who underwent hepatectomy in 4 medical centers, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from December 2011 to December 2017 were collected. There were 242 males and 134 females, aged 57(range, 48-63)years. According to the criteria of TO, patients were classified as two cate-gories, including patients achieving TO and not achieving TO. Measurement data with normal distri-bution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were represented as absolute numbers, and comparison between groups was conducted using the chi-square test, Yates adjusted chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the non-parameter rank sum test. Univariate and multivariate analyses were conducted using the Logistic regression model. The Kaplan-Meier method was used to draw survival curve. Survival analysis was conducted using the Log-rank test. Results:(1) TO situations. Of the 376 ICC patients who underwent hepatectomy, 199 cases achieved TO, including 40 cases with lymph node dissection and 159 cases without lymph node dissection, 177 cases did not achieve TO, including 76 cases with lymph node dissection and 101 cases without lymph node dissection. (2) Influencing factors for TO after hepatectomy of ICC patients. Results of multivariate analysis showed that lymph node dissection, microvascular invasion, nerve invasion and the volume of intraoperative blood loss >800 mL were independent risk factors for achieving TO after hepatec-tomy of ICC patients ( odds ratio=2.22, 2.95, 3.58, 4.09,95% confidence interval as 1.34-3.69, 1.43-6.07, 1.40-9.17, 1.35-12.43, P<0.05). Of the 116 patients with lymph node dissection, 40 cases achieved TO, 103 cases achieved R 0 resection, 38 cases had postoperative complications, 67 cases had delayed hospital stay. The above indicators were 159, 255, 41, 65 of 260 patients without lymph node dissection. There were significant differences in the above indicators between patients with and without lymph node dissection ( χ2=22.90, 15.16, 13.95, 37.78, P<0.05). (3) Follow-up. All the 376 patients were followed up for 19(range, 1-74)months. Of 199 patients achieving TO, the 1-, 2-and 3-year survival rates of 40 patients with lymph node dissection were 54.0%, 36.6% and 26.1%, respectively, versus 67.7%, 42.7% and 34.4% of 159 patients without lymph node dissection, showing no significant difference between them ( χ2=1.89, P>0.05). Of 177 patients not achieving TO, the 1-, 2-and 3-year survival rates of 76 cases with lymph node dissection were 58.9%, 25.7% and 10.3%, respectively, versus 53.0%, 28.5% and 17.2% of 101 cases without lymph node dissection, showing no significant difference between them ( χ2=0.25, P>0.05). Conclusions:Lymph node dissec-tion, microvascular invasion, nerve invasion and the volume of intraoperative blood loss >800 mL are independent risk factors for achieving TO after hepatectomy of ICC patients. Lymph node dissec-tion may increase the postoperative complication rate, prolong the hospital stay and decrease the rate of achieving TO. However, it does not affect the prognosis of patients.

Objective To establish and validate a Nomogram model for predicting the overall survival(OS)of the patients with intrahepatic cholangiocarcinoma(ICC)based on domestic multicenter data,and screen the beneficiaries of adjuvant chemotherapy based on the prediction model.Methods From December 2011 to December 2017,the data of 278 patients with postoperative pathological diagnosis of ICC from 4 medical centers in our country were collected retrospectively COX regression model was used to screen the independent risk factors of OS and constructed a Nomogram model.This model was used to stratify the risk of OS for all patients and to screen the beneficiaries of adjuvant chemotherapy.Results A total of 278 patients were enrolled,and 23 cases(8.3%)received adjuvant chemotherapy.COX multivariate analysis showed that drinking history,ECOG score,method of hepatectomy,lymph node status,number of tumors,and tumor differentiation were independent risk factors for postoperative OS.The Nomogram model had a C-index of 0.690(95%CI:0.646-0.734)in the training cohort and 0.740(95%CI:0.863-0.617)in the validation cohort.According to risk stratification by Nomogram model,in the high-risk group there was a statistically significant difference in survival between adjuvant chemotherapy and non-adjuvant chemotherapy(P=0.033),whereas in the low-risk group,there was no significant difference in survival(P=0.59).Conclusions Nomogram model based on independent risk factors of OS demonstrated excellent predictive capability for survival and could be used to screen,and identify the patients with ICC who benefit from adjuvant chemotherapy.

Objective:To compare the clinical efficacy of laparoscopic and open surgery in the treatment of hepatocellular carcinoma (HCC) at specific sites of liver.Methods:Data of patients with HCC undergoing hepatectomy in Mengchao Hepatobiliary Hospital of Fujian Medical University from September 2014 to May 2019 were retrospective analyzed. A total of 205 patients were enrolled, including 174 males and 31 females, aged (56.7±11.3) years. According to the surgical methods, patients were divided into laparoscopic group ( n=105) and open group ( n=100). The Child-Pugh score, maximum tumor diameter, tumor location, intraoperative blood loss, postoperative complication rate, liver function(glutamate transaminase, alanine transaminase, etc.) and length of hospital stay were compared between the two groups. Postoperative survival and recurrence were followed up. Survival curves and rates were analyzed by Kaplan-Meier and log-rank test. Results:There were no significant differences in Child-Pugh score, maximum tumor diameter, tumor location between the two groups. Compared to the open group, the laparoscopic group had a decreased blood loss [100 (50, 200) ml vs 150 (100, 200) ml], a lower incidence of postoperative complications[7.6%(8/105) vs 17.0%(17/100)], and a shorter hospital stay [(8.6±1.9) days vs (13.0±3.4) days](all P<0.05). The postoperative glutamate transaminase and alanine transaminase levels were lower in the laparoscopic group than those in the open group. The 1, 3, 5-year overall survival and recurrence-free survival were not significantly different between the two groups (χ 2=0.56, 0.21, P=0.456, 0.648). Conclusion:Laparoscopic surgery in the treatment of HCC at specific sites of liver is a safe, feasible and effective procedure.

Objective To analyze result of the external quality assessment for laboratories of toxicological pathology diagnosis in organizations in China. Methods A total of 86 organizations that participated in the 2020-2021 external quality assessment in laboratory of toxicological pathology diagnosis (hereinafter referred to as "reference units") were selected as research subjects using convenient sampling method, and the assessment results were analyzed. Results The median of total score was 92, and the 0-100 percentiles were 64-100 in these 86 reference units. Among these reference units, 76 were rated as excellent, 10 as qualified, with the excellent and the qualified rate of 88.4% and 11.6%, respectively. No reference unit was rated as unqualified. The rates of excellence of the reference units in public health institutions, pharmaceutical research institutions, drug safety evaluation centers and testing companies were 95.7%, 84.2%, 85.7% and 86.7%, and the qualified rates were 4.3%, 15.8%, 14.3% and 13.3%, respectively. The distribution of excellence and qualification among the four types of reference units showed no statistical difference (P>0.05). The distribution of sample scores according to the three grades of poor, good, and excellent were 4.9%, 20.7%, and 74.5% in public health institutions, 8.6%, 23.7%, and 67.8% in pharmaceutical research institutions, 12.5%, 25.0%, and 62.5% in drug safety evaluation centers, and 5.4%, 17.5%, and 77.1% in testing companies. The proportion of excellence unit in public health institutions was higher than that in pharmaceutical research institutions (P<0.05). Conclusion The overall toxicological pathology diagnostic capabilities in China are good, and various types of reference units demonstrate comparable technical capabilities. However, there is a need for standardization of diagnostic terminology.

Objective:To investigate the effects of heme oxygenase-1 (HO-1) on hepatic sinusoidal endothelial cells (LSECs) proliferation, migration, and hepatocyte proliferation.Methods:Eighteen male C57BL/6 mouse aged 6-8 weeks old were underwent partial hepatectomy. Cell proliferation and HO-1 expression in residual liver tissue were detected by immunofluorescence histochemistry at 0 d, 2 d and 4 d after operation. In vitro, LSECs were transfected with adenovirus carrying HO-1 gene (HO-1 group), and the cells were transfected with empty vector adenovirus and the non-transfected cells were used as control. In addition, LSECs from different transfection groups were co-cultured with hepatocyte without contact to evaluate the effect of HO-1 expression on promoting hepatocyte proliferation. Western Blotting and RT-PCR were used to detect the protein and mRNA expression of HO-1, inhibitor of DNA binding and or differentiation (Id1), hepatocyte growth factor (HGF) and Wnt2. Cell proliferation was detected by EdU. The ability of cell migration was detected by Transwell migration assay.Results:Compared with 0 d after hepatectomy, LSECs proliferation and HO-1 expression within LSECs were increased significantly at 4 d after surgery. EdU positive rate of LSECs in HO-1 group (27.20±4.80)% was higher than that in empty vector group (12.47±3.30)% and non-transfected group (15.97±2.50)%. The number of LSECs migration in HO-1 group (258.70±36.56) was higher than that in empty vector group (122.00±38.16) and non-transfected group (107.70±30.01). The protein and mRNA expression level of HO-1, Id1, HGF and Wnt2 in HO-1 group were higher than that in empty vector group and non-transfected group. EdU positive rate of hepatocytes that co-cultured with LSECs in HO-1 group (18.33±2.52) % was higher than that in empty vector group (11.33±1.53)% and non-transfected group (11.7±2.08)%. The differences were statistically significant (all P<0.05). Conclusion:Up-regulation of HO-1 promoted LSECs proliferation and migration of, as well as up-regulation of HO-1 in LSECs enhanced the capacity of LSECs to promote hepatocyte proliferation.

OBJECTIVE: To evaluate the diagnostic ability of toxicity pathology in patho-toxicological testing institutions in China. METHODS: The institutions participated in the 2018 Interlaboratory Comparison Activity of Toxicity Pathology Testing(hereinafter referred to as reference unit) were selected as the research subjects. The heart, spleen, skin, soft tissue, liver and mammary gland of SD rats of different groups in the 2-year carcinogenesis test were selected. The femur, knee joint and nose of Beagle dogs in the 4-week toxicity test and a total of 10 pathological tissues were selected as the comparison samples. The pathological diagnosis was carried out by the pathological diagnostic personnel of the reference unit, and the diagnostic results were reported. The expert appointed by the Toxicology and Pathology Committee of Chinese Toxicology Association compared the diagnostic results with the appointed value. RESULTS: A total of 167 pathological diagnostic personnel from 75 reference units in 24 provinces and municipalities participated in the comparison activity. The reference units were mainly distributed in East China, South China and North China, accounting for 77.3%(58/75). Totally 75 reference units fed back 750 effective diagnostic results. The qualified rates of diagnosis on heart, spleen, skin, soft tissue and breast samples were higher than 60.0%. The qualified rates of diagnosis on femur and knee joint, and nose samples were low(30.7% and 6.7%, respectively). There were 1(1.3%), 46(61.4%) and 28(37.3%) reference units rated as unqualified, qualified and excellent, respectively. CONCLUSION: Most of the testing institutions in China have a high level of patho-toxicological diagnostic ability, that can provide reliable diagnostic results for toxicology safety evaluation tests.

OBJECTIVE: To investigate the chronic toxicity and carcinogenicity of kresoxim-methyl in rats. METHODS: Specific pathogen free SD rats were randomly divided into control group and low-, medium-and high-dose groups according to the body weight of rats, 120 rats in each group with half male and half female rats. The chronic toxicity and carcinogenesis was induced in rats for 104 weeks by oral feeding. The dose of kresoxim-methyl in feed of male and female rats was 0, 75, 300 and 1 200 mg/kg. During the process of experiment, the body weight of rats was weighed. The blood biochemistry, organ coefficient and histopathology were examined at the end of the exposure, and the tumor incidence was calculated. RESULTS: There was no significant difference in mortality of the female or male rats in the four groups(P>0.05). At the 32 nd, 48 th and 56 th week after exposure, the body mass of female rats in the high dose group was lower than that in control group(P<0.05); at the 8 th, 16 th, 24 th and 32 nd week, the body mass of male rats in the high dose group was lower than that in the control group(P<0.05). The organ coefficients of heart and adrenal gland of female rats in the high dose group were higher than those in the control group and the low dose group(P<0.05). The organ coefficient of liver of male rats in the high dose group was lower than that in the control group(P<0.05). The alkaline phosphatase of male rats in the three dose groups was lower than that in the control group(P<0.05). The blood glucose of male rats in the high dose group was higher than that in the control group(P<0.05). The aspartate aminotransferase of male rats in the high dose group was lower than that in the control group(P<0.05). There was no significant difference among the three indexes in female rats(P>0.05). The tumor incidence of the control group and the low, medium and high dose groups were 68.3%, 75.0%, 75.0% and 78.8%, respectively, with no significant difference(P>0.05). The tumor incidence of the female rats was higher than that of the male rats(87.0% vs 61.5%,P<0.01).The tumor multiplicity of the above four groups were 38.3%, 35.8%, 35.0%, 39.8%, respectively, with no significant difference(P>0.05). The tumor multiplicity in female rats was higher than that in male rats(56.9% vs 17.6%,P<0.01). CONCLUSION: The no observed adverse effect level of kresoxim-methyl to female and male SD rats was 24.726 and 20.002 mg/(kg·d), respectively. No carcinogenicity of kresoxim-methyl to SD rats was observed.

OBJECTIVE: To observe the pathological changes of rat silicosis model at different time points. METHODS: The specific pathogen free SD rats were randomly divided into control group and 7, 15, 21, 30, 45, 60, 75 and 90 day model groups based on their body weight, with 5 rats in each group. Non-exposed endotracheal intubation was performed. Silicosis rat model was established by intratracheal instillation of 250 g/L silica suspension in each rat, and 0.9% sodium chloride solution was perfused into the trachea of rats in the control group. The rats in the control group were sacrificed on the 90 th day after exposure, and the model rats in the other 8 groups were sacrificed on the 7 th, 15 th, 21 st, 30 th, 45 th, 60 th, 75 th and 90 th days after the end of exposure. The gross appearance of the lung tissue of rats was observed. The rat lung tissues were stained with hematoxylin-eosin and Masson staining to observe the pathological changes, and Ashcroft score was evaluated. RESULTS: The gross observation showed that the lungs of rats in the model groups had varying degree of gray changes, hardened texture, and spots and nodules on the surface of the lobes. These changes were aggravated with the increase of time after dust exposure. The results of histopathological examination of the lungs showed that the rats developed acute alveolar inflammation, and a large number of macrophages and neutrophils were seen in the lung tissues in the 7 th and 15 th day model groups. Cellular nodules appeared in the lung tissue, and fibrosis appeared in the center of the nodule in the rats of 21 st, 30 th, and the 45 th day model groups; the silicosis nodules appeared in the lung tissues of rats in the 60 th, 75 th, and 90 th day model groups, and the small nodules gradually merged into larger ones. Simultaneously, with the increase of time after dust exposure, the lung tissue of rats gradually showed severe pulmonary fibrosis. The lung organ coefficient and Aschcroft score of rats increased with the increase of time after dust exposure(P<0.01). CONCLUSION: The rat lung changes after dust exposure. Acute alveolar inflammation occurs on the 7 th to 15 th day after dust exposure; cellular nodules develop on the 21 st to 45 th day after dust exposure; silicosis nodules develop on the 60 th to 90 th day after dust exposure. The severity of lung fibrosis after dust exposure showed a time-effect relationship in rats.

Interleukin-27 (IL-27), a heterodimeric cytokine, plays a protective role in diabetes. Ghrelin, a gastric hormone, provides a hunger signal to the central nervous system to stimulate food intake. The relationship between IL-27 and ghrelin is still unexplored. Here we investigated that signal transducer and activator of transcription 3 (STAT3)-mechanistic target of rapamycin (mTOR) signaling mediates the suppression of ghrelin induced by IL-27. Co-localization of interleukin 27 receptor subunit alpha (WSX-1) and ghrelin was observed in mouse and human gastric mucosa. Intracerebroventricular injection of IL-27 markedly suppressed ghrelin synthesis and secretion while stimulating STAT3-mTOR signaling in both C57BL/6J mice and high-fat diet-induced-obese mice. IL-27 inhibited the production of ghrelin in mHypoE-N42 cells. Inhibition of mTOR activity induced by siRNA or rapamycin blocked the suppression of ghrelin production induced by IL-27 in mHypoE-N42 cells. siRNA also abolished the inhibitory effect of IL-27 on ghrelin. IL-27 increased the interaction between STAT3 and mTOR in mHypoE-N42 cells. In conclusion, IL-27 suppresses ghrelin production through the STAT3-mTOR dependent mechanism.

This study analyzed the distribution of high-risk population, the compliance and detected lesions of colorectal cancer screening from the Cancer Screening Program in urban areas of Kunming,Yunnan Province from 2014 to 2017. A total of 127 960 residents were included,of which 14 791 (11.70%) cases were diagnosed with high risk of colorectal cancer by the National Cancer Center High Risk Population Assessment System. A total of 3 484 cases completed colonoscopy clinical screening and the rate of participation was 23.55%. The screening results showed that 592 positive cases were detected, and the positive rate was 17.17%. The detection rates of polyps,adenomas,advanced adenomas,precancerous lesions and colorectal cancer were 16.27%,13.12%,7.18%,7.63% and 0.26%, with 567, 457, 250, 266 and 9 cases, respectively.