Objective To explore the microRNA-16 (miR-16) and nuclear-transcription factor-κB1 (NF-κB1) expressions in human brain gliomas and their correlations with cell invasion and growth of malignant gliomas SHG44,U87 and U373.Methods (1) Twenty-nine cases of human glioma tissue samples and 6 normal brain tissues,collected in our hospital from January 2000 to January 2011,were chosen in our study; quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expressions ofmiR-16 and NF-κB1 in these tissues.(2) In vitro cultured U87,U373 and SHG44 cells were divided into blank-control group,nonsense sequence transfected group and miR-16 mimics transfected group; 48 h after the transfection,qRT-PCR was used to detect the expressions of miR-16 and NF-κB1; tmnswell assay was used to observe the cell invasion capability; 72 h after the transfection,Western blotting was employed to detect the protein expressions of NF-κB1,matrix metallopeptidase 9 (MMP-9) and MMP-2.(3) Luciferase reporter assay was used to detect the target regulating role of miR-16 in NF-κB1 gene.(4) U87 cells were used as negative control group,and U87 cells carried stably expressed miR-16 gene were implanted into intracranial and subcutaneous nude mice (U87-miR-16 group); immunofluorescence was used to detect the MMP-9 expression,and immunohistochemical staining was used to detect the protein expressions of Ki-67,NF-κ B1 and MMP-9; subcutaneous tumor volume was measured and the growth curve was drawn.Results (1) The qPCR results showed that the expression of miR-16 in human brain glioma tissues was significantly lower than that in normal brain tissues; and gradually decreased miR-16 expressions were noted in gliomas of graded Ⅰ,Ⅱ,Ⅲ and Ⅳ (P＜0.05); NF-κB1 expression in human brain glioma tissues was significantly higher than that in normal brain tissues; and gradually increased NF-κB1 expressions were noted in gliomas of graded Ⅰ,Ⅱ,Ⅲ and Ⅳ (P＜0.05).(2) As compared with those in the blank-control group and nonsense sequence transfected group,miR-16 mimics transfected group had significantly increased miR-16 expression,decreased NF-κB1 mRNA expression,decreased invasiveness,and decreased protein expressions of NF-κB1 and MMP-9 (P＜0.05).(3) Luciferase reporter assay showed that the fluorescence normalized ratio in the pMIR-NF-κB1 group was signfcaintly higher than that in the pMIR-NF-κB1+pre-miR-16 group (P＜0.05).(4) As compared with the negative control group,the U87-miR-16 group on the 24-42 d of implantation had significantly smaller volume of tumors (P＜0.05),and lower MMP9 expression,and NF-κB1,MMP-9 and Ki-67 expressions (the proliferation index of Ki-67:13.91％ and 32.98％).Conclusion MiR-16 inhibits glioma cell invasion and growth through down-mgulating NF-κB1 and MMP-9 expressions.

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 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 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.

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.

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.

OBJECTIVE: To explore the chronic toxicity and carcinogenicity of paclobutrazol in SD rats. METHODS: Specific pathogen free SD rats at the age of weaning were randomly divided into control group and low-,medium-,and high-dose groups according the body weight,with 120 rats in each group,half male and half female. The study of combined chronic toxicity and carcinogenicity test in rats was carried out in 2 years by feeding the rats with paclobutrazol. The doses in the 4 groups were 0. 0,11. 7,48. 5 and 193. 9 mg·kg~(-1)·d~(-1) for female rats and 0. 0,13. 5,54. 2 and 241. 9 mg·kg~(-1)·d~(-1) for male rats. The body weight of rats was weighted during the experiment. The blood routine,blood biochemistry,organ coefficient and histopathology examinations were performed at the end of paclobutrazol exposure. The mortality and tumor incidence in rats were calculated. RESULTS: The decrease of body weights in female and male rats in dose groups was observed at 1-2 weeks after the experiment,compared with the same sex control group at the same time point( P < 0. 05).At the end of the exposure,the body weights of female and male rats in all three dose groups were lower than that in the same sex rats of control group( P < 0. 05). The mortality rates of female and male rats in the four groups were not significantly different( P > 0. 05). The brain organ coefficients of female rats in the three dose groups were higher than those female rats in the control group( P < 0. 05). The organ coefficients of liver,kidney and ovary of female rats in highdose group were higher than that of female rats in control group( P < 0. 05). The level of total bilirubin in male rats in the three dose groups was lower than that in control group( P < 0. 05). The organ coefficients of brain and lung in male rats in the medium-and high-dose groups were higher than that in the control group( P < 0. 05). The liver organ coefficient in male rats in the high-dose group was higher than that in the control group( P < 0. 05). A total of 244 rats had 402 spontaneous tumors with a tumor incidence rate of 50. 8%(244/480). The incidence of tumor in control,low-,mediumand high-dose groups were 61. 7%( 74/120), 42. 5%( 51/120), 50. 0%( 60/120) and 49. 2%( 59/120)respectively. There was no statistical significance in the incidence of tumors in three dose groups compared with that of the control group. CONCLUSION: Under the dose conditions designed in this study,the lowest observed adverse effect level of paclobutrazol were 11. 7 and 13. 5 mg · kg~(-1)· d~(-1) in females and males respectively. Paclobutrazol was not found carcinogenic to SD rats.

OBJECTIVE: To observe the diagnostic capacity and its influencing factors in the toxicologic pathology diagnostic laboratories in China. METHODS: Inter-laboratory comparison of toxicologic pathology diagnosis was cosponsored by Chinese Society of Toxicology-Toxicologic Pathology Specialty Section and Guangdong Province Hospital for Occupational Disease Prevention and Treatment. Nine digital slices of digestive system lesions were screened as comparison samples,and the reference institution with toxicologic pathology diagnostic laboratories completed the diagnosis within the prescribed time. According to the three grades of “excellent”,“satisfaction”and “dissatisfaction”,the evaluation was carried out.RESULTS: A total of 74 reference institution participated in this comparison,which distributed in 20 provinces and 4 municipalities and 156 pathologists. The reference institutions were mainly distributed in North China,Southern China and East China. There was an average of 2 pathologists per laboratory,and in the quantity of academic title,the junior,intermediate,and senior was 15,70 and 46 persons respectively. Parasitic hepatocyte cysts( 97. 3%),adenocarcinoma of small intestine( 95. 9%) and polyarteritis nodosa of the pancreas( 89. 2%) had the highest rate of “excellent”grade,while the duodenal gland inflammation( 67. 6%),foam cell aggregation in colonic propria( 40. 5%) and hepatoma adenoma( 32. 4%) had the highest rate of dissatisfaction grade in the evaluation of single case. In the overall evaluation,reference laboratories reached the “excellent”grade and the “satisfaction”grade were 78. 4% and 21. 6% respectively.The number of pathologists provided by each reference laboratory had impacts on the overall evaluation level and the single case evaluation( neoplastic lesions) in the evaluation of single case( P < 0. 05). The types of the reference laboratory,the regional distribution and the grade of the academic title had no effect on the diagnostic ability( P > 0. 05). CONCLUSION: The reference laboratory is superior in diagnosing the digestive system lesions in the inter-laboratory comparison activity.The number of pathologists in the reference laboratory is one of the influencing factors of its diagnostic ability.

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.