Objective To investigate the correlation of variations of ABCB11 gene and primary intrahepatic stone (PIS).Methods The retrospective case-control study was conducted.The clinical data of 319 patients with PIS and 344 healthy controls who were admitted to the Southwest Hospital of the Third Military Medical University between December 2012 and December 2015 were collected.Three hundred and ninteen patients with PIS and 344 healthy controls were respectively allocated into the PIS and control groups.Twenty-seven exons in ABCB11 gene were detected via polymerase chain reaction (PCR) and DNA sanger sequencing.Observation indicators included:(1) variations and genotype frequency distribution of ABCB11 gene in the 2 groups;(2) correlation analysis between variations of ABCB11 gene and clinical data of patients with PIS:preoperative indicators of liver function test,recurrent episodes of cholangitis,preoperative obstructive jaundice,type and recurrence of stones.Comparison between groups in variations and genotype frequency distribution of ABCB11 gene was analyzed by the Logistic regression.The Kruskal-Wallis H test was performed to explore the correlation between genotype of ABCB11 gene and clinical test results of patients with PIS.Correlation between genotype of ABCB11 gene and clinicopathological data of patients with PIS was analyzed by the chi-square test.Results (1) Variations and genotype frequency distribution of ABCB11 gene in the 2 groups:whole-exome sequencing results showed that synonymous mutations of rs3815675,rs2287616 and rs497692 and missense mutations of rs2287617,rs2287622 and rs118109635 in the PIS group were respectively detected in exon 4,9,24 and 9,13,21.CT genotype frequency of rs118109635 was 4.70％(15/319) in the PIS group and 1.45％ (5/344) in the control group,respectively,with a statistically significant difference [OR=3.49,95％ confidence interval (CI):1.17-10.40,P＜0.05].GG and AG+GG genotype frequency of rs497692 were 46.08％ (147/319),87.46％ (279/319) in the PIS group and 37.79％ (130/344),79.36％ (273/344) in the control group,respectively,with a statistically significant difference (OR=1.73,1.65,95％ CI:1.05-2.83,1.04-2.61,P＜0.05).(2) Correlation analysis between variations of ABCB11 gene and clinical data of patients with PIS:levels of glutamyl-transpeptidase (GGT),alkaline phosphatase (ALP) and direct bilirubin (DBil) in the PIS group were 167 U/L (range,7-1 968 U/L),166 U/L (range,36-1 527 U/L),4 μmol/L(range,1-272 μmol/L) in the CC genotype of rs118109635 and 433 U/L(range,17-864 U/L),232 U/L (range,85-613 U/L),6 μmol/L(range,2-173 μmol/L) in the CT genotype of rs118109635,respectively,with a statistically significant difference (H=6.025,5.879,8.056,P＜0.05).Globulin level of PIS group was respectively 32 g/L (range,20-40 g/L),34 g/L(range,17-50 g/L) and 33 g/L(range,14-49 g/L) in the AA,AG and GG genotype of rs497692,respectively,with a statistically significant difference (H=12.119,P＜0.05).Of 81 patients with recurrence of PIS,GG and GA genotypes of rs2287617 were detected in 78 and 3 patients,respectively,with a statistically significant difference (x2=5.367,P＜0.05);TT,TC and CC genotypes of rs2287622 were detected in 12,39 and 30 patients,respectively,with a statistically significant difference (x2=6.153,P＜0.05).Of 127 patients with obstructive jaundice,116 and 11 patients had CC and CT genotypes of rs118109635,respectively,with a statistically significant difference (x2=7.381,P＜0.05);11,43 and 73 patients had AA,AG and GG genotypes of rs497692,respectively,with a statistically significant difference (x2 =11.364,P＜0.05).Conclusion There is a correlation between rs118109635 and rs497692 of ABCB11 gene and PIS,meanwhile,the above variation loci are associated with obstruction of biliary tract and cholestasis.

AIMTo study the characteristics of neural information encoding of the epileptic networks involved caudate-putamen(CPu) and the hippocampi induced by tetanization of the right CPu in rats.

METHODSExperiments were performed on 59 SD rats. Acute or chronic tetanization of the right CPu (ATRC or CTRC) (60Hz,0.4-0.6 mA, 2 s) was used to induce rat epilepsy.

RESULTS(1) The bursting or primary unit afterdischarges of single neurons were asymmetric in dual hippocampi induced by the ATRC. (2) Continuous sharp waves were observed in ipsilateral or contralateral CPu induced by the CTRC. The oscillatory network seizures with phase shift appeared between two sharp waves in ipsilateral CPu. The frequency of oscillatory waves was negatively correlated with the time and fluctuated from 70 Hz to 110 Hz, then to 35 Hz, and finally to 30 Hz. (3) In the contralateral side primary network after discharges in the CPu were induced by the CTRC. Therefore, the characteristic primary network afterdischarges could be shifted from the CPu or to the HPC, but amplified. On the other hand, HPC sharp waves could be depressed when the CPu network seizures occurred.

CONCLUSIONThe reestablishment of CPu-hippocampal epileptic networks could be transhemispherically promoted by over-activation of the right CPu network, in which bilateral hippocampal neuronal network and CPu neural network were involved in some particular pathophysiological information encoding.

Animals ; Caudate Nucleus ; metabolism ; Epilepsy ; physiopathology ; Hippocampus ; metabolism ; Male ; Neurons ; metabolism ; Putamen ; metabolism ; Rats ; Rats, Sprague-Dawley

AIMThe electrographic and behavioral kindling effects were induced by chronic tetanization of the right caudate-putamen (CPu) to study the target-behavior expression involved in the CPu or hippocampus (HPC) network abnormalities.

METHODSExperiments were performed on 58 SD rats. Tetanization (60Hz,0.4 - 0.6mA, 2s) was delivered into the CPu or the HPC, once a day, for 7-12 days. Animal behaviors were observed every day and depth electrographs were recorded at the beginning or at the end of the experiments.

RESULTSChronic tetanization of the CPu or of the HPC induced: (1) Rhythmic sharp waves in the CPu and paroxysmal epileptiform events in the HPC electrographs. (2) Primary behavioral seizures, secondary behavioral seizures, and kindling effects, including wet dog shakes (WEDS), rearing, face washing, immobility, chewing and head nodding. (3) Lower rate of primary WEDS (P < 0.01), and higher rate of secondary WEDS (P < 0.01) in the CPu-tetanized rats. (4) Longer silent period of behavioral seizures before kindling appeared in the CPu-tetanized rats.

CONCLUSIONKindling effects in the CPu-tetanized rats resembles those in the HPC-tetanized rats. The CPu might participate in the origin of epileptic focus and be involved in reestablishment of limbic epileptic networks, which may be responsible for the target-behavioral seizures.

Animals ; Behavior, Animal ; Caudate Nucleus ; Electric Stimulation ; Epilepsy ; physiopathology ; Kindling, Neurologic ; Male ; Rats ; Rats, Sprague-Dawley ; Seizures ; physiopathology

Objective: To analyze the status of occupational medical examination (OME) institutions in Guangdong Province and the critical control points affecting their future development. Methods: A total of 211 OME institutions registered in Guangdong Province were selected as the research subjects. Their current statue was investigated, and the risk assessment of their future development was carried out based on hazard analysis and critical control point theory. Results: The OME institutions were mainly concentrated in the Pearl River Delta, accounting for 72.0%. The public and private medical and health institutions accounted for 70.6% and 29.4% respectively. The filing rates of different OME categories from high to low in the order were physical factors, chemical factors, dust, other, radiation factors, biological factors (P<0.01), and the filing rates were 89.6%, 88.6%, 84.8%, 63.0%, 7.1% and 1.0%, respectively. The rates of excellence in the field assessment from high to low in the order were hearing atlas analysis personnel, lung function examination operators, chest film reading personnel, chief examination physician, technical director, quality director (P<0.01), and the rates of excellence were 49.4%, 26.2%, 20.6%, 10.8%, 8.2% and 4.6%, respectively. A total of 37 institutions did not submit OME information, of which 23 institutions did not carry out OME work after filing. The required diagnosis rate and confirmed diagnosis rate of suspected occupational diseases in 2020 were 34.3% and 55.3%, respectively. In 2021, the detection rate of suspected occupational diseases was only 1.1‰. Among the institutions with biological monitoring records, 64.1% did not participate in external quality assessment program in laboratory, and the unqualified rate of 38 participating institutions was 55.3%. The risk assessment results show that the future development of OME institutions needs to focus on private institutions, institutions that have not reported OME information, institutions that have missed diagnosis and missed reporting of suspected occupational diseases, institutions that have not participated in external quality assessment program in laboratory and core personnel such as quality managers, technical leaders, and main inspection physicians. Conclusion: OME institutions in Guangdong Province show the characteristics of centralized filing category, centralized filing region and centralized filing institution nature. Combined with the potential risks of OME institutional capacity building, it is necessary to implement classified management, strengthen information construction, supervision and management, implement post responsibilities, and promote the high-quality development of OME institutions.

Objective To analyze the distribution features of newly reported cases of occupational welder′s pneumoconiosis (OWP) in Guangdong Province from 2013 to 2022. Methods Data of newly reported cases of OWP from National Occupational Disease Network Direct Reporting System of Guangdong Province from 2013 to 2022 was analyzed using conventional data analyzing Methods. Results A total of 294 cases of OWP were reported in Guangdong Province from 2013 to 2022 with an overall downward trend. The average age at diagnosis for new OWP cases was 44±6 years old, and the median of dust exposure duration was 11 years. Males accounted for 99.3% of the cases, and 94.2% of the cases were phase Ⅰ OWP. Guangzhou City had the highest regional distribution with 74.8% of the cases. The industry distribution was mainly manufacturing, accounting for 86.7% of the cases. The scale of enterprises was most common in small enterprises, followed by large and medium-sized enterprises, accounting for 38.4%, 30.6% and 24.5% of the cases respectively. The economic types of enterprises were mostly private enterprises, followed by state-owned enterprises, accounting for 54.1% and 32.0% of the cases respectively. Conclusion In Guangdong Province, the newly reported OWP cases were clustered in terms of disease stage, regional distribution, industry, enterprise scale and enterprise economic type. There was a tendency of younger age at diagnosis and shorter dust exposure duration.

Intraductal papillary neoplasm of the bile duct (IPNB) is a rare type of biliary tract neoplasms characterized by biliary dilatation, papillary neoplasm or cystic changes, with or without mucous secretion. The etiology and mechanism of IPNB are still unclear. Studies have shown that its pathogenesis is closely related to cholestasis and repeated biliary tract infection caused by cholestasis and clonorchionchus infection and other diseases. Signaling pathways such as Ras-MAPK and Wnt/β-catenin play important roles in progression of IPNB. IPNB lacks specific clinical features. Its symptoms depend on the location of tumor and the degree of bile duct obstruction. The main manifestations are abdominal pain, obstructive jaundice, fever, and recurrent cholangitis. IPNB can be divided into pancreatobiliary type, intestinal type, gastric type and eosinophilic type according to epithelial tissue morphology and immunohistochemical staining markers. Based on the location of main lesions, IPNB can be divided into intrahepatic, extrahepatic and diffuse types. The prognosis of patients of IPNB receiving radical surgery is better than those receiving palliative treatment, and all patients with indications are recommended to receive radical surgery. The authors summarize the etiology, progression mechanism, clinical manifestations, pathological features, diagnosis and treat-ment status of IPNB, and provide a review of its research progress.

OBJECTIVETo explore the molecular mechanism underlying the biological function of lncRNA PTENP1 in bladder cancer.

METHODSExpressions of PTENP1, PTEN and miR-17 were examined by quantitative reverse transcriptase PCR (qRT-PCR) in 12 bladder cancer tissues. The expression of PTEN was examined by Western blotting in bladder cancer cell lines T24 and 5637 overexpressing PTENP1. Luciferase reporter assay was performed to confirm the targeting of miR-17 to PTENP1 and PTEN. T24 and 5637 cell lines with stable overexpression of PTENP1 and mir-17 were used to investigate effect of PTNE and miR-17 on the function of PTENP1 in bladder cancer.

RESULTSThe expression of miR-17 was up-regulated and PTENP1 and PTEN were down-regulated in bladder cancer tissues, where a positive correlation was found between PTENP1 and PTEN expressions and a negative correlation between PTENP1 and miR-17 (P<0.05). Overexpression of PTENP1 in bladder cancer cell lines T24 and 5637 obviously enhanced the expression of PTEN protein. miR-17 was found to target both PTENP1 and PTEN and promote the growth of bladder cancer. miR-17 could partially restore the tumor-suppressing activity of PTENP1 in bladder cancer.

CONCLUSIONBy binding with miR-17, lncRNA PTENP1 functions as a PTEN competing endogenous RNA (ceRNA) to suppress the progression of bladder cancer.

OBJECTIVETo investigate the role of microRNA-34a (miR-34a) in regulating the cell cycles of bladder cancer cell line J82 and explore the underlying mechanism.

METHODSJ82 cells were transfected with a miR-34a mimic or an inhibitor to induce miR-34a overexpression or silencing. The RNA level of miR-34a in the transfected cells was detected by real-time PCR, and CD44 expressions at the mRNA and protein levels were detected by real-time PCR and Western blotting. Luciferase reporter assay was used to detect the activation of 3'UTR of CD44, and flow cytometry was performed to analyze the cell cycle changes.

RESULTSThe expression level of miR-34a was significantly increased and CD44 expression significantly lowered in cells transfected with miR-34a mimic; miR-34a inhibitor transfection caused reverse effects on miR-34a and CD44 expressions. MiR-34a mimics downregulated while miR-34a inhibitor enhanced the activation of 3'UTR of CD44 with corresponding changes in the expressions of some cell cycle-related proteins. MiR-34a mimics and miR-34a inhibitor induced opposite changes in J82 cell cycle, which were partly reversed by CD44.

CONCLUSIONMiRNA-34a regulates cell cycles by targeting CD44 in human bladder carcinoma cell line J82.

Cell Cycle ; Cell Line, Tumor ; Down-Regulation ; Humans ; Hyaluronan Receptors ; metabolism ; MicroRNAs ; metabolism ; RNA, Messenger ; Real-Time Polymerase Chain Reaction ; Transfection ; Urinary Bladder Neoplasms ; pathology

Objective To investigate the role of microRNA-34a (miR-34a) in regulating the cell cycles of bladder cancer cell line J82 and explore the underlying mechanism. Methods J82 cells were transfected with a miR-34a mimic or an inhibitor to induce miR-34a overexpression or silencing. The RNA level of miR-34a in the transfected cells was detected by real-time PCR, and CD44 expressions at the mRNA and protein levels were detected by real-time PCR and Western blotting. Luciferase reporter assay was used to detect the activation of 3'UTR of CD44, and flow cytometry was performed to analyze the cell cycle changes. Results The expression level of miR-34a was significantly increased and CD44 expression significantly lowered in cells transfected with miR-34a mimic; miR-34a inhibitor transfection caused reverse effects on miR-34a and CD44 expressions. MiR-34a mimics downregulated while miR-34a inhibitor enhanced the activation of 3'UTR of CD44 with corresponding changes in the expressions of some cell cycle-related proteins. MiR-34a mimics and miR-34a inhibitor induced opposite changes in J82 cell cycle, which were partly reversed by CD44. Conclusion MiRNA-34a regulates cell cycles by targeting CD44 in human bladder carcinoma cell line J82.

Objective To investigate the role of microRNA-34a (miR-34a) in regulating the cell cycles of bladder cancer cell line J82 and explore the underlying mechanism. Methods J82 cells were transfected with a miR-34a mimic or an inhibitor to induce miR-34a overexpression or silencing. The RNA level of miR-34a in the transfected cells was detected by real-time PCR, and CD44 expressions at the mRNA and protein levels were detected by real-time PCR and Western blotting. Luciferase reporter assay was used to detect the activation of 3'UTR of CD44, and flow cytometry was performed to analyze the cell cycle changes. Results The expression level of miR-34a was significantly increased and CD44 expression significantly lowered in cells transfected with miR-34a mimic; miR-34a inhibitor transfection caused reverse effects on miR-34a and CD44 expressions. MiR-34a mimics downregulated while miR-34a inhibitor enhanced the activation of 3'UTR of CD44 with corresponding changes in the expressions of some cell cycle-related proteins. MiR-34a mimics and miR-34a inhibitor induced opposite changes in J82 cell cycle, which were partly reversed by CD44. Conclusion MiRNA-34a regulates cell cycles by targeting CD44 in human bladder carcinoma cell line J82.