Influence of coarse particulate matter on chickenpox in Jiading District, Shanghai, 2009-2018: A distributed lag non-linear time series analysis.

Although the link between ambient air pollution and some infectious diseases has been studied, few studies have explored so far, the relationship between chickenpox and particulate matter. Daily chickenpox counts in Jiading District, Shanghai, were collected from 2009 to 2018. Time series analysis was conducted to describe the trends of the daily number of chickenpox cases and the concentration of particulate matter 10 µm or less (PM10). The distributed lag non-linear model (DLNM) was developed to assess the lag and non-linear relationship between the number of chickenpox cases and PM10 concentration adjusting for meteorological factors and other pollutants. Spatiotemporal scanning was used to detect the clustering of chickenpox cases. There was a concomitant relationship between the number of chickenpox cases and PM10 concentration, especially in the period of high PM10 concentration. DLNM results showed a nonlinear relationship between the number of chickenpox cases and PM10 concentration with the maximum effect of PM10 being lagged for 13-14 days, which was consistent with the average incubation period of chickenpox. PM10 was significantly associated with the daily number of chickenpox cases when above 300 µg/m3. The risk of chickenpox increased with increasing PM10 concentration and the association was strongest at the lag of 14 day (RR = 1.13, 95% CI: 1.04-1.23) for PM10 concentration of 500 µg/m3 versus 50 µg/m3. The study provides evidence that high PM10 concentration increases the risk of chickenpox spreading.

TRIM24 promotes hepatocellular carcinoma progression via AMPK signaling.

Hepatocellular carcinoma (HCC) is one of the most common cancers diagnosed worldwide. However, the mechanism underlying HCC pathogenesis remains unknown. In the present study, TRIM24 was found increased in human HCC clinical samples and positively correlated with HCC tumor grade. Furthermore, TRIM24 knockdown inhibits proliferation and migration in a human HCC cell line in vitro while also inhibiting tumor growth in vivo. Mechanistically, TRIM24 appears to promote liver tumor development via AMPK signaling as AMPK knockdown alleviated the in vitro and in vivo effects of TRIM24 knockdown in a human HCC cell line. Taken together, these data enhance our understanding of HCC development in addition to highlighting TRIM24-regulated AMPK signaling as a potential therapeutic target for HCC treatment.

Low concentrations of bilirubin inhibit activation of hepatic stellate cells in vitro.

Hepatic stellate cell (HSC) activation serves a key role in liver fibrosis, and is associated with chronic liver diseases. Bilirubin, a product of heme degradation, has been demonstrated to have antioxidant properties. The present study investigated the effects of physiological concentrations of bilirubin on rat HSC activation. Rat HSCs were isolated and cultured for several generations to induce activation. The activated HSCs were subsequently treated with 0, 1, 10 or 20 mg/l bilirubin and assayed for parameters of cell activation. As the bilirubin concentration increased, HSCs demonstrated reduced production of reactive oxygen species, reduced protein expression levels of α­smooth muscle actin, a decreased mRNA expression ratio of tissue inhibitor of matrix metalloproteinase­1/matrix metalloproteinase­2, decreased proliferation and increased apoptosis. In conclusion, elevated bilirubin levels, within its physiological concentration range, appeared to inhibit HSC activation. These findings suggested a potential role for bilirubin in the treatment of fibrosis that requires further investigation.

BCAT1, a key prognostic predictor of hepatocellular carcinoma, promotes cell proliferation and induces chemoresistance to cisplatin.

BACKGROUND & AIMS: BCAT1 initiates the catabolism of branched-chain amino acids. Here, we investigated the function of BCAT1 and its transcriptional regulatory mechanism in hepatocellular carcinoma (HCC). METHODS: RNASeq was used to evaluate BCAT1 mRNA levels in HCC and normal matched specimens. After the exogenous expression of BCAT1 in BEL-7404 cells and the suppression of endogenous BCAT1 expression with shRNA in HepG2 cells, the cell proliferation, clone-forming ability and cell-cycle changes were measured with MTT assay, colony-forming assay and flow cytometry respectively. A xenograft model was used to investigate the effect of BCAT1 on cancer growth in vivo. Chromatin immunoprecipitation and luciferase reporter technologies were used to confirm the transcriptional regulation of the BCAT1 gene by MYC. The expression of the BCAT1 and MYC proteins in 122 HCC tissues was determined with an immunohistochemical analysis. RESULTS: BCAT1 mRNA was clearly increased in HCC tissues and hepatomas. The ectopic expression of BCAT1 in BEL-7404 cells enhanced their proliferation, clone formation, tumourigenic properties, S-G2 /M phase transition and chemoresistance to cisplatin. The suppression of BCAT1 expression in HepG2 cells significantly inhibited their proliferation, clone formation, and S-G2 /M phase transition and caused their chemosensitization to cisplatin. MYC affected the transcriptional regulation of BCAT1. Clinical data showed that BCAT1 expression correlated with a significantly poorer prognosis. CONCLUSION: BCAT1 plays a pathogenic role in HCC by causing cell proliferation and chemoresistance. The MYC transcription factor is involved in regulating the transcriptional activity of BCAT1. BCAT1 expression has prognostic significance for the survival of patients with HCC.

EphA1 receptor silencing by small interfering RNA has antiangiogenic and antitumor efficacy in hepatocellular carcinoma.

The Eph family of receptor tyrosine kinases has emerged as one of the pivotal regulators of tumor angiogenesis. EphA1, the first identified member of the Eph receptor family, has been found to be overexpressed in several types of human tumors. A recent report indicated that EphA1 was overexpressed in hepatocellular carcinoma (HCC) and that elevated expression of EphA1 can promote proliferation of HCC cells through stimulation by exogenous Ephrin-A1. To investigate the role of EphA1 in angiogenesis and progression of HCC, we down-regulated EphA1 by RNA interference (RNAi) technology, in an HCC-derived cell line with a high level of EphA1 expression. We established a stable knockdown clone named SiEphA1/Huh-7. The knockdown resulted in decreased proliferation of Huh-7 cells, as well as decreased motility and invasion capability in vitro. siRNA-based EphA1 knockdown also down-regulated the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-2 and -9. Interestingly, the suppression of EphA1 expression in Huh-7 cells reduced their outgrowth when inoculated in the subcutaneous space in the flank of nude mice, presumably through angiogenesis inhibition since microvessel density was found to be inhibited.

Establishment of an infected necrotizing pancreatitis model by retrograde pancreatic duct injection of sodium taurocholate and E. coli in rats.

A stable and reliable infected necrotizing pancreatitis (INP) model in rats was established in order to study the pathophysiological mechanism and pathological development rule of INP and explore the new therapeutic methods for the diseases. Forty-six SD rats were randomly divided into 5 groups. The animals in group A received the injection of 5% sodium taurocholate into the pancreatic duct and those in group B underwent that of E. coli into the pancreatic duct. The rats in groups C, D and E were subjected to the injection of 5% sodium taurocholate in combination with different concentrations of E. coli (10(3), 10(4), 10(5)/mL, respectively) into the pancreatic duct. The dose of injection was 0.1 mL/100 g and the velocity of injection was 0.2 mL/min in all the 5 groups. Eight h after the injection, the survival rate of animals was recorded and the surviving rats were killed to determine the serum content of amylase and perform pathological examination and germ cultivation of the pancreatic tissue. The results showed that acute necrotizing pancreatitis model was induced by injection of 5% sodium taurocholate into the pancreatic duct. The positive rate of germ cultivation in group A was 12.5%. The acute necrotizing pancreatitis model was not induced by injection of E. coli into the pancreatic duct and the positive rate of germ cultivation in group B was 0. The INP model was established in groups C to E. The positive rate of germ cultivation was 60%, 100% and 100% and 8-h survival rate 100%, 100% and 70% in groups C, D and E, respectively. It was concluded that a stable and reliable model of INP was established by injection of 5% sodium taurocholate in combination with 10(4)/mL E. coli into the pancreatic duct with a dose of 0.1 mL/100 g and a velocity of 0.2 mL/min. The pathogenesis of INP might be that the hemorrhage and necrosis of pancreatic tissue induced by sodium taurocholate results in weakness of pancreatic tissue in fighting against the germs. Meanwhile, the necrotic pancreatic tissue provides a good proliferative environment for the germs.

Establishment of an Infected Necrotizing Pancreatitis Model by Retrograde Pancreatic Duct Injection of Sodium Taurocholate and E. coli in Rats / 华中科技大学学报（医学）（英德文版）

A stable and reliable infected necrotizing pancreatitis (INP) model in rats was established in order to study the pathophysiological mechanism and pathological development rule of INP and explore the new therapeutic methods for the diseases. Forty-six SD rats were randomly divided into 5 groups. The animals in group A received the injection of 5% sodium taurocholate into the pancreatic duct and those in group B underwent that of E. Coli into the pancreatic duct. The rats in groups C, D and E were subjected to the injection of 5% sodium tanrocholate in combination with different con-centrations of E. Coli (103, 104, 105/mL, respectively) into the pancreatic duct. The dose of injection was 0.1 mL/100 g and the velocity of injection was 0.2 mL/min in all the 5 groups. Eight h after the injection, the survival rate of animals was recorded and the surviving rats were killed to determine the serum content of amylase and perform pathological examination and germ cultivation of the pancre-atic tissue. The results showed that acute necrotizing panereatitis model was induced by injection of 5% sodium taurocholate into the pancreatic duct. The positive rate of germ cultivation in group A was 12.5%. The acute necrotizing pancreatitis model was not induced by injection of E. Coli into the pan-creatic duct and the positive rate of germ cultivation in group B was 0. The INP model was estab-lished in groups C to E. The positive rate of germ cultivation was 60%, 100% and 100% and 8-h sur-vival rate 100%, 100% and 70% in groups C, D and E, respectively. It was concluded that a stable and reliable model of INP was established by injection of 5% sodium taurocholate in combination with 104/mL E. Coli into the pancreatic duct with a dose of 0.1 mL/100 g and a velocity of 0.2 mL/min. The pathogenesis of INP might he that the hemorrhage and necrosis of pancreatic tissue in-duced by sodium taurocholate results in weakness of pancreatic tissue in fighting against the germs.Meanwhile, the necrotic pancreatic tissue provides a good proliferative environment for the germs.

[Experimental therapeutic study for activated coagulation by hemorrhagic shock in rats].

The study was aimed to investigate the changes of blood coagulation factors during hemorrhagic shock in rats and the effects of various of resuscitation fluids on expression of blood coagulation factors in rats with hemorrhagic shock and to clarify its possible mechanism. 50 SD rats were randomly divided into 5 groups: control, sham operation, shock, resuscitation 1 (infusion with Ringer's lactate) and resuscitation 2 (infusion with 6% VOLUVEN), 10 rats per group. The rats in resuscitation 1 and resuscitation 2 groups were subjected to hemorrhagic shock, after hemorrhage shock for 1 hour resuscitation was performed with Ringer's lactate and 6% VOLUVEN. After resuscitation for 2 hours the changes of t-PA, PAI-1, TF were measured. At the same time, the rats in shock and the sham operation groups were blooded out so as to test. The results showed that the levels of plasma t-PA, t-PA/PAI, TF in the shock and resuscitation 1 groups were significantly higher than that in control and sham operation groups (P<0.01). The levels of plasma t-PA, t-PA/PAI in resuscitation 1 group were higher than that in shock group (P<0.01), the levels of plasma t-PA, t-PA/PAI and TF in the resuscitation 2 group were significantly lower than that in shock and resuscitation 1 groups (P<0.01). It is concluded that hemorrhagic shock may trigger the coagulation cascade reaction, results in hyperfunctioning of fiberinolysis and activation of platelets and coagulation system, and so the coagulation factor is greatly consumed. Unbalance of coagulation system plays an important role in the progress of shock. Efficacy of resuscitation with 6% VOLUVEN plus Ringer's lactate may be better than Ringer's lactate alone in regulating blood coagulation after hemorrhagic shock in rats.