Objective To investigate the effect of melatonin (MT) on the proliferation and apoptosis in human pancreatic cancer cell SW1990 in vitro.Methods SW1990 cell line were treated with MT at different concentrations (0.1,0.5,1.0,2.5 and 5.0 mmol/L) and at different time points (24 h,48 h and 72 h).Cell proliferation was evaluated by MTT and apoptosis was determined by AnnexinV/Pl,cell cycle was determined by flow cytometry,and Western Blot was used to detect the expression of Bcl-2 and Bax.Results MT could inhibit the proliferation of SW1990 cell in a time and dose dependent manner.48 h after 0.1～5.0 mmol/L MT treatment,the proliferation inhibitory rate was 7.4%～85.8%,the proportion of SW1990 cell in phase G0/G1 was 72.6%～85.33%.48 h after 1～5.0 mmol/L MT treatment,the apoptosis rate was 21.5% ～41.7%,and the expression of Bcl-2 was down-regulated and the ratio of Bcl-2/Bax decreased.Conclusions MT could inhibit the proliferation of SW1990 pancreatic cancer cells by up-regulating the expression of Bax and down-regulating the expression of Bcl-2,as well as enhancing apoptosis and blocking SW1990 cell in phase G0/G1.

Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat.This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression.Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.

Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat.This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression.Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.

Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat.This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression.Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.

Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat.This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression.Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.

OBJECTIVETo investigate the effects of modified vacuum sealing drainage (VSD) technique in treating refractory sinus in the lower leg.

METHODSFrom January 2010 to December 2011, 11 patients with refractory sinus in the lower leg, including 7 males and 4 females, with an average age of 34.5 years (ranged,23 to 56). These patients were treated with modified VSD technique after thorough cleaning sinus and continuous washing. After 14 to 21 days of treatment, removed VSD and re-debrided the sinus and sutured wound.

RESULTSInfections got control after operation, sinus in the lower leg healed. All patients were followed up from 6 to 14 months with an average of 10 months, no recidivations were found.

CONCLUSIONModified VSD technique is an effective method in the treatment of stubborn sinus in the lower leg.

Adult ; Drainage ; methods ; Female ; Fracture Fixation, Internal ; adverse effects ; Humans ; Leg Bones ; injuries ; surgery ; Male ; Middle Aged ; Postoperative Complications ; therapy ; Vacuum