AIM: To evaluate the effectiveness and safety of percutaneous hepatic cryoablation in combination with percutaneous ethanol injection (PEI) in patients with unresectable hepaocellular carcinoma (HCC).METHODS: A total ...AIM: To evaluate the effectiveness and safety of percutaneous hepatic cryoablation in combination with percutaneous ethanol injection (PEI) in patients with unresectable hepaocellular carcinoma (HCC).METHODS: A total of 105 masses in 65 HCC patients underwent percutaneous hepatic cryoablation. The cryoablation was performed with the Cryocare system (Endocare, Irvine, CA, USA) using argon gas as a cryogen.Two freeze-thaw cycles were performed, each reaching a temperature of -180 ℃ at the tip of the probe. PEI was given in 36 patients with tumor masses larger than 6 cm in diameter 1-2 weeks after cryoablation and then once per week for 4 to 6 sessions. The efficacy was evaluated with survival, change of tumor size and alpha-fetoprotein (AFP) levels. RESULTS: During a follow-up duration of 14 months in average with a range of 5 to 21 months, 33 patients (50.8 %)were free of tumors, 22 patients (33.8 %) alive with tumor recurrence: two had bone metastases, three were found to have lung metastases, and the remaining 17 recurrences occurred in the liver, of whom only 3 developed a cryosite recurrence. Among the 41 patients who were followed up for more than one year, 32(78 %) were alive despite of tumor recurrence. Seven patients (10.8 %) died due to disease recurrence. Three patients (4.6 %) died due to some noncancer-related causes. Among the 43 patients who had a CT scan available for review, 38 (88.4 %) had a shrinkage of tumor mass. Among the 22 patients who received biopsies of cryoablated tumor mass, all biopsies except one, showed only dead or scar tissues. Of the patients who had an increased AFP preablatively, 91.3 % had a decrease of AFP to normal or nearly normal levels during postablative 3-6 months. Complications of cryoablation included liver capsular cracking in one patient,transient thrombocytopenia in 4 patients and asymptomatic right-sided pleural effusions in 2 patients. Two patients developed liver abscess at the previous cryoablation site at 2 and 4 months, respectively,following cryoablation, a展开更多
AIM: To study the therapeutic value of combination o cryosurgery and 125iodine seed implantation for locally advanced pancreatic cancer. METHODS: Forty-nine patients with locally advanced pancreatic cancer (males 36, ...AIM: To study the therapeutic value of combination o cryosurgery and 125iodine seed implantation for locally advanced pancreatic cancer. METHODS: Forty-nine patients with locally advanced pancreatic cancer (males 36, females 13), with a median age of 59 years, were enrolled in the study. Twelve patients had liver metastases. In all cases the tumors were considered unresectable after a comprehensive evaluation. Patients were treated with cryosurgery, which was performed intraoperatively or percutaneously unde guidance of ultrasound and/or computed tomography (CT), and 125iodine seed implantation, which was performed during cryosurgery or post-cryosurgery under guidance of ultrasound and/or CT. A few patients received regional celiac artery chemotherapy. RESULTS: Thirteen patients received intraoperative cryosurgery and 36 received percutaneous cryosurgery Some patients underwent repeat cryosurgery. 125Iodine seed implantation was performed during freezing procedure in 35 patients and 3-9 d after cryosurgery in 14 cases. Twenty patients, 10 of whom had hepaticmetastases received regional chemotherapy. At 3 mo after therapy, CT was repeated to estimate tumor response to therapy. Most patients showed varying degrees of tumor necrosis. Complete response (CR) of tumor was seen in 20.4% patients, partial response (PR), in 38.8%, stable disease (SD), in 30.6%, and progressive disease (PD), in 10.2%. Adverse effects associated with cryosurgery included upper abdomen pain and increased serum amylase. Acute pancreatitis was seen in 6 patients one of whom developed severe pancreatitis. All adverse effects were controlled by medical management with no poor outcome. There was no therapy-related mortality. During a median follow-up of 18 mo (range of 5-40), the median survival was 16.2 mo, with 26 patients (53.1%) surviving for 12 mo or more. Overall, the 6-, 12-, 24- and 36-mo survival rates were 94.9%, 63.1%, 22.8% and 9.5%, respectively. Eight patients had survival of 24 mo or more. The patient with the longest survival (40 展开更多
AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into ...AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into the study, 50 patients with HBV-related ACLF and 29 patients with chronic hepatitis B (CHB), from the First Affiliated Hospital of Medical College from January 2009 to June 2012. The ACLF patients were diagnosed according to the criteria recommended by The 19th Conference of the Asian Pacific Association for the Study of the Liver in 2009. Twenty healthy individuals with a similar gender and age structures to the two patient groups were also included as the normal controls (NC). Of the 50 ACLF patients, 28 were subsequently classified as non-survivors: 19 patients died from multiorgan failure, 3 underwent liver transplantation, and 6 discontinued therapy during follow-up because of financial reasons. The remaining 22 ACLF patients whose liver and anticoagulation function recovered to nearly normal levels within the next 6 mo were classified as survivors. The number of circulating Treg and Th17 cells was determined upon diagnosis and during the 8th week of follow-up through flow cytometry. RESULTS: The percentage of circulating Treg cells in the ACLF group was significantly higher than that in the CHB group (5.50% ± 1.15% vs 3.30% ± 1.13%, P < 0.01). The percentages of circulating Th17 cells in the ACLF and the CHB groups were significantly higher than that in the NC group (6.32% ± 2.22% vs 1.56% ± 0.44%, P < 0.01; 3.53% ± 1.65% vs 1.56% ± 0.44%, P < 0.01). No significant difference in Treg cell to Th17 cell ratio was observed between the ACLF group and the CHB group (0.98 ± 0.44 vs 1.12 ± 0.64, P = 0.991), whereas those in the two HBV infection groups were significantly lower than that in the NC group (1.85 ± 1.22; both P < 0.01). The percentage of Treg cells in the survivors during the 8th week of follow-up was significantly lower than that during peak ACLF severity [total bilirubin (TBIL) 展开更多
The effect of paleo-Pacific subduction on the geological evolution of the western Pacific and continental China is likely complex. Nevertheless, our analysis of the distribution of Mesozoic granitoids in the eastern c...The effect of paleo-Pacific subduction on the geological evolution of the western Pacific and continental China is likely complex. Nevertheless, our analysis of the distribution of Mesozoic granitoids in the eastern continental China in space and time has led us to an interesting conclusion： The basement of the continental shelf beneath East and South China Seas may actually be of exotic origin geologically unrelated to the continental lithosphere of eastern China. By accepting the notion that the Jurassic- Cretaceous granitoids in the region are genetically associated with western Pacific subduction and the concept that subduction may cease to continue only if the trench is being jammed, then the termination of the granitoid magmatism throughout the vast region at -88±2 Ma manifests the likelihood of ＂sudden＂, or shortly beforehand （- 100 Ma）, trench jam of the Mesozoic western Pacific subduction. Trench jam happens if the incoming ＂plate＂ or portion of the plate contains a sizeable mass that is too buoyant to subduct. The best candidate for such a buoyant and unsubductable mass is either an oceanic plateau or a micro-continent. We hypothesize that the basement of the Chinese continental shelf represents such an exotic, buoyant and unsubductable mass, rather than seaward extension of the continental lithosphere of eastern China. The locus of the jammed trench （i.e., the suture） is predictably located on the shelf in the vicinity of, and parallel to, the arc-curved coastal line of the southeast continental China. It is not straightforward to locate the locus in the northern section of the East China Sea shelf because of the more recent （〈20 Ma） tectonic re-organization associated with the opening of the Sea of Japan. We predict that the trench jam at - 100 Ma led to the re-orientation of the Pacific plate motion in the course of NNW direction as inferred from the age-progressive Emperor Seamount Chain of Hawaiian hotspot origin （its oldest unsubdued Meiji and Detroit seamounts are -82 M展开更多
Acacetin(5,7-dihydroxy-4′-methoxyflavone), a potential neuroprotective agent, has an inhibitory effect on lipopolysaccharide-induced neuroinflammatory reactions. However, whether acacetin has an effect on inflammator...Acacetin(5,7-dihydroxy-4′-methoxyflavone), a potential neuroprotective agent, has an inhibitory effect on lipopolysaccharide-induced neuroinflammatory reactions. However, whether acacetin has an effect on inflammatory corpuscle 3(NLRP3) after cerebral ischemia-reperfusion injury has not been fully determined. This study used an improved suture method to establish a cerebral ischemia-reperfusion injury model in C57BL/6 mice. After ischemia with middle cerebral artery occlusion for 1 hour, reperfusion with intraperitoneal injection of 25 mg/kg of acacetin(acacetin group) or an equal volume of saline(0.1 mL/10 g, middle cerebral artery occlusion group) was used to investigate the effect of acacetin on cerebral ischemia-reperfusion injury. Infarct volume and neurological function scores were determined by 2,3,5-triphenyltetrazolium chloride staining and the Zea-Longa scoring method. Compared with the middle cerebral artery occlusion group, neurological function scores and cerebral infarction volumes were significantly reduced in the acacetin group. To understand the effect of acacetin on microglia-mediated inflammatory response after cerebral ischemia-reperfusion injury, immunohistochemistry for the microglia marker calcium adapter protein ionized calcium-binding adaptor molecule 1(Iba1) was examined in the hippocampus of ischemic brain tissue. In addition, tumor necrosis factor-α, interleukin-1β, and interleukin-6 expression in ischemic brain tissue of mice was quantified by enzyme-linked immunosorbent assay. Expression of Iba1, tumor necrosis factor-α, interleukin-1β and interleukin-6 was significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Western blot assay results showed that expression of Toll-like receptor 4, nuclear factor kappa B, NLRP3, procaspase-1, caspase-1, pro-interleukin-1β, and interleukin-1β were significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Our findings indicate that acacetin has a protectiv展开更多
Rheumatoid arthritis(RA)is a chronic inflammatory disease that eventually leads to disability.Inflammatory cell infiltration,severe joint breaking and systemic bone loss are the main clinical symptoms.In this study,we...Rheumatoid arthritis(RA)is a chronic inflammatory disease that eventually leads to disability.Inflammatory cell infiltration,severe joint breaking and systemic bone loss are the main clinical symptoms.In this study,we established a collagen-induced arthritis(CIA)model and found a large number of M1 macrophages and pyroptosis,which are important sources of proinflammatory cytokines.Punicalagin(PUN)is an active substance extracted from pomegranate peel.We found that it inhibited joint inflammation,cartilage damage and systemic bone destruction in CIA mice.PUN effectively alleviated the high expression of inflammatory cytokines in synovial tissue in vivo.PUN treatment shifted macrophages from the M1 phenotype to the M2 phenotype after stimulation with lipopolysaccharide(LPS)and interferon(IFN)-γ.The expression of inducible nitric oxide synthase(i NOS)and other proinflammatory cytokines released by M1 macrophages was decreased in the PUN treatment group.However,simultaneously,the expression of markers of anti-inflammatory M2 macrophages,such as arginase(Arg)-1 and interleukin(IL)-10,was increased.In addition,PUN treatment attenuated pyroptosis by downregulating the expression of NLRP3 and caspase-1,thereby preventing inflammatory cell death resulting from the release of IL-1βand IL-18.Mechanistically,PUN inhibited the activation of receptor activators of the nuclear factor-κB(NF-κB)signaling pathway,which contributes to M1 polarization and pyroptosis of macrophages.We concluded that PUN ameliorated pathological inflammation by inhibiting M1 phenotype polarization and pyroptosis and has great potential as a therapeutic treatment for human RA.展开更多
AIM:To determine the safety and efficacy of efficacy of percutaneous cryosurgery for treatment of patients with hepatic colorectal metastases. METHODS: Three hundred and twenty-six patients with non-resectable hepatic...AIM:To determine the safety and efficacy of efficacy of percutaneous cryosurgery for treatment of patients with hepatic colorectal metastases. METHODS: Three hundred and twenty-six patients with non-resectable hepatic colorectal metastases underwent percutaneous cryosurgery under the guidance of ultrasound or CT. Follow-up was 1 mo after cryosurgery and then every 4 mo thereafter by assessment of tumor markers, liver ultrasonography, and abdominal CT. For lesions suspicious of recurrence, a liver biopsy was performed and subsequent repeat cryosurgery was given if histology was positive for cancer. RESULTS: All patients underwent a total of 526 procedures of cryosurgery. There were 151 patients who underwent repeat procedures of cryosurgery for recurrent tumors in the liver and extrahepatic places. At 3 mo after cryosurgery, carcinoembryonic antigen (CEA) levels in 197 (77.5%) patients who had elevated markers before cryosurgery decreased to normal range. Among 280 patients who received CT following-up, cryotreated lesions showed complete response (CR) in 41 patients (14.6%), partial response (PR) in 115 patients (41.1%), stable disease (SD) in 68 patients (24.3%) and progressive disease (PD) in 56 patients (20%). The recurrence rate was 47.2% during a median follow-up of 32 mo (range, 7-61). Sixty one percent of the recurrences were seen in liver only and 13.9% in liver and extrahepatic areas. The recurrence rate at cryotreated site was only 6.4% for all cases. During a median follow-up of 36 mo (7-62 mo), the median survival of all patient was 29 mo (range 3-62 mo). Overall survival was 78%, 62%, 41%, 34% and 23% at 1, 2, 3, 4 and 5 years, respectively, after the treatment. Patients with tumor size less than 3 cm, tumor in right lobe of liver, lower CEA levels (< 100 ng/dL) and post- cryosurgery TACE had higher survival rate. There wasno significant difference in terms of survival based on the number of tumors, pre-cryosurgery chemotherapy and the timing of the development of metastases (synchronous vs metachron展开更多
文摘AIM: To evaluate the effectiveness and safety of percutaneous hepatic cryoablation in combination with percutaneous ethanol injection (PEI) in patients with unresectable hepaocellular carcinoma (HCC).METHODS: A total of 105 masses in 65 HCC patients underwent percutaneous hepatic cryoablation. The cryoablation was performed with the Cryocare system (Endocare, Irvine, CA, USA) using argon gas as a cryogen.Two freeze-thaw cycles were performed, each reaching a temperature of -180 ℃ at the tip of the probe. PEI was given in 36 patients with tumor masses larger than 6 cm in diameter 1-2 weeks after cryoablation and then once per week for 4 to 6 sessions. The efficacy was evaluated with survival, change of tumor size and alpha-fetoprotein (AFP) levels. RESULTS: During a follow-up duration of 14 months in average with a range of 5 to 21 months, 33 patients (50.8 %)were free of tumors, 22 patients (33.8 %) alive with tumor recurrence: two had bone metastases, three were found to have lung metastases, and the remaining 17 recurrences occurred in the liver, of whom only 3 developed a cryosite recurrence. Among the 41 patients who were followed up for more than one year, 32(78 %) were alive despite of tumor recurrence. Seven patients (10.8 %) died due to disease recurrence. Three patients (4.6 %) died due to some noncancer-related causes. Among the 43 patients who had a CT scan available for review, 38 (88.4 %) had a shrinkage of tumor mass. Among the 22 patients who received biopsies of cryoablated tumor mass, all biopsies except one, showed only dead or scar tissues. Of the patients who had an increased AFP preablatively, 91.3 % had a decrease of AFP to normal or nearly normal levels during postablative 3-6 months. Complications of cryoablation included liver capsular cracking in one patient,transient thrombocytopenia in 4 patients and asymptomatic right-sided pleural effusions in 2 patients. Two patients developed liver abscess at the previous cryoablation site at 2 and 4 months, respectively,following cryoablation, a
基金The Science-development Grand of Science-technology Department of Guangdong Province Grand of Health Department of Guangdong Province
文摘AIM: To study the therapeutic value of combination o cryosurgery and 125iodine seed implantation for locally advanced pancreatic cancer. METHODS: Forty-nine patients with locally advanced pancreatic cancer (males 36, females 13), with a median age of 59 years, were enrolled in the study. Twelve patients had liver metastases. In all cases the tumors were considered unresectable after a comprehensive evaluation. Patients were treated with cryosurgery, which was performed intraoperatively or percutaneously unde guidance of ultrasound and/or computed tomography (CT), and 125iodine seed implantation, which was performed during cryosurgery or post-cryosurgery under guidance of ultrasound and/or CT. A few patients received regional celiac artery chemotherapy. RESULTS: Thirteen patients received intraoperative cryosurgery and 36 received percutaneous cryosurgery Some patients underwent repeat cryosurgery. 125Iodine seed implantation was performed during freezing procedure in 35 patients and 3-9 d after cryosurgery in 14 cases. Twenty patients, 10 of whom had hepaticmetastases received regional chemotherapy. At 3 mo after therapy, CT was repeated to estimate tumor response to therapy. Most patients showed varying degrees of tumor necrosis. Complete response (CR) of tumor was seen in 20.4% patients, partial response (PR), in 38.8%, stable disease (SD), in 30.6%, and progressive disease (PD), in 10.2%. Adverse effects associated with cryosurgery included upper abdomen pain and increased serum amylase. Acute pancreatitis was seen in 6 patients one of whom developed severe pancreatitis. All adverse effects were controlled by medical management with no poor outcome. There was no therapy-related mortality. During a median follow-up of 18 mo (range of 5-40), the median survival was 16.2 mo, with 26 patients (53.1%) surviving for 12 mo or more. Overall, the 6-, 12-, 24- and 36-mo survival rates were 94.9%, 63.1%, 22.8% and 9.5%, respectively. Eight patients had survival of 24 mo or more. The patient with the longest survival (40
基金Supported by The Major National Science and Technology Projects for Infectious Diseases (11th and 12th Five Year, China),No. 2008ZX10002-007, No. 2012ZX10002-007the Foundation of Shaanxi Provincial Science and Technology Plan Projects,No. 2011K14-09-09
文摘AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into the study, 50 patients with HBV-related ACLF and 29 patients with chronic hepatitis B (CHB), from the First Affiliated Hospital of Medical College from January 2009 to June 2012. The ACLF patients were diagnosed according to the criteria recommended by The 19th Conference of the Asian Pacific Association for the Study of the Liver in 2009. Twenty healthy individuals with a similar gender and age structures to the two patient groups were also included as the normal controls (NC). Of the 50 ACLF patients, 28 were subsequently classified as non-survivors: 19 patients died from multiorgan failure, 3 underwent liver transplantation, and 6 discontinued therapy during follow-up because of financial reasons. The remaining 22 ACLF patients whose liver and anticoagulation function recovered to nearly normal levels within the next 6 mo were classified as survivors. The number of circulating Treg and Th17 cells was determined upon diagnosis and during the 8th week of follow-up through flow cytometry. RESULTS: The percentage of circulating Treg cells in the ACLF group was significantly higher than that in the CHB group (5.50% ± 1.15% vs 3.30% ± 1.13%, P < 0.01). The percentages of circulating Th17 cells in the ACLF and the CHB groups were significantly higher than that in the NC group (6.32% ± 2.22% vs 1.56% ± 0.44%, P < 0.01; 3.53% ± 1.65% vs 1.56% ± 0.44%, P < 0.01). No significant difference in Treg cell to Th17 cell ratio was observed between the ACLF group and the CHB group (0.98 ± 0.44 vs 1.12 ± 0.64, P = 0.991), whereas those in the two HBV infection groups were significantly lower than that in the NC group (1.85 ± 1.22; both P < 0.01). The percentage of Treg cells in the survivors during the 8th week of follow-up was significantly lower than that during peak ACLF severity [total bilirubin (TBIL)
基金supported by the National Natural Science Foundation of China(41130314,91014003)Chinese Academy of Sciences Innovation(Y42217101L),grants from Regional and Local Authorities(Shandong Province and City of Qingdao)+1 种基金supported by National Oceanography Laboratory in Qingdaosupported by the National Natural Science Foundation of China(NSFC)
文摘The effect of paleo-Pacific subduction on the geological evolution of the western Pacific and continental China is likely complex. Nevertheless, our analysis of the distribution of Mesozoic granitoids in the eastern continental China in space and time has led us to an interesting conclusion： The basement of the continental shelf beneath East and South China Seas may actually be of exotic origin geologically unrelated to the continental lithosphere of eastern China. By accepting the notion that the Jurassic- Cretaceous granitoids in the region are genetically associated with western Pacific subduction and the concept that subduction may cease to continue only if the trench is being jammed, then the termination of the granitoid magmatism throughout the vast region at -88±2 Ma manifests the likelihood of ＂sudden＂, or shortly beforehand （- 100 Ma）, trench jam of the Mesozoic western Pacific subduction. Trench jam happens if the incoming ＂plate＂ or portion of the plate contains a sizeable mass that is too buoyant to subduct. The best candidate for such a buoyant and unsubductable mass is either an oceanic plateau or a micro-continent. We hypothesize that the basement of the Chinese continental shelf represents such an exotic, buoyant and unsubductable mass, rather than seaward extension of the continental lithosphere of eastern China. The locus of the jammed trench （i.e., the suture） is predictably located on the shelf in the vicinity of, and parallel to, the arc-curved coastal line of the southeast continental China. It is not straightforward to locate the locus in the northern section of the East China Sea shelf because of the more recent （〈20 Ma） tectonic re-organization associated with the opening of the Sea of Japan. We predict that the trench jam at - 100 Ma led to the re-orientation of the Pacific plate motion in the course of NNW direction as inferred from the age-progressive Emperor Seamount Chain of Hawaiian hotspot origin （its oldest unsubdued Meiji and Detroit seamounts are -82 M
基金supported by the Natural Science Foundation of Xinjiang Uygur Autonomous Region of China,No.2016D01C120(to JB)
文摘Acacetin(5,7-dihydroxy-4′-methoxyflavone), a potential neuroprotective agent, has an inhibitory effect on lipopolysaccharide-induced neuroinflammatory reactions. However, whether acacetin has an effect on inflammatory corpuscle 3(NLRP3) after cerebral ischemia-reperfusion injury has not been fully determined. This study used an improved suture method to establish a cerebral ischemia-reperfusion injury model in C57BL/6 mice. After ischemia with middle cerebral artery occlusion for 1 hour, reperfusion with intraperitoneal injection of 25 mg/kg of acacetin(acacetin group) or an equal volume of saline(0.1 mL/10 g, middle cerebral artery occlusion group) was used to investigate the effect of acacetin on cerebral ischemia-reperfusion injury. Infarct volume and neurological function scores were determined by 2,3,5-triphenyltetrazolium chloride staining and the Zea-Longa scoring method. Compared with the middle cerebral artery occlusion group, neurological function scores and cerebral infarction volumes were significantly reduced in the acacetin group. To understand the effect of acacetin on microglia-mediated inflammatory response after cerebral ischemia-reperfusion injury, immunohistochemistry for the microglia marker calcium adapter protein ionized calcium-binding adaptor molecule 1(Iba1) was examined in the hippocampus of ischemic brain tissue. In addition, tumor necrosis factor-α, interleukin-1β, and interleukin-6 expression in ischemic brain tissue of mice was quantified by enzyme-linked immunosorbent assay. Expression of Iba1, tumor necrosis factor-α, interleukin-1β and interleukin-6 was significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Western blot assay results showed that expression of Toll-like receptor 4, nuclear factor kappa B, NLRP3, procaspase-1, caspase-1, pro-interleukin-1β, and interleukin-1β were significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Our findings indicate that acacetin has a protectiv
基金supported by the National Natural Science Foundation of China(82072425,82072498,81902181,81873990,81873991,and 81672238)the Jiangsu Provincial Medical Youth Talent(QNRC2016751)+4 种基金the Natural Science Foundation of Jiangsu Province(BK20180001)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the Special Project of Diagnosis and Treatment Technology for Key Clinical Diseases in Suzhou(LCZX202003)the Program for Introduction of Clinical Medical Teams to Suzhou(SZYJTD201714)Program from Suzhou Science and Technology Bureau(SYS2019101)。
文摘Rheumatoid arthritis(RA)is a chronic inflammatory disease that eventually leads to disability.Inflammatory cell infiltration,severe joint breaking and systemic bone loss are the main clinical symptoms.In this study,we established a collagen-induced arthritis(CIA)model and found a large number of M1 macrophages and pyroptosis,which are important sources of proinflammatory cytokines.Punicalagin(PUN)is an active substance extracted from pomegranate peel.We found that it inhibited joint inflammation,cartilage damage and systemic bone destruction in CIA mice.PUN effectively alleviated the high expression of inflammatory cytokines in synovial tissue in vivo.PUN treatment shifted macrophages from the M1 phenotype to the M2 phenotype after stimulation with lipopolysaccharide(LPS)and interferon(IFN)-γ.The expression of inducible nitric oxide synthase(i NOS)and other proinflammatory cytokines released by M1 macrophages was decreased in the PUN treatment group.However,simultaneously,the expression of markers of anti-inflammatory M2 macrophages,such as arginase(Arg)-1 and interleukin(IL)-10,was increased.In addition,PUN treatment attenuated pyroptosis by downregulating the expression of NLRP3 and caspase-1,thereby preventing inflammatory cell death resulting from the release of IL-1βand IL-18.Mechanistically,PUN inhibited the activation of receptor activators of the nuclear factor-κB(NF-κB)signaling pathway,which contributes to M1 polarization and pyroptosis of macrophages.We concluded that PUN ameliorated pathological inflammation by inhibiting M1 phenotype polarization and pyroptosis and has great potential as a therapeutic treatment for human RA.
文摘AIM:To determine the safety and efficacy of efficacy of percutaneous cryosurgery for treatment of patients with hepatic colorectal metastases. METHODS: Three hundred and twenty-six patients with non-resectable hepatic colorectal metastases underwent percutaneous cryosurgery under the guidance of ultrasound or CT. Follow-up was 1 mo after cryosurgery and then every 4 mo thereafter by assessment of tumor markers, liver ultrasonography, and abdominal CT. For lesions suspicious of recurrence, a liver biopsy was performed and subsequent repeat cryosurgery was given if histology was positive for cancer. RESULTS: All patients underwent a total of 526 procedures of cryosurgery. There were 151 patients who underwent repeat procedures of cryosurgery for recurrent tumors in the liver and extrahepatic places. At 3 mo after cryosurgery, carcinoembryonic antigen (CEA) levels in 197 (77.5%) patients who had elevated markers before cryosurgery decreased to normal range. Among 280 patients who received CT following-up, cryotreated lesions showed complete response (CR) in 41 patients (14.6%), partial response (PR) in 115 patients (41.1%), stable disease (SD) in 68 patients (24.3%) and progressive disease (PD) in 56 patients (20%). The recurrence rate was 47.2% during a median follow-up of 32 mo (range, 7-61). Sixty one percent of the recurrences were seen in liver only and 13.9% in liver and extrahepatic areas. The recurrence rate at cryotreated site was only 6.4% for all cases. During a median follow-up of 36 mo (7-62 mo), the median survival of all patient was 29 mo (range 3-62 mo). Overall survival was 78%, 62%, 41%, 34% and 23% at 1, 2, 3, 4 and 5 years, respectively, after the treatment. Patients with tumor size less than 3 cm, tumor in right lobe of liver, lower CEA levels (< 100 ng/dL) and post- cryosurgery TACE had higher survival rate. There wasno significant difference in terms of survival based on the number of tumors, pre-cryosurgery chemotherapy and the timing of the development of metastases (synchronous vs metachron
