Tissue engineering has become a promising strategy for repairing damaged cartilage and bone tissue. Among the scaffolds for tissue-engineering applications, injectable hydrogels have demonstrated great potential for u...Tissue engineering has become a promising strategy for repairing damaged cartilage and bone tissue. Among the scaffolds for tissue-engineering applications, injectable hydrogels have demonstrated great potential for use as three-dimensional cell culture scaffolds in cartilage and bone tissue engineering, owing to their high water content, similarity to the natural extracellular matrix(ECM), porous framework for cell transplantation and proliferation, minimal invasive properties, and ability to match irregular defects. In this review, we describe the selection of appropriate biomaterials and fabrication methods to prepare novel injectable hydrogels for cartilage and bone tissue engineering. In addition, the biology of cartilage and the bony ECM is also summarized. Finally, future perspectives for injectable hydrogels in cartilage and bone tissue engineering are discussed.展开更多
AIM: To investigate the effect of moxibustion on intestinal flora and release of interleukin-12 (IL-12) and tumor necrosis factor-α (TNF-α) from the colon in rat with ulcerative colitis (UC). METHODS: A rat model of...AIM: To investigate the effect of moxibustion on intestinal flora and release of interleukin-12 (IL-12) and tumor necrosis factor-α (TNF-α) from the colon in rat with ulcerative colitis (UC). METHODS: A rat model of UC was established by local stimulation of the intestine with supernatant from colonic contents harvested from human UC patients. A total of 40 male Sprague-Dawley rats were randomly divided into the following groups: normal (sham), model (UC), herb-partition moxibustion (HPM-treated), and positive control sulfasalazine (SA-treated). Rats treated with HPM received HPM at acupuncture points ST25 and RN6, once a day for 15 min, for a total of 8 d. Rats in the SA group were perfused with SA twice a day for 8 d. The colonic histopathology was observed by hematoxylin-eosin. The levels of intestinal flora, including Bifidobacterium, Lactobacillus, Escherichia coli (E. coli), and Bacteroides fragilis (B. fragilis), were tested by real-time quantitative polymerase chain reaction to detect bacterial 16S rRNA/DNA in order to determine DNA copy numbers of each specific species. Immunohistochemical assays were used to observe the expression of TNF-α and IL-12 in the rat colons. RESULTS: HPM treatment inhibited immunopathology in colonic tissues of UC rats; the general morphological score and the immunopathological score were significantly decreased in the HPM and SA groups compared with the model group [3.5 (2.0-4.0), 3.0 (1.5-3.5) vs 6.0 (5.5-7.0), P < 0.05 for the general morphological score, and 3.00 (2.00-3.50), 3.00 (2.50-3.50) vs 5.00 (4.50-5.50), P < 0.01 for the immunopathological score]. As measured by DNA copy number, we found that Bifidobacterium and Lactobacillus, which are associated with a healthy colon, were significantly higher in the HPM and SA groups than in the model group (1.395 ± 1.339, 1.461 ± 1.152 vs 0.045 ± 0.036, P < 0.01 for Bifidobacterium, and 0.395 ± 0.325, 0.851 ± 0.651 vs 0.0015 ± 0.0014, P < 0.01 for Lactobacillus). On the other hand, E. coli and B. fragilis, which are as展开更多
Advanced intrahepatic cholangiocarcinoma(ICC)has a dismal prognosis.Here,we report the efficacy and safety of combining toripalimab,lenvatinib,and gemcitabine plus oxaliplatin(GEMOX)as first-line therapy for advanced ...Advanced intrahepatic cholangiocarcinoma(ICC)has a dismal prognosis.Here,we report the efficacy and safety of combining toripalimab,lenvatinib,and gemcitabine plus oxaliplatin(GEMOX)as first-line therapy for advanced ICC.Thirty patients with pathologically confirmed advanced ICC received intravenous gemcitabine(1 g/m2)on Days 1 and 8 and oxaliplatin(85 mg/m2)Q3W for six cycles along with intravenous toripalimab(240 mg)Q3W and oral lenvatinib(8 mg)once daily for one year.The expression of programmed death-ligand 1(PD-L1)and genetic status was investigated in paraffin-embedded tissues using immunohistochemistry and whole-exome sequencing(WES)analysis.The primary endpoint was the objective response rate(ORR).Secondary outcomes included safety,overall survival(OS),progression-free survival(PFS),disease control rate(DCR)and duration of response(DoR).As of July 1,2022,the median follow-up time was 23.5 months,and the ORR was 80%.Twenty-three patients achieved partial response,and one achieved complete response.Patients(21/30)with DNA damage response(DDR)-related gene mutations showed a higher ORR,while patients(14/30)with tumor area positivity≥1(PD-L1 staining)showed a trend of high ORR,but without significant difference.The median OS,PFS,and DoR were 22.5,10.2,and 11.0 months,respectively.The DCR was 93.3%.Further,56.7%of patients experienced manageable grade≥3 adverse events(AEs),commonly neutropenia(40.0%)and leukocytopenia(23.3%).In conclusion,toripalimab plus lenvatinib and GEMOX are promising first-line regimens for the treatment of advanced ICC.A phase-III,multicenter,double-blinded,randomized study to validate our findings was approved by the National Medical Products Administration(NMPA,No.2021LP01825).展开更多
Background Triggering receptors expressed on myeloid cells （TREM） proteins are a family of cell surface receptors expressed broadly by cells of the myeloid lineage. The aim of this study was to investigate the clini...Background Triggering receptors expressed on myeloid cells （TREM） proteins are a family of cell surface receptors expressed broadly by cells of the myeloid lineage. The aim of this study was to investigate the clinical significance of soluble TREM-1 （sTREM-1） in pleural effusions, and to determine the effects of pneumonia on pleural sTREM-1 concentrations. Methods Pleural fluid was collected from 109 patients who presented to the respiratory institute （35 with malignant pleural effusion, 31 with tuberculous pleural effusion, 21 with bacterial pleural effusion, and 22 with transudate）. The concentrations of sTREM-1, tumor necrosis factor-a （TNF-a） and interleukin-113 （IL-113） were determined in effusion and serum samples by enzyme linked immunosorbent assay （ELISA）. Results The concentrations of sTREM-1 in bacterial pleural effusion were significantly higher than those in malignant, tuberculous, and transudative groups （all P 〈0.001）. An sTREM-1 cutoff value of 768.1 ng/L had a sensitivity of 86% and a specificity of 93%. Pleural sTREM-1 levels were positively correlated with levels of TNF-a and IL-113. Patients with complicating bacterial pneumonia did not have elevated concentration of sTREM-1 in pleural effusion when compared with patients without pneumonia. Conclusions Determination of pleural sTREM-1 may improve the ability of clinicians to differentiate pleural effusion patients of bacterial origin from those with other etiologies. The occurrence of bacterial pneumonia did not affect pleural sTREM-1 concentrations.展开更多
AIM:To investigate the effect of herb-partitioned moxibustion combined with acupuncture on the expression of intestinal epithelial tight junction(TJ) proteins.METHODS:Sixty patients diagnosed with mild to moderate Cr...AIM:To investigate the effect of herb-partitioned moxibustion combined with acupuncture on the expression of intestinal epithelial tight junction(TJ) proteins.METHODS:Sixty patients diagnosed with mild to moderate Crohn’s disease(CD)were allocated into the herb-partitioned moxibustion combined with acupuncture(HMA)group(n=30)or the mesalazine(MESA)group(n=30)using a parallel control method.There were 2 sets of acupoints used alternately for HMA treatment.The following points were included in Set A:ST25(Tianshu),RN6(Qihai),and RN9(Shuifen)for herb-partitioned moxibustion and ST36(Zusanli),ST37(Shangjuxu),LI11(Quchi),and LI4(Hegu)for acupuncture.The points for Set B included BL23(Shenshu)and BL25(Dachangshu)for herb-partitioned moxibustion and EX-B2 of T6-T1(Jiajixue)fo r acupuncture.The patients received the same treatment6 times a week for 12 consecutive weeks.The MESA group received 1 g of mesalazine enteric coated tablets4 times daily for 12 consecutive weeks.Intestinaltissues were stained and examined to compare the morphological and ultrastructural changes before and after the treatment session.Immunohistochemistry and in situ hybridization assays were used to detect the expression of intestinal epithelial TJ proteins zonula occludens-1(ZO-1),occludin,and claudin-1.The m RNA levels were also evaluated.RESULTS:After the treatment,both herb-partitioned moxibustion combined with acupuncture and mesalazine improved intestinal morphology and ultrastructure of CD patients;the patients treated with HMA showed better improvement.HMA significantly increased the expression of ZO-1(P=0.000),occludin(P=0.021),and claudin-1(P=0.016).MESA significantly increased the expression of ZO-1(P=0.016)and occludin(P=0.026).However,there was no significant increase in the expression of claudin-1(P=0.935).There was no statistically significant difference between the two groups for the expression of occludin and claudin-1(P>0.05).The HMA group showed a significant improvement in ZO-1 expression compared to the MESA group(2333.34±35展开更多
柔性多状态开关(soft open point,SOP)作为可在配电网中替代传统联络开关的新型柔性一次设备,已成为主动配电网领域的研究热点。针对基于模块化多电平变流器(modularmultilevelconverter,MMC)的SOP装置,提出了一种改进型下垂控制策略,...柔性多状态开关(soft open point,SOP)作为可在配电网中替代传统联络开关的新型柔性一次设备,已成为主动配电网领域的研究热点。针对基于模块化多电平变流器(modularmultilevelconverter,MMC)的SOP装置,提出了一种改进型下垂控制策略,将具有功率分配特性的可调下垂系数与基于虚拟惯量的惯性下垂系数相结合。该控制策略可以根据换流站输出功率的变化相应地改变可调下垂系数以改善各端换流站的功率分配能力,提高系统稳定性。此外,该改进型下垂控制策略通过直流电容动态方程将系统频率与直流电压进行耦合,通过快速调整下垂系数调节各端MMC的输出功率,实现对弱交流电网的频率支撑,提高系统可靠性。最后,基于PSCAD/EMTDC仿真软件搭建了四端SOP系统模型,验证了所提控制策略的正确性与有效性。展开更多
AIM: To evaluate urine β2-microglobulin(β2-M), retinol-binding protein(RBP) excretion, and renal impairment with adefovir dipivoxil(ADV) for chronic hepatitis B. METHODS: We enrolled 165 patients with chronic hepati...AIM: To evaluate urine β2-microglobulin(β2-M), retinol-binding protein(RBP) excretion, and renal impairment with adefovir dipivoxil(ADV) for chronic hepatitis B. METHODS: We enrolled 165 patients with chronic hepatitis B infection who were treated with ADV monotherapy(n = 90) or ADV plus lamivudine combination therapy(n = 75). An additional 165 chronic hepatitis B patients treated with entecavir were recruited as controls. We detected serum creatinine, urine β2-M, and RBP levels, and estimated the glomerular filtration rate(e GFR) at the initiation of antiviral therapy and every 6 mo for a period of five years. RESULTS: Urine β2-M abnormalities were observed in patients during the first(n = 3), second(n = 7), third(n = 11), fourth(n = 16), and fifth(n = 21) year of ADV treatment. Urinary RBP abnormalities were observed in patients during the first(n = 2), second(n = 8), third(n = 12), fourth(n = 15), and fifth(n = 22) year of ADV treatment. e GFR decreased 20%-30% from baseline in 20 patients, 30%-50% in 12 patients, and > 50% in 3 patients during the five years of treatment. Further analysis indicated that decreases in e GFR of ≥ 30% relative to the baseline level correlated significantly with urine RBP and β2-M abnormalities. In contrast, both serum creatinine and e GFR remained stable in patients treated with entecavir, and only one of these patients developed a urine β2-M abnormality, and two developed urine RBP abnormalities during the five years of treatment. CONCLUSION: Urine RBP and β2-M are biomarkers of renal injury during long-term ADV treatment for chronic hepatitis B, and indicate when treatment should be switched to entecavir.展开更多
AIM:To investigate the mechanisms of Lactobacillus plantarum(L.plantarum)action on gut barrier in preoperative and postoperative experimental obstructive jaundice in rats.METHODS:Forty rats were randomly divided into ...AIM:To investigate the mechanisms of Lactobacillus plantarum(L.plantarum)action on gut barrier in preoperative and postoperative experimental obstructive jaundice in rats.METHODS:Forty rats were randomly divided into groups of sham-operation,bile duct ligation(BDL),BDL +L.plantarum,BDL+internal biliary drainage(IBD),and BDL+IBD+L.plantarum.Ten days after L.plantarum administration,blood and ileal samples were collected from the rats for morphological examination,and intestinal barrier function,liver function,intestinal oxidative stress and protein kinase C(PKC)activity measurement.The distribution and expression of the PKC and tight junction(TJ)proteins,such as occludin,zonula occludens-1,claudin-1,claudin-4,junction adhesion molecule-A and F-actin,were examined by confocal laser scanning microscopy,immunohistochemistry,Western blotting,real-time fluorescent quantitative polymerase chain reaction assay.RESULTS:L.plantarum administration substantially restored gut barrier,decreased enterocyte apoptosis,improved intestinal oxidative stress,promoted the activity and expression of protein kinase(BDL vs BDL+L.plantarum,0.295±0.007 vs 0.349±0.003,P<0.05;BDL+IBD vs BDL+IBD+L.plantarum,0.407±0.046 vs 0.465±0.135,P<0.05),and particularly enhanced the expression and phosphorylation of TJ proteins in the experimental obstructive jaundice(BDL vs BDL+L.plantarum,0.266±0.118 vs 0.326±0.009,P<0.05).The protective effect of L.plantarum was more prominent after internal biliary drainage(BDL+IBD vs BDL +IBD+L.plantarum,0.415±0.105 vs 0.494±0.145,P<0.05).CONCLUSION:L.plantarum can decrease intestinal epithelial cell apoptosis,reduce oxidative stress,and prevent TJ disruption in biliary obstruction by activating the PKC pathway.展开更多
基金supported by NSFC (nos 61471168, 61571187,61301043,and 61527806)China Postdoctoral Science Foundation (2016T90403)the Economical Forest Cultivation and Utilization of 2011 Collaborative Innovation Center in Hunan Province [(2013)448]
文摘Tissue engineering has become a promising strategy for repairing damaged cartilage and bone tissue. Among the scaffolds for tissue-engineering applications, injectable hydrogels have demonstrated great potential for use as three-dimensional cell culture scaffolds in cartilage and bone tissue engineering, owing to their high water content, similarity to the natural extracellular matrix(ECM), porous framework for cell transplantation and proliferation, minimal invasive properties, and ability to match irregular defects. In this review, we describe the selection of appropriate biomaterials and fabrication methods to prepare novel injectable hydrogels for cartilage and bone tissue engineering. In addition, the biology of cartilage and the bony ECM is also summarized. Finally, future perspectives for injectable hydrogels in cartilage and bone tissue engineering are discussed.
基金Supported by National Natural Science Foundation of China, No. 81001549National Basic Research Program of China (973 program), No. 2009CB522900+1 种基金Shanghai Health System of Outstanding Young Talent Cultivation Program, No. XYQ2011068Shanghai Rising-Star Program, No. 10QA1406100
文摘AIM: To investigate the effect of moxibustion on intestinal flora and release of interleukin-12 (IL-12) and tumor necrosis factor-α (TNF-α) from the colon in rat with ulcerative colitis (UC). METHODS: A rat model of UC was established by local stimulation of the intestine with supernatant from colonic contents harvested from human UC patients. A total of 40 male Sprague-Dawley rats were randomly divided into the following groups: normal (sham), model (UC), herb-partition moxibustion (HPM-treated), and positive control sulfasalazine (SA-treated). Rats treated with HPM received HPM at acupuncture points ST25 and RN6, once a day for 15 min, for a total of 8 d. Rats in the SA group were perfused with SA twice a day for 8 d. The colonic histopathology was observed by hematoxylin-eosin. The levels of intestinal flora, including Bifidobacterium, Lactobacillus, Escherichia coli (E. coli), and Bacteroides fragilis (B. fragilis), were tested by real-time quantitative polymerase chain reaction to detect bacterial 16S rRNA/DNA in order to determine DNA copy numbers of each specific species. Immunohistochemical assays were used to observe the expression of TNF-α and IL-12 in the rat colons. RESULTS: HPM treatment inhibited immunopathology in colonic tissues of UC rats; the general morphological score and the immunopathological score were significantly decreased in the HPM and SA groups compared with the model group [3.5 (2.0-4.0), 3.0 (1.5-3.5) vs 6.0 (5.5-7.0), P < 0.05 for the general morphological score, and 3.00 (2.00-3.50), 3.00 (2.50-3.50) vs 5.00 (4.50-5.50), P < 0.01 for the immunopathological score]. As measured by DNA copy number, we found that Bifidobacterium and Lactobacillus, which are associated with a healthy colon, were significantly higher in the HPM and SA groups than in the model group (1.395 ± 1.339, 1.461 ± 1.152 vs 0.045 ± 0.036, P < 0.01 for Bifidobacterium, and 0.395 ± 0.325, 0.851 ± 0.651 vs 0.0015 ± 0.0014, P < 0.01 for Lactobacillus). On the other hand, E. coli and B. fragilis, which are as
基金National Natural Science Foundation of China(81972232,81830102,82150004)Clinical Research Plan of SHDC(SHDC‑2020CR1003A,SHDC-2020CR1022B)+3 种基金National Key Research and Development Program of China(2019YFC1316000,2019YFC1315800,and 2019YFC1315802)the Key Disease Joint Research Program of Xuhui District(XHLHGG202103),the Clinical Medicine Research Pilot Project of Shanghai Medical School of Fudan University(2020,21DGF501035/00)the Shanghai Municipal Natural Science Foundation(20JC1419103,21ZR1412200)Beijing Mutual Care Public Welfare Foundation(GDXZ-08-05)Sanming Project of Medicine in Shenzhen(SZSM202003009),and Shanghai Municipal Key Clinical Specialty Construction Project(shslczdzk02401).
文摘Advanced intrahepatic cholangiocarcinoma(ICC)has a dismal prognosis.Here,we report the efficacy and safety of combining toripalimab,lenvatinib,and gemcitabine plus oxaliplatin(GEMOX)as first-line therapy for advanced ICC.Thirty patients with pathologically confirmed advanced ICC received intravenous gemcitabine(1 g/m2)on Days 1 and 8 and oxaliplatin(85 mg/m2)Q3W for six cycles along with intravenous toripalimab(240 mg)Q3W and oral lenvatinib(8 mg)once daily for one year.The expression of programmed death-ligand 1(PD-L1)and genetic status was investigated in paraffin-embedded tissues using immunohistochemistry and whole-exome sequencing(WES)analysis.The primary endpoint was the objective response rate(ORR).Secondary outcomes included safety,overall survival(OS),progression-free survival(PFS),disease control rate(DCR)and duration of response(DoR).As of July 1,2022,the median follow-up time was 23.5 months,and the ORR was 80%.Twenty-three patients achieved partial response,and one achieved complete response.Patients(21/30)with DNA damage response(DDR)-related gene mutations showed a higher ORR,while patients(14/30)with tumor area positivity≥1(PD-L1 staining)showed a trend of high ORR,but without significant difference.The median OS,PFS,and DoR were 22.5,10.2,and 11.0 months,respectively.The DCR was 93.3%.Further,56.7%of patients experienced manageable grade≥3 adverse events(AEs),commonly neutropenia(40.0%)and leukocytopenia(23.3%).In conclusion,toripalimab plus lenvatinib and GEMOX are promising first-line regimens for the treatment of advanced ICC.A phase-III,multicenter,double-blinded,randomized study to validate our findings was approved by the National Medical Products Administration(NMPA,No.2021LP01825).
基金This study was supported by research grants from National Natural Science Foundation of China （No. 30660064）, Natural Science Foundation of Guangxi Zhuang Autonomous Region （No. 0639044）, and the Bureau of Health, Guangxi Zhuang Autonomous Region, China （No. 200621）. None of the authors have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.
文摘Background Triggering receptors expressed on myeloid cells （TREM） proteins are a family of cell surface receptors expressed broadly by cells of the myeloid lineage. The aim of this study was to investigate the clinical significance of soluble TREM-1 （sTREM-1） in pleural effusions, and to determine the effects of pneumonia on pleural sTREM-1 concentrations. Methods Pleural fluid was collected from 109 patients who presented to the respiratory institute （35 with malignant pleural effusion, 31 with tuberculous pleural effusion, 21 with bacterial pleural effusion, and 22 with transudate）. The concentrations of sTREM-1, tumor necrosis factor-a （TNF-a） and interleukin-113 （IL-113） were determined in effusion and serum samples by enzyme linked immunosorbent assay （ELISA）. Results The concentrations of sTREM-1 in bacterial pleural effusion were significantly higher than those in malignant, tuberculous, and transudative groups （all P 〈0.001）. An sTREM-1 cutoff value of 768.1 ng/L had a sensitivity of 86% and a specificity of 93%. Pleural sTREM-1 levels were positively correlated with levels of TNF-a and IL-113. Patients with complicating bacterial pneumonia did not have elevated concentration of sTREM-1 in pleural effusion when compared with patients without pneumonia. Conclusions Determination of pleural sTREM-1 may improve the ability of clinicians to differentiate pleural effusion patients of bacterial origin from those with other etiologies. The occurrence of bacterial pneumonia did not affect pleural sTREM-1 concentrations.
基金Supported by National Natural Science Foundation of China,No.30772831,No.81473757the National Basic Research Program of China,973 Program,No.2009CB522900
文摘AIM:To investigate the effect of herb-partitioned moxibustion combined with acupuncture on the expression of intestinal epithelial tight junction(TJ) proteins.METHODS:Sixty patients diagnosed with mild to moderate Crohn’s disease(CD)were allocated into the herb-partitioned moxibustion combined with acupuncture(HMA)group(n=30)or the mesalazine(MESA)group(n=30)using a parallel control method.There were 2 sets of acupoints used alternately for HMA treatment.The following points were included in Set A:ST25(Tianshu),RN6(Qihai),and RN9(Shuifen)for herb-partitioned moxibustion and ST36(Zusanli),ST37(Shangjuxu),LI11(Quchi),and LI4(Hegu)for acupuncture.The points for Set B included BL23(Shenshu)and BL25(Dachangshu)for herb-partitioned moxibustion and EX-B2 of T6-T1(Jiajixue)fo r acupuncture.The patients received the same treatment6 times a week for 12 consecutive weeks.The MESA group received 1 g of mesalazine enteric coated tablets4 times daily for 12 consecutive weeks.Intestinaltissues were stained and examined to compare the morphological and ultrastructural changes before and after the treatment session.Immunohistochemistry and in situ hybridization assays were used to detect the expression of intestinal epithelial TJ proteins zonula occludens-1(ZO-1),occludin,and claudin-1.The m RNA levels were also evaluated.RESULTS:After the treatment,both herb-partitioned moxibustion combined with acupuncture and mesalazine improved intestinal morphology and ultrastructure of CD patients;the patients treated with HMA showed better improvement.HMA significantly increased the expression of ZO-1(P=0.000),occludin(P=0.021),and claudin-1(P=0.016).MESA significantly increased the expression of ZO-1(P=0.016)and occludin(P=0.026).However,there was no significant increase in the expression of claudin-1(P=0.935).There was no statistically significant difference between the two groups for the expression of occludin and claudin-1(P>0.05).The HMA group showed a significant improvement in ZO-1 expression compared to the MESA group(2333.34±35
文摘柔性多状态开关(soft open point,SOP)作为可在配电网中替代传统联络开关的新型柔性一次设备,已成为主动配电网领域的研究热点。针对基于模块化多电平变流器(modularmultilevelconverter,MMC)的SOP装置,提出了一种改进型下垂控制策略,将具有功率分配特性的可调下垂系数与基于虚拟惯量的惯性下垂系数相结合。该控制策略可以根据换流站输出功率的变化相应地改变可调下垂系数以改善各端换流站的功率分配能力,提高系统稳定性。此外,该改进型下垂控制策略通过直流电容动态方程将系统频率与直流电压进行耦合,通过快速调整下垂系数调节各端MMC的输出功率,实现对弱交流电网的频率支撑,提高系统可靠性。最后,基于PSCAD/EMTDC仿真软件搭建了四端SOP系统模型,验证了所提控制策略的正确性与有效性。
基金Supported by National Key Program for Infectious Diseases of China(to Yang YD),No.2013ZX1000200112th FiveYear Significant New Drugs Creation Plan of the Ministry of Science and Technology of China(to Yang YD),No.2011ZX09302-003-03
文摘AIM: To evaluate urine β2-microglobulin(β2-M), retinol-binding protein(RBP) excretion, and renal impairment with adefovir dipivoxil(ADV) for chronic hepatitis B. METHODS: We enrolled 165 patients with chronic hepatitis B infection who were treated with ADV monotherapy(n = 90) or ADV plus lamivudine combination therapy(n = 75). An additional 165 chronic hepatitis B patients treated with entecavir were recruited as controls. We detected serum creatinine, urine β2-M, and RBP levels, and estimated the glomerular filtration rate(e GFR) at the initiation of antiviral therapy and every 6 mo for a period of five years. RESULTS: Urine β2-M abnormalities were observed in patients during the first(n = 3), second(n = 7), third(n = 11), fourth(n = 16), and fifth(n = 21) year of ADV treatment. Urinary RBP abnormalities were observed in patients during the first(n = 2), second(n = 8), third(n = 12), fourth(n = 15), and fifth(n = 22) year of ADV treatment. e GFR decreased 20%-30% from baseline in 20 patients, 30%-50% in 12 patients, and > 50% in 3 patients during the five years of treatment. Further analysis indicated that decreases in e GFR of ≥ 30% relative to the baseline level correlated significantly with urine RBP and β2-M abnormalities. In contrast, both serum creatinine and e GFR remained stable in patients treated with entecavir, and only one of these patients developed a urine β2-M abnormality, and two developed urine RBP abnormalities during the five years of treatment. CONCLUSION: Urine RBP and β2-M are biomarkers of renal injury during long-term ADV treatment for chronic hepatitis B, and indicate when treatment should be switched to entecavir.
基金Supported by The National Natural Science Foundation of China,No.30471687Chinese Ministry of Science and Technology,No.2008CB517403
文摘AIM:To investigate the mechanisms of Lactobacillus plantarum(L.plantarum)action on gut barrier in preoperative and postoperative experimental obstructive jaundice in rats.METHODS:Forty rats were randomly divided into groups of sham-operation,bile duct ligation(BDL),BDL +L.plantarum,BDL+internal biliary drainage(IBD),and BDL+IBD+L.plantarum.Ten days after L.plantarum administration,blood and ileal samples were collected from the rats for morphological examination,and intestinal barrier function,liver function,intestinal oxidative stress and protein kinase C(PKC)activity measurement.The distribution and expression of the PKC and tight junction(TJ)proteins,such as occludin,zonula occludens-1,claudin-1,claudin-4,junction adhesion molecule-A and F-actin,were examined by confocal laser scanning microscopy,immunohistochemistry,Western blotting,real-time fluorescent quantitative polymerase chain reaction assay.RESULTS:L.plantarum administration substantially restored gut barrier,decreased enterocyte apoptosis,improved intestinal oxidative stress,promoted the activity and expression of protein kinase(BDL vs BDL+L.plantarum,0.295±0.007 vs 0.349±0.003,P<0.05;BDL+IBD vs BDL+IBD+L.plantarum,0.407±0.046 vs 0.465±0.135,P<0.05),and particularly enhanced the expression and phosphorylation of TJ proteins in the experimental obstructive jaundice(BDL vs BDL+L.plantarum,0.266±0.118 vs 0.326±0.009,P<0.05).The protective effect of L.plantarum was more prominent after internal biliary drainage(BDL+IBD vs BDL +IBD+L.plantarum,0.415±0.105 vs 0.494±0.145,P<0.05).CONCLUSION:L.plantarum can decrease intestinal epithelial cell apoptosis,reduce oxidative stress,and prevent TJ disruption in biliary obstruction by activating the PKC pathway.
