AIM:To compare efficacy of combined lamivudine(LAM)and adefovir dipivoxil(ADV)therapy with that of entecavir(ETV)monotherapy for hepatitis B virus(HBV)-related decompensated liver cirrhosis.METHODS:A total of 120 na v...AIM:To compare efficacy of combined lamivudine(LAM)and adefovir dipivoxil(ADV)therapy with that of entecavir(ETV)monotherapy for hepatitis B virus(HBV)-related decompensated liver cirrhosis.METHODS:A total of 120 na ve patients with HBVrelated decompensated cirrhosis participated in this study.Sixty patients were treated with combined LAM and ADV therapy(LAM+ADV group),while the other60 were treated with ETV monotherapy(ETV group)for two years.Tests for liver and kidney function,alpha-fetoprotein,HBV serum markers,HBV DNA load,prothrombin time(PT),and ultrasonography or computed tomography scan of the liver were performed every1 to 3 mo.Repeated measure ANOVA and theχ2test were performed to compare the efficacy,side effects,and the cumulative survival rates at 48 and 96 wk.RESULTS:Forty-five patients in each group were observed for 96 wk.No significant differences in HBV DNA negative rates and alanine aminotransferase(ALT)normalization rates at weeks 48(χ2=2.12 and 2.88)and96(χ2=3.21 and 3.24)between the two groups were observed.Hepatitis B e antigen seroconversion rate in the LAM+ADV group at week 96 was significantly higher in the ETV group(43.5%vs 36.4%,χ2=4.09,P<0.05).Viral breakthrough occurred in 2 cases(4.4%)by week 48 and in 3 cases(6.7%)by week 96 in the LAM+ADV group,and no viral mutation was detected.In the ETV group,viral breakthrough occurred in 1 case(2.2%)at the end of week 96.An increase in albumin(F=18.9 and 17.3),decrease in total bilirubin and in ALT(F=16.5,17.1 and 23.7,24.8),reduced PT(F=22.7 and 24.5),and improved Child-Turcotte-Pugh and the model for end-stage liver disease scores(F=18.5,17.8,and 24.2,23.8)were observed in both groups.The cumulative rates of mortality and liver transplantation were 16.7%(10/60)and 18.3%(11/60)in the LAM+ADV and ETV groups,respectively.CONCLUSION:Both LAM+ADV combination therapy and ETV monotherapy can effectively inhibit HBV replication,improve liver function,and decrease mortality.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 determine the baseline hepatitis B surface antigen(HBsAg) levels during the different phases of chronic hepatitis B(CHB) patients in China.METHODS: Six hundred and twenty-three hepatitis B virus or un-infected...AIM: To determine the baseline hepatitis B surface antigen(HBsAg) levels during the different phases of chronic hepatitis B(CHB) patients in China.METHODS: Six hundred and twenty-three hepatitis B virus or un-infected patients not receiving antiviral therapy were analyzed in a cross-sectional study. The CHB patients were classified into five phases: immunetolerant(IT, n = 108), immune-clearance(IC, n = 161), hepatitis B e antigen negative hepatitis(ENH, n = 149), low-replicative(LR, n = 135), and liver cirrhosis(LC, n = 70). HBsAg was quantified(Abbott ARCHITECT assay) and correlated with hepatitis B virus(HBV) DNA, and serum alanine aminotransferase/aspartate aminotransferase(ALT/AST) in each phase of CHB was also determined.RESULTS: Median HBsAg titers were different in each phase of CHB(P < 0.001): IT(4.85 log10 IU/mL), IC(4.36 log10 IU/mL), ENH(2.95 log10 IU/mL), LR(3.18 log10 IU/mL) and LC(2.69 log10 IU/mL). HBsAg titers were highest in the IT phase and lowest in the LC phase. Serum HBsAg titers showed a strong correlation with HBV viral load in the IC phase(r = 0.683, P < 0.001). No correlation between serum HBsAg level and ALT/AST was observed.CONCLUSION: The mean baseline HBsAg levels differ significantly during the five phases of CHB, providing evidence on the natural history of HBV infection. HBsAg quantification may predict the effects of immunemodulator or oral nucleos(t)ide analogue therapy.展开更多
Background:Serum chitinase-3-like protein 1(CHI3L1)is a potential biomarker for fibrosis assessment.We aimed to evaluate serum CHI3L1 as a noninvasive diagnostic marker for chronic hepatitis B virusrelated fibrosis.Me...Background:Serum chitinase-3-like protein 1(CHI3L1)is a potential biomarker for fibrosis assessment.We aimed to evaluate serum CHI3L1 as a noninvasive diagnostic marker for chronic hepatitis B virusrelated fibrosis.Methods:Serum CHI3L1 levels were measured by ELISA in 134 chronic hepatitis B(CHB)patients.Significant fibrosis was defined as a liver stiffness>9.7 kPa.The performance of CHI3L1 was assessed and compared to that of other noninvasive tests by receiver operating characteristic(ROC)analysis.Results:Serum CHI3L1 levels were significantly higher in CHB patients with significant hepatic fibrosis(≥F2)than in those without significant hepatic fibrosis(<F2)(56.5 ng/mL vs.81.9 ng/mL,P<0.001).In CHB patients,the specificity and sensitivity of CHI3L1 for predicting significant fibrosis were 75.6%and 59.1%,respectively,with a cut-off of 76.0 ng/mL and an area under the ROC curve of 0.728(95%CI:0.637–0.820).Conclusions:Serum CHI3L1 levels could be an effective new serological biomarker for the diagnosis of liver fibrosis.Moreover,CHI3L1 is feasible in monitoring disease progression.展开更多
Phenolic compounds such as chlorogenic acid,cryptochlorogenic acid,neochlorogenic acid and caffeic acid are widely distributed in fruits,vegetables and traditional Chinese medicines with a wide range of biological act...Phenolic compounds such as chlorogenic acid,cryptochlorogenic acid,neochlorogenic acid and caffeic acid are widely distributed in fruits,vegetables and traditional Chinese medicines with a wide range of biological activities.Tyrosinase plays a critical role in the food industry,but recent studies have proposed unexplored aspects of clinical application.Tyrosinase-catalyzed oxidation of four polyphenols as well as its underlying mechanism remains unclear.In the current work,we investigated the kinetic properties of tyrosinase-catalyzed oxidation of the four polyphenols of interest.To measure the unstable o-quinone products,an analytical method using 3-methyl-2-benzothiazolinone hydrazone(MBTH)was established.The optimal incubation time,buffer pH,temperature and enzyme concentration for the enzyme activity in the presence of each polyphenol of interest were investigated.Under the final optimized conditions,the kinetics and substrate specificity of four polyphenols were examined.K inetic data showed that tyrosinase had the greatest substrate affinity to chlorogenic acid compared with its isomers and caffeic acid.The catalytic efficiency with chlorogenic acid was 8-to 15-fold higher than that with the other 3 polyphenols.Molecular docking study demonstrated that the tight binding of chlorogenic acid at the peripheral site should be the major reason for the specificity to chlorogenic acid.In light of this,the rational design of high-affinity inhibitors against tyrosinase may focus on the binding of both the Cu site and peripheral site.This study will supply a basis for the selection of phenolic acids in food industry and health carc.展开更多
The finite autocorrelation time of thermal noise is crucial to unidirectional transportation on the molecular scale.Therefore,it is important to understand the cause of the intrinsic picosecond autocorrelation time of...The finite autocorrelation time of thermal noise is crucial to unidirectional transportation on the molecular scale.Therefore,it is important to understand the cause of the intrinsic picosecond autocorrelation time of thermal noise in water.In this work,we use molecular dynamics simulations to compare the autocorrelation behaviors of the thermal noise,hydrogen bonds,and molecular rotations found in water.We found that the intrinsic picosecond autocorrelation time for thermal noise is caused by finite molecular rotation relaxation,in which hydrogen bonds play the role of a bridge.Furthermore,the simulation results show that our method of calculating the autocorrelation of thermal noise,by observing the fiuctuating force on an oxygen atom of water,provides additional information about molecular rotations.Our findings may advance the understanding of the anomalous dynamic nanoscale behavior of particles,and the applications of terahertz technology in measuring the structural and dynamical information of molecules in solutions.展开更多
BACKGROUND Primary encapsulating peritoneal sclerosis(EPS)is a rare but devastating disease that causes fibrocollagenous cocoon-like encapsulation of the bowel,resulting in bowel obstruction.The pathogenesis,preventio...BACKGROUND Primary encapsulating peritoneal sclerosis(EPS)is a rare but devastating disease that causes fibrocollagenous cocoon-like encapsulation of the bowel,resulting in bowel obstruction.The pathogenesis,prevention,and treatment strategies of EPS remain unclear so far.Since most patients are diagnosed during exploratory laparotomy,for the non-surgically diagnosed patients with primary EPS,the surgical timing is also uncertain.CASE SUMMARY A 44-year-old female patient was referred to our center on September 6,2021,with complaints of abdominal distention and bilious vomiting for 2 d.Physical examination revealed that the vital signs were stable,and the abdomen was slightly distended.Computerized tomography scan showed a conglomerate of multiple intestinal loops encapsulated in a thick sac-like membrane,which was surrounded by abdominal ascites.The patient was diagnosed with idiopathic EPS.Recovery was observed after abdominal paracentesis,and the patient was discharged on September 13 after the resumption of a normal diet.This case raised a question:When should an exploratory laparotomy be performed on patients who are non-surgically diagnosed with EPS.As a result,we conducted a review of the literature on the clinical manifestations,intraoperative findings,surgical methods,and therapeutic effects of EPS.CONCLUSION Recurrent intestinal obstructions and abdominal mass combined with the imaging of encapsulated bowel are helpful in diagnosing idiopathic EPS.Small intestinal resection should be avoided.展开更多
Background:Albuvirtide is a once-weekly injectable human immunodeficiency virus(HIV)-1 fusion inhibitor.We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-riton...Background:Albuvirtide is a once-weekly injectable human immunodeficiency virus(HIV)-1 fusion inhibitor.We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs.Methods:We carried out a 48-week,randomized,controlled,open-label non-inferiority trial at 12 sites in China.Adults on the World Health Organization(WHO)-recommended first-line treatment for>6 months with a plasma viral load>1000 copies/mL were enrolled and randomly assigned(1:1)to receive albuvirtide(once weekly)plus ritonavir-boosted lopinavir(ABT group)or the WHO-recommended second-line treatment(NRTI group).The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks.Non-inferiority was prespecified with a margin of 12%.Results:At the time of analysis,week 24 data were available for 83 and 92 patients,and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups,respectively.At 48 weeks,80.4%of patients in the ABT group and 66.0%of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL,meeting the criteria for non-inferiority.For the per-protocol population,the superiority of albuvirtide over NRTI was demonstrated.The frequency of grade 3 to 4 adverse events was similar in the two groups;the most common adverse events were diarrhea,upper respiratory tract infections,and grade 3 to 4 increases in triglyceride concentration.Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group.Conclusions:The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug.This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure.Trial registration:ClinicalTrials.gov Identifier:NCT02369965;https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No.ChiCTR-TRC-14004276;http://www.chictr.org.cn/enindex.aspx.展开更多
To realize good point connection between high-strength steel and aluminum alloy,a process of drawing-upsetting-extrusion-clinching was proposed.First,the sheets were drawn;then,the bottom of the protrusion part was ex...To realize good point connection between high-strength steel and aluminum alloy,a process of drawing-upsetting-extrusion-clinching was proposed.First,the sheets were drawn;then,the bottom of the protrusion part was extruded,forming the necessary initial interlock;and finally,the protrusion part was reverse press clinched,forming a certain height of the clinched head.Taking DP980 high-strength steel and A15083 aluminum alloy as the connection objects and using the method of numerical simulation combined with experimental test,the mold was made,and the experiment was carried out on the basis of numerical simulation.The experimental results proved the feasibility of the process and the effectiveness of the numerical model.The simulation and experimental results show that the necessary interlock in the drawing-upsetting-extrusion stage is the premise of effective connection.The relative protrusion height should be around 55.6%after reverse-press-clinching.The best comprehensive mechanical properties measured by strength test were shear resistance of 2644 N,fatigue life of 24,535 times and peel resistance of 1522 N.Through failure analysis,the relationship between the interlock Tu and the neck thickness Tn of the joint with the best comprehensive mechanical properties was established as Tu=0.35Tn.The design method of die and process parameters when the sheet thickness changes was researched by numerical simulation.The results show that the clearance between the punch and the die and the bottom thickness are directly proportional to the sheet thickness,and the drawing depth is directly proportional to the punch radius.展开更多
Background:The optimal surgical approach for four-level cervical spondylotic myelopathy remains controversial.The purpose of this study was to compare clinical and radiological outcomes and complications between the a...Background:The optimal surgical approach for four-level cervical spondylotic myelopathy remains controversial.The purpose of this study was to compare clinical and radiological outcomes and complications between the anterior and posterior approaches for four-level cervical spondylotic myelopathy.Methods:A total of 19 patients underwent anterior decompression and fusion and 25 patients underwent posterior laminoplasty and instrumentation in this study.Perioperative information,intraoperative blood loss,clinical and radiological outcomes,and complications were recorded.Japanese Orthopedic Association(JOA)score,36-item short form survey(SF-36)score and cervical alignment were assessed.Results:There were no significant differences in JOA scores between the anterior and posterior group preoperatively(11.6±1.6 vs.12.1±1.5),immediately postoperatively(14.4±1.1 vs.13.8±1.3),or at the last follow-up(14.6±1.0 vs.14.2±1.1)(P>0.05).The JOA scores significantly improved immediately postoperatively and at the last follow-up in both groups compared with their preoperative values.The recovery rate was significantly higher in the anterior group both immediately postoperatively and at the last follow-up.The SF-36 score was significantly higher in the anterior group at the last follow-up compared with the preoperative value(69.4 vs.61.7).Imaging revealed that there was no significant difference in the Cobb angle at C2-C7 between the two groups preoperatively(-2.0°±7.3°vs.-1.4°±7.5°).The Cobb angle significantly improved immediately postoperatively(12.3°±4.2°vs.9.2°±3.6°)and at the last follow-up(12.4°±3.5°vs.9.0°±2.6°)in both groups compared with their preoperative values(P=0.00).Three patients had temporary dysphagia in the anterior group and four patients had persistent axial symptoms in the posterior group.Conclusions:Both the anterior and posterior approaches were effective in treating four-level cervical spondylotic myelopathy in terms of neurological clinical outcomes and radiological features.However,the JOA score recovery rate and SF-36 score in the anterior group were significantly higher.Persistent axial pain could be a major concern when undertaking the posterior approach.展开更多
Background The outbreak of coronavirus disease 2019(COVID-19)is now becoming an enormous threat to public health.The clinical spectrum of COVID-19 is extensive,of which critical cases are with rapid disease progressio...Background The outbreak of coronavirus disease 2019(COVID-19)is now becoming an enormous threat to public health.The clinical spectrum of COVID-19 is extensive,of which critical cases are with rapid disease progression and high mortality.The aim of our study is to summarize the characteristics of different subtypes and explore risk factors of illness severity for early identification and prompt treatment.Methods In this retrospective study,we collected data of patients confirmed COVID-19 in Zhejiang Province from 17 January to 12 February 2020.According to the definition of clinical classification,we divided confirmed cases into four types,and summarize epidemiological and clinical characteristics,laboratory and radiograph findings,treatments,and outcomes,respectively.Moreover,we used univariate and multivariate ordinal logistic regression models to explore risk factors for the severity of illness in patients with COVID-19.Results A total of 788 patients were enrolled in our study,of whom 52 cases(6.6%)were mild type,658 cases(83.5%)were common type,61 cases(7.2%)were severe type,and 17 cases(2.2%)were critical type.Multivariate ordinal logistic regression demonstrated increasing odds of the severity of illness in patients with COVID-19 associated with male(odds ratio[OR]=1.7,95%confidence interval[CI]:1.2–2.6 P=0.008),fever(OR=3.6,95%CI:2.1–6.3,P<0.001),cough(OR=1.7,95%CI:1.0–2.9,P=0.041),hemoptysis(OR=3.4,95%CI:1.1–10.3,P=0.032),gastrointestinal symptoms(OR=1.9,95%CI:1.0–3.5,P=0.047),hypertension(OR=2.6,95%CI:1.2–5.6,P=0.013).With the increase of age-grading,risk for the severity of illness was gradually higher(≤18 years[OR=1.0],19–40 years[OR=12.7,95%CI:4.5–36.0,P<0.001],41–65 years[OR=14.8,95%CI:5.2–42.1,P<0.001],≥66 years[OR=56.5,95%CI:17.1–186.5,P<0.001]).Conclusions Clinicians should pay close attention to these features in patients with COVID-19 including older age,male,fever,cough,hemoptysis,gastrointestinal symptoms and hypertension to identify the severity of illness as early as possible.展开更多
基金Project(P2018-013)supported by the Open Foundation of State Key Laboratory of Materials Processing and Die&Mould Technology,Huazhong University of Science and Technology,China
基金Project(41672298) supported by the National Natural Science Foundation of ChinaProject(2017YFC0602901) supported by the National Key Research and Development Program of China
基金Project(41672298)supported by the National Natural Science Foundation of ChinaProject(2017YFC0602901)supported by the National Key Research and Development Program of China。
基金Supported by the National Key Program for Infectious Diseases of China to Yang YD,2013ZX1000200112th Five-Year Significant New Drugs Creation Plan of the Ministry of Science and Technology of China toYangYD,2011ZX09302-003-03
文摘AIM:To compare efficacy of combined lamivudine(LAM)and adefovir dipivoxil(ADV)therapy with that of entecavir(ETV)monotherapy for hepatitis B virus(HBV)-related decompensated liver cirrhosis.METHODS:A total of 120 na ve patients with HBVrelated decompensated cirrhosis participated in this study.Sixty patients were treated with combined LAM and ADV therapy(LAM+ADV group),while the other60 were treated with ETV monotherapy(ETV group)for two years.Tests for liver and kidney function,alpha-fetoprotein,HBV serum markers,HBV DNA load,prothrombin time(PT),and ultrasonography or computed tomography scan of the liver were performed every1 to 3 mo.Repeated measure ANOVA and theχ2test were performed to compare the efficacy,side effects,and the cumulative survival rates at 48 and 96 wk.RESULTS:Forty-five patients in each group were observed for 96 wk.No significant differences in HBV DNA negative rates and alanine aminotransferase(ALT)normalization rates at weeks 48(χ2=2.12 and 2.88)and96(χ2=3.21 and 3.24)between the two groups were observed.Hepatitis B e antigen seroconversion rate in the LAM+ADV group at week 96 was significantly higher in the ETV group(43.5%vs 36.4%,χ2=4.09,P<0.05).Viral breakthrough occurred in 2 cases(4.4%)by week 48 and in 3 cases(6.7%)by week 96 in the LAM+ADV group,and no viral mutation was detected.In the ETV group,viral breakthrough occurred in 1 case(2.2%)at the end of week 96.An increase in albumin(F=18.9 and 17.3),decrease in total bilirubin and in ALT(F=16.5,17.1 and 23.7,24.8),reduced PT(F=22.7 and 24.5),and improved Child-Turcotte-Pugh and the model for end-stage liver disease scores(F=18.5,17.8,and 24.2,23.8)were observed in both groups.The cumulative rates of mortality and liver transplantation were 16.7%(10/60)and 18.3%(11/60)in the LAM+ADV and ETV groups,respectively.CONCLUSION:Both LAM+ADV combination therapy and ETV monotherapy can effectively inhibit HBV replication,improve liver function,and decrease mortality.
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 National Key Program for Infectious Diseases of China to Yang YD,No.2013ZX10002001the 12th Five-Year Significant New Drugs Creation Plan of the Ministry of Science and Technology of China to Li LJ,No.2011ZX09302-003-03
文摘AIM: To determine the baseline hepatitis B surface antigen(HBsAg) levels during the different phases of chronic hepatitis B(CHB) patients in China.METHODS: Six hundred and twenty-three hepatitis B virus or un-infected patients not receiving antiviral therapy were analyzed in a cross-sectional study. The CHB patients were classified into five phases: immunetolerant(IT, n = 108), immune-clearance(IC, n = 161), hepatitis B e antigen negative hepatitis(ENH, n = 149), low-replicative(LR, n = 135), and liver cirrhosis(LC, n = 70). HBsAg was quantified(Abbott ARCHITECT assay) and correlated with hepatitis B virus(HBV) DNA, and serum alanine aminotransferase/aspartate aminotransferase(ALT/AST) in each phase of CHB was also determined.RESULTS: Median HBsAg titers were different in each phase of CHB(P < 0.001): IT(4.85 log10 IU/mL), IC(4.36 log10 IU/mL), ENH(2.95 log10 IU/mL), LR(3.18 log10 IU/mL) and LC(2.69 log10 IU/mL). HBsAg titers were highest in the IT phase and lowest in the LC phase. Serum HBsAg titers showed a strong correlation with HBV viral load in the IC phase(r = 0.683, P < 0.001). No correlation between serum HBsAg level and ALT/AST was observed.CONCLUSION: The mean baseline HBsAg levels differ significantly during the five phases of CHB, providing evidence on the natural history of HBV infection. HBsAg quantification may predict the effects of immunemodulator or oral nucleos(t)ide analogue therapy.
基金the Research Ethics Committee of The First Affiliated Hospital of Zhejiang University School of Medicine(No.2018-918).
文摘Background:Serum chitinase-3-like protein 1(CHI3L1)is a potential biomarker for fibrosis assessment.We aimed to evaluate serum CHI3L1 as a noninvasive diagnostic marker for chronic hepatitis B virusrelated fibrosis.Methods:Serum CHI3L1 levels were measured by ELISA in 134 chronic hepatitis B(CHB)patients.Significant fibrosis was defined as a liver stiffness>9.7 kPa.The performance of CHI3L1 was assessed and compared to that of other noninvasive tests by receiver operating characteristic(ROC)analysis.Results:Serum CHI3L1 levels were significantly higher in CHB patients with significant hepatic fibrosis(≥F2)than in those without significant hepatic fibrosis(<F2)(56.5 ng/mL vs.81.9 ng/mL,P<0.001).In CHB patients,the specificity and sensitivity of CHI3L1 for predicting significant fibrosis were 75.6%and 59.1%,respectively,with a cut-off of 76.0 ng/mL and an area under the ROC curve of 0.728(95%CI:0.637–0.820).Conclusions:Serum CHI3L1 levels could be an effective new serological biomarker for the diagnosis of liver fibrosis.Moreover,CHI3L1 is feasible in monitoring disease progression.
基金The study was supported by grants from the National Natural Science Foundation of China(No.81773811)Yunnan Applied Basic Research Project(No.2017FB074)+1 种基金the Yunnan Provincial Tobacco Monopoly Bureau Grants(No.2017YN09)the Fundamental Research Funds for the Central Universities(No.2020kfyXGYJ061).
文摘Phenolic compounds such as chlorogenic acid,cryptochlorogenic acid,neochlorogenic acid and caffeic acid are widely distributed in fruits,vegetables and traditional Chinese medicines with a wide range of biological activities.Tyrosinase plays a critical role in the food industry,but recent studies have proposed unexplored aspects of clinical application.Tyrosinase-catalyzed oxidation of four polyphenols as well as its underlying mechanism remains unclear.In the current work,we investigated the kinetic properties of tyrosinase-catalyzed oxidation of the four polyphenols of interest.To measure the unstable o-quinone products,an analytical method using 3-methyl-2-benzothiazolinone hydrazone(MBTH)was established.The optimal incubation time,buffer pH,temperature and enzyme concentration for the enzyme activity in the presence of each polyphenol of interest were investigated.Under the final optimized conditions,the kinetics and substrate specificity of four polyphenols were examined.K inetic data showed that tyrosinase had the greatest substrate affinity to chlorogenic acid compared with its isomers and caffeic acid.The catalytic efficiency with chlorogenic acid was 8-to 15-fold higher than that with the other 3 polyphenols.Molecular docking study demonstrated that the tight binding of chlorogenic acid at the peripheral site should be the major reason for the specificity to chlorogenic acid.In light of this,the rational design of high-affinity inhibitors against tyrosinase may focus on the binding of both the Cu site and peripheral site.This study will supply a basis for the selection of phenolic acids in food industry and health carc.
基金supported by the National Key Research and Development Program of China(No.2018YFE0205501 and 2018YFB1801500)the National Natural Science Foundation of China(No.11904231)the Shanghai Sailing Program(No.19YF1434100)。
文摘The finite autocorrelation time of thermal noise is crucial to unidirectional transportation on the molecular scale.Therefore,it is important to understand the cause of the intrinsic picosecond autocorrelation time of thermal noise in water.In this work,we use molecular dynamics simulations to compare the autocorrelation behaviors of the thermal noise,hydrogen bonds,and molecular rotations found in water.We found that the intrinsic picosecond autocorrelation time for thermal noise is caused by finite molecular rotation relaxation,in which hydrogen bonds play the role of a bridge.Furthermore,the simulation results show that our method of calculating the autocorrelation of thermal noise,by observing the fiuctuating force on an oxygen atom of water,provides additional information about molecular rotations.Our findings may advance the understanding of the anomalous dynamic nanoscale behavior of particles,and the applications of terahertz technology in measuring the structural and dynamical information of molecules in solutions.
基金Supported by the Key Projects of Support Plan of Nanchang Science and Technology Bureau,Jiangxi Province,China,No.[2020]153
文摘BACKGROUND Primary encapsulating peritoneal sclerosis(EPS)is a rare but devastating disease that causes fibrocollagenous cocoon-like encapsulation of the bowel,resulting in bowel obstruction.The pathogenesis,prevention,and treatment strategies of EPS remain unclear so far.Since most patients are diagnosed during exploratory laparotomy,for the non-surgically diagnosed patients with primary EPS,the surgical timing is also uncertain.CASE SUMMARY A 44-year-old female patient was referred to our center on September 6,2021,with complaints of abdominal distention and bilious vomiting for 2 d.Physical examination revealed that the vital signs were stable,and the abdomen was slightly distended.Computerized tomography scan showed a conglomerate of multiple intestinal loops encapsulated in a thick sac-like membrane,which was surrounded by abdominal ascites.The patient was diagnosed with idiopathic EPS.Recovery was observed after abdominal paracentesis,and the patient was discharged on September 13 after the resumption of a normal diet.This case raised a question:When should an exploratory laparotomy be performed on patients who are non-surgically diagnosed with EPS.As a result,we conducted a review of the literature on the clinical manifestations,intraoperative findings,surgical methods,and therapeutic effects of EPS.CONCLUSION Recurrent intestinal obstructions and abdominal mass combined with the imaging of encapsulated bowel are helpful in diagnosing idiopathic EPS.Small intestinal resection should be avoided.
基金Frontier Biotechnologies Inc.,Ministry of Science and Technology of China(Nos.2013ZX09101001 and 2017ZX09201007)the Beijing Municipal of Science and Technology Major Project(Nos.D141100000314005,D141100000314002,and D161100000416003)+1 种基金the National Natural Science Foundation of China(Nos.81772165,81974303,and 81571973)Beijing Key Laboratory for HIV/AIDS Research(No.BZ0089)。
文摘Background:Albuvirtide is a once-weekly injectable human immunodeficiency virus(HIV)-1 fusion inhibitor.We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs.Methods:We carried out a 48-week,randomized,controlled,open-label non-inferiority trial at 12 sites in China.Adults on the World Health Organization(WHO)-recommended first-line treatment for>6 months with a plasma viral load>1000 copies/mL were enrolled and randomly assigned(1:1)to receive albuvirtide(once weekly)plus ritonavir-boosted lopinavir(ABT group)or the WHO-recommended second-line treatment(NRTI group).The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks.Non-inferiority was prespecified with a margin of 12%.Results:At the time of analysis,week 24 data were available for 83 and 92 patients,and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups,respectively.At 48 weeks,80.4%of patients in the ABT group and 66.0%of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL,meeting the criteria for non-inferiority.For the per-protocol population,the superiority of albuvirtide over NRTI was demonstrated.The frequency of grade 3 to 4 adverse events was similar in the two groups;the most common adverse events were diarrhea,upper respiratory tract infections,and grade 3 to 4 increases in triglyceride concentration.Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group.Conclusions:The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug.This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure.Trial registration:ClinicalTrials.gov Identifier:NCT02369965;https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No.ChiCTR-TRC-14004276;http://www.chictr.org.cn/enindex.aspx.
文摘To realize good point connection between high-strength steel and aluminum alloy,a process of drawing-upsetting-extrusion-clinching was proposed.First,the sheets were drawn;then,the bottom of the protrusion part was extruded,forming the necessary initial interlock;and finally,the protrusion part was reverse press clinched,forming a certain height of the clinched head.Taking DP980 high-strength steel and A15083 aluminum alloy as the connection objects and using the method of numerical simulation combined with experimental test,the mold was made,and the experiment was carried out on the basis of numerical simulation.The experimental results proved the feasibility of the process and the effectiveness of the numerical model.The simulation and experimental results show that the necessary interlock in the drawing-upsetting-extrusion stage is the premise of effective connection.The relative protrusion height should be around 55.6%after reverse-press-clinching.The best comprehensive mechanical properties measured by strength test were shear resistance of 2644 N,fatigue life of 24,535 times and peel resistance of 1522 N.Through failure analysis,the relationship between the interlock Tu and the neck thickness Tn of the joint with the best comprehensive mechanical properties was established as Tu=0.35Tn.The design method of die and process parameters when the sheet thickness changes was researched by numerical simulation.The results show that the clearance between the punch and the die and the bottom thickness are directly proportional to the sheet thickness,and the drawing depth is directly proportional to the punch radius.
文摘Background:The optimal surgical approach for four-level cervical spondylotic myelopathy remains controversial.The purpose of this study was to compare clinical and radiological outcomes and complications between the anterior and posterior approaches for four-level cervical spondylotic myelopathy.Methods:A total of 19 patients underwent anterior decompression and fusion and 25 patients underwent posterior laminoplasty and instrumentation in this study.Perioperative information,intraoperative blood loss,clinical and radiological outcomes,and complications were recorded.Japanese Orthopedic Association(JOA)score,36-item short form survey(SF-36)score and cervical alignment were assessed.Results:There were no significant differences in JOA scores between the anterior and posterior group preoperatively(11.6±1.6 vs.12.1±1.5),immediately postoperatively(14.4±1.1 vs.13.8±1.3),or at the last follow-up(14.6±1.0 vs.14.2±1.1)(P>0.05).The JOA scores significantly improved immediately postoperatively and at the last follow-up in both groups compared with their preoperative values.The recovery rate was significantly higher in the anterior group both immediately postoperatively and at the last follow-up.The SF-36 score was significantly higher in the anterior group at the last follow-up compared with the preoperative value(69.4 vs.61.7).Imaging revealed that there was no significant difference in the Cobb angle at C2-C7 between the two groups preoperatively(-2.0°±7.3°vs.-1.4°±7.5°).The Cobb angle significantly improved immediately postoperatively(12.3°±4.2°vs.9.2°±3.6°)and at the last follow-up(12.4°±3.5°vs.9.0°±2.6°)in both groups compared with their preoperative values(P=0.00).Three patients had temporary dysphagia in the anterior group and four patients had persistent axial symptoms in the posterior group.Conclusions:Both the anterior and posterior approaches were effective in treating four-level cervical spondylotic myelopathy in terms of neurological clinical outcomes and radiological features.However,the JOA score recovery rate and SF-36 score in the anterior group were significantly higher.Persistent axial pain could be a major concern when undertaking the posterior approach.
基金Project supported by the National Natural Science Foundation of China(No.81700549)the National Major Science and Technology Research Projects for the Control and Prevention of Major Infectious Diseases in China(No.2017ZX10202202)the Medical and Health Research Program of Zhejiang Province(No.2015KYB144),China。
文摘Background The outbreak of coronavirus disease 2019(COVID-19)is now becoming an enormous threat to public health.The clinical spectrum of COVID-19 is extensive,of which critical cases are with rapid disease progression and high mortality.The aim of our study is to summarize the characteristics of different subtypes and explore risk factors of illness severity for early identification and prompt treatment.Methods In this retrospective study,we collected data of patients confirmed COVID-19 in Zhejiang Province from 17 January to 12 February 2020.According to the definition of clinical classification,we divided confirmed cases into four types,and summarize epidemiological and clinical characteristics,laboratory and radiograph findings,treatments,and outcomes,respectively.Moreover,we used univariate and multivariate ordinal logistic regression models to explore risk factors for the severity of illness in patients with COVID-19.Results A total of 788 patients were enrolled in our study,of whom 52 cases(6.6%)were mild type,658 cases(83.5%)were common type,61 cases(7.2%)were severe type,and 17 cases(2.2%)were critical type.Multivariate ordinal logistic regression demonstrated increasing odds of the severity of illness in patients with COVID-19 associated with male(odds ratio[OR]=1.7,95%confidence interval[CI]:1.2–2.6 P=0.008),fever(OR=3.6,95%CI:2.1–6.3,P<0.001),cough(OR=1.7,95%CI:1.0–2.9,P=0.041),hemoptysis(OR=3.4,95%CI:1.1–10.3,P=0.032),gastrointestinal symptoms(OR=1.9,95%CI:1.0–3.5,P=0.047),hypertension(OR=2.6,95%CI:1.2–5.6,P=0.013).With the increase of age-grading,risk for the severity of illness was gradually higher(≤18 years[OR=1.0],19–40 years[OR=12.7,95%CI:4.5–36.0,P<0.001],41–65 years[OR=14.8,95%CI:5.2–42.1,P<0.001],≥66 years[OR=56.5,95%CI:17.1–186.5,P<0.001]).Conclusions Clinicians should pay close attention to these features in patients with COVID-19 including older age,male,fever,cough,hemoptysis,gastrointestinal symptoms and hypertension to identify the severity of illness as early as possible.
基金the National Major Science and Technology Research Projects for the Control and Prevention of Major Infectious Diseases in China(No.2017ZX10202202)the National Natural Science Foundation of China(No.81770574)。
