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Chronic hepatitis B virus (HBV) infection remains a global health burden. Timely and effective antiviral therapy is beneficial for patients with HBV infection. With existing antiviral drugs, including nucleos(t)ide analogs and interferon-alfa, patients can achieve viral suppression with improved prognosis. However, the rate of hepatitis B surface antigen loss is low. To achieve a functional cure and even complete cure in chronic hepatitis B patients, new antivirals need to be developed. In this review, we summarized the advantages and disadvantages of existing antiviral drugs and focused on new antivirals including direct-acting antiviral drugs and immunotherapeutic approaches.
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Humans , Antiviral Agents/therapeutic use , Hepatitis B/drug therapy , Hepatitis B Surface Antigens , Hepatitis B virus , Hepatitis B, Chronic/drug therapy , Hepatitis C, Chronic/drug therapyABSTRACT
ObjectiveTo investigate the therapeutic effect of Xuebijing injection （XBJ） on sodium taurocholate （Na-Tc）-induced severe acute pancreatitis （SAP） in rats. MethodForty rats were randomly assigned into 5 groups： sham operation group， SAP model group， and low-， medium-， and high-dose （4， 8， 12 mL·kg·d-1， respectively） XBJ groups. SAP model was established by retrograde injection of Na-Tc （1 mL·kg-1） into the biliary and pancreatic ducts. XBJ was injected intraperitoneally 3 days before and 0.5 h after modeling. The ascitic fluid volume and the pancreas weight-to-body weight ratio were measured. The pathological changes of pancreatic tissue were observed via hematoxylin-eosin （HE） staining. The protein levels of formyl peptide receptor 1 （FPR1） and nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） in pancreatic tissue were detected by immunohistochemistry. Western blot was employed to determine the expression levels of NADH-ubiquinone oxidoreductase chains 1-6 （MT-ND1， MT-ND2， MT-ND3， MT-ND4， MT-ND5， and MT-ND6） in rat plasma. ResultCompared with sham operation group， the SAP model group showcased increased ascitic fluid volume and pancreas weight-to-body weight ratio （P<0.05）， serious lesions in pancreatic tissue， increased total pathological score （P<0.05）， and up-regulated protein levels of FPR1 and NLRP3 in pancreatic tissue （P<0.05）. The model group had lower MT-ND2 level （P<0.05） and higher MT-ND1， MT-ND3， and MT-ND6 levels in plasma （P<0.05） than the sham operation group， while MT-ND4 and MT-ND5 had no significant differences between the two groups. Compared with SAP model group， the XBJ treatment decreased ascitic fluid volume and pancreas weight-to-body weight ratio （P<0.01）， ameliorated pancreatic lesions， and down-regulated the protein levels of FPR1 and NLRP3 in pancreatic tissue （P<0.01）. The treatments， especially high-dose XBJ （P<0.01）， down-regulated the expression of MT-ND1 （P<0.01）， MT-ND3 （P<0.01）， MT-ND6 （P<0.01）， and MT-ND4 and did not change that of MT-ND5. ConclusionXBJ may antagonize partial mitochondrial N-formyl peptides and excessive inflammatory response mediated by FPR1/NLRP3 to treat SAP in rats.
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Benign gallbladder diseases are common diseases in general surgery, including gallstones, polypoid lesions, cholecystitis, etc. In China, the treatment of benign gallbladder diseases is still not standardized, which mainly shows in following aspects: (1)the tendency of cholecystectomy to all gallbladder diseases may result in the incidence of abdominal pain, distension, diarrhea and bile duct injury after surgery; (2)the attitude of "no-surgery" in which the standard cholecystectomy fails to implement in time for the benign gallbladder diseases with potential high-risk factors for gallbladder cancer, as a result, patients develop occurrence of gallbladder cancer. Especially, gallbladder sparing surgery is an unscientific surgery for benign gallbladder diseases, the gallbladder may become a high-risk factor for cancer after the operation. Implementation of standard cholecystectomy in time for benign gallbladder diseases with potential high risk gallbladder cancer can not only significantly reduce the incidence of gallbladder cancer, but also significantly improve the early diagnosis and the prognosis. Based on current literatures, the authors analyze the treatment status of benign gallbladder diseases, and investigate the disputes and problems in surgical indications, operation time and the selection of treatments of benign gallbladder diseases.
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Objective::To investigate the protective effect of modified Yinchenhao Tang on α-isothiocyanate(ANIT)-induced cholestatic liver disease (CSLD). Method::Wistar rats were randomly divided into 7 groups: blank control group, model control group, compound Glycyrrhizin capsules group(22.5, 45 mg·kg-1), modified Yinchenhao Tang low, middle and high dose groups(4.1, 8.1, 16.2 g·kg-1). A model of cholestatic liver injury was prepared by intragastric administration of ANIT (100 mg·kg-1). Glycyrrhizin capsules and modified Yinchenhao Tang were administered intragastrically on the second day of modeling for 4 consecutive days. And bile duct intubation was performed on the fifth day to measure the bile flow rate of the rats, and serum was taken to test the total bilirubin(TBIL), direct bilirubin(DBIL), indirect bilirubin(IBIL), alanine aminotransferase(ALT) and total bile acid(TBA) serological indicators of each group. Pathological changes of liver tissues were observed by hematoxylin-eosin (HE) staining. The expression levels of G protein-coupled bile acid receptor(TGR5), nucleotide binding oligomerization domain-like receptor 3(NLRP3) and cysteinyl aspartate specific proteinase-1(Caspase-1) proteins in the iver tissues were detected by Western blot. Result::Compared with the blank control group, bile flow rate in the model group decreased significantly(P<0.01). TBIL, DBIL, IBIL, ALT and TBA level in serum were significantly increased(P<0.01), liver tissue lesions were severe, and significantly increased the expression of liver tissue TGR5 and Caspase-1.Compare with model group, the compound Glycyrrhizin capsules group had no significant effect on bile flow rate and TBIL, DBIL, IBIL, ALT and TBA level in serum. Bile flow rate increased and TBIL, DBIL, IBIL, ALT and TBA level in serum decreased significantly in modified Yinchenhao Tang high dose group. The compound Glycyrrhizin capsules group and modified Yinchenhao Tang group have different extents of improvement the pathological changes of the lung tissues, and the protein expression of TGR5 and Caspase-1 were significantly decreased in the liver tissue(P<0.01). Conclusion::Modified Yinchenhao Tang can effectively treat CSLD in rats, and its mechanism may be related to bile acid and bile acid receptor TGR5-mediated inflammatory factors.
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Objective To explore the feasibility of serum Klotho level in the elderly donors to predict the renal graft function in the recipients. Methods Clinical data of 16 elderly donors and 27 recipients undergoing renal transplantation were collected. The general status of the recipients was observed. The levels of serum Klotho and serum creatinine (Scr) in the elderly donors were measured on the day of renal transplantation. The Scr levels in the recipients were measured at postoperative 1, 3 and 12 months respectively. The estimated glomerular filtration rate (eGFR) was calculated. The correlation between the serum Klotho level of the donors and postoperative graft function of the recipients was analyzed. Results The cold ischemia time during renal transplantation was (649±245) min. The incidence rate of delayed graft function (DGF) was 26%. The incidence rate of acute rejection was 7%. In the elderly donors, the serum Klotho level was 537 (245-793) pg/mL and the Scr level was (164±62) μmol/L. At postoperative 1, 3 and 12 months, the Scr levels in the recipients were (136±47), (132±43) and (133±46) μmol/L, respectively. The corresponding eGFR was (52±20), (52±19) and (53±21) mL/(min?1.73m2), respectively. The serum Klotho level in the elderly donors was negatively correlated with the renal graft function at postoperative 1 month in the recipients (P < 0.05). The sensitivity and specificity of serum Klotho level in predicting the renal graft insufficiency at postoperative 1 month were 0.909 and 0.769. Conclusions The preoperative serum Klotho level in the elderly donors have predictive value for renal graft function in the recipients at postoperative 1 month.
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Hilar biliary stricture is usually divided into malignant stricture and benign stricture. How to effectively deal with hilar biliary stricture has always been the focus in biliary surgery. Because it involves bile duct, hepatic artery,portal vein and liver parenchyma, the choice of surgical path is very important. The approach based on perihilar surgical technique can better expose the operative area and have the advantage of performing precise treatment, thus effectively improving the radical cure rate of hilar cholangiocarcinoma and reducing the surgical difficulty.
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Objective To study the use of preoperative indocyanine green retention test at 15 minutes (ICG R15) in the prediction of liver functional reserve in patients with hilar cholangiocarcinoma (HCCA).Methods The clinical data of 62 patients with HCCA treated in our department from March 2016 to March 2018 was reviewed.The relationship between preoperative ICG R15 and postoperative hepatic insufficiency was analyzed.The relationship between preoperative ICG R15 and Child-Pugh scoring was also studied.Univariate analysis was used to evaluate the risk factors of postoperative liver dysfunction.Logistic regression was used to assess the independent risk factors of postoperative liver dysfunction.The regression equation between independent risk factors and postoperative liver dysfunction was established.Results Among the 62 patients,ICG R15 was less than 10.0％ in 26 patients,between 10.0％ and 19.0％ in 17 patients,between 20.0％ and 29.0％ in 9 patients,between 30.0％ and 39.0％ in 5 patients,and over 40.0％ in 5 patients.There were 29 patients with a Child-Pugh A grading and 33 patients with a Child-Pugh B grading in the preoperative evaluation of liver function.The Wilcoxon W rank sum test was used to compare the preoperative ICG R15 in patients with Child-Pugh grading A and B separately.The ICG R15 in Child-Pugh grading A patients was significantly lower than those in Child-Pugh B grading patients (P ＜0.05).There were no significant differences in age,gender,history of previous liver diseases,duration of operation,and intraoperative blood loss (P ＞ 0.05) between the normal liver function group and the liver dysfunction group.However,there was a significant difference in the preoperative ICG R15 and preoperative bilirubin levels (P ＜ 0.05) between the two groups.The preoperative ICG R15 and preoperative bilirubin levels were significant risk factors of postoperative hepatic insufficiency.Regression analysis suggested that preoperative ICG R15 level was an independent risk factor of postoperative hepatic insufficiency (P ＜ 0.05).A regression equation:logit(P) =0.185 × preoperative ICG R15-3.152 could be constructed.Conclusions ICG R15 is an ideal clinical indicator for evaluation of preoperative liver functional reserve in patients with HCCA.It predicted the recovery of postoperative liver function.
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Objective:To explore the effects of hypoxia-inducible factor 2α genes on under hypoxia on proliferation,apoptosis, cell cycle distribution and migration of invasiveness of human hepatocellular carcinoma cell HepG2.Methods: Human hepatoma cell line HepG2 induced by cobalt chloride (CoCl2) was selected as the research object,construction of siRNA specific carrier HIF-2α, transfection of HepG2 cells under hypoxia.Real-time PCR,Western blot method in the detection of before and after transfection in each group of HIF-2α mRNA and protein expression;MTT method to detect the proliferation of HepG2 cells before and after transfection;apoptosis rate and distribution of cell cycle of HepG2 cells before and after transfection were detected by flow cytometry;Transwell test was used to detect the invasion and migration ability of HepG2 cells before and after transfection.Results: Under hypoxia,significant increased HIF-2α expression in hepatocellular carcinoma HepG2 cells.Specific transfection of HIF-2α siRNA in HepG2 cells after HIF-2α mRNA and protein expression levels were significantly inhibit cell proliferation decreased,apoptosis rate increased in the ratio of G0/G1 phase cells increased synthesis phase (S) and late (G2/M) synthesis cell ratio decreased,which in vitro invasion and migration of cells was inhibited.Conclusion:Expression of HIF-2α increases in hepatocellular carcinoma HepG2 cells under hypoxia. Specific siRNA can be cut by HIF-2α gene expression in HepG2 cells under hypoxia,to inhibit HepG2 cell proliferation,invasion, migration,and change the distribution of cell cycle and induce its apoptosis.
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Objective To study the influence of targeted silencing of DEK on the proliferation and cell cycle of human hepatoma cell lines.Methods The human hepatoma cells line HepG2 were routinely cuhured and the cells were divided into blank control group,siRNA control group and DEK siRNA group when the cells grew to 90％ tusion.The cells in blank control group were cultured normally without any treatment;the cells in siRNA control group and DEK siRNA group were transfected with siRNA expression vector and DEK siRNA expression vector mediated by LipofectamineTM2000 liposomes,respectively.The expression of DEK mRNA in HepG2 cells was detected by real-time polymerase chain reaction;the expression of DEK and CyclinD1 protein in HepG2 cells was detected by Western blot;the proliferation of HepG2 cells was detected by methyl thiazolyl tetrazolium method,and the cell cycle was observed by flow cytometry.Results The expression of DEK mRNA in the blank control group,siRNA control group and DEK siRNA group was 0.826 ±0.052,0.776 ±0.051 and 0.420 ±0.050 respectively;the expression of DEK protein in the blank control group,siRNA control group and DEK siRNA group was 0.691 ± 0.073,0.726±0.061 and 0.311 ±0.038 respectively;the expression of CyclinDl protein in the blank control group,siRNA cuntrol group and DEK siRNA group was 0.712 ± 0.069,0.780 ± 0.074 and 0.434 ± 0.039 respectively.The expressions of DEK mRNA,DEK protein and CyclinD1 protein in DEK siRNA group were significantly lower than those in the blank control group and siRNA control group (P ＜ 0.05);there was no statistic difference in the expression of DEK mRNA,DEK protein and CyclinD1 protein between the blank control group and siRNA control group(P ＜0.05).The proliferation ability of HepG2 cells in DEK siRNA group after transfection of 24,48,72,96,120 h was significantly lower than that in the blank control group and siRNA control group(P ＜0.05);there was no statistic difference in the proliferation ability of HepG2 cells between the blank control group and siRNA control group at each time point(P ＜ 0.05).The proportion of G0 + G1 phase cells in DEK siRNA group was significantly higher than that in the blank control group and siRNA control group(P ＜ 0.05);the proportions of S phase and G2 + M phase cells in DEK siRNA group were significantly lower than those in the blank control group and siRNA control group(P ＜ 0.05);there was no statistic difference in the proportion of G0 + G1 phase,S phase and G2 + M phase cells between the blank control group and siRNA control group (P ＜ 0.05).The result of Pearson correlation analysis showed that the expression of CyclinD1 protein was positively correlated with the expression of DEK mRNA and protein(r =0.909,0.899;P ＜ 0.05).Conclusion DEK siRNA can inhibit the proliferation of HepG2 cells,and change the cell cycle distribution through down regulating the expression of DEK gene in HepG2 cells.This process may be related to the down regulation of the expression of CyclinD1.
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Objective To study the prognostic role of plasma neutrophil gelatinase-associated lipocalin (NGAL) early after renal transplantation.Methods A total of 37 kidney recipients were enrolled from Department of Organ Transplantation,Guangdong Second Provincial General Hospital within a 12-month period of time.Plasma NGAL was measured immediately before and at 6 and 12 h post-transplantation.Changes of serum creatinine were documented daily within the first week postoperation.Acute kidney injury (AKI)/graft rejection during the first week after transplantation was the outcome variable.Results The levels of serum NGAL in the 37 patients were (311.14 ± 102.69),(317.81 ± 107.28) and (312.16 ± 134.80) μg/L respectively immediately before and at 6 and 12 h post-transplantation.There was no significant difference in serum NGAL levels before and 6 h or 12 h after operation (P =0.70,and P =0.96).There were no significant differences in gender and age between the two groups (P =0.29,and P =0.20).There was significant difference in creatinine levels between the AKI group and the non-AKI group (P =0.002) and between pre-operation and 6 or 12 h postoperation.The preoperative levels of serum NGAL in AKI group and non-AKI group were (333.58 ± 116.30) and (300.36 ± 96.15) μg/L (P =0.36),and those were (383.3 ± 147.16) and (286.32 ± 65.97) μg/L (P＜0.01) at 6 h,and (437.33 ± 164.16) and (252.08 ± 57.53) μg/L (P＜ 0.001) at 12 h after operation.The sensitivity and specificity of serumNGAL (317μg/L at 12 h after operation as the cutoff value) predicting AKI was 100％ and 92％ respectively,which was much better than that of serum creatinine at the corresponding time point (sensitivity =66.7％,and specificity =61.9％).Conclusion Plasma NGAL,particularly at 12 h after transplantation,is a very sensitive and specific biomarker for predicting AKI.
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Objective To investigate the distribution of insulin resistance (HOMA-IR) index and its influencing factorsamong middle and old aged people with normal glucose and to provide the basis for early screening and prevention of type 2diabetes. Methods A total of 229 residents were selected with health records showed normal blood glucose (fasting bloodglucose < 7.0mmol/L, postprandial 2h blood glucose<11.1 mmol/L) and more than 40 years old from July, 2012 to June,2015. Height, weight, waist and hip circumference, and the fasting plasma glucose (FPG), insulin (FINS), lowdensity lipoprotein (LDL), uric acid, tumor necrosis factor (TNF) and interleukin -6 (IL-6) were recorded to analyzethe distribution of HOMA-IR and its influencing factors. Results Totally 229 people were included, of which 113 were male(49.34%), 116 female(50.66%) . The average age was(63.58 + 8.85) years old. The average HOMA-IR index was 0.94(1.08) and there were 21 people that HOMA-IR exceed the standard (HOMA-IR≥2.68), accounting for 9.17%.TheHOMA-IR index of different gender, age, waist circumference, hip circumference, uric acid in the elderly had significantdifference (P < 0.05) .Multiple linear regression analysis showed that HOMA-IR index was positively correlated withfemale, waist circumference and IL-6 and was negatively correlated with age. Conclusion The possibility of IR was higherin women with relatively low age, female, central obesity and high IL-6 levels among the middle and old aged people withnormal blood glucose.
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Objective To evaluate the MRI findings of synovial hemangioma.Methods Twenty-three patients with synovial hemangioma were analyzed retrospectively,and MRI characteristics were summarized.Results Of the 23 patients,there were localized type in 6 and diffuse type in 17.Localized tumors located in the articular synovial tissue and didn't invade articular capsule and peripheral tissues.T hey had envelope,well-defined margin and regular shape.5 cases showed heterogeneous signal with iso-intense or hypo-intense on T1WI,hyper-intense and internal patchy or multiple pinstripe hypo-intense on T2WI and fat-suppression sequence.Diffuse tumors distributed inside and outside the articulation,and invaded the articular capsule or peripheral tissues.17 cases were heterogeneous signal with iso-intense or hypo-intense and internal patchy or sinuous hyper-intense on T1WI,hyper-intense and internal patchy,nodular and multiple pinstripe hypo-intense on T2WI and fat-suppression sequence.Thick flow void of the vessels were showed in 6 cases and phlebolithes were showed in 3 cases.15 cases underwent contrast-enhanced scan,and the tumors showed patchy,nodular or tortuous vascular heterogeneous enhancement with internal patchy,nodular or cord-like non-enhanced areas.Conclusion Fatty-fibrous tissues and flow void of the vessels in the tumor are valuable MRI features for diagnosis of the synovial hemangioma.
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MTT assay was used in this study to investigate the inhibitory effect of danshensu on the activity of 2.2.15 cells among human hepatoma cell line (HepG2); indirect fluorescence labeling method was used to measure the changes of reactive oxygen levels in the cells; ELISA method was used to determine hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) levels in cellular supernatants; HBV DNA level was measured with fluorogenic quantitative PCR method. The inhibitory effect of danshensu on HBV RT(hepatitis B virus reverse transcriptase) was studied by using enzyme inhibition dynamics, and the effect of danshensu on secondary structure of HBV reverse transcriptase was monitored by using circular dichroism. The results showed that danshensu had a good inhibitory effect on the growth of HepG2.2.15 cells, with a half inhibitory concentration (IC₅₀) of (15.35±2.43) μmol•L⁻¹; danshensu could significantly inhibit HBsAg and HBeAg expressions, and showed an inhibitory effect on HBV DNA replication. In addition, danshensu was an effective inhibitor for HBV reverse transcriptase [IC₅₀ (21.32±2.43) μmol•L⁻¹]. The fluorescence labeling results showed that the reactive oxygen levels in the cells were increased with the increase of danshensu concentration. Circular dichroism analysis showed that danshensu could induce partial change of conformation of HBV reverse transcriptase and gradually increased α-helical content. These results indicated that danshensu could make the structure of the enzyme become closer by binding to HBV reverse transcriptase, which was not conducive to the formation of the active center, so it could finally decrease the activity of HBV reverse transcriptase. Such decrease in enzyme activity would directly affect the HBV DNA replication, and combined with the decrease of the antigen levels, the effect of danshensu on HBV was increased.
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<p><b>OBJECTIVE</b>To evaluate the quality and clinical applicability of pyrosequencing assay kit for detecting hepatitis B virus resistance (HBV DRT).</p><p><b>METHODS</b>Serial dilutions of the International Standard for HBV DNA were used to test the detection limit of the PCR for HBV DRT. Plasmids containing the either a wild-type (WT) copy or one of 10 mutant (MT) copies of the HBV RT gene were used to prepare a series of samples with various mutation ratios. To construct the linear relationship between the true mutation rate and the detected mutation rate, each sample was repeated at least 10 times. A total of 102 clinical samples were analyzed by Sanger sequencing and retested by the PCR for HBV DRT to determine the concordance of these two methods.</p><p><b>RESULTS</b>The lower detection limit of the PCR for HBV DRT was 50 IU/ml. Except for the RT236 MT, the correlation between the true mutation rate and the detected mutation rate for the other nine resistance-related mutation sites were excellent, with R² more than 0.98 (P less than 0.001). Among the 102 clinical samples, four were not amplified successfully by PCR. The results were significantly different between the PCR for HBV DRT method and the Sanger sequencing method (x² = 71.2, P less than 0.001), and concordance was observed for 897/969 (92.6%) amino acid positions in 98 samples. Concordant results were achieved in 46/98 (46.9%) samples at all 10 mutation sites. For detection of a single mutation site, concordance rates ranged from 71.5% to 100% at the 10 mutation sites, respectively. Analysis of discordant samples showed that in 87.5% (63/72), Sanger sequencing detected WT and the PCR for HBV DRT detected WT/MT. In 5.6% (4/72) of samples, Sanger sequencing detected WT/MT and the PCR for HBV DRT detected WT. In the remaining 6.9% (5/72) of samples, Sanger sequencing detected WT but PCR for HBV DRT detected MT.</p><p><b>CONCLUSION</b>The PCR for HBV DRT showed high sensitivity and accuracy in detecting antiviral drug-resistant mutations. The method is superior to Sanger sequencing for detecting minor mutations and can be used for early detection of a resistance mutation.</p>
Subject(s)
Humans , Antiviral Agents , Base Sequence , Drug Resistance, Viral , Hepatitis B virus , Mutation , Plasmids , Polymerase Chain Reaction , Sequence Analysis, DNAABSTRACT
Tegument is the unique structure of a herpesvirion which occupies the space between nucleocapsid and envelope. Accumulating data have indicated that interactions among tegument proteins play a key role in virion morphogenesis. Morphogenesis of gammaherpesviruses including Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) is poorly understood due to the lack of efficient de novo lytic replication in cell culture. Murine gammaherpesvirus-68 (MHV-68) is genetically related to these two human herpesviruses and serves as an effective model to study the lytic replication of gammaherpesviruses. We previously showed that ORF33 of MHV-68 encodes a tegument protein and plays an essential role in virion maturation in the cytoplasm. However, the molecular mechanism of how ORF33 participates in virion morphogenesis has not been elucidated. In this study we demonstrated that ORF38 of MHV-68 is also a tegument protein and is localized to cytoplasmic compartments during both transient transfection and viral infection. Immuno-gold labeling assay showed that ORF38 is only present on virions that have entered the cytoplasmic vesicles, indicating that ORF38 is packaged into virions during secondary envelopment. We further showed that ORF38 co-localizes with ORF33 during viral infection; therefore, the interaction between ORF38 and ORF33 is conserved among herpesviruses. Notably, we found that although ORF33 by itself is distributed in both the nucleus and the cytoplasm, in the presence of ORF38, ORF33 is co-localized to trans-Golgi network (TGN), a site where secondary envelopment takes place.
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Animals , Humans , Mice , DNA Replication , Genetics , Gammaherpesvirinae , Genetics , Virulence , Viral Envelope Proteins , Genetics , Viral Matrix Proteins , Genetics , Virion , Genetics , Virus Replication , trans-Golgi Network , GeneticsABSTRACT
Objective To explore the characteristics of ischemia-reperfusion induced infant lung damage and the potential mechanisms of the injuried.Methods Both infant (15-21 days old) and adult (5-6 months old) rabbits were subjected to either ischemia-reperfusion or sham operation.Ischemia-reperfusion was induced by clamping the right pulmonary hilum for 1 hour and then removal of the clamp for 4 hours under anesthesia.The lung tissue were sampled for histological examination by light and electron microcopies and for biological evaluation of mitochondrial alterations.Production and expression of free radical species-hydroxyl radical (ROS-HR),malondialdehyde (MDA),superoxide dismutase (SOD),glutathione peroxidase (GSH-PX),myeloid differentiation factor-88 (MyD-88),and nuclear factor-κB (NF-κB) in the lung tissue were also examined.In addition,circulating levels of interleukin-β and tumor necrosis factor-α were measured during the ischemia-reperfusion process.Results In comparison to adult lungs,the infant lungs had more increased neutrophil infiltration,edema,swelled alveolar epithelial and endothelial cells,and severer mitochondrial impairment reflected by damage of the inner membrane as well as decrease in the membrane potential after ischemia-reperfusion.The lungs in infant animals subjected to sham operation displayed higher levels of ROS-HR and MDA and lower levels of SOD and GSH-PX than those in adult controls.The lungs in infants with ischemia-reperfusion were found to further produce more ROS-HR,and MDA,and less SOD and GSH-PX than the ischemia-reperfused adult lungs.Moreover,the circulating levels of interleukin-1β and tumor necrosis factor-α were elevated during the period of ischemia-reperfusion,particularly in the infant animals,which appeared to be associated with the expression of MyD-88 and NF-κB in the lungs.Conclusion Lung ischemia-reperfusion causes more severe lung damage in infants than in adults,probably due to combination of low antioxidant capacity and overproduction of ROS in infants.
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<p><b>OBJECTIVE</b>To explore the efficacy of concurrent chemoradiotherapy combined with Kanglaite Injection (KI) for locally advanced pancreatic carcinoma patients.</p><p><b>METHODS</b>Totally 50 patients unsuitable for surgery were randomly assigned to the treatment group and the control group, 25 in each group. Patients in the control group were treated with gemcitabine and concurrent 3D-CRT, while those in the treatment group were also treated with intravenous injection of KI (at 100 mL/d) for 21 successive days, 28 days as one cycle, two cycles with one week interval. The short-term curative effect, the survival time, the improvement of symptoms, the tumor markers, and adverse reactions were respectively observed for two years.</p><p><b>RESULTS</b>The short-term curative effective rate (CR + PR) was 52.17% (12/23), and the disease control rate (CR + PR + SD) was 95.65% (22/23) in the treatment group. The short-term curative effective rate (CR + PR) was 41.67% (10/24), and the disease control rate (CR + PR + SD) was 87.50% (21/24) in the control group. There was no statistical difference between the two groups (P > 0.05). The 2-year survival rate was 34.78% (8/23) in the treatment group, better than that in the control group (25.00%, 6/24). The median survival time was 17.2 months in the treatment group and 12.4 months in the control group with statistical difference (P < 0.05). The response rate of pain relief and weight gain were 75.00% and 82.61% in the treatment group respectively, and they were 50.00% and 54.67% in the control group respectively, showing statistical difference between the two groups (P < 0.05). After treatment, the levels of CA19-9 (U/mL) and CEA (ng/mL) were respectively reduced to 118. 00 +/- 78.89 and 7.41 +/- 2.37 respectively in the treatment group, showing statistical difference when compared with those of the control group (being 216.00 +/- 153.23 and 12.25 +/- 7.53 respectively, P < 0.05).</p><p><b>CONCLUSION</b>The concurrent chemoradiotherapy com- bined with KI for locally advanced pancreatic carcinoma patients obtained better results.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Combined Modality Therapy , Deoxycytidine , Therapeutic Uses , Drugs, Chinese Herbal , Therapeutic Uses , Pancreatic Neoplasms , Pathology , Therapeutics , Phytotherapy , Radiotherapy, ConformalABSTRACT
<p><b>BACKGROUND</b>Our previous studies suggested that low-dose gossypol combined with steroid hormones has a reversible antifertility role in adult male rats, and the course of treatment was shorter than that of either gossypol or steroid hormones alone. This result suggested that low-dose gossypol and steroid hormones have a drug synergistic effect on antifertility. The aim of the study was to find the target organs of the antifertility synergistic effect of the combined regimen.</p><p><b>METHODS</b>Thirty-two adult male rats were divided into four groups randomly: group GH, rats were fed orally with gossypol acetic acid (GA, 12.5 mg×kg(-1)×d(-1)) and desogestrel (DSG, 0.125 mg×kg(-1)×d(-1))/ethinylestradiol (EE, 0.025 mg×kg(-1)×d(-1))/testosterone undecanoate (TU, 100 mg×kg(-1)×d(-1)); group G, a single dose of GA (12.5 mg×kg(-1)×d(-1)) was given; group H, the same dosage of DSG/EE/TU as in group GH were administered; group C, rats were treated with vehicle (1% methyl cellulose) as control. Testes and epididymis were removed at 8 weeks post-treatment for evaluating their weight, volumes, volume fraction, and total volume of testicular tissue structures and the seminiferous tubule diameter using stereological assay. Sperm cell numbers and the motility of epididymal sperm were quantitated by flow cytometry and morphological methods.</p><p><b>RESULTS</b>Compared with group C, spermatogenesis was normal in group G and suppressed in groups H and GH. Similar changes of testicular tissue structures and sperm number were found in groups H and GH. The decreases of epididymal sperm number and motility in group GH were greater than that of the low-dose gossypol or steroid hormones alone group.</p><p><b>CONCLUSIONS</b>The suppression of spermatogenesis was induced by steroid hormones in the combined regimen, and the epididymis was the target organ of low-dose gossypol. Combined use of low-dose gossypol and steroid hormones played a comprehensive antifertility role in their synergistic effect on reducing the number and motility of epididymal sperm.</p>
Subject(s)
Animals , Male , Rats , Desogestrel , Pharmacology , Epididymis , Ethinyl Estradiol , Pharmacology , Flow Cytometry , Gossypol , Pharmacology , Random Allocation , Sperm Motility , Spermatogenesis , Spermatozoa , Testis , Testosterone , PharmacologyABSTRACT
Objective To evaluate the application of pooling HIV nucleic acid amplification testing (NAAT) among men who had sex with men (MSM) population, and to investigate suitable HIV screening strategy and the feasibility of calculation of HIV incidence using pooling NAAT among MSM population in China.Methods Four thousand eight hundred and fifty-six samples were collected from MSM population from April 2008 to September 2009 among with 4 156 were in Heilongjiang province and 700 were in Beijing in China. After standard testing with an HIV ELISA and WB confirmation testing, HIV antibody-negative samples were pooled and screened for HIV using NAAT.A three-stage pooling strategy was adopted.The HIV positive rate estimated by the four HIV screening strategies was calculated.In addition, 4 156 HIV positive specimens from Heilongjiang province were screened with the BED capture enzyme immunoassay (BED-CEIA).The HIV-1 incidences were estimated by BED-CEIA assay and pooling NAAT individually.ResultsOne hundred and forty-three of 4 856 subjects were HIV infected.130 were 3rd and 4th generation ELISA positive; 13 were antibody-negative but acutely HIV infected.According to the evaluation of four HIV screening strategies, routine HIV screening test together with pooling NAAT was more effective than other strategies for screening out window period generation ELISA+WB+pooling NAAT' were 2.68%(95% confidence interval CI=2.22%-3.14%), 2.82%(95%CI=2.35%-3.29%), 2.94%(95%CI=2.46%-3.42%) and 2.94%(95%CI=2.46%-3.42%), respectively.The differences were not significant (χ2=0.854 3, P=0.836 4).Of the 88 HIV positive samples from Heilongjiang province, 44 participants were tested as recent HIV infections by BED-CEIA assay. The estimated HIV-1 incidence was 2.36% (95%CI=1.63%-3.08%) and 2.92% (95%CI=1.01%-4.83%) based on BED-CEIA assay and pooling NAAT,respectively.Conclusions Pooling NAAT is a effective screening test in HIV negative population to detect window period infection among MSM population in China.
ABSTRACT
<p><b>OBJECTIVE</b>This study was to compare the performance of three HIV antibody confirmatory assay kits in confirming early HIV infection.</p><p><b>METHODS</b>Five HIV antibody-positive plasma specimens were ten-fold serially diluted and then detected by ELISA. The above diluted specimens were detected with the following three HIV antibody confirmatory assay kits to analyze their sensitivity, including Wantai-RIBA (Recombinant immunoblot assay, Beijing Wantai Biological Pharmacy, China), MP-WB (HIV Blot 2.2 WB, MP Biomedicals Asia Pacific Pte. Ltd., Singapore) and INNO-LIA (INNO-LIA(TM) HIV I/II Score, Innogenetics N.V., Belgium), respectively. These kits were further used to detect 48 ELISA-reactive specimens from 11 sets of HIV seroconversion specimens (a total of 48 samples) which were previously detected as HIV antibody-positive by ELISA.</p><p><b>RESULTS</b>When 5 samples were diluted to 100 fold, Wantai-RIBA still can detect them positive. Among the 48 HIV antibody-positive specimens detected with ELISA, the confirmation positive rate for Wantai-RIBA, MP-WB and INNO-LIA were 97.92% (47/48), 81.25% (39/48) and 91.67% (44/48), respectively. There was statistically significant difference between the confirmatory results of Wantai-RIBA and MP-WB (χ(2) = 6.13, P < 0.05), as well as between those of INNO-LIA and MP-WB (χ(2) = 5.48, P < 0.05); however, there was no statistically significant difference between those of Wantai-RIBA and INNO-LIA (χ(2) = 1.33, P > 0.05). For other six HIV seroconversion panels containing indeterminate specimens, the average seroconversion period of time for Wantai-RIBA, MP-WB and INNO-LIA were 0.7, 13.3 and 3.7 days, respectively.</p><p><b>CONCLUSION</b>Compared with MP-WB, Wantai-RIBA and INNO-LIA could reduce the window period to confirm early HIV infection.</p>