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Objective:To explore the role of combined detection of cell free BMPR1A and PLAC8 gene methylation in plasma in predicting postoperative recurrence of hepatocellular carcinoma.Methods:Case series study. Patients with stage Ⅰ-Ⅳ hepatocellular carcinoma who were treated at the Third Affiliated Hospital of Sun-Yat-sen University from January 2022 to July 2023 were selected. All enrolled patients underwent alpha fetoprotein (AFP) and imaging assessments 1 month, 3 months, 6 months, 9 months, and 12 months after treatment. Simultaneously, peripheral blood of patients was extracted for plasma circulating tumor DNA (ctDNA) methylation detection, and the results of free BMPR1A and PLAC8 gene methylation detection in patients′ plasma after treatment were compared with the positive rate of traditional tumor marker AFP detection. Draw the receiver operating characteristic curve (ROC) of the subjects to demonstrate the effectiveness of this method in predicting the recurrence of hepatocellular carcinoma. Based on the results of cell free DNA methylation and whether AFP is more than 7 μg/L, hepatocellular carcinoma patients were divided into high-risk methylation group (12 cases), low-risk methylation group (21 cases), high-risk AFP group (15 cases), and Kaplan Meier survival analysis was performed on them.Results:The sensitivity and specificity of combined detection of free BMPR1A PLAC8 gene methylation in plasma for predicting liver cancer recurrence were 66.7% and 88.9%, respectively. The area under curve (AUC) of BMPR1A PLAC8 gene methylation detection for liver cancer recurrence were 0.770 and 0.778, and the AFP was 0.522 in ROC curve analysis. Compared to imaging examinations, cell free DNA methylation detection can detect the recurrence of hepatocellular carcinoma on average by 58.3 days in advance(53.8 days vs 112.1 days). The progression free survival rate of the high-risk group based on free DNA methylation prediction at 400 days was 22.2%, significantly lower than the low-risk group (76.2%, P<0.001). Conclusion:Compared to AFP, detecting the methylation of BMPR1A and PLAC8 genes can predict the recurrence of hepatocellular carcinoma more accurately, making it a practical method for monitoring liver cancer recurrence.
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Objective To investigate the changing trend of platelet count (PLT) and related influencing factors in patients with hepatitis B virus-related chronic-on-acute liver failure (HBV-ACLF) after artificial liver support system (ALSS) therapy. Methods A total of 152 patients with HBV-ACLF who were hospitalized and treated in The Third Affiliated Hospital of Sun Yat-Sen University from January 2018 to November 2021 were included in the study, among whom 102 patients received plasma exchange (PE) and 50 patients received double plasma molecular absorption system combined with low-dose PE, and their clinical data and laboratory marker were measured. The independent samples t -test or the Mann-Whitney U test was used for the comparison of continuous data between two groups, and the chi-square test was used for the comparison of categorical data between two groups; a multivariate logistic regression analysis was used to investigate the risk factors for PLT > 50×10 9 /L after ALSS therapy; the receiver operating characteristic (ROC) curve was used to investigate the value of baseline PLT in predicting PLT > 50×10 9 /L after ALSS therapy. Results The patients were mostly middle-aged male adults; among the 152 patients, 70 (46.1%) had liver cirrhosis on admission, 114 (75.0%) received three sessions of ALSS therapy, and 88% had a baseline PLT count of > 50×10 9 /L. There was a significant reduction in PLT from baseline to after ALSS therapy (79.5±47.7 vs 112.5±64.1, t =4.965, P 0.05). The multivariate logistic regression analysis showed that cirrhosis (odds ratio [ OR ]=3.097, 95% confidence interval [ CI ]: 1.255-7.645, P =0.014) and PLT > 50×10 9 /L at baseline ( OR =0.019, 95% CI : 0.002-0.154, P 50×10 9 /L after ALSS therapy. The ROC curve analysis of baseline PLT showed that PLT > 80.5×10 9 /L at baseline was the optimal cut-off value affecting PLT > 50×10 9 /L after treatment, with an area under the ROC curve of 0.818. Conclusion The influence of ALSS therapy on PLT is temporary, but cirrhotic patients have a weaker PLT generation ability than non-cirrhotic patients. PLT > 80.5×10 9 /L at baseline is the optimal cut-off value to reduce the risk of bleeding after ALSS therapy.
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Hepatitis B virus (HBV) infection is closely associated with the adverse events such as liver cirrhosis, liver cancer, and liver failure and remains a serious threat to human health. Pegylated interferon is an indispensable drug for the treatment of chronic hepatitis B (CHB), and interferon-stimulated genes are associated with a variety of viruses, but few studies have mentioned their association with hepatitis B and their predictive effect after the treatment of hepatitis B with interferon. This article introduces the predictive factors for interferon treatment of CHB and summarizes the association of interferon-stimulated genes with hepatitis B and their predictive effect, so as to provide a reference for clinical work and basic research.
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Objective To compare the immunoregulatory effects of Radix Millettia Speciosa (RM Speciosa) and Radix Millettia Championi (RM Championi)on immunosuppressed mice.Methods Kunming mice were randomly divided into normal control group,CTX model group,LMS positive group,RM Speciosa groups and RM Championi groups (20,10 and 5 g/kg).The mice were treated respectively with drug or NS once a day for consecutive 20 days.Mice in the other groups were injected intraperitoneally with CTX at days 8,10 and 12 to establish immunosuppressed mice model except the normal group.The changes of body weight,immune organ weight,white blood cell (WBC)number,carbon particle clearance capability of macrophages and delayed type hypersensitivity (DTH)of mice in all groups were determined and compared.Results Compared with that in CTX group,the WBC number was significantly increased (P0.05).Conclusion Both RM Speciosa and RM Championi can improve the immune function of CTX-induced immunosuppressed mice,and RM Speciosa is slightly superior to RM Championi in improving specific cellular immunity.
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<p><b>OBJECTIVE</b>To compare the effects on anesthesia recovery between assisted-electroacupuncture fast tracking anesthesia and simple fast tracking anesthesia in patients with minim ally invasive percutaneous nephrolithotomy (mPCNL).</p><p><b>METHODS</b>Eighty cases of mPCNL were selected and randomly divided into a treatment group and a control group. Fentanyl (1-2 microg/kg), sevoflurane (8%) and rocuronium (0.5 mg/kg) were applied to perform anesthesia induction in both groups, and endotracheal inhalation of sevoflurane and intravenous pump injection of remifentanil were adopted to main anesthesia status during the operation. 20 min before anesthesia induction, bilateral Neiguan (PC 6), Neimadian, Hegu (LI 4), Yangxi (LI 5), Zhongji (CV 3), Qichong (ST 30), Zuwuli (LR 10) were selected and punctured in the treatment group, and elecctroacupuncture was given after arrival of qi until 30 min after the wake-up from anesthesia and withdrawal of endotracheal tube. The dosage for anesthesia maintenance, recovery time of awareness, extubation time, incidences of nausea, vomiting and chill and irritation of urethral catheters were observed and recorded.</p><p><b>RESULTS</b>(1) The dosages of remifentanil and sevoflurane in the treatment group during the operation were obviously less than those in the control group [remifentanil: (5. 27 +/-1.23) micro g/kg h vs (7.35+/-1.70) micro g/kg . h; sevoflurane: (1.12+/-0.43) vol% vs (2.35+/-0.87) vol% , both P<0. 001]. (2) The recovery time of awareness and extubation time in the treatment group were significantly earlier than those in the control group [recovery time of awareness: (5.65 +/- 2.34) min vs (8. 87 +/- 6. 84) min, P<0. 01; extubation time : (7. 23+/-4. 35) min vs (10. 62+/-8. 16) min, P<0. 05]. (3) The incidences of nausea, vomiting and chill in the treatment group were significantly less than those in the control group (all P<0. 05). (4) The irritation of urethral catheters on urethra in the treatment group was significantly less than that in the control group (P<0. 001).</p><p><b>CONCLUSION</b>The assisted-electroacupuncture anesthesia could reduce the dosage of remifentanil and sevoflurane in mPCNL fast tracking anesthesia in urinary surgery, reduce the incidences of nausea, vomiting, chill and irritation of urethral catheters during recovery stage, and prompt recovery of mPCNL patients.</p>
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Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Periodo de Recuperación de la Anestesia , Anestésicos Intravenosos , Electroacupuntura , Fentanilo , Éteres Metílicos , Nefrostomía Percutánea , Piperidinas , Náusea y Vómito Posoperatorios , TerapéuticaRESUMEN
Objective To evaluate the effects of nucleoside/nucleotide analogue treatment on immunoglobulin and complement in patients with chronic hepatitis B (CHB).MethodsA total of 157 CHB patients were recruited and divided into CHB group,liver cirrhosis (LC) group and severe hepatitis B (SHB) group.There were 50 patients who received oral antiviral treatment (lamivudine 100 mg/d,or entecavir 0.5 mg/d,or telbivudine 600 mg/d).Serum levels of complement 3 and 4 (C3,C4),C-reaction protein (CRP),hemolytic complement (CH50),immunoglobulin G,M,A (IgG,IgM,IgA),hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were detected by enzyme-linked immunosorbent assay (ELISA) or immunoturbidimetry.Hepatitis B virus (HBV) DNA was quantified by real-time polymerase chain reaction (RT-PCR) before and 1,2,3 and 4 weeks after nucleoside antiviral therapy.Comparison of means was done by t test and Mann-Whitney test.The correlation was analyzed by Pearson correlation coefficient test.ResultsSerum IgA and IgM levels of SHB and LC patients were significantly higher than those of CHB patients (P＜0.01).Levels of C3,C4,CH50 and CRP were significantly different among three groups.Levels of C3,IgM,IgG and HBV DNA in HBeAg positive patients were significantly different from those in HBeAg negative patients.There was a statistically significant difference of IgA,IgM,C3 and CH50 levels between patients with high HBV DNA level and low HBV DNA level in HBeAg-positive patients.While in the HBeAg-negative patients,only the IgA level was significantly different with HBV DNA levels.After anti-viral treatment,immunoglobulin and HBV DNA levels were all decreased in three groups,while the serum complement level was increased compared to baseline,and the differences became significant at week 4 of treatment. HBV DNA level was negatively correlated with C3 (r=-0.78,P=0.021) and HBeAg titer was positively correlated with C3 (r=0.87,P=0.015).ConclusionsThe immunoglobulin,CRP,C3,C4,and C H50 could reflect the inflammatory activity in liver.The changes of C3 level can predict the efficacy of antiviral therapy.
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<p><b>OBJECTIVE</b>To get mesenchymal stem cells (MSCs) from hepatitis B patient and to valuate the safety and quality after long-term culture in vitro.</p><p><b>METHODS</b>The cells obtained directly from bone marrow and cultured in Mesen Pro medium supplemented with FGF, and the morphology of MSCs was observed. Surface antigens of the MSCs were analyzed by flow-cytometry. The bacteria, virus, endotoxin and residual serum of cell suspension were detected. The MSCs and perpheral blood T lymphocytes were co-cultured in 48 well plates for 72 h and the T lymphocyte proliferation was measured by using MTT reduction method and the effect of MSCs on T lymphocyte transformation stimulated by PHA was also observed. The oncogenicity of MSCs was verified by the tumorigenesis test in sofo agar. The genetic stability of MSCs was examined by karyotype analysis.</p><p><b>RESULT</b>The MSCs from hepatitis B patient could be passaged to many generations and had strong abilities of proliferation. They expressed stem cell-surface antigens and maintained normal karyotype, prevented the pollution of bacteria and viruses, inhibited the immune response of allogenic T lymphocytes and no oncogenicity found.</p><p><b>CONCLUSION</b>The MSCs have proliferative potentials, can be passaged in long-term cultures in Mesen Pro medium without oncogenicity, can maintain normal karyotype, can inhibit the immune response of T lymphocytes and can alleviate the grafe-versus diseases. The MSCs can be served as a new type of cells in cell and gene therapy.</p>
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Humanos , Células de la Médula Ósea , Biología Celular , Técnicas de Cultivo de Célula , Proliferación Celular , Células Cultivadas , Citometría de Flujo , Hepatitis B , Células Madre Mesenquimatosas , Biología Celular , Control de Calidad , Linfocitos T , Biología CelularRESUMEN
Objective To investigate the susceptibility of bone marrow mesenchymal stem cell (BMSC) to hepatitis B virus (HBV) infection during induction toward hepatocyte and the role of asialoglycoprotein receptor (ASGPR) in BMSC HBV infection. Methods BMSC obtained from hepatitis B patients were tested for HBV infection and then cultured with HBV infectious serum in vitro and induced to differentiate into hepatocyte through exposure to hepatocyte growth factor (HGF), fibroblast growth factor-4(FGF-4), and epidermal growth factor(EGF). Subsequently these cells were determined for the presence of hepatitis B virus e antigen( HBeAg), hepatitis B virus surface antigen(HBsAg) and ASGPR. All experiments were repeated for 3 times in 5 different samples. The results were analyzed by non-parametric test. Results After 6 days of exposure, BMSC-derived hepatocyte-like cells expressed hepatic special genes and proteins, including alpha fetoprotein(AFP),cytokeratin18 (CK18), albumin (Alb), and manifested hepatocyte functions, including glycogen synthesis, urea secretion and albumin synthesis. Expressions of CK18 and Alb were increased, and AFP was decreased with time of induction. The BMSC were resistant to HBV infection both in vitro and in vivo or after induction toward hepatocyte. ASGPR expression level was low in BMSC, which was increased in the induced BMSC but still lower than that of the control HepG2 cells. Conclusions BMSC are resistant to HBV infection both in vitro and in vivo. The low level expression of ASGPR may be a reason for this.