Effect of Pegylated Interferon Plus Tenofovir Combination on Higher Hepatitis B Surface Antigen Loss in Treatment-naive Patients With Hepatitis B e Antigen -positive Chronic Hepatitis B: A Real-world Experience

PurposeThe loss of serum hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B (CHB) is considered an ideal clinical outcome but rarely achieved with current standard of care. We evaluated the effectiveness in inducing HBsAg seroclearance in a real-world clinical cohort of Chinese patients with CHB treated with a combination of pegylated interferon (Peg-IFN) with tenofovir disoproxil fumarate (TDF) or monotherapy with each agent.MethodsA total of 330 patients with CHB were assigned to receive Peg-IFN plus TDF for 48 weeks (Peg-IFN plus TDF group), Peg-IFN alone for 48 weeks (Peg-IFN group), or TDF alone for 144 weeks (TDF group). The primary end point was the percentages of patients who achieved HBsAg seroclearance at week 72. Differences from the baseline characteristics and treatment data were compared using the χ² test for categorical variables or 1-way ANOVA for continuous variables. A Kaplan–Meier test was performed to compare the HBsAg loss among the 3 groups. Discrimination of responders versus nonresponders was quantified using AUC curves. Optimal cut-offs were selected based on Youden's J statistic defined as J = sensitivity + specificity-1.FindingsAt week 72, the Kaplan–Meier cumulative HBsAg loss was 11.5% in the Peg-IFN plus TDF group, 5.7% in the Peg-IFN group, and 0% in the TDF group. The percentage of patients with HBsAg loss was comparable in the Peg-IFN plus TDF and Peg-IFN groups (P = 0.143), but both were significantly higher than that in the TDF group (P = 0.000 and P = 0.010). In addition, a significantly higher percentage of patients in the combination group and Peg-IFN group had serum HBsAg of <100 IU/mL compared with the TDF group (32.7% vs 23.6% vs 9.2%; P < 0.001) but no significant differences in the percentages of patients with HBsAg <1000 IU/mL, the undetectable serum HBV DNA and hepatitis B e antigen seroconversion. Our model predicted serum HBsAg loss at week 72 (AUC = 0.846) if the HBsAg level was reduced by > 1.5 log₁₀ IU/mL from baseline at treatment week 24, an optimal timepoint for prediction of HBsAg loss in this cohort.ImplicationsA 48-week course of Peg-IFN and TDF combination therapy led to profound reduction in serum HBsAg level, resulting in a significantly higher rate of HBsAg loss compared with TDF monotherapy. Patients with steep HBsAg decline >1.5 log₁₀ IU/mL at week 24 well signaled a higher probability of achieving HBsAg loss at week 72.     

Circular RNA PPP1CC promotes Porphyromonas gingivalis-lipopolysaccharide-induced pyroptosis of vascular smooth muscle cells by activating the HMGB1/TLR9/AIM2 pathway

ObjectivePorphyromonas gingivalis (Pg) plays a critical role in the occurrence and development of atherosclerosis. Lipopolysaccharide from Pg (Pg-LPS) could lead to pyroptosis of vascular smooth muscle cells (VSMCs) and induce instability of atherosclerotic plaque. Therefore, pyroptosis of VSMCs could promote the process of atherosclerosis. However, the exact mechanism of Pg-LPS-induced pyroptosis of VSMCs is unclear.MethodsWe determined pyroptosis and expression of interleukin (IL)-1β and IL-18 in VSMCs using 4′,6-diamidino-2-phenylindole staining and ELISA after stimulation by Pg-LPS. We established a knockdown plasmid containing the circular (circ)RNA PPP1CC and transfected it into VSMCs. Luciferase assays were performed to reveal the association between microRNAs miR-103a-3p and miR-107 and circRNA PPP1CC.ResultsStimulation of Pg-LPS led to pyroptosis of VSMCs. Knockdown of circRNA PPP1CC relieved the Pg-LPS-induced pyroptosis of VSMCs and suppressed the expression of HMGB1, TLR9, AIM2, and cleaved caspase-1. Luciferase assays showed that PPP1CC directly targeted and competitively adsorbed miR-103a-3p and miR-107, weakening the inhibitory effect of these microRNAs on the expression of HMGB1.ConclusionKnockdown of circRNA PPP1CC relieved Pg-LPS-induced pyroptosis of VSMCs. Pyroptosis of VSMCs appears to promote atherosclerosis and may represent a novel therapeutic target for its treatment.     

18F-FDG PET/CT features of ureteral metastases from breast cancer: a case report

Breast cancer metastasis to the ureter is rare. Fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET)/computed tomography (CT) is widely used to identify primary lesions of metastatic tumours, however, 18F-FDG PET/CT imaging features of ureteral metastasis from breast cancer are rarely reported. Herein, the case of a 46-year-old woman with recurrent left flank pain for 5 months, who was admitted to the Cancer Hospital of Guangxi Medical University and Guangxi Cancer Research Institute, is described. She had undergone right radical mastectomy 5 years previously and had received tamoxifen treatment for 5 years. Assessment by 18F-FDG PET/CT revealed tumours on the ureter presenting as a long segmental lesion, radioactive concentrations, and a low maximum standardized uptake value (SUVmax), with no radioactive concentrations in the urine and no significant change in the ureteral contour. The severity of the ureteral lesion was not consistent with the severity of hydronephrosis. A tumour biopsy was performed laparoscopically, and postoperative pathological examination confirmed a primary breast cancer tumour. The patient did not consent to treatment and was lost to follow-up.     

基于ZigBee的婴儿培养箱温度监测与报警系统

研制婴儿培养箱温度集中监测与报警系统,并对采集数据的准确性和稳定性进行评估.建立基于ZigBee的无线传感器树簇型网络拓扑模型,婴儿培养箱内放置传感器终端节点,病房走廊放置无线路由器节点,护士站放置协调器节点与监控主机相连;各节点软件基于C++编写,监控主机软件使用SQL Server 2005作为数据库平台,实时分析终端节点温度及电池电压数据,并产生声光报警.初步实验结果表明,该无线传感器网络能精确、稳定地读取婴儿培养箱箱内温度及终端节点供电电压值.与专业检测设备作对比测试,相对误差小于2％.该系统采集数据正确、实时,能提高医疗安全性,减少医疗不良事件发生,具有广泛的应用前景.     

Rapamycin attenuates articular cartilage degeneration by inhibiting β-catenin in a murine model of osteoarthritis

Purpose: To investigate whether systemic injection of rapamycin attenuates articular cartilage degeneration by inhibiting β-catenin in a murine model of osteoarthritis (OA).

Materials and methods: Ten-week-old male C57BL/6j wild-type (WT) mice and SOST-knockout (SOST^?/?) mice were randomized to a sham group, a vehicle-treated group, and a rapamycin-treated group. Mice in the vehicle-treated group underwent destabilizing of the medial meniscus (DMM) in the right knee, and were then treated with vehicle. Mice in the rapamycin treatment group underwent DMM and were treated with rapamycin. Safranin O-Fast green staining and Osteoarthritis Research Society International (OARSI) modified Mankin score were used to evaluate the histopathological features of the articular cartilage in the knee. The expression of light chain 3 (LC3) was evaluated by immunofluorescence, whereas the expression of ATG5, matrix metallopeptidase 13 (MMP-13), vascular endothelial growth factor (VEGF), sclerostin, and β-catenin were evaluated by immunohistochemistry. TUNEL staining was used to determine apoptosis of chondrocytes.

Results: In vehicle-treated mice when compared with mice in the sham group, the OARSI scores, expression of MMP-13, VEGF, sclerostin, β-catenin, and chondrocyte apoptosis were significantly increased, whereas the expression of LC3 and ATG5 were significantly decreased. A systemic injection of rapamycin activated chondrocyte autophagy, which increased the expression of LC3 and ATG-5, and reduced OARSI scores, the expression of β-catenin, MMP-13, and VEGF, and chondrocyte apoptosis in rapamycin treated mice when compared with vehicle-treated mice.

Conclusions: Systemic injection of rapamycin attenuated articular cartilage degeneration by inhibiting β-catenin in a murine model of OA.     

Complement Activation Contributes to the Injury and Outcome of Kidney in Human Anti-glomerular Basement Membrane Disease

Purpose

Linear or granular deposition of complement 3 (C3) along glomerular basement membrane (GBM) is generally revealed in kidneys of human anti-GBM disease. However, the mechanism of complement activation and its association with clinical features and outcomes are less clear.

Methods

We measured the plasma and urinary levels of complement components, C1q, mannose-binding lectin (MBL), factor B (Ba), C3, C3a, C4, C4a, C5, C5a and soluble C5b-9 (SC5b-9), using ELISA in 20 patients with renal biopsy proven anti-GBM disease.

Results

The end product of complement activation, SC5b-9, was elevated both in plasma and urine. The levels of C3 and C4 were normal in plasma, while elevated in urine. The levels of C5a and SC5b-9 were increased in plasma from 15% and 30% patients respectively, while they were raised in urine from almost all patients (100% and 92%). The levels of plasma SC5b-9 and urinary C5a were positively correlated with the serum creatinine at presentation (r?=?0.56, P?=?0.01; r?=?0.68, P?=?0.02, respectively) and the percentage of crescents in glomeruli (r?=?0.60, P?=?0.005; r?=?0.75, P?=?0.005, respectively). The plasma level of SC5b-9 was further identified as the predictor for renal failure during follow up (HR, 1.46; 95% CI, 1.12-1.90; P?=?0.005).

Conclusion

Complement cascade goes to the end in human anti-GBM disease and resides mainly in kidney. It plays pathogenic role in renal injury, by the possible proinflammatory effect of C5a and/or cell lysis effect of C5b-9. C5a and C5b-9 may be useful in clinical monitoring and predicting.