Liver fibrosis is one of the most common liver diseases with substantial morbidity and mortality. However, effective therapy for liver fibrosis is still lacking. Considering the key fibrogenic role of activated hepatic stellate cells (aHSCs), here we reported a strategy to deplete aHSCs by inducing apoptosis as well as quiescence. Therefore, we engineered biomimetic all-trans retinoic acid (ATRA) loaded PLGA nanoparticles (NPs). HSC (LX2 cells) membranes, presenting the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), were coated on the surface of the nanoparticles, while the clinically approved agent ATRA with anti-fibrosis ability was encapsulated in the inner core. The biomimetic coating of TRAIL-expressing HSC membranes does not only provide homologous targeting to HSCs, but also effectively triggers apoptosis of aHSCs. ATRA could induce quiescence of activated fibroblasts. While TM-NPs (i.e. membrane coated NPs without ATRA) and ATRA/NPs (i.e. non-coated NPs loaded with ATRA) only showed the ability to induce apoptosis and decrease the α-SMA expression in aHSCs, respectively, TM-ATRA/NPs induced both apoptosis and quiescence in aHSCs, ultimately leading to improved fibrosis amelioration in both carbon tetrachloride-induced and methionine and choline deficient L-amino acid diet induced liver fibrosis mouse models. We conclude that biomimetic TM-ATRA/NPs may provide a novel strategy for effective antifibrosis therapy.

Renal arteriovenous malformations (AVMs) are infrequent vascular morphological anomalies. About 20% of AVMs are congenital renal AVMs (CRAVMs). A 53-year-old female patient presented with a 5-day history of gross hematuria and right flank pain. The patient underwent the selective renal arteriography and embolization under local anesthesia. Renal computed tomography angiography (CTA) and digital subtraction angiography (DSA) results showed bleeding of the right renal arteriovenous malformation, both nidus and aneurysm, which indicated that the patient had both cirsoid and cavernosal types of CRAVM. Endovascular management was chosen to treat the patient. The patient was cured and discharged, then followed-up for 3 months. These results show that early identification using radiologic tests is important for diagnosis and treatment of CRAVM.

The patient, a 32-year-old man, sought medical care in a local hospital on 30 January 2020 (day 1) for chief complaints of fever, dizziness and dry cough for 6 days. He had tried cephalosporin and paracetamol by himself without efficiency. He denied any potential contact with coronavirus disease-2019 (COVID-19) patients or living in epidemic areas. This patient was diagnosed with HIV infection 12 years ago, and initiated antiretroviral therapy containing zidovudine (300 mg twice/day), lamivudine (300 mg once/day) and efavirenz (600 mg once/night) 6 years ago with CD4+ T-cells count of 294 cells/μl. This regimen was maintained and recent CD4+ T-cell count on October 2019 elevated to 430 cells/μl. On admission, his temperature was 37.8 °C (Fig. 1) and oxygen saturation was around 98% with 33% oxygen inhalation. His white blood cells (WBC) count was 3.7 × 109/l with decreased lymphocytes (1.04 × 109/l), whereas it was 3.26 × 109/l 4 months previously. His C-reactive protein (CRP) was 15.5 mg/l and CD4+ T-cell count was 324 cells/μl. Chest computed tomography (CT) image showed multifocal bilateral multifocal ground-glass opacities (GGOs) (Fig. S1, https://links.lww.com/QAD/B743). In consideration of no COVID-19 contact, piperacillin/tazobactam, levofloxacin and oseltamivir were given. On day 3, his temperature maintained at over 39 °C and WBC count decreased to 2.6 × 109/l with a significant lymphopenia of 0.71 × 109/l and CRP was 15.5 mg/l. Rechecked chest CT showed progressed GGOs and consolidations (Fig. S1, https://links.lww.com/QAD/B743). Imipenem/cilastatin was used. Peak temperature decreased to around 38 °C. With concern of possible severe acute respiratory syndrome (SARS)-CoV-2 infection, nucleic acid detection of sputum was performed on day 4 and the result was shown to be positive on day 5. Detections of other respiratory viruses including influenza A/B, adenovirus, respiratory syncytial virus and parainfluenza virus were all negative. Lopinavir/ritonavir (LPV/r, 400 mg/100 mg twice/day) combined with interferon-α inhalation was given on day 5 to take the place of previous prescriptions, and efavirenz was stopped.Fig. 1: Temperature and clinical course of this patient.Since diagnosed of COVID-19, he was transferred to our center on day 7, and arbidol (200 mg three times/day) was added to his treatment. Chest CT on day 8 showed apparent absorption of all lesions (Fig. S1, https://links.lww.com/QAD/B743), and his lymphocyte count was 1.5 × 109/l. CRP returned to normal. Detection of SARS-CoV-2 in sputum on day 8 turned negative and stayed negative until discharge. He kept afebrile since day 5. And, on day 12, rechecked chest CT showed lesions similar to that on day 8 (Fig. S1, https://links.lww.com/QAD/B743). On days 10 and 13, we tested SARS-CoV-2 in stools and both results were negative. On day 14, the patient was discharged. He denied any comfortabilities in a follow-up visit 2 weeks later. Laboratory tests showed the WBC count was 6.6 × 109/l, with a normal lymphocytes count (1.8 × 109/l) and a chest CT image showed completed absorption of all lesions. To our knowledge, this is the first case report to describe SARS-CoV-2 infection in a patient with AIDS. Similarly, low morbidity of co-infection of coronavirus and HIV was also found in patients with SARS and Middle East respiratory syndrome (MERS) as reported previously [1,2]. Defect of immunity was regarded to be one potential susceptibility towards COVID-19 in patients with older age and malignancies [3,4]. However, the immunocompromised states of AIDS patients seemed to have no relevance with respect to COVID-19. One possible reason might be that protease inhibitors were used in some AIDS patients, which were reported to have an antiviral effect towards coronavirus [5,6]. Meanwhile, we speculated that AIDS patients were more likely to wear protective equipment because of concerns of opportunistic infections, and AIDS patients with mild or moderate symptoms might avoid going to see a doctor for personal reasons [7], which might lead to an extra transmission risk of SARS-CoV-2. Even through, at the beginning of admission, this patient had persistent high fever with multifocal lesions on the chest CT, durations of symptoms and of lesion progression on the CT image were similar to other moderate COVID-19 patients [8,9]. One explanation might be that impaired immunity of AIDS patients would attenuate the immune response towards coronavirus, which was supposed to cause more damage to the lungs [10]. Meanwhile, immune dysfunction was also regarded to delay the clearance of virus. However, paradoxically, the duration of positive RT-PCR results of SARS-CoV-2 in this patient was shorter than the average level [8]. As LPV/r and arbidol were used after this patient was afebrile, it was hard to conclude from this patient that LPV/r and arbidol could benefit patients with respect to coronavirus clearance. Meanwhile, attention should be paid to irregularities in the administration of antibiotics in AIDS patients with fever during this period. More data are needed to better understand the pathogenesis and prognosis in patients with coinfection of SARS-CoV-2 and HIV. Acknowledgements We appreciate all of the clinical providers, nurses and scientific researchers for their efforts in fighting COVID-19. Sources of Funding: This work was supported by National Science and Technology Major Project (Dr Su; 2018ZX10715014-004-002). Conflicts of interest There are no conflicts of interest.

Objective To investigate the in vitro inhibitory effects of regulatory T cells ( Treg ) from unpregnant mice and pregnancy-induced regulatory T cells ( piTreg) on the proliferation of na?ve T cells and their differences .Methods The numbers of piTreg cells from allogeneic pregnant mice ( C57/B6 fe-male×BALB/c male) on day 12.5 (E12.5d) of gestation and Treg cells from unpregnant C57/B6 mice were detected respectively by flow cytometry .The percentages of piTreg cells and Treg cells in CD 4+T cells of age-matched female mice and their intracellular expression of Foxp 3 were analyzed .The in vitro inhibitory effects of piTreg cells and Treg cells on the CFSE-labeled na?ve T cells ( effector cells ) were compared in a one-way mixed lymphocyte culture system using mitomycin C-inactivated CD4-T cells as stimulator cells . Results The level of piTreg cells in splenic mononuclear cells was significantly higher than that of Treg cells (P<0.001) from normal mice.Foxp3 was highly expressed in both piTreg cells and Treg cells , howev-er slightly increased in piTreg cells .Moreover , piTreg cells had a significant stronger in vitro inhibitory effect on na?ve T cells proliferation than that of Tregs cells (P<0.006), which was in a cell-dependent manner. Conclusion The present study suggests that the piTreg cells have a stronger inhibitory effect on na ?ve T cell proliferation as compared with Terg cells from unpregnant mice , The differential activity of CD 4+CD25+Treg might be mediated by the paternal antigens during pregnancy .

The occurrence of de novo malignant neoplasms has been shown in post-transplant recipients receiving immunosuppressive treatment. We present a case of a rare extragastrointestinal stromal tumor (EGIST) located in the pelvic cavity of a kidney transplant patient. A 57-year-old female patient was admitted to our department because of non-specific lower abdominal pain 6 months after renal transplantation. An abdominal computed tomography scan showed a 4.5 cm diameter pelvic tumor mass. The tumor was resected en bloc and confirmed as not being connected to the gastrointestinal wall. Microscopically, the tumor consisted of typical spindle cells with 2−3 mitotic figures per 50 high-power fields. Immunohistochemically, the tumor cells were strongly positive for CD117 (c-kit), and negative for CD34, SMA, s-100 protein, and desmin. Genetically, the tumor showed a silent mutation in exon 18 of the PDGFRA gene at codon 824 GTC > GTT (V824V) [rs2228230]. No recurrence was noted 24 months after the operation. This case draws our attention to the importance of considering EGISTs (including GISTs), even though they are extremely uncommon, in the differential diagnosis of mesenchymal neoplasms, especially in transplant patients.

小鼠皮肤移植模型是研究T淋巴细胞识别同种异体抗原机制的标准方法,亦是探讨免疫排斥反应及鉴定近交系小鼠的基本方法之一[1].根据移植皮片的来源不同,目前常用的小鼠皮肤移植方法有背-背法、耳-背法、尾-背法等[2].我们在参考相关文献的基础上,建立小鼠耳朵来源皮片的皮肤移植模型,现报告如下。

Elucidation of maternal-fetal tolerance mechanisms clarifies the role of regulatory T cells (Treg) in transplant tolerance. This study aim to investigate the effect of pregnancy on paternal skin allograft survival. Flow cytometry techniques, mixed lymphocytes reaction (MLR), PCR, real-time PCR and skin transplantation were key methods. Treg increased significantly from 4.2% before pregnancy to peak at 6.8% day 8 after pregnancy. Both heme oxygenase-1 (HO-1) and indoleamine 2,3-dioxygenase (IDO) mRNA express high in placenta while low in spleen (P<0.05). Although Treg increased during pregnancy, and splenocytes from the pregnant mice showed lower MLR response toward the paternal stimulator, single time pregnancy showed no significant protective effect on paternal skin allograft survival in the tested condition.

母胎耐受机制的阐明,将为器官移植免疫耐受方案的研究提供重要启示.本研究旨在阐明妊娠状态对父系来源移植皮片的存活是否有保护作用.2月龄雌性C57BL/6小鼠和2～4月龄BALB/c雄性小鼠同笼受孕.采用流式细胞技术确定妊娠过程中调节性T细胞（Treg）比例的时间变化规律.以单向混合淋巴细胞反应（MLR）手段比较研究妊娠对于父系来源脾细胞刺激后产生的增殖反应的影响.通过同种异体小鼠全厚皮片移植模型,观察妊娠对于父系来源移植皮片的存活是否具有保护作用.并用分子生物学技术研究此种效能的可能机制.结果显示,C57BL/6小鼠妊娠过程中,Treg占CD4+T细胞的比例从妊娠前的4.2%逐渐上升,受孕8天左右达到高峰值（6.8%）,此后开始下降并逐渐回复至基线水平.MLR结果表明,针对父系来源脾细胞的刺激,妊娠组较对照组呈现显著的低反应性,其平均刺激指数分别是7.8和13.6（P＜0.05）.定量PCR研究表明,血红素加氧酶-1和吲哚胺2,3双加氧酶mRNA在胎盘高表达,在脾脏低表达（P＜0.05）.父系来源的移植皮片的平均存活时间在妊娠组和非妊娠组分别是7.67和7.08天,无统计学差异（P＞0.05）.由此认为,在小鼠妊娠过程中,尽管出现了具有免疫抑制功能的Treg的比例增加,尽管有针对父系来源刺激细胞的较低的MLR反应性,但是单次妊娠对于父系来源的移植皮片的存活,在本研究条件下,未能显示具有统计学意义的保护作用.

We aim to investigate the effect of transforming growth factor (TGF)-β1 on the expression of enhancer of split- and hairy-related protein-2 (SHARP-2) messenger RNA (mRNA) and its signaling pathway. In this study, several cell lines including LLC-PK1 (a porcine kidney tubular epithelial cell line), MDCK (Madin-Darby canine kidney) and CTLL-2 (cytotoxic T-lymphocyte line) were treated with recombinant human TGF-β1, and a series of experiments were carried out, involving Northern blot analysis of total RNA from these cells. Further, several specific chemical inhibitors were applied before TGF-β1 treatment to probe the signaling pathway. The results showed that TGF-β1 can significantly up-regulate SHARP-2 mRNA expression in the LLC-PK1 cell line. The peak level of induction was found 2 h after TGF-β1 stimulation. While one phospho-inositide 3-kinases (PI-3) kinase inhibitor, LY294002, completely blocked the effect of TGF-β1 on SHARP-2 mRNA expression in LLC-PK1 cells at a low concentration, other inhibitors, including PD98059, staurosporine, AG490, wortmannin, okadaic acid and rapamycin, had no effect. The effect of LY294002 was dose-dependent. We conclude that, in LLC-PK1 cells at least, TGF-β1 can effectively induce the SHARP-2 mRNA expression and that the PI-3 kinase pathway can mediate this effect.

BACKGROUND Alemtuzumab, a humanized CD52 monoclonal antibody, with its profound lymphocyte depletion property, was expected to be a promising induction therapy agent for kidney transplantation (KTx). However, currently no consensus is available about its efficacy and safety. The aim of this meta-analysis was to make a profound review and an objective appraisal of this issue. METHODS Relevant papers were searched, essentially in the PubMed database and the Cochrane library. After a thorough review, randomized controlled trials (RCTs) comparing the outcome of KTx using alemtuzumab induction therapy (test group) with a control group were collected according to the inclusion criteria. Data of general characteristic of studies and major outcomes of Ktx were extracted and meta-analyses were performed with RevMan 4.2 software. The odds ratio (OR) with a 95% confidence intervals (CI) was the principle measurement of effect. RESULTS Five RCTs were included. The chi square test showed no significant between-study heterogeneity, thus fixed effect model was employed. Sub-group analysis with studies including alemtuzumab induction followed by a tacrolimus-based immunosuppressive regimen showed that the acute rejection rate (ARR) was lower relative to the control (OR = 0.59, 95% CI 0.34 - 1.01, P = 0.05). However, meta-analysis with all included studies revealed that neither ARR nor patient/graft survival rates differ significantly between the test and the control group, but the cytomegalovirus (CMV) infection rate was higher in the test group (OR 2.50, 95% CI 1.22 - 5.12, P = 0.01). A great number of the test group recipients safely remained on a regimen that was steroid-free and with a reduced dose of conventional immunosuppressive drugs. CONCLUSIONS Alemtuzumab induction therapy for KTx was an effective and safe protocol in the tested follow-up period. Steroid avoidance and a dose reduction of conventional immunosuppressive drugs after alemtuzumab induction therapy may have clinical importance. However, high quality RCTs with larger population and longer follow-up are needed for a more accurate and objective appraisal of this novel protocol.

目的 应用实时荧光定量聚合酶链式反应(Q-PCR)方法测定端粒长度.方法 选取9种人类细胞株,提取基因组DNA,采用Q-PCR方法测定相对T/S比率,DNA印迹法测定末端限制性片段(TRF)长度,进行二者之间的相关性分析.结果 定量PCR测定端粒长度相对T/S比率为0.68±0.57,DNA印迹法测量平均TRF值为8.57±2.34,两种方法测定结果的相关性分析R2=0.7807(P＜0.01).结论 采用荧光定量PCR方法测量端粒长度具有重复性好、省时、简便、可靠的特点,可高通量处理大量样品.