Comprehensive analysis of m6 A methylome and transcriptome by Nanopore sequencing in clear cell renal carcinoma.

N6 -methyladenosine (m6 A) is the most prevalent epigenetic modification on eukaryotic messenger RNAs. Recent studies have focused on elucidating the key role of m6 A modification patterns in tumor progression. However, the relationship between m6 A and transcriptional regulation remains elusive. Nanopore technology enables the quantification of m6 A levels at each genomic site. In this study, a pair of tumor tissues and adjacent normal tissues from clear cell renal cell carcinoma (ccRCC) surgical samples were collected for Nanopore direct RNA sequencing. We identified 9644 genes displaying anomalous m6 A modifications, with 5343 genes upregulated and 4301 genes downregulated. Among these, 5224 genes were regarded as dysregulated genes, encompassing abnormal regulation of both m6 A modification and RNA expression. Gene Set Enrichment Analysis revealed an enrichment of these genes in pathways related to renal system progress and fatty acid metabolic progress. Furthermore, the χ2 test demonstrated a significant association between the levels of m6 A in dysregulated genes and their transcriptional expression levels. Additionally, we identified four obesity-associated genes (FTO, LEPR, ADIPOR2, and NPY5R) among the dysregulated genes. Further analyses using public databases revealed that these four genes were all related to the prognosis and diagnosis of ccRCC. This study introduced the novel approach of employing conjoint analysis of m6 A modification and RNA expression based on Nanopore sequencing to explore potential disease-related genes. Our work demonstrates the feasibility of the application of Nanopore sequencing technology in RNA epigenetic regulation research and identifies new potential therapeutic targets for ccRCC.

Outcome of split-liver transplantation from pediatric donors weighing 25 kg or less.

The lower limit of body weight for "splitable" liver grafts remains unknown. To examine the outcome of split-liver transplantation (SLT) from pediatric donors ≤25 kg relative to conventional graft-type liver transplantation from deceased donors under corresponding conditions, a total of 158 patients who received primary liver transplantation, including 22 SLTs from donors ≤25 kg, 46 SLTs from donors >25 kg, 76 whole-liver transplantations, and 14 reduced-liver transplantations in donors ≤25 kg between January 2018 and December 2019, were included in the study. There was no significant difference in the complications, patient survival, and graft survival between each of the latter three groups and the SLT ≤25 kg group. Pediatric End-Stage Liver Disease (PELD) score was the independent predictor of graft loss (death or retransplantation). Graft weight was the independent predictor of hepatic artery thrombosis. SLT using well-selected pediatric donors ≤25 kg is an effective strategy to increase organ availability, especially for low-body-weight recipients, compared with conventional graft type from deceased donors under the condition of corresponding donor weight without increasing morbidity and mortality.

HBsAg seroconversion in de novo hepatitis B virus-infected paediatric liver transplant recipients with anti-viral therapy.

We investigated the clinical characteristics and therapeutic strategies for paediatric liver transplant (PLT) recipients who experienced de novo hepatitis B virus infection and the features of HBsAg seroconversion. A total of 821 PLT were performed in HBV-free recipients between January 2013 and January 2019 in Paediatric Organ Transplant Center, Tianjin First Central Hospital. Twenty-one recipients developed de novo HBV infection, the clinical data were analysed. The overall incidence of de novo HBV infection was 2.5%. Only one recipient received an HBcAb-negative graft, 20 recipients received HBcAb-positive grafts. The incidence of de novo HBV infection in HBcAb-negative and HBcAb-positive graft recipients were 0.2% and 6.3%, respectively. Fifteen de novo HBV-infected recipients showed HBsAg seroconversion, the incidence of HBsAg seroconversion was 71.4%. The median time from the diagnosis of de novo HBV infection to HBsAg seroconversion was 15 (1, 73) months. Recipients with hepatitis B surface antigen (HBsAg) titre <1000 IU/L and negative hepatitis B e antigen (HBeAg) at the time of de novo HBV infection diagnosis were more likely to achieve HBsAg seroconversion. Nucleotide analogues were effective in treating recipients with de novo HBV infection. De novo HBV infection does not impact liver graft function as well as recipient and graft survival rate. De novo HBV infection does not impact PLT recipient outcomes under close monitoring and appropriate treatment. High incidence of HBsAg seroconversion can be achieved after anti-viral therapy.

Impact of allograft types on outcomes after pediatric liver transplantation due to biliary atresia.

BACKGROUND: Several surgical strategies, including split donor transplantation and living donor transplantation, have been used to increase the donor liver pool. This report focuses on the effects of whole, split, and LDLT on recipient outcomes. METHODS: We retrospectively analyzed the records of all patients with biliary atresia at Tianjin First Central Hospital between April 2013 and December 2019. RESULTS: A total of 882 patients were included and divided into three groups by graft type, with 198 in the whole-liver-transplantation group, 78 in the split liver transplantation group, and 606 in the LDLT group. The median follow-up time was 39 months, patient survival rates of three groups were 94.4%, 88.5%, and 95.0%, respectively, and graft survival rates were 90.2%, 83.3%, and 94.7%, respectively. We divided the split liver transplantation group into two subgroups according to the donor's age, and patient survival rates exhibited a significant difference only in the group whose donor age was over 45 years. The postoperative complication rates were significantly higher with respect to hepatic artery thrombosis, portal stenosis, and AR; and lower in hepatic venous stenosis, PTLDs, CMV virus, and EBV infection in the WLT group. Our multivariate model showed that donor age ≥45 years, RBC transfusion, pneumonia, and HAT were the independent predictors of allograft loss. CONCLUSIONS: The survival of split liver transplantation group was slightly lower. The types of complications are different from different graft types. Therefore, postoperative monitoring and treatment need to be adjusted according to the different graft types used.

The diagnosis and management of intestinal obstruction after pediatric liver transplantation.

BACKGROUND: The aim of this study was to analyze the risk factors, causes, and management of intestinal obstruction after pediatric liver transplantation. METHODS: Retrospective analysis was performed on pediatric liver transplantation recipients from January 1st 2013 to December 31st 2019 at Organ Transplant Center, Tianjin First Central Hospital. The cases of intestinal obstruction were analyzed. RESULTS: A total of 1034 pediatric liver transplantations were performed during the study period, 66 intestinal obstructions were diagnosed in 61 recipients. Three recipients suffered intestinal obstructions twice, and one recipient suffered three times. Forty of the 66 cases were treated with non-surgical treatment, including fasting, gastrointestinal decompression, purgation, enema, and parenteral nutrition. Surgical intervention was performed in 26 cases. Diaphragmatic hernia, intestinal inflammatory stenosis, PTLD, and intestine perforation are essential causes of intestinal obstruction in pediatric liver transplant recipients. Diaphragmatic hernia was independent risk factors for intestinal obstruction. The 1-, 2- and 3-year survival rate of the recipients with or without intestinal obstruction were 98.4%, 96.5%, 96.5% and 95.3%, 94.4%, 94.0%, respectively, without significant difference. CONCLUSIONS: Most cases of intestinal obstruction after liver transplantation in children can be remitted by non-surgical treatment, but there are still some cases need to be treated by surgery. Both measures are related to ideal outcomes, intestinal obstruction does not increase the mortality rate in pediatric liver transplantation.

Protective effect of Idelalisib on carbon tetrachloride-induced liver fibrosis via microRNA-124-3P/phosphatidylinositol-3-hydroxykinase signalling pathway.

Liver fibrosis is the repair process of abnormal connective tissue hyperplasia after liver damage caused by different causes. Inhibition of PI3K/Akt signalling pathway can reduce the deposition of extracellular matrix, inhibit the proliferation of hepatic stellate cells (HSCs), and promote its apoptosis to achieve the purpose of therapy. This study aimed to investigate the effect of Idelalisib (PI3K inhibitor) on carbon tetrachloride (CCl4 )-induced liver fibrosis in mice. We used CCl4 -induced liver fibrosis mouse model in vivo and TGF-ß1-stimulated HSCs to evaluate the antifibrosis activity of Idelalisib. In vivo, Idelalisib significantly alleviated CCl4 -induced liver damage, collagen deposition, and hydroxyproline accumulation in mice. Immunohistochemistry and Western blot results showed that Idelalisib could significantly inhibit the expressions of COL1 and α-SMA in a concentration-dependent manner. In cell experiments, Idelalisib significantly inhibited the expressions of COL1, SMA, and p-Smad3 in TGF-ß-induced HSCs, thereby inhibiting HSC activation. Flow cytometry and Western blot results showed that Idelalisib significantly promoted TGFß-induced apoptosis of HSCs after 48 h of administration, but had no significant effect after 24 h. Idelalisib promoted the apoptosis of activated HSCs by inhibiting the PI3K/Akt/FOXO3 signalling pathway. To further explore the mechanism by which Idelalisib inhibited PI3K, we predicted the miRNA targeting PI3K through the database and crossed it with the down-regulated miRNA reported in liver fibrosis mice in the past five years. Finally, we identified miR-124-3p and miR-143-3p. We then demonstrated that Idelalisib significantly promoted miR-124-3p and miR-142-3p in vitro and in vivo. Dual-luciferase report analysis showed that Idelalisib significantly inhibited luciferase activity but had no significant effect on the luc-MUT transfection assay. Finally, we demonstrated that Idelalisib reversed the effects of miR-124-3p inhibitor on the PI3K/Akt/FOXO3 asterisk pathway and caspase-3. Idelalisib has potential as a candidate drug for alleviating liver fibrosis.

Prophylactic Strategy Against De Novo Hepatitis B Virus Infection for Pediatric Recipients Who Receive Hepatitis B Core Antibody-Positive Liver Grafts.

The goal of this study was to evaluate the efficacy of a perioperative prophylactic strategy against de novo hepatitis B virus (HBV) infection in pediatric liver transplantation (LT) recipients with hepatitis B core antibody (HBcAb)-positive grafts. A total of 482 pediatric recipients transplanted between 2013 and 2017 were enrolled, and 170 recipients received HBcAb-positive liver grafts. The overall graft and recipient survival rates in HBcAb-positive and HBcAb-negative graft recipients were 91.8% versus 91.3% and 95.3% versus 94.2% at the end of follow-up. Preoperative hepatitis B surface antibody (HBsAb) titer ≥ 1000 IU/L and postoperative HBsAb titer ≥200 IU/L were our prophylactic targets for recipients receiving HBcAb-positive grafts. While 11 recipients developed de novo HBV infection, 10 received HBcAb-positive grafts. Both the preoperative and postoperative HBsAb targets were achieved in 78 recipients, the infection rate of de novo HBV was 1.3%; 24 recipients met the preoperative target, the infection rate was 4.2%; 52 recipients met the postoperative target, the infection rate was 1.9%; and 16 recipients met neither the preoperative nor postoperative HBsAb target, 43.8% of the recipients were infected with de novo HBV, which was significantly higher than the recipients who met both or either of the preoperative and postoperative targets. Split-liver grafts positive for HBcAb showed higher risk of de novo HBV infection. Postoperative application of lamivudine to recipients whose preoperative HBsAb titer < 1000 IU/L did not show preventive effect. Out of 11 infected recipients, 3 showed seroconversion under entecavir treatment. In conclusion, the graft and recipient survival rates were similar in pediatric LT recipients receiving HBcAb-positive or HBcAb-negative grafts. Our prophylactic strategy was effective for preventing de novo HBV infection in HBcAb-positive liver graft recipients.

Application of pediatric donors in split liver transplantation: Is there an age limit?

The experience of using pediatric donors in split liver transplant is exceedingly rare. We aim to investigate the outcomes of recipients receiving split pediatric grafts. Sixteen pediatric recipients receiving split liver grafts from 8 pediatric donors < 7 years were enrolled. The donor and recipient characteristics, perioperative course, postoperative complications, and graft and recipient survival rates were evaluated. The mean follow-up time was 8.0 ± 2.3 months. The graft and recipient survival rates were 100%. The liver function remained in the normal range at the end of the follow-up time in all recipients. No life-threatening complications were seen in these recipients, and the only surgery-related complication was portal vein stenosis in 1 recipient. Cytomegalovirus infection was the most common complication (62.5%). The transaminase level was significant higher in extended right lobe recipients in the early postoperative days, but the difference vanished at the end of first week; postoperative complications and graft and recipient survival rates did not differ between left and right graft recipients. Notably, the youngest split donor graft (2.7 years old) was associated with ideal recipient outcomes. Split liver transplant using well-selected pediatric donors is a promising strategy to expand pediatric donor source in well-matched recipients.

Microwave photonic radar with a fiber-distributed antenna array for three-dimensional imaging.

A microwave photonic (MWP) radar with a fiber-distributed antenna array for three-dimensional (3D) imaging is proposed and demonstrated for the first time. Photonic frequency doubling, wavelength-division multiplexing and radio-over-fiber techniques are employed for radar signal generation, replication, and distribution. Based on the delay-dependent beat frequency division, parallel de-chirp processing is completed in the center office (CO), leading to multi-channel 2D ISAR imaging and further 3D reconstruction. The influence of the fiber transmission delay is discussed and the phase noise caused thereby is compensated in 3D imaging algorithm, improving the coherence between channels. An experiment of a Ku-band MWP radar with a transmitter (Tx) and 16 equivalent receivers (Rxs) is conducted and 3D imaging of three trihedral corner reflectors is achieved with a range resolution of 7.3 cm, a cross-rage resolution of 5.6 cm and an elevation resolution of 0.85°. The results verify the capability of MWP radar in high-resolution 3D imaging.

Risk factors of de novo hepatitis B virus infection in pediatric hepatitis B core antibody positive liver graft recipients under prophylactic therapy.

BACKGROUND AND AIM: We aim to investigate the risk factors of de novo hepatitis B virus (HBV) infection in pediatric liver transplantation recipients receiving hepatitis B core antibody positive grafts and to evaluate the efficacy of our prophylactic strategies. METHODS: One hundred thirty-nine pediatric recipients receiving hepatitis B core antibody positive grafts operated from September 2016 to September 2018 were retrospectively enrolled, and all the patients received prophylactic treatment to prevent de novo HBV infection. Donor and recipient features, operative information along with graft, and recipient outcomes were compared between recipients with or without de novo HBV infection. Univariate and multivariate analyses were applied to identify the risk factors of de novo HBV infection. RESULTS: The mean follow-up time was 23.5 ± 15.7 months, and the overall incidence of de novo HBV infection was 3.6%. Recipients with de novo HBV infection showed equal graft and recipient outcome compared with the recipients without de novo HBV infection during the follow-up time. Recipient preoperative hepatitis B surface antibody titer of < 1000 IU/L (odds ratio [OR] = 9.652, P = 0.024), graft HBV DNA of > 1000 copies (OR = 9.050, P = 0.032), and intraoperative fresh-frozen plasma transfusion of > 400 mL (OR = 10.462, P = 0.023) were identified as independent risk factors for de novo HBV infection. CONCLUSION: Hepatitis B core antibody positive grafts can safely be used in pediatric liver transplantation under rational prophylactic therapy.

Successful living donor liver transplantation plus domino-auxiliary partial orthotopic liver transplantation for pediatric patients with metabolic disorders.

PURPOSE: To investigate the efficacy of living donor liver transplantation (LDLT) plus domino-auxiliary partial orthotopic liver transplantation (D-APOLT) in pediatric patients with metabolic disorders. METHODS: From May 2017 to October 2018, two patients with ornithine aminotransferase deficiency (OTCD) and one patient with type I Crigler-Najjar syndrome (CNS1) received LDLT, their livers were prepared as donors for D-APOLT. Two patients with CNS1 received domino liver grafts from OTCD patients; one OTCD patient received a domino liver graft from a CNS1 patient. RESULTS: The mean follow-up was 26.6 months. The liver function and ammonia remained in the normal range at the end of the follow-up in all recipients. One D-APOLT patient experienced portal vein thrombosis 2 days after transplantation and required reoperation, this patient presented an imbalance of portal blood perfusion between the native and the domino liver at 8 months after liver transplant. The imbalance was improved by interventional radiology treatment. Two LDLT patients experienced early mild acute rejection. CONCLUSIONS: The non-cirrhotic livers from pediatric patients with metabolic liver disease can be used as domino donor grafts for selected pediatric patients with different metabolic liver disease. D-APOLT achieves ideal recipient outcomes and provides a strategy to expand donor source for children.

A Novel MIMO-SAR System Based on Simultaneous Digital Beam Forming of Both Transceiver and Receiver.

Orthogonal frequency division multiplexing (OFDM) chirp waveform, which is composed of two or more successive identical linear frequency modulated sub pulses, is a newly proposed orthogonal waveform scheme for multi-input multi-output (MIMO) synthetic aperture radar (SAR) systems. However, according to the waveform model, there will be range ambiguity if the mapping width exceeds the maximum unambiguous width determined by the transmitted signal. This greatly limits its application in high-resolution wide-swath (HRWS) remote sensing. The traditional system divides the echoes by digital beam forming (DBF) to solve this problem, but the energy utilization rate is low. A MIMO-SAR system using simultaneous digital beam forming of both transceiver and receiver to avoid range ambiguity is designed in this paper. Compared with traditional system, the novel system designed in this paper obtain higher energy utilization and waveform orthogonality.

Engeletin inhibits Lipopolysaccharide/d-galactosamine-induced liver injury in mice through activating PPAR-γ.

Liver injury is a serious clinical syndrome that characterized by inflammatory response. Engeletin is known to have anti-inflammatory activity. However, the effects of engeletin on liver injury remain unclear. We aimed to assess the protective effect of engeletin on Lipopolysaccharide (LPS)/d-galactosamine (D-gal)-induced liver injury in mice. Engeletin was administered intraperitoneally 1 h before and 12 h after LPS/D-gal treatment. The results showed that engeletin treatment on LPS/D-gal-induced liver injury in mice have a significant protective effect, as confirmed by the attenuation of liver histopathologic changes, MPO activity, and serum AST and ALT levels. At the meanwhile, it also showed that engeletin inhibited the levels of IL-ß and TNF-α in serum and liver tissues. Besides, engeletin blocked the activation of NF-κB induced by LPS/D-gal and induced the expression of PPAR-γ in a dose-dependently manner. These findings suggested that engeletin may have a protective effect against liver injury.

Automatic Regularization of TomoSAR Point Clouds for Buildings Using Neural Networks.

Tomographic SAR (TomoSAR) is a remote sensing technique that extends the conventional two-dimensional (2-D) synthetic aperture radar (SAR) imaging principle to three-dimensional (3-D) imaging. It produces 3-D point clouds with unavoidable noise that seriously deteriorates the quality of 3-D imaging and the reconstruction of buildings over urban areas. However, existing methods for TomoSAR point cloud processing notably rely on data segmentation, which influences the processing efficiency and denoising performance to a large extent. Inspired by regression analysis, in this paper, we propose an automatic method using neural networks to regularize the 3-D building structures from TomoSAR point clouds. By changing the point heights, the surface points of a building are refined. The method has commendable performance on smoothening the building surface, and keeps a precise preservation of the building structure. Due to the regression mechanism, the method works in a high automation level, which avoids data segmentation and complex parameter adjustment. The experimental results demonstrate the effectiveness of our method to denoise and regularize TomoSAR point clouds for urban buildings.

Three-Dimensional Imaging Method for Array ISAR Based on Sparse Bayesian Inference.

The problem of synthesis scatterers in inverse synthetic aperture radar (ISAR) make it difficult to realize high-resolution three-dimensional (3D) imaging. Radar array provides an available solution to this problem, but the resolution is restricted by limited aperture size and number of antennas, leading to deterioration of the 3D imaging performance. To solve these problems, we propose a novel 3D imaging method with an array ISAR system based on sparse Bayesian inference. First, the 3D imaging model using a sparse linear array is introduced. Then the elastic net estimation and Bayesian information criterion are introduced to fulfill model order selection automatically. Finally, the sparse Bayesian inference is adopted to realize super-resolution imaging and to get the 3D image of target of interest. The proposed method is used to process real radar data of a Ku band array ISAR system. The results show that the proposed method can effectively solve the problem of synthesis scatterers and realize super-resolution 3D imaging, which verify the practicality of our proposed method.

The potential mechanism of bursal-derived BP8 on B cell developments.

The bursa of Fabricius, the key humoral immune organ unique to birds, is critical for B cell differentiation and antibody production. BP8 (AGHTKKAP) is a novel immunomodulatory peptide that regulates B-cell development. Gene microarray was used to investigate the mechanism of BP8 on B cell development. BP8 regulated expressions of 1,570 genes that were involved in retinol metabolism, the Wnt signaling pathway, MAPK pathway, Jak-Stat pathway, Notch signaling pathway, cytokine-cytokine receptor interaction, and Ca(2+) signals. Finally, BP8 triggered ADH7 and RDH10 expression, interacted with retinol binding protein, and regulated retinol uptake in vitro and vivo. These data reveal a bursal-derived multifunctional factor, BP8, as a novel biomaterial which is essential for the development of the immune system and represents an important linker between the B cell development and retinol metabolism. This study elucidates the mechanisms involved in humoral immune system and has implications in treating human diseases.

Characterization and Comparison of the Structural Features, Immune-Modulatory and Anti-Avian Influenza Virus Activities Conferred by Three Algal Sulfated Polysaccharides.

Three marine macroalgae, i.e., Grateloupia filicina, Ulva pertusa and Sargassum qingdaoense, were selected as the deputies of Rhodophyta, Chlorophyta and Ochrophyta for comparative analysis of the molecular structures and biological activities of sulfated polysaccharides (SP). The ratio of water-soluble polysaccharides, the monosaccharide composition and the sulfated contents of three extracted SPs were determined, and their structures were characterized by Fourier transformation infrared spectroscopy. In addition, biological activity analysis showed that all three SPs had immune-modulatory activity both in vitro and in vivo, and SPs from S. qingdaoense had the best effect. Further bioassays showed that three SPs could not only enhance the immunity level stimulated by inactivated avian influenza virus (AIV) in vivo but also significantly inhibited the activity of activated AIV (H9N2 subtype) in vitro. G. filicina SP exhibited the strongest anti-AIV activity. These results revealed the variations in structural features and bioactivities among three SPs and indicated the potential adjuvants for immune-enhancement and anti-AIV.

Rituximab for relapsing-remitting multiple sclerosis.

BACKGROUND: This is an update of the Cochrane review "Rituximab for relapsing-remitting multiple sclerosis" (first published in The Cochrane Library 2011, Issue 12).More than 80% of individuals with multiple sclerosis (MS) experience a relapsing-remitting disease course. Approximately 10 years after disease onset, an estimated 50% of individuals with relapsing-remitting MS (RRMS) convert to secondary progressive MS. MS causes a major socioeconomic burden for the individual patient and for society. Effective treatment that reduces relapse frequency and prevents progression could impact both costs and quality of life and help to reduce the socioeconomic burden of MS. Alternative and more effective MS treatments with new modes of action and good safety are needed to expand the current treatment repertoire. It has been shown that B lymphocytes are involved in the pathophysiology of MS and rituximab lyses B-cells via complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity. Current clinical trials are evaluating the role of rituximab as a B-cell depletion therapy in the treatment of RRMS. OBJECTIVES: The safety and effectiveness of rituximab, as monotherapy or combination therapy, versus placebo or approved disease-modifying drugs (DMDs) (interferon-ß (IFN-ß), glatiramer acetate, natalizumab, mitoxantrone, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab) to reduce disease activity for people with RRMS were assessed. SEARCH METHODS: The Trials Search Co-ordinator searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Specialised Register (9 August 2013). We checked the references in identified trials and manually searched the reports (2004 to August 2013) from neurological associations and MS societies in Europe and America. We also communicated with researchers who were participating in trials on rituximab and contacted Genentech, BiogenIdec and Roche. SELECTION CRITERIA: All randomised, double-blind, controlled parallel group clinical trials with a length of follow-up equal to or greater than one year evaluating rituximab, as monotherapy or combination therapy, versus placebo or approved DMDs for patients with RRMS without restrictions regarding dosage, administration frequency and duration of treatment. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures of The Cochrane Collaboration. Two review authors independently assessed trial quality and extracted data. Disagreements were discussed and resolved by consensus among the review authors. Principal investigators of included studies were contacted for additional data or confirmation of data. MAIN RESULTS: One trial involving 104 adult RRMS patients with an entry score ≤ 5.0 on the Expanded Disability Status Scale (EDSS) and at least one relapse during the preceding year was included. This trial evaluated rituximab as monotherapy versus placebo, with a single course of 1000 mg intravenous rituximab (on day 1 and day 15). A significant attrition bias was found at week 48 (24.0%). Patients receiving rituximab had a significant reduction in total number of gadolinium-enhancing lesions at week 24 (mean number 0.5 versus 5.5; relative reduction 91%) and in annualised rate of relapse at week 24 (0.37 versus 0.84) but not at week 48 (0.37 versus 0.72). Disability progression was not included as an outcome in this trial. More patients in the rituximab group had adverse events within the 24 hours after the first infusion (78.3% versus 40.0%), such as chills, headache, nausea, pyrexia, pruritus, fatigue, throat irritation, pharyngolaryngeal pain, and most were mild-to-moderate events (92.6%). The most common infection-associated adverse events (> 10% in the rituximab group) were nasopharyngitis, upper respiratory tract infections, urinary tract infections and sinusitis. Among them, only urinary tract infections (14.5% versus 8.6%) and sinusitis (13.0% versus 8.6%) were more common in the rituximab group. One ongoing trial was identified. AUTHORS' CONCLUSIONS: There is not sufficient evidence to support the use of rituximab as a disease-modifying therapy for RRMS because only one RCT was included. The quality of the study was limited due to high attrition bias, the small number of participants, and short follow-up. The beneficial effects of rituximab for RRMS remain inconclusive. However, short-term treatment with a single course of rituximab was safe for most patients with RRMS. Mild-to-moderate infusion-associated adverse events were common, as well as nasopharyngitis, upper respiratory tract infections, urinary tract infections and sinusitis. The potential benefits of rituximab for treating RRMS need to be evaluated in large-scale studies that are of high quality along with long-term safety.

microRNA-221 rescues the loss of dopaminergic neurons in a mouse model of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is one of the most common systemic neurodegenerative diseases and is related to the loss of dopaminergic neurons in the substantia nigra. Several studies verified that microRNA (miRNAs) targeting the Bim/Bax/caspase-3 signaling axis is involved in the apoptosis of dopaminergic neurons in substantia nigra. In this study, we aimed to explore the role of miR-221 in PD. METHODS: To examine the function of miR-221 in vivo, we used a well-established 6-OHDA-induced PD mouse model. Then we conducted adenovirus-mediated miR-221 overexpression in the PD mice. RESULTS: Our results showed that miR-221 overexpression improved motor behavior of the PD mice. We demonstrated that overexpression of miR-221 reduced the loss of dopaminergic neurons in the substantia nigra striatum by promoting their antioxidative and antiapoptosis capacities. Mechanistically, miR-221 targets Bim, thus inhibiting Bim and Bax caspase-3 mediated apoptosis signaling pathways. CONCLUSION: Our findings suggest miR-221 participates in the pathological process of PD and might be a potential drug target and provide new insight into PD treatment.

Axitinib attenuates the progression of liver fibrosis by restoring mitochondrial function.

Liver fibrosis can progress to cirrhosis and hepatocellular carcinoma, which may eventually lead to liver failure and even death. No direct anti-fibrosis drugs are available at present. Axitinib is a new generation of potent multitarget tyrosine kinase receptor inhibitors, but its role in liver fibrosis remains unclear. In this study, a CCl4-induced hepatic fibrosis mouse model and a TGF-ß1-induced hepatic stellate cell model were used to explore the effect and mechanism of axitinib on hepatic fibrosis. Results confirmed that axitinib could alleviate the pathological damage of liver tissue induced by CCl4 and inhibit the production of glutamic-oxalacetic transaminase and glutamic-pyruvic transaminase. It also inhibited collagen and hydroxyproline deposition and the protein expression of Col-1 and α-SMA in CCl4-induced liver fibrosis. In addition, axitinib inhibited the expression of CTGF and α-SMA in TGF-ß1-induced hepatic stellate cells. Further studies showed that axitinib inhibited mitochondrial damage and reduced oxidative stress and NLRP3 maturation. The use of rotenone and antimycin A confirmed that axitinib could restore the activity of mitochondrial complexes I and III, thereby inhibiting the maturation of NLRP3. In summary, axitinib inhibits the activation of HSCs by enhancing the activity of mitochondrial complexes I and III, thereby alleviating the progression of liver fibrosis. This study reveals the strong potential of axitinib in the treatment of liver fibrosis.