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Abstract Objective To analyze the clinical characteristics and treatment of pediatric tufted angiomas(TA)complicated by Kasabach-Merritt Phenomenon (KMP). Method A retrospective analysis was conducted on the clinical data and follow-up data of 13 patients diagnosed with TA complicated by KMP. Five male and 8 female patients with an average age of 5.7 months (range, 29 days to 1 year) were treated with surgery between January 2009 and June 2012. According to the size and location of lesions and the degree of thrombocytopenia, complete or subtotal resection was performed. The median follow-up period was 3.4 years (range, 1.7 years to 5.2 years). Therapeutic outcomes were evaluated by platelet count and lesion size. Results Curative treatment of KMP is defined as restoration of normal hemostasis and elimination of tumor cells. Twelve patients achieved curative treatment and one died of multiple organ failure after operation. Ten patients received complete resection and three patients received incomplete resection. Thrombocyte count, hemoglobin and blood coagulation were respectively restored to normal levels within 1–3 days and 1–2 weeks post complete resection operation. One of the three patients who received subtotal resection operation died. In the other two patients, the platelet count fluctuated over time but remained above 60 × 109 /L, a significantly higher level than the preoperational level. Residual lesions slowly disappeared after continuous medication 3–6 months post operation. Conclusion Early s urgical treatment of patients with TA complicated with KMP resulted in significantly higher curative rate and reduced side-effects of drugs. Highlights • Surgical treatment is effective for most TA patients complicated by KMP • TA Patients complicated by KMP could die of consumptive coagulopathy • Early surgical treatment of patients resulted in significantly better treatment outcome [ABSTRACT FROM AUTHOR]

In the present study, quercetin (QUR)-loaded mixed micelles (QUR-M) were prepared with the aim of improving the physicochemical and anticancer efficacy of QUR in lung cancer cells. The mixed micelles comprised tocopheryl polyethylene glycol 1000 succinate (TPGS) and a 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine derivative of polyethylene glycol. The nanosized QUR-M exhibited a pH-responsive and controlled release of QUR that is likely to be beneficial in cancer treatment. The results of an MTT assay clearly demonstrated that the anticancer effect of QUR-M in A549 cancer cells was stronger compared with that of free QUR at 24 and 48 h time points. The half-maximal inhibitory concentrations of QUR and QUR-M were observed to be 12.45 and 6.42 µg/ml, respectively. When stained with Hoechst 33342 and observed using a confocal laser scanning microscope, A549 cells treated with QUR-M exhibited severe chromatin condensation and apoptotic body formation of the nuclei. Overall, high intracellular uptake, sustained drug release and the presence of TPGS in the mixed micelles may result in an increased inhibitory effect against cell proliferation and improved therapeutic efficacy in lung cancers. [ABSTRACT FROM AUTHOR]

Background: For hepatitis B patients who do not meet the treatment criteria recommended by guidelines, therapy decisions depend on hepatic histology. Angiopoietin-like protein 2 (Angptl2) is a mediator of chronic inflammation that contributes to extracellular matrix remodeling. The aim of this study was to explore the predictive value of Angptl2 as a novel biomarker of liver histology.Methods: Hepatitis B patients with normal to minimally raised ALT were recruited. Serum Angptl2 concentrations were detected using commercial ELISA kit. The fibrosis score were assessed according to Ishak criteria. Significant fibrosis was defined as ISHAK score ≥ 3.Results: Of 460 patients, 223 cases served as training cohort and 237 ones as validation cohort. Serum Angptl2 concentration was significantly associated with fibrosis scores in both training and validation group. Angptl2 combined index (ACI) for assessing significant fibrosis was developed from training cohort, based on Angptl2 and conventional variables. ACI showed areas under receiver-operating characteristic curve (AUC) of 0.835 for predicting significant fibrosis, which was superior to APRI (AUC = 0.776, P = 0.049), FIB-4 (AUC = 0.750, P = 0.010), Hui model (AUC = 0.756, P = 0.028), and had a better trend than Forn's index (AUC = 0.796, P = 0.083) in training cohort. Finally, validation cohort revealed its robustness and reliability.Conclusion: Higher Angptl2 level represents as a potential biomarker independently associated with fibrosis stages. Compared with APRI, Hui model, FIB-4, Forn's index, ACI did better in diagnosing significant fibrosis in hepatitis B patients.Trial Registration: The complete clinical trials protocol is available by request at clinicaltrials.gov ( NCT01962155 ) and chictr.org ( ChiCTR-DDT-13003724 ). [ABSTRACT FROM AUTHOR]

Background: Gastric duplication cysts are rare congenital alimentary tract anomalies and most cases are recognized during childhood. There were few reports about gastric duplication cysts in newborns and even fewer reports about laparoscopic resection of gastric duplication cysts in newborns.Case Presentation: We report a series of five newborns with gastric duplication cysts which were successfully resected by laparoscopy between January 2010 and April 2015. Case 1, a male newborn was admitted because of severe salivation, choking cough and dyspnea for 30 min after birth. Case 2, a male, was suspected of duodenal ileus by antenatal examination. Case 3, a female was admitted because of vomiting for 5 days. Case 4,a female without significant symptoms simply visited us for the abdominal cyst detected by antenatal examination. Case 5, a male was admitted because of vomiting for 4 days. All patients were performed with a surgery after assistant examinations. Case 1 was died of respiratory failure and the other patients recovered uneventfully.Conclusion: Gastric duplication cysts in newborns are very rare. Laparoscopic surgery play an important role on the diagnosis and treatment. Our experience and practice indicate that laparoscopic resection of gastric duplication cysts in newborns is viable and there is also a need to increase sample size to prove its safety and effectiveness. [ABSTRACT FROM AUTHOR]

In the present study, eleven compounds (1-11) including nine alkaloids (1-9), one triterpenoid saponin (10) and one formamide (11) were isolated from Talaromyces sp. LGT-2, an endophytic fungus from Tripterygium wilfordi. Their structures were determined based on NMR and ESI-MS spectral data, as well as comparing with previous literature data. This is the first report of the isolation of alkaloids (1-9) from Talaromyces genus. In the next step, all compounds were screened for their anti-monoamine oxidase, anti-acetylcholinesterase, antibacterial and antitumor activities. Compound 11 showed moderate anti-monoamine oxidase activity with IC50 value of 61 μM; compounds 3, 4, 8 showed weaker anti-acetylcholinesterase activity; compounds 1, 3, 4, 7, 8, 9 showed moderate antibacterial activities; compounds 7, 8, 9 showed cytotoxicity against B16 cancer cell line with inhibitory rate of 86%, 82%, 78%, respectively, at the concentration of 500 μg/mL. [ABSTRACT FROM AUTHOR]

Background: Many previous studies have shown the potential therapeutic effect of acupuncture for allergic rhinitis. Most of these studies, however, were limited by the short duration of observations and lack of sham acupuncture as the control group. Our preliminary experiments showed that the use of a warm needling achieved a much more persistent effect in the treatment of allergic rhinitis (AR) compared with simple acupuncture therapy. Hence, we have designed a multicenter, randomized controlled trial (RCT) in which the first-line medication loratadine will be used as the control group, and the effect of warm needling therapy will be evaluated through long-term observation.Methods/design: The trial is designed as a multicenter, parallel-group, randomized, single-blinded (outcome assessors), non-inferiority trial. A total of 98 patients with persistent AR will be randomly assigned into two groups. Patients in the treatment group will be treated with warm needling at GV14 and acupuncture at EX-HN3, ST2, LI20, EX-HN8, GV23, LU7, LU5 and LI4 three times a week, for a total of 4 weeks. Patients in the control group will be treated with oral loratadine 10 mg/day for 4 weeks. The primary outcome will be the change in the Total Nasal Symptom Score (TNSS) from baseline to that at 6 months after treatment during the follow-up period. The secondary outcomes will include the Total Non-nasal Symptom Score and the Rhinoconjunctivitis Quality of Life Questionnaire, changes in the TNSS from baseline to that at 2 and 4 weeks during treatment, and 3 months after treatment during the follow-up period. Outcomes will be measured at 2 and 4 weeks, and 3 and 6 months after treatment. Any side effects of treatment will be observed and recorded.Discussion: We expect that the study results will provide evidence to determine the effects of warm needling compared with loratadine. Our final goal of the study is to evaluate the difference in the short-term and long-term effects between the two therapeutic methods, especially the long-term effect of warm needling.Trial Registration: ClinicalTrials.gov NCT02339714 . Registered on 14 January 2015. [ABSTRACT FROM AUTHOR]

Osteosarcoma is a prevalent type of cancer and has a high metastatic ability, particularly for metastasis to the lungs. Effective treatment strategies have improved, however, the detailed molecular mechanism underlying the onset of this malignancy remains to be fully elucidated. The current study investigated the role of the tripartite motif (TRIM) family protein TRIM59 in osteosarcoma growth and metastasis. It was identified that TRIM59 was overexpressed in clinical osteosarcoma tissues and cultured osteosarcoma cell lines. In addition, the MTT assay demonstrated that in U2OS and MG63 cells, knockdown of TRIM59 by specific siRNA inhibited proliferation, whereas overexpression of TRIM59 promoted cell proliferation. Furthermore, overexpression of TRIM59 significantly increased the U2OS cell migrative and invasive abilities in a Transwell chamber assay. In addition, TRIM59 was able to negatively regulate the protein levels of P53 without significantly affecting the mRNA levels in U2OS and MG63 cells. These data suggest the oncogenic abilities of TRIM59 in osteosarcoma, which promote osteosarcoma cell proliferation, migration and invasion. [ABSTRACT FROM AUTHOR]

Introduction Understanding the mechanisms by which some individuals are able to naturally control HIV- 1 infection is an important goal of AIDS research. We here describe the case of an HIV-1+ woman, CASE1, who has spontaneously controlled her viremia for the last 14 of her 20 years of infection. Methods CASE1 has been clinically monitored since 1993. Detailed immunological, virological and histological analyses were performed on samples obtained between 2009 and 2011. Results As for other Elite Controllers, CASE1 is characterized by low to undetectable levels of plasma HIV-1 RNA, peripheral blood mononuclear cell (PBMC) associated HIV-1 DNA a reduced in vitro susceptibility of target cells to HIV-1 infection. Furthermore, a slow rate of virus evolution was demonstrated in spite the lack of assumption of any antiretroviral agent. CASE1 failed to transmit HIV-1 to either her sexual male partner or to her child born by vaginal delivery. Normal values and ratios of T and B cells were observed, along with normal histology of the intestinal mucosa. Attempts to isolate HIV-1 from her PBMC and gut-derived cells were unsuccessful, despite expression of normal cell surface levels of CD4, CCRC5 and CXCR4. CASE1 did not produce detectable anti-HIV neutralizing antibodies in her serum or genital mucosal fluid although she displayed potent T cell responses against HIV-1 Gag and Nef. CASE1 also possessed multiple genetic polymorphisms, including HLA alleles (B*14, B*57, C*06 and C*08.02) and HLA-C single nucleotide polymorphisms (SNPs, rs9264942 C/C and rs67384697 del/del), that have been previously individually associated with spontaneous control of plasma viremia, maintenance of high CD4+ T cell counts and delayed disease progression Conclusions CASE1 has controlled her HIV-1 viremia below the limit of detection in the absence of antiretroviral therapy for more than 14 years and has not shown any sign of immunologic deterioration or disease progression. Co-expression of multiple protective HLA alleles, HLA-C SNPs and strong T cell responses against HIV-1 proteins are the most likely explanation of this very benign case of spontaneous control of HIV-1 disease progression. [ABSTRACT FROM AUTHOR]

Purpose: The indication for laparoscopic total or partial adrenalectomy in patients with aldosterone producing adrenal adenoma remains controversial. We compared retroperitoneoscopic partial and total adrenalectomy for aldosterone producing adrenal adenoma in a prospective, randomized, multicenter trial. Materials and Methods: Patients with aldosterone producing adrenal adenoma were randomized to retroperitoneoscopic partial or total adrenalectomy. Patient characteristics, surgical data, complications and postoperative clinical results were analyzed statistically. Results: From July 2000 to March 2004, 212 patients were enrolled in this study, including 108 and 104 who underwent total and partial adrenalectomy, respectively. The 2 groups were comparable in patient age, gender, body mass index and tumor site. Mean followup was 96 months in each group. No conversion to open surgery was needed and no major complications developed. Partial adrenalectomy required a shorter operative time than total adrenalectomy but this did not attain statistical significance. Intraoperative blood loss in the partial adrenalectomy group was significant higher than in the total adrenalectomy group (p <0.05) but no patient needed blood transfusion. All patients in each group showed improvement in hypertension, and in all plasma renin activity and aldosterone returned to normal after surgery. No patient required potassium supplements postoperatively. In the total and partial adrenalectomy groups 32 (29.6%) and 29 patients (27.9%), respectively, were prescribed a decreased dose of or fewer antihypertensive medicines at final followup. Conclusions: Retroperitoneoscopic partial adrenalectomy is technically safe. It has therapeutic results similar to those of total adrenalectomy in patients with primary aldosteronism due to aldosteronoma. [ABSTRACT FROM AUTHOR]

Objective: This paper intends to report our experiences by using an operation of off-pump occlusion of transthoracic minimal invasive surgery (OPOTTMIS) on the treatment of consecutive 210 patients with simple congenital heart diseases (CHD) including atrial septal defect (ASD), ventricular septal defect (VSD) and patent ductus arteriosus (PDA). Methods: The retrospective clinical data of OPOTTMIS in our institute were collected and compared to other therapeutic measures adopted in the relevant literatures. After operation, all the patients received electrocardiography (ECG) and echocardiography (echo) once a month within the initial 3 months, and no less than once every 3 ∼ 6 months later. Results: The successful rate of the performed OPOTTMIS operation was 99.5%, the mortality and complication incidence within 72 hours were 0.5% and 4.8%, respectively. There were no major complications during perioperation such as cardiac rupture, infective endocarditis, strokes, haemolysis and thrombosis. The post-operation follow-up outcomes by ECG and echo checks of 3 months to 5 years showed that there were no III° AVB, no obvious Occluder migration and device broken and no moderate cardiac valve regurgitation, except 1 VSD and 1 PDA with mild residual shunts, and 2 PDA with heart expansion after operation. However, all the patients' heart functions were in class I∼II according to NYH standard. Conclusion: The OPOTTMIS is a safe, less complex, feasible and effective choice to selected simple CHD patients with some good advantages and favorable short term efficacies. [ABSTRACT FROM AUTHOR]

Human lymphocyte antigen (HLA)-restricted CD8+ cytotoxic T lymphocytes (CTL) target and kill HIV-infected cells expressing cognate viral epitopes. This response selects for escape mutations within CTL epitopes that can diminish viral replication fitness. Here, we assess the fitness impact of escape mutations emerging in seven CTL epitopes in the gp120 Env and p24 Gag coding regions of an individual followed longitudinally from the time of acute HIV-1 infection, as well as some of these same epitopes recognized in other HIV-1-infected individuals. Nine dominant mutations appeared in five gp120 epitopes within the first year of infection, whereas all four mutations found in two p24 epitopes emerged after nearly two years of infection. These mutations were introduced individually into the autologous gene found in acute infection and then placed into a full-length, infectious viral genome. When competed against virus expressing the parental protein, fitness loss was observed with only one of the nine gp120 mutations, whereas four had no effect and three conferred a slight increase in fitness. In contrast, mutations conferring CTL escape in the p24 epitopes significantly decreased viral fitness. One particular escape mutation within a p24 epitope was associated with reduced peptide recognition and high viral fitness costs but was replaced by a fitness-neutral mutation. This mutation appeared to alter epitope processing concomitant with a reduced CTL response. In conclusion, CTL escape mutations in HIV-1 Gag p24 were associated with significant fitness costs, whereas most escape mutations in the Env gene were fitness neutral, suggesting a balance between immunologic escape and replicative fitness costs. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effects of angiotensin receptor blocker (ARB) telmisartan on the expression and distribution of protein kinase C (PKC)-α in the kidneys of diabetic mice. Methods: Diabetic mice were induced with streptozotocin and a group of them were randomly selected for treatment with telmisartan. After 6 weeks, the expression and localization of PKC-α in the renal cortex, and the outer and inner medulla were assessed by immunohistochemistry and semiquantitative Western blotting. In addition, expressions of PKC-α, transforming growth factor-β1 (TGF-β1), and vascular endothelial growth factor (VEGF) in glomeruli were measured by semiquantitative immunohistochemistry. Results: Diabetic and normal mice showed similar distributions of PKC-α in the kidneys. The expression of PKC-α was found in glomeruli, epithelial cells of proximal tubules, and medullary-collecting duct, while not in the medullary and cortical thick ascending limb, and was different in the epithelial cells of proximal tubules of diabetic nephropathy (DN) mice, PKC-α was mostly translocated from the basement membrane to the apical membrane, whereas it was largely translocated from the apical membrane to the basement membrane in epithelial cells of the inner medullary-collecting duct. Western blotting detected increased expression of PKC-α in the renal cortex and outer medulla, but not in the inner medulla of DN mice. Enhanced expressions of PKC-α, TGF-β1, and VEGF were shown in the glomeruli of DN mice, where PKC-α exhibited a correlation to VEGF, but no correlation to TGF-β1. ARB telmisartan attenuated alterations of PKC-α as mentioned earlier in the DN mice. Conclusion: Our findings suggest that PKC-α may play a role in the pathogenesis of DN, and that the nephroprotective effects of ARB telmisartan may be partly associated with its influence on PKC-α. [ABSTRACT FROM AUTHOR]

Summary: Urethral trauma caused by urethral dilation often leads to complications including gross hemorrhage and inflammation. The injury of the urethral mucosa is, in a large part, due to the shearing forces imposed on it during the introduction of dilation devices. In this article, a radially expanding sheath for urethral dilation is hypothesized by the authors. This device aims to reduce the axial forces during the insertion of dilators, thereby protecting the urethral mucosa from friction. When performing the endoscopy, the device could act as a barrier between urethral mucosa and the endoscope. Moreover, in the situation of encountering difficulties in catheterization, the sheath could also be used as a guide-wire to lead the catheter through its lumen course. Thus, it is proposed that this radially expanding sheath could be a potential powerful approach for reducing the risks and complications of urethral dilation. [Copyright &y& Elsevier]

Abstract Background Alveolar osteitis (AO) is one of the most commonly encountered complication following tooth extraction, however, to date there is no standard methods of prevention and treatment. The study aims to investigate the efficiency of minocycline hydrochloride ointment (MHO) for the treatment of alveolar osteitis compared with traditional treatment with iodoform gauze (IG). Methods/design STROBE checklist was followed to report this study. All patients underwent tooth extraction either in our department or other hospitals, whom presented with postoperative pain, were screened out to meet the inclusion and exclusion criteria of this study about AO. Patients who fulfilled the inclusion criteria were enrolled in our prospective cohort study, and MHO or IG was administered. The Visual analog scale scores were used to assess the pain score of patients. The healing status of the extraction sockets was followed up. Differences in responses between groups were analyzed using Mann-Whitney U tests. Chi-square test was performed to explore the differences in the teeth position of AO. Results Of 41,371 patients underwent tooth extraction with post-operative follow-up in our departments, only 20 patients (0.05%) suffered from AO. 31 patients with AO, whose teeth were extracted in other places, were also enrolled. The incidence of AO was significantly higher in third molars than other teeth (P

To determine whether receptors for B lymphocyte stimulator (BLyS) are altered on B cells of patients with systemic lupus erythematosus (SLE).Total available receptors for BLyS were measured by analysis of binding of recombinant soluble BLyS to peripheral blood B cells in 36 SLE patients, 29 healthy controls, and 10 disease controls. Antibodies to the receptors BAFF‐R, BCMA, and TACI were used to define expression of the individual BLyS receptors on subsets of B cells in blood, spleen, and tonsils. Two different antibodies to BAFF‐R, which were differentially sensitive to BAFF‐R occupancy, were used to compare BAFF‐R on B cells in an additional 20 healthy subjects and 25 SLE patients. Assays of B cell survival after stimulation in vitro were used to determine the sensitivity of B cells to exogenous BLyS.Total available receptors for BLyS were decreased in patients with SLE, independent of changes of subsets in the blood in these patients. The decrease correlated with changes in disease activity. Although total surface BAFF‐R was not significantly different between healthy controls and SLE patients, BAFF‐R was occupied in SLE patients. B cells from these patients were less responsive to exogenous BLyS.BAFF‐R is consistently occupied on blood B cells in SLE. Occupancy of BAFF‐R on blood B cells is likely to contribute to disease mechanisms in SLE and could serve as a biomarker of disease activity. Targeting BLyS as a therapeutic strategy will require overcoming the persistent binding of BLyS to BAFF‐R. [ABSTRACT FROM AUTHOR]

Purpose: To study the anti-arthritic effect of total anthraquinone from Polygonum cuspidatum (TAPC) on type II collagen-induced arthritis (CIA) in rats, and to investigate the underlying mechanism(s). Methods: CIA rats were prepared and treated orally with TAPC at doses of 50, 100 and 200 mg/kg/day, for 24 days. Paw volume and arthritis score were measured prior to TAPC treatment, and subsequently at 3-day intervals on days 3, 6, 9, 12, 15, 18, 21 and 24. Serum levels of TNF-α, IL-6 and IL-17 were determined by enzyme-linked immunosorbent assay (ELISA), while synovial tissue TNF-α, IL-6 and IL-17mRNA expressions were assayed by real time-polymerase chain reaction (RT-PCR). Thymus and spleen indices were also determined. Results: TAPC (50, 100 and 200 mg/kg) significantly alleviated paw swelling (p < 0.05), arthritis scores (p < 0.05) and thymus and spleen indices (p < 0.05) of CIA rats, when compared with the control rats. In addition, TAPC significantly decreased serum levels of the pro-inflammatory cytokines TNF-α, IL-6 and IL-17 (p < 0.01); and down-regulated their mRNA expressions in synovial tissues (p < 0.01). Conclusion: These results suggest that TAPC exerts good anti-arthritic activity in rats, most probably via suppression of inflammatory responses. [ABSTRACT FROM AUTHOR]

The epidemiologic profile of infective endocarditis has changed substantially over the past few years, especially in industrialized countries. Our study evaluates the clinical and pathologic characteristics of infective endocarditis patients treated by cardiac surgery in China during a 12-year period. We retrospectively evaluated 220 surgically treated infective endocarditis patients and analyzed their changes from the beginning of 1998 through 2009. The mean age of the patients increased from 36.9 to 42.7 years during those 12 years (P=0.036). The chief predisposing disease was congenital heart disease (32.8%), rather than rheumatic heart disease (13.2%); this rate did not change significantly during the 12 years. The prevalent congenital lesion was bicuspid aortic valve, the rate of which (55.6%) increased significantly over the 3 time intervals studied (P=0.016). The frequency of infective endocarditis after non-dental surgical and nonsurgical intervention was significantly greater (23.3%) during 1998 through 2001, compared with the 2 intervals that followed (9%; P=0.019). Streptococcus viridans was the most frequent causative agent overall (25.6%). Forty-seven of the 220 patients (21.4%) carried the clinical diagnosis of some other form of heart disease before surgery, but at surgery they were found to have infective endocarditis as the fundamental disease process. Of 47 patients, 33 (70.2%) had either very small or no vegetations but had focal necrosis and inflammation of valve tissue that supported the diagnosis of infective endocarditis. [ABSTRACT FROM AUTHOR]

Diffuse large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma. In the least curable (ABC) subtype of DLBCL, survival of the malignant cells is dependent on constitutive activation of the nuclear factor-κB (NF-κB) signaling pathway. In normal B cells, antigen receptor-induced NF-κB activation requires CARD11, a cytoplasmic scaffolding protein. To determine whether CARD11 contributes to tumorigenesis, we sequenced the CARD11 gene in human DLBCL tumors. We detected missense mutations in 7 of 73 ABC DLBCL biopsies (9.6%), all within exons encoding the coiled-coil domain. Experimental introduction of CARD11 coiled-coil domain mutants into lymphoma cell lines resulted in constitutive NF-κB activation and enhanced NF-κB activity upon antigen receptor stimulation. These results demonstrate that CARD11 is a bona fide oncogene in DLBCL providing a genetic rationale for the development of pharmacological inhibitors of the CARD11 pathway for DLBCL therapy. [ABSTRACT FROM AUTHOR]

Summary Cerebellar ataxia, characterized by motor incoordination, postural instability, and gait abnormality [ 1–3 ], greatly affects daily activities and quality of life. Although accumulating genetic and non-genetic etiological factors have been revealed [ 4–7 ], effective therapies for cerebellar ataxia are still lacking. Intriguingly, corticotropin-releasing factor (CRF), a peptide hormone and neurotransmitter [ 8, 9 ], is considered a putative neurotransmitter in the olivo-cerebellar system [ 10–14 ]. Notably, decreased levels of CRF in the inferior olive (IO), the sole origin of cerebellar climbing fibers, have been reported in patients with spinocerebellar degeneration or olivopontocerebellar atrophy [ 15, 16 ], yet little is known about the exact role of CRF in cerebellar motor coordination and ataxia. Here we report that deficiency of CRF in the olivo-cerebellar system induces ataxia-like motor abnormalities. CRFergic neurons in the IO project directly to the cerebellar nuclei, the ultimate integration and output node of the cerebellum, and CRF selectively excites glutamatergic projection neurons rather than GABAergic neurons in the cerebellar interpositus nucleus (IN) via two CRF receptors, CRFR1 and CRFR2, and their downstream inward rectifier K + channel and/or hyperpolarization-activated cyclic nucleotide-gated (HCN) channel. Furthermore, CRF promotes cerebellar motor coordination and rescues ataxic motor deficits. The findings define a previously unknown role for CRF in the olivo-cerebellar system in the control of gait, posture, and motor coordination, and provide new insight into the etiology, pathophysiology, and treatment strategy of cerebellar ataxia. [ABSTRACT FROM AUTHOR]