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Multimodal integration facilitates object recognition and response to sensory cues. This depends on spatiotemporal coincidence of sensory information, recruitment of NMDA-type glutamate receptors and inhibitory feedback. Shepherd's crook neurons (SCNs) in the avian optic tectum (TeO) are an ideal model for studying cellular mechanism of multimodal integration. They receive different sensory modalities through spatially segregated dendrites, are important for stimulus selection and have an axon-carrying dendrite (AcD). We performed whole-cell patch-clamp experiments in chicken midbrain slices of both sexes. We emulated visual and auditory inputin vitroby stimulating presynaptic afferents electrically. Simultaneous stimulation enhanced responses inversely depending on stimulation amplitude demonstrating the principle of inverse effectiveness. Contribution of NMDA-type glutamate receptors prolonged postsynaptic events for visual inputs only, causing a strong modality-specific difference in synaptic efficacy. We designed a multicompartment model to study the effect of morphological and physiological parameters on multimodal integration by varying the distance between soma and axonal origin and the amount of NMDA receptor (NMDAR) contribution. These parameters changed the preference of the model for one input channel and adjusted the range of input rates at which multimodal enhancement occurred on naturalistic stimulation. Thus, the unique morphology and synaptic features of SCNs shape the integration of input at different dendrites and generates an enhanced multimodal response.SIGNIFICANCE STATEMENTMultimodal integration improves perception and responses to objects. The underlying cellular mechanism depends on a balance between excitation and inhibition, and NMDA-type glutamate receptors that are involved in the multiplicative nature of enhancement following the principle of inverse effectiveness. Based on a detailed analysis of an identified multimodal cell type in the vertebrate midbrain, we studied the influence of cellular morphology and unimodal synaptic properties on multimodal integration. We can show that the combination of cellular morphology and modality-specific synaptic properties including NMDA receptor (NMDAR) contribution is optimal for nonlinear, multimodal enhancement and determines the dynamic response range of the integrating neuron. Our findings mechanistically explain how synaptic properties and cellular morphology of a midbrain neuron contribute to multimodal enhancement.

OBJECTIVES To characterize, using magnetic resonance imaging (MRI), the distribution of blood flow and oxygen transport in human fetuses with subtypes of congenital heart disease (CHD) that present with neonatal cyanosis. METHODS Blood flow was measured in the major vessels of 152 late-gestation human fetuses with CHD and 40 gestational-age-matched normal fetuses, using cine phase-contrast MRI. Oxygen saturation (SaO2 ) was measured in the major vessels of 57 fetuses with CHD and 40 controls. RESULTS Compared with controls, we found lower combined ventricular output in fetuses with single-ventricle physiology, with the lowest being observed in fetuses with severe forms of Ebstein's anomaly. Obstructive lesions of the left or right heart were associated with increased flow across the contralateral side. Pulmonary blood flow was reduced in fetuses with Ebstein's anomaly, while those with Ebstein's anomaly and tricuspid atresia had reduced umbilical flow. Flow in the superior vena cava was elevated in fetuses with transposition of the great arteries, normal in fetuses with hypoplastic left heart, tetralogy of Fallot or tricuspid atresia and reduced in fetuses with Ebstein's anomaly. Umbilical vein SaO2 was reduced in fetuses with hypoplastic left heart or tetralogy of Fallot. Ascending aorta and superior vena cava SaO2 were reduced in nearly all CHD subtypes. CONCLUSIONS Fetuses with cyanotic CHD exhibit profound changes in the distribution of blood flow and oxygen transport, which result in changes in cerebral, pulmonary and placental blood flow and oxygenation. These alterations of fetal circulatory physiology may influence the neonatal course and help account for abnormalities of prenatal growth and development that have been described in newborns with cyanotic CHD. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

vitamin B12 supplementation on cognitive performance and inflammation in patients with Alzheimer’s disease (AD). Design: This was a randomized, single-blind, placebo-controlled trial. Participants: Patients (n=120) diagnosed clinically as probable AD and in stable condition from Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases. Measurements: Individuals were randomly divided into the intervention group (n=60, folic acid 1.2 mg/d + vitamin B12 50 μg/d) and the placebo group (n=60). Cognitive performance, blood folate, vitamin B12, one carbon cycle metabolite, and inflammatory cytokine levels were measured at baseline and after 6 months. The data were analyzed using linear mixed models for repeated measures. Results: A total of 101 participants (51 in the intervention group and 50 in the placebo group) completed the trial. Folic acid plus vitamin B12 supplementation had a beneficial effect on the MoCA total scores (P=0.029), naming scores (P=0.013), orientation scores (P=0.004), and ADAS-Cog domain score of attention (P=0.008), as compared to those of the control subjects. Moreover, supplementation significantly increased plasma SAM (P

Background A spinal cord injury (SCI) is a devastating, life-changing event that has profoundly deleterious effects on an individual’s health and well-being. Dysregulation of neuromuscular, cardiometabolic, and endocrine organ systems following an SCI contribute to excess morbidity, mortality and a poor quality of life. As no effective treatments currently exist for SCI, the development of novel strategies to improve the functional and health status of individuals living with SCI are much needed. To address this knowledge gap, the current study will determine whether a Home-Based Multimodality Functional Recovery and Metabolic Health Enhancement Program that consists of functional electrical stimulation of the lower extremity during leg cycling (FES-LC) plus arm ergometry (AE) administered using behavioral motivational strategies, and testosterone therapy, is more efficacious than FES-LC plus AE and placebo in improving aerobic capacity, musculoskeletal health, function, metabolism, and wellbeing in SCI. Methods This single-site, randomized, placebo-controlled, parallel group trial will enroll 88 community-dwelling men and women, 19 to 70 years of age, with cervical and thoracic level of SCI, ASIA Impairment Scale grade: A, B, C, or D, 6 months or later after an SCI. Participants randomized to the multimodality intervention will undergo 16 weeks of home-based FES-LC and AE training plus testosterone undecanoate. Testosterone undecanoate injections will be administered by study staff in clinic or by a visiting nurse in the participant’s home. The control group will receive 16 weeks of home-based FES-LC and AE exercise plus placebo injections. The primary outcome of this trial is peak aerobic capacity, measured during an incremental exercise testing protocol. Secondary outcomes include whole body and regional lean and adipose tissue mass; muscle strength and power; insulin sensitivity, lipids, and inflammatory markers; SCI functional index and wellbeing (mood, anxiety, pain, life satisfaction and depressive symptoms); and safety. Discussion We anticipate that a multimodality intervention that simultaneously addresses multiple physiological impairments in SCI will result in increased aerobic capacity and greater improvements in other musculoskeletal, metabolic, functional and patient-reported outcomes compared to the control intervention. The findings of this study will have important implications for improving the care of people living with an SCI. Trial registration ClinicalTrials.gov: (NCT03576001). Prospectively registered: July 3, 2018.

Objectives Elastic stable intramedullary nails (ESIN) are commonly utilized to treat unstable pediatric tibia fractures but have been associated with complications. The purpose of this study was to identify risk factors for adverse radiographic outcomes after ESIN of pediatric tibia fractures. Methods A retrospective review of all patients who underwent diaphyseal tibia fracture stabilization with ESIN between 2010 and 2018 at 3 pediatric level 1 trauma centers was performed. Inclusion criteria were open growth plates, no intra-articular or physeal fracture involvement, and radiographic follow-up until union. Patient demographics, injury mechanism, fracture characteristics, and implant fill relative to the medullary canal were recorded. Radiographic outcome measures included achievement of and time to union, residual angular deformity, and additional procedures. Results One hundred seventy-two patients met inclusion criteria and were followed for a mean of 1.2 years. Nonunions were observed in 3% of the patient cohort. Another 10% required >6 months to heal, but did not require further surgical intervention. Angular deformities were common with 57% having a residual deformity ≥5 degrees and 14% having a residual deformity ≥10 degrees. Of the patients with a residual deformity between 5 and 10 degrees, 3% were symptomatic, where as 26% of the patients with a residual deformity ≥10 degrees were symptomatic. Greater angular deformities were associated with open fractures, compartment syndrome, and longer time to union. Patient age, weight, tibial comminution, and canal fill were not associated with nonunions or malunions. Conclusions ESIN of pediatric tibia fractures results in reliable healing for a majority of patients, but poses risks for residual angular deformities and delayed healing. Open fractures and compartment syndrome were associated with adverse radiographic outcomes.

OBJECTIVES: To determine the prevalence of extended-spectrum β-lactamase (ESBL) in patients undergoing transrectal prostate biopsy, to assess the incidence of postoperative sepsis, to correlate the development of sepsis with the presence of preoperative ESBL on rectal swabs, and to assess the adequacy of prophylactic antibiotic guidelines in the context of local ESBL prevalence. METHODS: Patients undergoing transrectal ultrasonography (TRUS)-guided biopsy at the Royal Melbourne Hospital between January 2012 and July 2016 had rectal swabs taken immediately prior to TRUS with specific cultures to identify the presence of ESBL. Patients were given a prophylactic antibiotic, 500 mg oral ciprofloxacin, 1 h before the TRUS procedure. Data were collected prospectively, with retrospective review of all readmitted patient files and audit data to ensure complete capture of events. RESULTS: A total of 387 TRUS-guided biopsy procedures were performed. Rectal swabs were correctly collected in 352 patients (91%). The median patient age was 65 years. In all, 25 (7%) ESBL-positive swabs were identified. Most ESBL were Escherichia coli. Half (50%) of ESBL were resistant to ciprofloxacin and all were sensitive to meropenem. A small increase in ESBL prevalence over time was not significant (R2 = 0.35). Four patients (1.1%) were readmitted with sepsis; ESBL Pseudomonas had previously grown in one patient, but sepsis was attributable to non-ESBL E. coli. In one of the readmitted patients ESBL E. coli was present, but this patient did not have ESBL preoperatively. There were no deaths or high-dependency/intensive care unit admissions. CONCLUSIONS: This study represents the largest Australian series to investigate ESBL prevalence, and reveals a rate lower than that of many other nations. Our sepsis rate is lower than many international series, perhaps because of our low ESBL rate and strict antibiotic prophylaxis. Preoperative swab results did not predict postoperative sepsis, and the process was therefore not useful for guiding antibiotic therapy. In this patient population, TRUS biopsy, with ciprofloxacin prophylaxis, remains a safe option for diagnostic prostate biopsy.

The purpose of this study was to uncover the potential impact of alcohol consumption on the tumorigenesis of colorectal cancer (CRC) and the underlying mechanism.Overall survival was compared in CRC patients either with alcohol consumption or not. Subsequently, a mouse model of CRC was established by azoxymethane (AOM) administration. Tumor number and size were compared in CRC mice fed with Lieber-DeCarli liquid diet or normal diet. At last, pathological differences in cell proliferation, apoptosis, inflammation, and intestinal permeability, in intestines harvested from CRC mice fed with Lieber-DeCarli liquid diet or normal diet were assessed.It was found that the prognosis was worse in CRC patients with alcohol consumption. In CRC mice fed with Lieber-DeCarli liquid diet, more tumor tissues were found than those in the controls. Besides, alcohol consumption remarkably impaired intestinal permeability, making it easier for bacteria to invade epithelial cells. Moreover, oral gavage of probiotics markedly improved intestinal permeability and reduced tumor number in CRC mice fed with Lieber-DeCarli liquid diet.Probiotics can inhibit the development of alcohol-induced CRC by protecting intestinal permeability.

Growing evidence has shown that long non-coding RNAs (lncRNAs) can serve as prospective markers for survival in patients with gastric cancer (GC). In this study, we mainly focused on the potential roles of LINC00511 in the development process of GC.RT-PCR was used to detect the expressions of LINC00511 and miR-124-3p in GC tumor tissues, adjacent tissues and GC cell lines. Furthermore, correlations between LINC00511 with miR-124-3p, and miR-124-3p with EZH2, were analyzed by Correlation analysis. Moreover, the overall survival (OS) of patients was analyzed using Kaplan-Meier method. Additionally, proliferation ability was measured by CCK-8 assay and invasion ability of GC cell line was detected by transwell assay. Besides, Western blot was performed to measure protein levels of GC tissues and GC cell lines. Finally, Dual-Luciferase reporter assay was performed to prove the potential binding sites between LINC00511 and miR-124-3p, miR-124-3p and EZH2.We found that LINC00511 was significantly increased in GC tissues and GC cell lines, which was associated with tumor growth, metastasis and predicted poor diagnosis of GC patients. MiR-124-3p was decreased in GC tissues and GC cell lines, which was negatively correlated with LINC00511 and EZH2. Furthermore, EZH2 was increased in GC tissues and GC cell lines, which was positively correlated with LINC00511. Moreover, LINC00511 inhibition repressed cell proliferation and invasion in MKN28 cells, the protein levels of Cyclin D1, ICAM-1, VCAM-1 and N-cadherin were repressed, while E-cadherin was increased. Besides, Luciferase gene reporter assay indicated that LINC00511 could sponge with miR-124-3p, which could directly target at EZH2, an oncogenic gene. We found that miR-124-3p/EZH2 axis regulated cell proliferation and invasion in MKN28 cells. Finally, the inhibited cell proliferation and invasion abilities were eliminated following with miR-124-3p inhibition in MKN28 cells with LINC00511 knockdown.According to the results, we found that LINC00511 was increased in GC tissues, which was associated with the poor OS in patients with GC. We uncovered a previously unappreciated LINC00511/miR-124-3p/EZH2 signaling axis in promoting cell proliferation and invasion in GC patients and GC cell lines, which suggested that it might be a potential target for treating human GC.

To retrospectively evaluate the clinical outcomes of percutaneous ultrasound (US)-guided radiofrequency ablation (RFA) in treatment of adrenal metastasis (AM), and to compare with adrenalectomy (Adx). From June 2008 to August 2018, a total of 60 patients with AM treated at our hospital were retrospectively reviewed, of whom 29 treated by RFA (RFA group) and 31 by Adx (Adx group). The technical success, local tumor progression (LTP) and overall survival (OS) after the treatment were evaluated and compared. In RFA group, the first technical success was 72.4% and the second technical success was 86.2%. In Adx group, all the AMs were successfully resected. After 24.5 ± 19.1 months follow-up period, a total of 8 patients (6 in RFA group and 2 in Adx group) were detected LTP. The 1-, 2- and 3- LTP rates after treatment were 17.1%, 30.9% and 44.7% in RFA group, and 6.5%, 6.5% and 6.5% in Adx group, respectively (P = 0.028). However, for AM ≤ 5 cm, the LTP between the two groups were comparable (P = 0.068). The 1-, 2- and 3- OS rates after treatment for AM were 85.0%, 42.4% and 27.8% in RFA group, and 93.0%, 66.1% and 52.3% in Adx group, respectively (P = 0.057). RFA offered shorter treatment time (23.6 ± 16.9 vs. 155.6 ± 58.8 min, P

Efficient processing of sensory input is essential to ensure an organism's survival in its natural environment. Growing evidence suggests that sensory neurons can optimally encode natural stimuli by ensuring that their tuning opposes stimulus statistics, such that the resulting neuronal response contains equal power at all frequencies (i.e., is “white”). Such temporal decorrelation or whitening has been observed across modalities, but the effects of neural heterogeneities on determining tuning and thus responses to natural stimuli have not been investigated. Here, we investigate how heterogeneities in sensory pyramidal neurons organized in three parallel maps representing the body surface determine responses to second-order electrosensory stimulus features in the weakly electric fishApteronotus leptorhynchus. While some sources of heterogeneities such as ON- and OFF-type responses to first-order did not affect responses to second-order electrosensory stimulus features, other sources of heterogeneity within and across the maps strongly determined responses. We found that these cells effectively performed a fractional differentiation operation on their input with exponents ranging from zero (no differentiation) to 0.4 (strong differentiation). Varying adaptation in a simple model explained these heterogeneities and predicted a strong correlation between fractional differentiation and adaptation. Using natural stimuli, we found that only a small fraction of neurons implemented temporal whitening. Rather, a large fraction of neurons did not perform any significant whitening and thus preserved natural input statistics in their responses. We propose that this information is needed to properly decode optimized information sent in parallel through temporally whitened responses based on context.SIGNIFICANCE STATEMENTWe demonstrate that heterogeneities in the same sensory neuron type can either have no or significant influence on their responses to second-order stimulus features. While an ON- or OFF-type response to first-order stimulus attributes has no significant influence on responses to second-order stimulus features, we found that only a small fraction of sensory neurons optimally encoded natural stimuli through high-pass filtering, thereby implementing temporal whitening. Surprisingly, a large fraction of sensory neurons performed little if no filtering of stimuli, thereby preserving natural stimulus statistics. We hypothesize that this pathway is necessary to properly decode optimized information contained in temporally whitened responses based on context.

Scavenger receptor CD36 participates in lipid metabolism and inflammatory pathways important for cardiovascular disease and chronic kidney disease (CKD). Few pharmacological agents are available to slow the progression of CKD. However, apolipoprotein A-I–mimetic peptide 5A antagonizes CD36 in vitro . To test the efficacy of 5A, and to test the role of CD36 during CKD, we compared wild-type to CD36 knockout mice and wild-type mice treated with 5A, in a progressive CKD model that resembles human disease. Knockout and 5A-treated wild-type mice were protected from CKD progression without changes in blood pressure and had reductions in cardiovascular risk surrogate markers that are associated with CKD. Treatment with 5A did not further protect CD36 knockout mice from CKD progression, implicating CD36 as its main site of action. In a separate model of kidney fibrosis, 5A-treated wild-type mice had less macrophage infiltration and interstitial fibrosis. Peptide 5A exerted anti-inflammatory effects in the kidney and decreased renal expression of inflammasome genes. Thus, CD36 is a new therapeutic target for CKD and its associated cardiovascular risk factors. Peptide 5A may be a promising new agent to slow CKD progression.

Autophagy, a tightly regulated lysosome-dependent catabolic pathway, is implicated in various pathological states in the nervous system. High-mobility group box 1 (HMGB1) is an inflammatory mediator known to be released into the local microenvironment from damaged cells. However, whether autophagy is induced and exogenous HMGB1 is involved in the process of spinal root avulsion remain unclear. Here, we investigated the induction effect of autophagy and the possible role of HMGB1 during spinal root avulsion. It was found that autophagy was activated in the anterior horn of the spinal cord as represented by the increased expression of the autophagic marker microtubule-associated protein light chain 3-II (LC3-II), degradation of sequestosome 1 (p62), and formation of autophagosomes, and that autophagy was inhibited after intraperitoneal injection of anti-HMGB1-neutralizing antibodies in the rat spinal root avulsion model. In addition, HMGB1-induced autophagy and activated mitogen-activated protein kinases (MAPKs) in primary spinal neurons, including c-Jun N-terminal kinase (JNK), extracellular-signal-regulated kinase (ERK), and p38MAPK. Inhibition of JNK or ERK activity significantly blocked the effect of HMGB1-induced autophagy in primary spinal neurons. Finally, HMGB1-induced autophagy increased cell viability in primary spinal neurons under oxygen-glucose deprivation conditions. The above results suggest that HMGB1 is a critical regulator of autophagy and HMGB1-induced autophagy plays an important role in protecting spinal neurons against injury, which may provide new insights into the pathophysiological process of spinal root avulsion.

Introduction: We studied the effects of ethnicity on early infant growth patterns in exclusively breast-fed (EBF) infants from a Singaporean multiethnic population. This was a prospective cohort study conducted in National University Hospital, Singapore. Materials and Methods: Healthy, EBF infants born at-term completing 37 weeks and above, and whose birthweight was appropriate for gestational age (>10th centile

Background and aims Therapeutic possibilities now exist to lower low-density lipoprotein cholesterol (LDL-C) to very low levels. However, substantial controversy remains in clinical practice with regard to its safety, and the question of whether low LDL-C levels per se may provoke adverse effects in humans arises. We aimed to explore the association of LDL-C with androgen and erectile dysfunction (ED) in a general population of men. Methods and results A total of 4203 men without hormone replacement therapy were enrolled from 22 sites in East China. Total testosterone (T) and Free T were assessed. Free androgen index (FAI) was calculated. The IIEF-5 questionnaire was used to assess ED. We found that free T and FAI gradually and markedly increased with increasing LDL-C levels. Using linear regression, after adjusting for age, educational level, economic status, smoking status, drinking status, BMI, diabetes, and use of lipid-lowering medication, LDL-C was positively associated with free T (B = 0.175, 95% CI: 0.084, 0.266) and FAI (B = 0.064, 95% CI: 0.016, 0.112). Meanwhile, there was a U-shaped curvilinear relationship between LDL-C and prevalence of ED. In the logistic regression analysis, compared to those with LDL-C among the 10th–90th percentile, the ORs of ED in men in the lowest and highest deciles were 1.938 (95% CI: 1.121, 3.349) and 1.804 (95% CI: 1.117, 2.916), respectively. Conclusion Lower LDL-C levels were significantly associated with lower free T and lower FAI in a general population of men. Moreover, both low and high levels of LDL-C might be risk factors for ED.

Wilms' tumor (WT) is the most common malignant tumor in the children's urogenital system. MiR-190b was found to participate in the development and progression of several cancers. However, the molecular mechanism of miR-190b in WT is still unclear.We detected the miR-190b in WT tissue samples compared to adjacent normal samples as well as in WT patients' blood sample compared to normal volunteers using qRT-PCR. With over-expression and knockdown of miR-190b in WT-derived cell line SK-NEP-1, we next studied cell proliferation, cell circle, apoptosis, invasion and migration abilities change caused by miR-190b ectopic expression. Dual-luciferase assay and Western-blot analysis were used to explain the mechanism of miR-190b in WT.MiR-190b was over-expressed in WT tissue and blood samples compared to normal group, relatively. Up-regulation of miR-190b in SK-NEP-1 cells significantly increased the growth and decreased the apoptosis of cells, while its down-regulation reduced cell proliferation and promoted cell apoptosis of SK-NEP-1. Also, cell invasion and migration abilities were significantly improved after miR-190b over-expression. Moreover, PTEN was proved to be a direct target of miR-190b and its protein level was remarkably decreased after miR-190b up-regulation.miR-190b over-expressed in WT and promoted cell proliferation, invasion and migration while reduced cell apoptosis of WT cells by repressing PTEN repression, which might provide a potential target for WT diagnosis and therapy.

To investigate the association between myasthenia gravis (MG) and human parvovirus B19 (B19V) infection in the thymus.The presence of human B19V DNA and protein was assessed in 138 samples-including 68 thymic hyperplasias (39 with MG), 58 thymomas (23 with MG), and 12 normal thymus tissues-using a nested polymerase chain reaction, immunohistochemistry, laser capture microdissection, and sequencing in a double-blinded manner.B19V DNA was detected mainly in thymic hyperplasia, and the positivity rate (41.18%, 28/68) was significantly higher than that in thymoma (3.45%, 2/58) (p0.001) but not that in normal thymic tissues. Correspondingly, the positivity rate in thymic hyperplasia with MG (30.77%, 12/39) was significantly higher than that in thymoma with MG (4.35%, 1/23) (p=0.021). However, it was higher in thymic hyperplasia without MG (55.17%, 16/29) than in thymic hyperplasia with MG (30.77%, 12/39) (p=0.043). Cells in thymic hyperplasia positive for B19V VP1/VP2 protein (63.24%, 43/68) were identified mainly in ectopic germinal centres and thymic corpuscle epithelial cells, but were rare in thymomas (1.72%, 1/58) (p0.001). Moreover, the positivity rate was significantly higher in thymic hyperplasia with MG (74.36%, 29/39) than in thymic hyperplasia without MG (48.28%, 14/29) (p=0.027).To our knowledge, the present study is the first to show that human B19V infection is closely associated with thymic hyperplasia and thymic-hyperplasia-associated MG, but is not related to thymoma or thymoma-associated MG. The findings reveal a previously unrecognized aetiopathogenic mechanism of thymic-hyperplasia-associated MG, evoking numerous questions that require further investigation.

We examined the effects of co-culturing CD4+ CD25+ Treg cells with sirolimus or cyclosporin A on Treg cell proliferation and differentiation and on transforming growth factor-β (TGF-β) and Foxp3 expression. CD4+ CD25+ Treg cells were harvested from mononuclear cells of spleens of C57BL/6 mice using immunomagnetic beads and divided into control, sirolimus, and cyclosporine groups. Following a 96-h co-culture, Treg cells were assayed by flow cytometry. FoxP3 and TGF-β mRNA levels and secretion were assayed by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Smad protein of the TGF-β signaling pathway was assayed by western blot and its effect on CD4+ CD25+ FoxP3+ Treg cell proliferation was determined. Sirolimus-promoted differentiation and proliferation was examined using a TGF-β neutralizing antibody. Sirolimus-treated CD4+ T cell TGF-β secretion increased 2.5X over control levels (P0.01), but that of the cyclosporine group decreased marginally (P0.05). The CD4+ cell proportion decreased significantly (41.25 vs 69.22%, P0.01) and slightly (65.21 vs 69.22, P0.05) in the cyclosporine and sirolimus groups, respectively. T cell Foxp3 mRNA expression was significantly higher in the sirolimus-treated than in the cyclosporine (53.7 vs 40.2%, P0.05) and control groups (P0.01), but was significantly lower in the cyclosporine group than in controls (23.6 vs 40.2%, P0.01). Overall, sirolimus promoted CD4+ CD25+ Treg cell proliferation and growth in vitro, whereas cyclosporin A inhibited proliferation. Sirolimus might promote CD4+ CD25+ FoxP3+ regulatory T cell proliferation by inducing TGF-β secretion in vivo.

SUMMARYHepatitis C virus (HCV) infection is one of the leading causes of death and morbidity associated with liver disease. Risk factors identified for the transmission of HCV include contaminated blood products, intravenous drug use, body piercing, an infected mother at birth, sexual activity, and dental therapy, among others. However, the exact diversity of the HCV genotype and genetic variation among patients with low-risk factors is still unknown. In this study, we briefly described and analysed the genotype distribution and genetic variation of HCV infections with low-risk factors using molecular biology techniques. The results suggested that genotype 1b was predominant, followed by genotypes 2a and 1a. Genetic variations in the 5′ UTR sequences of HCV were identified, including point mutations, deletions, and insertions. The frequency of genetic variations in 1b was higher than in 2a. This study provides considerable value for the prevention and treatment of liver disease caused by HCV among patients with low-risk factors and for the development of HCV diagnostic reagents and vaccines.

To explore the therapeutic effect of curcumin (Cur) and soybean oligosaccharides (SBOS) on ulcerative colitis (UC) through testing the intestinal flora and ulcerative colitis (UC). 80 male SD rats were selected divided into four groups with 20 rats in each group: normal group, sulfasalazine (SASP) group, model group and group of curcumin plus soy oligosaccharide. All animals were treated for 4 weeks. In the fifth week rats were decapitated. Macroscopic damage scores of colonic mucosa were calculated. A 4mL blood sample was taken to detect the contents of serum tumor necrosis factor -α (TNF-α) and interleukin 8 (IL-8) by the double antibody sandwich ABC-ELISA method (enzyme-linked immunosorbent assay). Colonic tissues with the most obvious lesions were obtained using a surgical scissor. A routine hematoxylin-eosin (HE) staining method was used to stain pathological specimens and images of staining results were obtained. Histological injury scores of colonic mucosa were calculated. Ulcerative colitis model rats had the highest macroscopic damage scores and histological injury scores of colonic mucosa. After treatment the contents of TNF-α and IL-8 decreased significantly in the group of curcumin plus soy oligosaccharide compared with the model group with statistical significance (P 0.05). The treatment could decrease TNF-α and IL- 8 expression and reduce colonic mucosa inflammation and tissue damage.

The objective of this study was to observe the distribution of macrophages (MPs) expressing transforming growth factor beta-1 (TGF-β1) in tissue samples from patients with different human chronic periapical diseases. In this study, samples were collected from 75 volunteers, who were divided into three groups according to classified standards, namely, healthy control (N = 25), periapical granuloma (N = 25), and periapical cyst (N = 25). The samples were fixed in 10% buffered formalin for more than 48 h, dehydrated, embedded, and stained with hematoxylin and eosin for histopathology. Double immunofluorescence was conducted to analyze the expression of TGF-β-CD14 double-positive MPs in periapical tissues. The number of double-positive cells (cells/mm2) were significantly higher in the chronic periapical disease tissues (P < 0.01) compared to that in the control tissue; in addition, the density of TGF-β1-CD14 double positive cells was significantly higher in the periapical cyst group than in the periapical granuloma group (P < 0.01). The number of TGF-β1 expressing macrophages varied with human chronic periapical diseases. The TGF-β1-CD14 double-positive cells might play an important role in the pathology of human chronic periapical diseases.

Objectives: We explored the efficacy of minimal invasive surgery including one-stage debridement and intervertebral fusion through extreme lateral channel (XLIF) combined with lateral or percutaneous posterior pedicle screw fixation for the treatment of lumbar spine tuberculosis. Methods: Twenty two patients with lumbar tuberculosis who underwent surgery with XLIF technique and internal fixation were included in the study. Their data about operative time, intraoperative blood loss, bone fusion, kyphosis correction, and clinical recovery were retrospectively collected and analyzed. Results: The mean intraoperative blood loss was 249.8±27.8 ml and the operative time 347.5±20.7 min. At the final follow-up, 11 to 15 months postoperatively, ESR and CRP were normal and pain (VAS) and Oswestry disability index (ODI) were significantly reduced (23.0±-3.1 vs 0.6±-0.7 and 57.2±-1.6 vs 6.4±-1.2 respectively) compared to preoperative values. Progression of the kyphotic deformity was effectively prevented (mean Cobb angle 23.9° +/-1.9° vs 24.5° +/-1.4°, P>0.05). There was one failure of the fixation associated to poor therapy adherence. All the patients showed neurological recovery. Conclusion: Debridement and interbody fusion by extreme lateral channel combined with lateral or percutaneous posterior pedicle screw fixation effectively retained the spine stability and provided clinical and neurologic recovery in selected patients with lumbar spine tuberculosis.

Introduction To compare percutaneous minimally invasive repair (PMIR) of acute acromioclavicular (AC) joint dislocation under ultrasound guidance (PMIR-UN) vs. C-arm navigation (PMIR-CN). Hypothesis PMIR-UN has similar functional and radiographic outcomes as PMIR-CN. Materials and methods We treated 48 patients with acute grade III or V AC joint dislocation with surgical reduction and fixation with Kirschner wires and cannulated screws. The patients were randomly divided into a PMIR-UN group (n = 24) and a PMIR-CN group (n = 24). We assessed functional outcomes, operative duration, incision length, and intraoperative radiation exposure. Shoulder joint function was evaluated with the Constant–Murley score, and postoperative efficacy was evaluated using the Karlsson criteria. Results The median follow-up duration was 13 months (range, 8–18 months). Satisfactory functional outcomes were obtained in both groups. Incision length, incidence of postoperative infection, pin migration, and postoperative efficacy did not differ between the two groups. Operative duration and intraoperative radiation dose were significantly greater in the PMIR-CN group than in the PMIR-UN group (P Discussion Based on the satisfactory results obtained in all patients, we conclude that PMIR-UN is a safe, easy, and reliable technique for the treatment of acute grade III or V AC joint dislocation. Type of study Low-powered prospective randomized trial. Level of evidence Level II.

Stem cell factor (SCF), an important stem cell cytokine, has multiple functions. Fibroblasts (FBs), mature mast cells, endothelial cells (ECs), and eosinophil granulocytes can produce SCF in the inflammatory process. Therefore, we aimed to observe SCF expression in FBs, ECs, and macrophages (MPs) in periapical tissues in human chronic periapical disease and investigate the effects of cells expressing SCF in pathogenesis of the disease. Healthy (N = 20), periapical cyst (N = 15), and periapical granuloma (N = 15) tissues were fixed in 10% formalin for 48 h, embedded in paraffin, and stained with hematoxylin and eosin to observe histological changes. SCF expression was observed in FBs, ECs, and MPs in periapical tissues by double immunofluorescence. CD334, CD31, and CD14 are specific markers of FBs, ECs, and MPs, respectively. Results showed that densities of CD334-SCF double-positive FBs, CD31-SCF double-positive ECs, and CD14-SCF double-positive MPs were significantly increased in periapical tissue groups (P0.01). There were no significant differences in CD334-SCF double-positive FB and CD31-SCF double-positive EC levels between the two periapical tissue groups (P0.05). CD14-SCF double-positive MP density was considerably higher in periapical granulomas than in cysts (P0.01). FB, EC, and MP levels were significantly high and densities of CD334-SCF double-positive FBs, CD31-SCF double-positive ECs, and CD14-SCF double-positive MPs improved considerably in chronic periapical tissues, suggesting that the cells might be related to occurrence, development, and pathogenesis of chronic periapical disease.

With the achievement of high coverage for routine immunization and supplementary immunization activities (SIAs), measles incidence in mainland China reached its lowest level in 2010. The proportion of measles cases in the vaccination-targeted population decreased during 2007–2010 after the SIAs. More than 60% of measles cases were in adults or infants, especially in the coastal and eastern provinces during 2009 and 2010. A total 567 isolates of measles virus were obtained from clinical specimens from 27 of 31 provinces in mainland China during 2009 and 2010. Except for two vaccine-associated cases, one genotype D4 strain, two genotype D9 strains, and four genotype D11 strains, the other 558 strains were genotype H1 cluster H1a. Genotype H1 has been the only endemic genotype detected in China since surveillance began in 1993. Only genotype H1 was found in mainland China during 1993–2008, except for one detection of genotype H2. More recently, multiple genotypes of imported measles were detected even with the background of endemic genetotype H1 viruses. Analysis of the 450-nucleotide sequencing window of the measles virus N gene showed that the overall genetic diversity of the recent geneotype H1 strains decreased between 2008 and 2010. The lower genetic diversity of H1 strains suggested that enhanced vaccination may have reduced the co-circulating lineages of endemic genotype H1 strains in mainland China.

Periprostatic abscess is a rare complication of hydrogel spacers in radiotherapy for prostate cancer. We present the case of a 61-year-old man who developed this condition. Abdominopelvis CT scan revealed a 54×35×75 mm collection in the location of the SpaceOAR, for which ultrasound-guided transperineal percutaneous drainage of the periprostatic abscess was performed. The patient remains well with serial CT scans showing near resolution of the collection.

Deletions of claudin-2 (Cldn2) and aquaporin1 (AQP1) reduce proximal fluid reabsorption (PFR) by about 30% and 50%, respectively. Experiments were done to replicate these observations and to determine in AQP1/claudin-2 double knockout mice (DKO) if the effects of deletions of these established water pores are additive. PFR was determined in inactin/ketamine-anesthetized mice by free-flow micropuncture using single-nephron I125-iothalamate (io) clearance. Animal means of PFR [% of glomerular filtration rate (GFR)] derived from TF/Piothalamateratios in 12 mice in each of four groups [wild type (WT), Cldn2−/−, AQP1−/−, and DKO) were 45.8 ± 0.85 (51 tubules), 35.4 ± 1 (54 tubules; P < 0.01 vs. WT), 36.8 ± 1 (63 tubules; P < 0.05 vs. WT), and 33.9 ± 1.4 (69 tubules; P < 0.01 vs. WT). Kidney and single-nephron GFRs (SNGFR) were significantly reduced in all mutant strains. The direct relationship between PFR and SNGFR was maintained in mutant mice, but the slope of this relationship was reduced in the absence of Cldn2 and/or AQP1. Transtubular osmotic pressure differences were not different between WT and Cldn2−/−mice, but markedly increased in DKO. In conclusion, the deletion of Cldn2, AQP1, or of both Cldn2 and AQP1 reduces PFR by 22.7%, 19.6%, and 26%, respectively. Our data are consistent with an up to 25% paracellular contribution to PFR. The reduced osmotic water permeability caused by absence of AQP1 augments luminal hypotonicity. Aided by a fall in filtered load, the capacity of non-AQP1-dependent transcellular reabsorption is sufficient to maintain PFR without AQP1 and claudin-2 at 75% of control.

To analyze the trends and epidemiological characteristics of notifiable communicable diseases from 2010 to 2015 in Beijing so as to provide reliable reference data.Data on the epidemiological characteristics was gathered and analyzed through the monitoring programs on notifiable diseases, reported by the China Information System for Disease Control and Prevention, from 2010 to 2015.A total of 764 290 cases of notifiable communicable diseases were reported from 2010 to 2015 in Beijing. The annual reported incidence on notifiable communicable diseases showed an annual downward (χ(2)=1.25×10(4), P0.01), with rates between 498.95/100 000 and 828.45/100 000. The annual reported incidence rates of intestinal infectious diseases and respiratory infectious diseases also showed an annual downward (χ(2)=1.25×10(4), P0.01; χ(2)=4.97×10(2), P0.01), which accounted for 39.72% and 33.01% among the total classes A and B reported cases, respectively. The average annual reported incidence rates in males were higher than that in females. The average annual incidence of children under 7 years old appeared higher than that of the other age groups that accounted for 47.79% of the total reported cases. High incidence mainly appeared in children that living scattering around which accounted for 31.64% of the total reported cases. The first three leading incidence rates seen in other infectious diseases were infectious diarrhea, hand-foot-and-mouth disease and dysentery for the last consecutive 6 years. The laboratory diagnosed rate on notifiable disease was 16.67%, but with a trend of annual increase.Intestinal infective diseases kept the highest incidence among all the notifiable communicable diseases, suggesting the necessity of improving the prevention and control programs on notifiable communicable diseases in preschool, especially in those children with their houses scattered around. Programs on laboratory diagnosis also need to be strengthened.

Testosterone deficiency and prostate cancer have an increasing prevalence with age. However, because of the relationship between prostate cancer and androgen receptor activation, testosterone therapy among patients with known prostate cancer has been approached with caution.We identified a cohort of 82 hypogonadal men with prostate cancer who were treated with testosterone therapy. They included 50 men treated with radiation therapy, 22 treated with radical prostatectomy, 8 on active surveillance, 1 treated with cryotherapy and 1 who underwent high intensity focused ultrasound. We monitored prostate specific antigen, testosterone, hemoglobin, biochemical recurrence and prostate specific antigen velocity.Median patient age was 75.5 years and median followup was 41 months. We found an increase in testosterone (p0.001) and prostate specific antigen (p = 0.001) in the entire cohort. Prostate specific antigen increased in patients on active surveillance. However, no patients were upgraded to higher Gleason score on subsequent biopsies and none have yet gone on to definitive treatment. We did not note any biochemical recurrence among patients treated with radical prostatectomy but 3 (6%) treated with radiation therapy experienced biochemical recurrence. It is unclear whether these cases were related to testosterone therapy or reflected the natural biology of the disease. We calculated mean prostate specific antigen velocity as 0.001, 0.12 and 1.1 μg/l per year in the radical prostatectomy, radiation therapy and active surveillance groups, respectively.In the absence of randomized, placebo controlled trials our study supports the hypothesis that testosterone therapy may be oncologically safe in hypogonadal men after definitive treatment or in those on active surveillance for prostate cancer.

Acute kidney injury (AKI) is a common complication in patients with decompensated cirrhosis and is also an important cause for poor outcome. This study aimed at investigating the clinical characteristics and long-term prognosis of AKI in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). A total of 1167 patients with HBV-related ACLF from January 2010 to January 2015 were enrolled and divided into two groups, AKI group (n=308) and non-AKI group (n=859). All patients were followed up to investigate clinical characteristics, long-term overall survival (OS) and risk factors. AKI occurrence was found to be 26.4% in patients with HBV-related ACLF. The patients in the AKI group and the non-AKI group had a 30-day OS of 44.8% and 70.3%, 90-day OS of 17.9% and 55.4%, and 1-year OS of 15.6% and 51.2%, respectively. Significant differences were observed in the 30-day, 90-day and 1-year OS among subgroups with different AKI stages. It was found that high WBC, neutrophil, ALT and MELD score were risk factors for 30-day mortality, whereas hepatic encephalopathy, high MELD score, mean arterial pressure and PLT were risk factors for 90-day mortality. Two criteria, the KDIGO and AKIN, showed parallel results in staging AKI in patients with HBV-related ACLF (κ=0.807, P

Mouse models of the transcriptional modulator Methyl-CpG-Binding Protein 2 (MeCP2) have advanced our understanding of Rett syndrome (RTT). RTT is a 'prototypical' neurodevelopmental disorder with many clinical features overlapping with other intellectual and developmental disabilities (IDD). Therapeutic interventions for RTT may therefore have broader applications. However, the reliance on the laboratory mouse to identify viable therapies for the human condition may present challenges in translating findings from the bench to the clinic. In addition, the need to identify outcome measures in well-chosen animal models is critical for preclinical trials. Here, we report that a novel Mecp2 rat model displays high face validity for modelling psychomotor regression of a learned skill, a deficit that has not been shown in Mecp2 mice. Juvenile play, a behavioural feature that is uniquely present in rats and not mice, is also impaired in female Mecp2 rats. Finally, we demonstrate that evaluating the molecular consequences of the loss of MeCP2 in both mouse and rat may result in higher predictive validity with respect to transcriptional changes in the human RTT brain. These data underscore the similarities and differences caused by the loss of MeCP2 among divergent rodent species which may have important implications for the treatment of individuals with disease-causing MECP2 mutations. Taken together, these findings demonstrate that the Mecp2 rat model is a complementary tool with unique features for the study of RTT and highlight the potential benefit of cross-species analyses in identifying potential disease-relevant preclinical outcome measures.