简介：AbstractPericyte, a kind of pluripotent cell, may regulate the irrigation flow and permeability of microcirculation. Pericytes are similar to the smooth muscle cells, which express several kinds of contractile proteins and have contractility. The dysfunction of pericytes is related to many microvascular diseases, including hypoxia, hypertension, diabetic retinopathy, fibrosis, inflammation, Alzheimer's disease, multiple sclerosis, and tumor formation. For a long time, their existence and function have been neglected. The distribution, structure, biomarker, related signaling pathways as well as the roles of pericytes on vascular diseases will be introduced in this review.

简介：无

简介：

简介：AbstractKeratinocytes, located in the outer part of human skin, are the main epidermal cell type and play an essential role in skins defense against infection. Besides creating a physical barrier between the environment and the internal body, keratinocytes exert powerful immune function in anti-pathogen infection in the skin. At the recognition stage, pattern recognition receptors (PRRs) expressed by keratinocytes sense pathogen-associated molecular patterns (PAMPs) existing in pathogens. Toll like receptors (TLRs) are the most important PRRs in keratinocytes. Other PRRs such as dectin-1 and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are also found to participate in this process. Activated PRRs enhance the secretion of cytokines, chemokines and the production of antimicrobial peptides (AMPs). Proinflammatory cytokines tumor necrosis factor-α, interleukin (IL)-1α, IL-6, IL-1β and IL-18, chemokines (C-X-Cmotif) ligand (CXCL) 1, CXCL2, CCL20, CCL2 and IL-8, AMPs human β-defensin (HBD) 2, HBD3 and LL37 are the main molecules expressed in this procedure. Thymic stromal lymphopoietin (TSLP), IL-36γ, IL-17 family member IL- 17C and anti-inflammatory cytokine IL-10 can also be secreted. Some molecules produced by keratinocytes such as ribonuclease 5 and 7, S100 proteins own antimicrobial properties. Keratinocytes defense responses can be regulated by internal and external factors. This review summarizes recent advances on the innate immune function of keratinocytes against infection, promoting the finding of a new direction for avoiding severe skin infection as well as the potential treatment of keratinocyte-associated inflammatory dermatosis.

简介：AbstractGenome editing serves as a powerful approach to interrogate the functions of both coding and noncoding sequences. In particular, clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR associated protein 9 (Cas9) system-based editing tools have revolutionized the way we study genome function in mammalian cells, and are being widely used for interrogating critical genes and DNA elements essential for many biological processes. Here, we review CRISPR/Cas9-based genetic tools with an emphasis on CRISPR-mediated high throughput genetic screens in the mammalian genome.

简介：AbstractBackground:After radical hysterectomy for cervical cancer, the most common complication is lower urinary tract symptoms. Post-operatively, bladder capacity can alter bladder function for a prolonged period. This study aimed to identify factors affecting bladder storage function.Methods:A multicenter, retrospective cohort study was conducted. Information of patients with stages IA2 to IIB cervical cancer with urodynamic study results were retrospectively collected from nine hospitals between June 2013 and June 2018 according to the inclusion criteria. Demographic, surgical, and oncological data were collected. The univariate and multivariate logistic regression was used to identify clinical factors associated with bladder storage function.Results:Two hundred and three patients with cervical cancer had urodynamic testing post-operatively. Ninety-five (46.8%) patients were diagnosed with stress urinary incontinence (SUI). The incidence of low bladder compliance (LBC) was 23.2%. Twenty-seven (13.3%) patients showed detrusor overactivity (DO). Fifty-seven patients (28.1%) presented with a decreased maximum cystometric capacity (DMCC). The probability of composite bladder storage dysfunction was 68.0%. Multivariate analysis confirmed that laparoscopy represents a protective factor for SUI with an odds ratio of 0.498 (P = 0.034). Patients who underwent a nerve-sparing procedure were less odds to experience SUI (P = 0.014). A significant positive correlation between LBC and DO was observed (P < 0.001). A greater length of the resected vagina and chemoradiotherapy were common risk factors for LBC and DO, while radiotherapy exerted a stronger effect than chemotherapy. Additionally, patients who received chemoradiotherapy frequently developed a DMCC. The follow-up time was not correlated with bladder storage function.Conclusion:A nerve-sparing procedure without longer resected vagina is recommended for protecting the bladder storage function.

简介：AbstractBackground:The relationship of uric acid (UA) with the thyroid function among healthy individuals remains unclear. We aimed to examine the relationship between UA contents and thyroid hormone levels in healthy Chinese individuals.Methods:This was a cross-sectional study of 1186 Chinese adults (736 men and 450 women) who underwent a health check-up at the Huadong Hospital Affiliated to Fudan University (Shanghai, China) between January 1, 2010 and July 31, 2018. Clinical and thyroid hormone levels were compared in different UA groups (in male and menopause women groups, MG1: UA < 5 mg/dL; MG2: 5 mg/dL ≤ UA< 7 mg/dL; and MG3: UA ≥ 7 mg/dL; in female groups, FG1 to FG3 represent the UA levels of <4 mg/dL, 4 mg/dL ≤ UA< 6 mg/dL, and ≥6 mg/dL, respectively). In addition, natural cubic spline regression, together with Pearson correlation analysis, was performed in investigating the correlation of UA with thyroid hormones.Results:After adjusting for confounding factors, low levels of UA (for males, UA < 5.30 mg/dL; for females, UA < 4.05 mg/dL) were negatively correlated with free triiodothyronine (FT3) both in men and women. UA levels between 4.83 and 6.06 mg/dL may act to protect FT3 in women, while UA levels between 6.39 and 7.09 mg/dL may protect FT3 in men. FT3 levels of low-range UA group reduced compared with mid-range UA and the high-range UA groups in both men and women.Conclusions:Our results provide epidemiologic evidence to support the negative correlation between low UA contents and FT3 in the Chinese Han population, suggesting that the reduced UA contents may serve as the risk factor to predict poor thyroid function in Chinese individuals.

简介：无

简介：AbstractBackground:Atrial fibrillation (AF) is the most common arrhythmia in patients with hypertrophic obstructive cardiomyopathy (HOCM). Data regarding the correlations of thyroid dysfunction and the incidence of AF in HOCM are quite limited. This study aimed to reveal the correlations between different thyroid status and the corresponding incidence of AF in a large HOCM cohort.Methods:A total of 806 HOCM patients with complete information on thyroid function tests and comprehensive cardiac evaluations were recruited. The participants were divided into the AF group (n = 159) and non-AF group (n = 647) according to established medical history and results of Holter monitoring. The thyroid status of the study population and the corresponding incidence of AF were assessed and analyzed.Results:Hypothyroidism accounted for the greatest proportion of thyroid dysfunction in HOCM patients. The incidence of AF significantly increased in individuals with both overt (P = 0.022) and subclinical (P = 0.007) hypothyroidism. Compared with participants in the non-AF group, those with positive AF episodes presented with lower free triiodothyronine (FT3) (2.86 ± 0.52 pg/mL vs. 3.01 ± 0.42 pg/mL, P = 0.001), higher free thyroxine (FT4) (1.24 ± 0.25 ng/dL vs. 1.15 ± 0.16 ng/dL, P < 0.001), and remarkably increased levels of thyrotropin (TSH) (12.6% vs. 5.3%, P = 0.001). Multivariable analyses demonstrated that the concentrations of FT3 (odds ratio [OR] = 0.470, 95% confidence interval [CI]: 0.272-0.813, P = 0.007) and FT4 (OR = 17.992, 95% CI: 5.750-56.296, P < 0.001), as well as TSH levels above normal ranges (OR = 2.276, 95% CI: 1.113-4.652, P = 0.024) were independently associated with the occurrence of AF in the large HOCM cohort.Conclusions:This study indicated a strong link between low thyroid function and the presence of AF in HOCM. Hypothyroidism (both overt and subclinical states) seems to be valuable for assessing the incidence of AF in patients with HOCM.

简介：摘要INTRODUCTIONThis case study explores the gains in hand function in an individual with a chronic spinal cord injury (SCI). The intervention was long-term paired associative simulation (PAS). We aimed to provide PAS until full recovery of hand muscle strength occurred, or until improvements ceased.CASE PRESENTATIONA 46-year-old man with traumatic C7 AIS B tetraplegia was administered PAS three times per week. After 24 weeks, PAS was combined with concomitant motor training of the remaining weak hand muscles. Outcome measures included the manual muscle test (MMT), motor-evoked potentials (MEPs), F-responses, hand functional tests, and the spinal cord independence measure (SCIM)．DISCUSSIONAfter 47 weeks of PAS the subject had improved self-care and indoor mobility and was able to perform complex motor tasks (SCIM score improved from 40 to 56). His left hand regained maximum MMT score (total 75; increase of score from baseline condition 19); the effect remained stable in the 32-week follow up. In the right-hand muscles, MMT scores of 4-5 were observed in follow up (total 71; increase from baseline 48). Improved values were also observed in other outcomes. This is the first demonstration of long-term PAS restoring muscle strength corresponding to MMT scores of 4-5 in an individual with chronic SCI. The effect persisted for several months, indicating that PAS induces stable plastic changes in the corticospinal pathway.

简介：AbstractPurpose:The majority of acute anterior shoulder dislocations are sustained during sports and wilderness activities. The management of acute dislocations in the pre-hospital setting is currently without guidelines based on the evidence. The study aims to assess the risk of acute complications in pre-hospital shoulder reduction and identify which pre-hospital reduction technique has the highest success rate in the published literature.Methods:The involved databases were Allied and Complementary Medicine, CENTRAL, CINAHL, Cochrane Database of Systematic Reviews, Embase, Europe PMC, Ovid MEDLINE®, Pedro, Proquest, Trip, and World Health Organization International Clinical Trials Registry platform. Only original research of high methodological quality was included, which was defined by the recently developed assessment tool-assessing the methodological quality of published papers (AMQPP) and investigated the management of acute anterior shoulder dislocations in the pre-hospital setting.Results:Two hundred and ninety-eight articles were identified and screened. A full text review was performed on 40 articles. Four articles published between 2015 and 2018 met the inclusion criteria. A total of 181 patients were included with the study duration ranging from 6 to 60 months. All studies reported zero immediate complication following pre-hospital reduction and there were no documented subsequent adverse events regardless of the technique used. Prompt resolution of neurological symptoms was observed following the early and successful pre-hospital reduction. First attempt success rate, when performed by skilled practitioners, ranged from 72.3% to 94.9%.Conclusion:Pre-hospital shoulder reduction appears to be a safe and feasible option when carried out with the appropriate expertise. A novel reduction technique adapted from the mountain medicine diploma course at the University of Paris North was found to have the highest first attempt reduction success rate of 94.9%. Other techniques described in the literature included Hippocratic, Stimson's, Counter-traction and external rotation with the success rates ranging from 54% to 71.7%.

简介：摘要BACKGROUND AND OBJECTIVESLong-term paired associative stimulation (PAS) is a non-invasive combination of transcranial magnetic stimulation and peripheral nerve stimulation and leads to improved hand motor function in individuals with incomplete traumatic tetraplegia. Spinal cord injuries (SCIs) can also be induced by neurological diseases. We tested a similar long-term PAS approach in patients with non-traumatic neurological SCI.METHODSIn this case series, five patients with non-traumatic tetraplegia received PAS to the weaker upper limb 3 to 5 times per week for 6 weeks. Patients were evaluated by manual muscle testing (MMT) before and immediately after the therapy and at the 1- and 6-month follow-ups. Patients were also evaluated for spasticity, hand mechanical and digital dynamometry, pinch test and Box and Block test.RESULTSMMT values of all patients improved at all post-PAS evaluations. The mean±standard error MMT increase was 1.44±0.37 points (P＝0.043) immediately after PAS, 1.57±0.4 points (P＝0.043) at the 1-month follow-up and 1.71±0.47 points (P＝0.043) at the 6-month follow-up. The pinch test, digital dynamometry and Box and Block test results also improved in all patients.CONCLUSIONS Long-term PAS may be a safe and effective treatment for improving hand function in patients with non-traumatic tetraplegia.SIGNIFICANCEThis is the first report demonstrating the therapeutic potential of PAS for neurological SCI.

简介：AbstractBackground:Atrial natriuretic peptide (ANP) and its natriuretic peptide receptors A (NPR-A) and C (NPR-C) are involved in the regulation of physiological and pathophysiological process of blood pressure. The present study aimed to determine the role of NPR-C in the development of salt-sensitive hypertension.Methods:The Dahl salt-sensitive (DS) and salt-resistant (DR) rats were used in this study. Animals were matched according to their age and weight, and then placed on either a high-salt (HS, 8%) or a normal-salt (NS, 0.4%) diet for 6 weeks randomly using random number table. The systolic blood pressure (SBP), plasmatic sodium concentration (PLNa), urinary sodium excretion (UVNa), and serum creatinine concentration (Scr) were measured. The concentration of ANP in blood and tissues (heart and kidney) was detected by enzyme-linked immunosorbent assay. The expression of ANP, NPR-A, and NPR-C in kidney was evaluated with western blot analysis. Regarding renal redox state, the concentration changes in malondialdehyde (MDA), lipofuscin, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), and nitric oxide synthase (NOS) in kidney were detected by a spectrophotometric method. The kidney damage was evaluated using pathological techniques and the succinodehydrogenase (SDHase) examination. Furthermore, after an intra-peritoneal injection of C-atrial natriuretic peptide (ANP)4-23 (C-ANP4-23), an NPR-C receptor agonist, the SBP, biochemical values in blood and urine, and renal redox state were evaluated. The paired Student’s t test and analysis of variance followed by the Bonferroni test were performed for statistical analyses of the comparisons between two groups and multiple groups, respectively.Results:The baseline SBP in all groups was within the normal range. At the end of the 6-week experiment, HS diet significantly increased the SBP in DS rats from 116.63 ± 2.90 mmHg to 162.25 ± 2.15 mmHg (t = -10.213, P < 0.001). The changes of SBP were not significant in DS rats on an NS diet and DR rats on an NS diet or on an HS diet (all P > 0.05). The significant increase of PLNa, UVNa, and Scr related to an HS diet was found in both DS and DR rats (all P < 0.05). However, significant changes in the concentration (t= -21.915, P < 0.001) and expression of renal ANP (t= -3.566, P = 0.016) and the expression of renal NPR-C (t = 5.864, P = 0.002) were only observed in DS hypertensive rats. The significantly higher desmin immunochemical staining score (t = -5.715, P = 0.005) and mitochondrial injury score (t = -6.325, P = 0.003) accompanied by the lower SDHase concentration (t= 3.972, P = 0.017) revealed mitochondrial pathologic abnormalities in podocytes in DS rats with an HS diet. The distinct increases of MDA (t= -4.685, P= 0.009), lipofuscin (t= -8.195, P= 0.001), and Nox (t= -12.733, P < 0.001) but not NOS (t = -0.328, P = 0.764) in kidneys were also found in DS hypertensive rats. C-ANP4-23 treatment significantly decreased the SBP induced by HS in DS rats (P < 0.05), which was still higher than NS groups with the vehicle or C-ANP4-23 treatment (P < 0.05). Moreover, the HS-induced increase of MDA, lipofuscin, Nox concentrations, and Nox4 expression in DS rats was significantly attenuated by C-ANP4-23 treatment as compared with those with HS diet and vehicle injection (all P < 0.05).Conclusions:The results indicated that the renal NPR-C might be involved in the salt-sensitive hypertension through the damage of mitochondria in podocytes and the reduction of the anti-oxidative function. Hence, C-ANP4-23 might serve as a therapeutic agent in treating salt-sensitive hypertension.

简介：AbstractBackground:Although the use of expanded-criteria donors (ECDs) alleviates the problem of organ shortage, it significantly increases the incidence of delayed graft function (DGF). DGF is a common complication after kidney transplantation; however, the effect of DGF on graft loss is uncertain based on the published literature. Hence, the aim of this study was to determine the relationship between DGF and allograft survival.Methods:We conducted a retrospective, multicenter, observation cohort study. A total of 284 deceased donors and 541 recipients between February 2012 and March 2017 were included. We used logistic regression analysis to verify the association between clinical parameters and DGF, and Cox proportional hazards models were applied to quantify the hazard ratios of DGF for kidney graft loss.Results:Among the 284 deceased donors, 65 (22.8%) donors were ECD. Of the 541 recipients, 107 (19.8%) recipients developed DGF, and this rate was higher with ECD kidneys than with standard-criteria donor (SCD) kidneys (29.2% vs. 17.1%; P = 0.003). The 5-year graft survival rate was not significantly different between SCD kidney recipients with and without DGF (95.8% vs. 95.4%; P= 0.580). However, there was a significant difference between ECD kidney recipients with and without DGF (71.4% vs. 97.6%; P = 0.001), and the adjusted hazard ratio (HR) for graft loss for recipients with DGF was 1.885 (95% confidence interval [CI] = 1.305–7.630; P = 0.024). Results showed that induction therapy with anti-thymocyte globulin was protective against DGF (odds ratio= 0.359; 95% CI= 0.197–0.652; P= 0.001) with all donor kidneys and a protective factor for graft survival (HR = 0.308; 95% CI = 0.130–0.728; P = 0.007) with ECD kidneys.Conclusion:DGF is an independent risk factor for graft survival in recipients with ECD kidneys, but not SCD kidneys.

简介：摘要：为了探讨呼吸肌训练对自行车运动员呼吸功能及运动能力的影响，对 10 名现役男子自行车运动员进行了四周的呼吸肌训练，并于每周进行高温高湿环境下最大摄氧量（ VO 2 max ）、每分通气量（ VE ）、呼吸频率（ RR ）和运动潮气量（ Vt ）反应有氧能力、呼吸功能的指标以及主观疲劳程度（ RPE ）和最大功率数据的采集。结果显示呼吸肌训练可以提高自行车运动员在高温高湿环境下的 VO 2 max 和最大运动功率，其中 VO 2 max 在呼吸肌训练 2 周后和 4 周后均较训练前提高了约 16.1% ，最大运动功率在呼吸肌训练 4 周后提升了 30W ，提升幅度为 11.1% ；此外呼吸肌训练可以有效提高平均每分通气量（ VE ）与运动时潮气量（ Vt ）， VE 和 Vt 在呼吸肌训练 4 周后高温高湿环境下较训练前分别升高约 19.5% 和 12.5% ，训练对高温高湿环境运动的肺通气功能有明显促进作用。建议自行车等有氧耐力性运动项目可以尝试练习呼吸肌群，从而帮助提升高温高湿环境下的有氧运动能力。