组织工程支架的隔离层对新生软骨Ⅱ型胶原蛋白表达的影响

目的研究隔离层在组织工程骨软骨复合支架中,对新生软骨Ⅱ型胶原蛋白表达的影响。方法将向软骨方向诱导后的兔骨髓间充质干细胞接种到骨软骨复合支架的软骨支架上,然后将具有隔离层和没有隔离层的骨软骨复合支架分别植入兔膝关节骨软骨全层缺损处。术后3月和6月分别取材,进行新生软骨Ⅱ型胶原蛋白蛋白的免疫组化染色、Western blot法检测Ⅱ型胶原蛋白的表达、实时荧光定量PCR(qRT-PCR)测定Ⅱ型胶原蛋白相关基因的表达。结果与无隔离层的对照组相比,具有隔离层的骨软骨复合支架所形成的新生软骨的Ⅱ型胶原蛋白和基因的表达均明显增强(P<0.05)。结论隔离层加入骨软骨复合支架后,能显著提高新生组织工程软骨Ⅱ型胶原蛋白表达的能力。     

腓骨肌萎缩症X型临床、电生理及Connexin 32新突变一例

目的报告1例X连锁型腓骨肌萎缩症(CMTX),探讨其临床表现、电生理特点和连接蛋白32(Cx32)基因突变特点。方法对1例临床诊断CMT患者进行详细的病史采集和临床查体,分析其电生理和神经活检检查结果,同时进行周围髓鞘结构蛋白22(PMP22)基因重复和Connexin32(Cx32)基因突变检测。结果患者临床表现为经典的遗传性感觉运动神经病,肌电图检查提示脱髓鞘损害伴轴索损害,同时出现传导阻滞;神经活检示脱髓鞘性周围神经损害;基因检测发现Cx32基因编码序列第414位碱基发生单碱基错义突变(414C>G),造成其编码的第138位的氨基酸由丝氨酸突变为精氨酸(Ser138Arg)。结论 414C>G突变为Cx32基因新突变,国内外文献未见报道。该基因型没有产生特殊的临床表现,但电生理表现为脱髓鞘为主的混合性周围神经病变,且具有传导阻滞的特点。Cx32基因不同的突变位点和形式可能是导致CMTX临床异质性的原因之一。     

Oral chronic graft‐versus‐host disease: current pathogenesis,therapy, and research

Optimal management of complex autoimmune diseases requires a multidisciplinary medical team including dentists to care for lesions of the oral cavity. In this review, we discuss the presentation, prevalence, diagnosis, and treatment of oral manifestations in chronic graft‐versus‐host disease (cGVHD), which is a major late complication in patients treated by allogeneic hematopoietic stem cell transplantation. We assess current general knowledge of systemic and oral cGVHD and present general treatment recommendations based on literature review and our clinical experience. Additionally, we review areas where the understanding of oral cGVHD could be improved by further research and address tools with which to accomplish the long‐term goal of providing better health and quality of life to patients with cGVHD.     

A phase II dose-ranging study of mirabegron in patients with overactive bladder

Introduction and hypothesis

Mirabegron is a potent and selective β₃-adrenoceptor agonist that may represent an alternative treatment option in place of antimuscarinics for patients with overactive bladder.

Methods

Patients completed a single-blinded, 2-week placebo run-in period followed by 12 weeks of randomized (n?=?928) double-blinded treatment with mirabegron oral controlled absorption system (OCAS) 25, 50, 100, or 200 mg once-daily (QD), placebo or tolterodine extended release (ER) 4 mg QD. The primary endpoint was change from baseline to end-of-treatment in mean number of micturition episodes/24 h. Secondary endpoints included changes in mean volume voided per micturition; mean number of urinary incontinence, urgency urinary incontinence, and urgency episodes/24 h; severity of urgency; nocturia; and quality of life measures. Safety parameters included vital signs, adverse events, laboratory tests, electrocardiogram measurements and post-void residual volume.

Results

Mirabegron 25, 50, 100, and 200 mg resulted in dose-dependent reductions (improvements) from baseline to end-of-treatment in micturition frequency of 1.9, 2.1, 2.1, and 2.2 micturitions/24 h respectively, versus 1.4 micturitions/24 h with placebo (p?≤?0.05 for the mirabegron 50-, 100-, and 200-mg comparisons). There was a statistically significant improvement with mirabegron compared with placebo for most secondary endpoints including quality of life variables. While there was a significant (p?<?0.05) increase from baseline in pulse rate in the mirabegron 100-mg and 200-mg groups, this was not associated with an increased incidence of cardiovascular adverse events.

Conclusions

The favorable efficacy and tolerability of mirabegron in this phase II dose-finding study has led to its successful advancement into a phase III clinical development program.     

A preliminary study of manipulation under anaesthesia for secondary frozen shoulder following breast cancer treatment

Introduction

The aim of this paper is to present the results of manipulation under anaesthesia (MUA) and injection of local anaesthetic and corticosteroid followed by a physiotherapy regime for secondary frozen shoulder after breast cancer treatment (surgery, radiotherapy), and to compare them with a control group.

Methods

Patients referred to the senior author for secondary frozen shoulder following breast cancer treatment over a ten-year period were investigated. Recorded data included age, treatment for breast cancer, length of symptoms, Oxford shoulder score (OSS) and range of motion before and after shoulder MUA. These data were compared with a control group of patients with frozen shoulder.

Results

A total of 263 patients were referred with 281 frozen shoulders. Of these, 7 patients (7 shoulders) had undergone previous breast cancer treatment and the remaining 256 patients (274 shoulders) formed the control group. None of the patients were diabetic. The mean preoperative OSS was 31 for the study group and 27 for the control group, improving to 43 for both groups following MUA. Forty-two per cent of the study group and fifteen per cent of the control group had a second MUA subsequently. At the long-term follow-up appointment, 71% of the study group patients were satisfied with their result.

Conclusions

The results of this preliminary study suggest that MUA, corticosteroid injection and subsequent physiotherapy have achieved good final results in a series of patients with frozen shoulder secondary to breast cancer treatment. Members of the multidisciplinary team looking after breast cancer patients should be aware of this management option and, on manifestation of this pathology, should refer the patient to an orthopaedic surgeon.     

木犀草素对重症急性胰腺炎小鼠胰腺的保护作用及可能的分子机制#br#

目的 探讨木犀草素对重症急性胰腺炎（SAP）小鼠胰腺的保护作用及其可能的分子机制。方法 将60只SPF级健康雄性C57BL/6小鼠随机分为3组,对照组、SAP模型组和治疗组,每组各20只。采用雨蛙素法构建模型,成功构建SAP模型后,应用ELASA法检测脂肪酶、淀粉酶、血红素加氧酶（HO)-1、肿瘤坏死因子（TNF）-α、丙二醛（MDA）及超氧化物歧化酶（SOD）水平。使用Western blotting和Real-time PCR测定各组小鼠核因子（NF）-κB、P38及p-P38 蛋白和mRNA水平。结果 与对照组比较,模型组和治疗组小鼠胰腺干湿重比、脂肪酶及淀粉酶、TNF-α水平、氧化应激指标HO-1及MDA水平均明显升高,SOD水平明显降低（P<0.05）;与模型组小鼠比较,治疗组小鼠胰腺干湿重比、脂肪酶及淀粉酶,TNF-α、MDA水平均明显降低,HO-1、SOD水平均明显升高（P<0.05）。与对照组比较,模型组和治疗组小鼠NF-κB、p-P38蛋白和mRNA水平明显升高（P<0.05）,P38蛋白和mRNA表达水平无显著变化（P>0.05）;与模型组小鼠比较,治疗组小鼠NF-κB、p-P38蛋白和mRNA水平均明显降低（P<0.05）。结论 木犀草素对SAP小鼠胰腺具有一定的保护作用,其可能的分子机制为缓解炎症应激和氧化应激,下调NF-κB及p-P38 蛋白的表达。     

插管注入开塞露在妇科便秘患者中的应用

目的:探讨插管注入开塞露对缓解妇科患者便秘的效果。方法:将140例妇科便秘患者随机分为对照组和试验组各70例,对照组采用传统的方法将开塞露直接纳肛,试验组用50ml注射器连接16号吸痰管轻插入肛门15-20cm,注入同等量开塞露通便,比较两者患者用药效果。结果:实验组患者排便时间明显比对照组提前(P<0.01);实验组排便效果优于对照组,差异有显著意义(P<0.01)。结论:插管注入开塞露纳肛在缓解妇产科便秘患者中安全、实用、可靠,优于传统方法。     

Stimulus repetition modulates gamma-band synchronization in primate visual cortex

When a sensory stimulus repeats, neuronal firing rate and functional MRI blood oxygen level-dependent responses typically decline, yet perception and behavioral performance either stay constant or improve. An additional aspect of neuronal activity is neuronal synchronization, which can enhance the impact of neurons onto their postsynaptic targets independent of neuronal firing rates. We show that stimulus repetition leads to profound changes of neuronal gamma-band (∼40–90 Hz) synchronization. Electrocorticographic recordings in two awake macaque monkeys demonstrated that repeated presentations of a visual grating stimulus resulted in a steady increase of visually induced gamma-band activity in area V1, gamma-band synchronization between areas V1 and V4, and gamma-band activity in area V4. Microelectrode recordings in area V4 of two additional monkeys under the same stimulation conditions allowed a direct comparison of firing rates and gamma-band synchronization strengths for multiunit activity (MUA), as well as for isolated single units, sorted into putative pyramidal cells and putative interneurons. MUA and putative interneurons showed repetition-related decreases in firing rate, yet increases in gamma-band synchronization. Putative pyramidal cells showed no repetition-related firing rate change, but a decrease in gamma-band synchronization for weakly stimulus-driven units and constant gamma-band synchronization for strongly driven units. We propose that the repetition-related changes in gamma-band synchronization maintain the interareal stimulus signaling and sharpen the stimulus representation by gamma-synchronized pyramidal cell spikes.Stimulus repetition typically leads to reduced neuronal firing rates and reduced functional MRI blood oxygen level-dependent signals, whereas behavior that is based on stimulus processing is not affected or is enhanced (1). Different models have been proposed to reconcile these behavioral and neurophysiological findings (1). In a “fatigue model,” neuronal responses are reduced in proportion to their amplitude, leaving relative response patterns unchanged; in a “sharpening model,” neurons that code features irrelevant to identification of a stimulus exhibit repetition suppression, leading to a sparser and sharpened representation of the repeated stimulus; and in a “facilitation model,” stimulus repetition leads to faster stimulus processing, and thereby smaller overall neuronal activity. Gotts and coworkers (2–4) suggested a “synchronization model” in which stimulus repetition leads to reduced firing rates accompanied by increased synchronization. The increased synchronization might explain how less-activated neuronal groups can maintain their impact onto postsynaptic neurons and, ultimately, behavior, while reducing metabolic costs at the same time. The synchronization model has received support from a number of studies in human subjects, using source-localized magnetoencephalography. Ghuman et al. (5) report enhanced frontotemporal 14-Hz synchronization for repeated vs. novel stimuli. Gilbert et al. (3) found that stimulus repetition leads to enhanced 5- to 15-Hz power in the right fusiform gyrus and enhanced 15- to 35-Hz power in striate and extrastriate cortex. Corresponding data were also reported for multisite microelectrodes recordings in striate and parietal cortex of awake cats, where von Stein et al. (6) found that interareal alpha-band synchronization was stronger for repeated compared with novel stimuli. The common finding across these studies is enhanced alpha/beta activity or coupling for repeated stimuli. The alpha coupling reported by von Stein et al. (6) occurs in a behavioral context and has a phase relationship and layer specificity that suggests a top-down–directed interaction. Thus, enhanced alpha/beta activity or coupling for repeated stimuli might reflect enhanced top-down signaling, perhaps related to enhanced predictability of repeated stimuli. However, increased synchronization with stimulus repetition according to the model of Gotts and coworkers (2–4) should also serve the maintenance of feedforward signaling of repeated stimuli in the face of reduced firing rates. Feedforward signaling has been strongly linked to local and interareal gamma-band synchronization (7–9). Local gamma-band synchronization likely enhances the postsynaptic impact of the precisely synchronized output spikes (10). Interareal gamma-band synchronization likely aligns excitability cycles such that inputs arrive when postsynaptic target neurons are receptive (11, 12). However, whether multiple presentations of a stimulus result in enhanced gamma-band synchronization remains unknown (details are provided in SI Discussion). We investigated gamma-band synchronization within and between macaque monkey areas V1 and V4 and report that stimulus repetition leads to profound changes in gamma-band synchronization within and between these areas.