BACKGROUND & AIMS: The dose, efficacy, and side effects of continuous intravenous infusion (CIVI) of morphine were compared with continuous subcutaneous infusion (CSCI) of morphine in patients with chronic cancer pain. Eligible patients were referred to the Palliative Care Program and were receiving a stable dose of CIVI of morphine. The design was a within-patient, one-way crossover; in which each patient provided data before and after a switch from CIVI to CSCI of morphine. "Rescue" doses were 50% of the hourly dose given every 2 hours as needed. Morphine was infused intravenously (i.v.) and subcutaneously (s.c.) via a McGaw/AccuPro Volumetric Infusion Pump. After baseline data, including side effects and pain assessment, were obtained, patients were evaluated twice daily for toxicity and analgesic efficacy. Those who had a stable CIVI dose for 48 consecutive hr were crossed over to the CSCI at the same dose as the intravenous (i.v.) phase. A stable dose was defined as no dose change, four or less rescue doses in the previous 24 hr, and a pain rating of none or mild. CIVI was considered equal to CSCI if these criteria were maintained for 96 consecutive hr. Fifty-seven patients were entered, and 40 were evaluable (15 women and 25 men). The median age was 67 (range 30-83 years). All 40 participants, after maintaining a stable dose throughout the i.v. phase, crossed to the s.c. phase and remained on s.c. for at least 48 hr. Thirty-two patients maintained a stable dose throughout the i.v. and s.c. phases. The mean stable i.v. dose (day 2) was 5.05 mg/hr, and the mean stable s.c. dose (day 4) was 5.7 mg/hr (P = 0.01). The mean number of rescue doses on day 2 was 0.83 per 24 hr versus 0.80 per 24 hours on day 4 (P = 0.6). The mean categorical pain score on day 2 was 0.83, and on day 4, 0.85 (P = 0.7). The mean visual analogue scale (VAS) on day 2 was 22.9 mm versus 17.6 mm on day 4 (P = 0.1). The mean incidence of side effects on day 2 was 1.7, and on day 4, 2.0 (P = 0.2). No patient was withdrawn or had a dose reduction due to unacceptable toxicity. There were two reports of local toxicity (mild erythema) at the SC needle insertion point, which required a site change. All of our 40 patients had adequate pain control with CIVI and CSCI morphine. Of the eight participants who were not maintained on the same i.v. and s.c. dose, all had adequate pain control and a similar side-effect profile on a higher s.c. morphine dose. These data suggest that the i.v. and s.c. routes are equianalgesic for most patients when administered as a continuous infusion. Pain control and side-effect profiles are quite similar and acceptable. s.c. morphine is an excellent alternative to i.v. morphine in both inpatients and outpatients requiring parenteral morphine for pain.

背景与目标： 比较了慢性癌症疼痛患者中吗啡连续静脉输注（CIVI）与吗啡连续皮下输注（CSCI）的剂量，疗效和副作用。符合条件的患者被转到姑息治疗计划，并接受稳定剂量的吗啡CIVI。该设计是患者内部的单向交叉。其中每个患者提供了从吗啡从CIVI切换到CSCI之前和之后的数据。 “救援”剂量是根据需要每2小时给予的每小时剂量的50％。吗啡通过McGaw / AccuPro容量输注泵静脉内（i.v.）和皮下（s.c.）输注。获得包括副作用和疼痛评估在内的基线数据后，每天对患者进行两次毒性和止痛效果评估。连续48个小时具有稳定CIVI剂量的患者以与静脉内（i.v.）阶段相同的剂量转入CSCI。稳定剂量定义为无剂量变化，在过去24小时内有四个或更少的急救剂量，疼痛等级为无或轻度。如果连续96个小时保持这些标准，则认为CIVI等于CSCI。入组患者57例，其中40例可评估（女性15例，男性25例）。中位年龄为67岁（范围为30-83岁）。在整个静脉内维持稳定剂量后，所有40位参与者阶段，跨到南卡罗来纳州相并保持在s.c.至少持续48小时。在整个静脉内，有32名患者维持了稳定的剂量。和s.c.阶段。平均稳定i.v.剂量（第2天）为5.05 mg / hr，平均稳定s.c.剂量（第4天）为5.7 mg / hr（P = 0.01）。第2天的平均急救剂量为每24小时0.83，而第4天为每24小时0.80（P = 0.6）。第2天的平均类别疼痛评分为0.83，第4天的平均疼痛评分为0.85（P = 0.7）。第2天的平均视觉模拟量表（VAS）为22.9毫米，而第4天为17.6毫米（P = 0.1）。第2天的副作用的平均发生率为1.7，而第4天的平均发生率为2.0（P = 0.2）。没有患者因不可接受的毒性而退出或剂量减少。有两份关于SC针插入点的局部毒性（轻度红斑）的报道，需要进行部位改变。我们所有的40名患者均通过CIVI和CSCI吗啡可以很好地控制疼痛。在没有保持相同i.v.的八位参与者中和s.c.剂量较高时，所有患者均具有足够的疼痛控制能力，并且在较高的s.c.下具有相似的副作用。吗啡剂量。这些数据表明和s.c.当以连续输注方式给药时，对于大多数患者而言，这些途径均具有镇痛作用。疼痛控制和副作用状况非常相似且可以接受。南卡罗来纳州吗啡是静脉注射的绝佳替代品。需要胃肠外吗啡治疗的住院患者和门诊患者中的吗啡疼痛。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :Sympathetically maintained pain could either be mediated by ephaptic interactions between sympathetic efferent and afferent nociceptive fibers or by catecholamine-induced activation of nociceptive nerve endings. We report here single fiber recordings from C nociceptors in a patient with sympathetically maintained pain, in whom sympathetic blockade had repeatedly eliminated the ongoing pain in both legs. We classified eight C-fibers as mechano-responsive and six as mechano-insensitive nociceptors according to their mechanical responsiveness and activity-dependent slowing of conduction velocity (latency increase of 0.5+/-1.1 vs. 7.1+/-2.0 ms for 20 pulses at 0.125 Hz). Two C-fibers were activated with a delay of several seconds following strong endogenous sympathetic bursts; they were also excited for about 3 min following the injection of norepinephrine (10 microl, 0.05%) into their innervation territory. In these two fibers, a prolonged activation by injection of low pH solution (phosphate buffer, pH 6.0, 10 microl) and sensitization of their heat response following prostaglandin E2 injection were recorded, evidencing their afferent nature. Moreover, their activity-dependent slowing was typical for mechano-insensitive nociceptors. We conclude that sensitized mechano-insensitive nociceptors can be activated by endogenously released catecholamines and thereby may contribute to sympathetically maintained pain. No evidence for ephaptic interaction between sympathetic efferent and nociceptive afferent fibers was found.

背景与目标： ：交感神经维持的疼痛可能由交感传入和传入的伤害性纤维之间的神经元相互作用或儿茶酚胺诱导的伤害性神经末梢的激活介导。我们在这里报告了在交感神经痛患者中，C伤害感受器的单纤维记录，在该患者中，交感神经阻滞反复消除了双腿持续的疼痛。根据它们的机械响应性和依赖于传导速度的活动性减慢，我们将8根C纤维归为机械响应性伤害感受器，将6根C纤维归类为对机械响应不敏感的伤害感受器（20脉冲在0.125时延迟时间为0.5 /-1.1与7.1 /-2.0 ms的增加）赫兹）。在强烈的内源性交感神经爆发后，几秒钟的延迟激活了两根C纤维。在将去甲肾上腺素（10微升，0.05％）注入其神经支配区域后，他们还兴奋了约3分钟。在这两根纤维中，记录了通过注射低pH溶液（磷酸盐缓冲液，pH 6.0，10微升）而延长的活化作用以及注射前列腺素E2后对其热响应的敏化，证明了它们的传入性质。此外，它们对机械不敏感的伤害感受器的活动依赖性减慢作用是典型的。我们得出结论，致敏的对机械不敏感的伤害感受器可以被内源性释放的儿茶酚胺激活，从而可能有助于交感神经维持性疼痛。没有发现交感传入纤维和伤害性传入纤维之间的神经元相互作用的证据。

BACKGROUND & AIMS: AIM:To research possible associations between previous exposure to specific torture techniques and prevalent pain in the head and face, back, and feet. METHODS:221 refugees, 193 males and 28 females, previously exposed to torture in their home country, were subject to a clinical interview at a rehabilitation clinic for torture victims. The interview focused on exposure to torture and somatic symptoms prevalent at examination. RESULTS:The mean number of times imprisoned was 2.3; the mean number of months imprisoned was 19.7; the mean duration from initial imprisonment to final release was 3.7 years; and the mean duration from final release to preliminary interview was 8.4 years. The most frequent physical torture method reported was beating (92.3%) and the main mental torture method was deprivation (84.6%). Pain in the head and face was found to be strongly associated with torture against head and face (OR 3.89, 95% CI 1.49-10.20) and with the cumulative number of physical torture methods exposed to. Pain in the back was associated with sexual torture (OR 2.75, 95% CI 1.07-7.12). Besides beating of the lower extremities (OR 5.98, 95% CI 2.47-14.48), the strongest predictor for pain in the feet was general abuse of the whole body (OR 5.64, 95% CI 1.93-16.45). CONCLUSION:In spite of many factors being potentially co-responsible for prevalent pain, years after the torture took place it presents itself as strongly associated with specific loci of pain, with generalized effects, and with somatizing.

背景与目标： 目的：研究先前暴露于特定的酷刑技术与头部和面部，背部和脚部普遍疼痛之间的可能联系。
方法：221名难民，193名男性和28名女性先前在其本国遭受酷刑，在康复诊所接受酷刑受害者的临床采访。访谈的重点是检查时所遭受的酷刑和躯体症状的暴露。
结果：平均入狱次数为2.3次；平均入狱数为19.7个月；从最初入狱到最终释放的平均时间为3.7年；从最终发布到初步面试的平均时间为8.4年。报告的最经常的酷刑方法是殴打（92.3％），主要的心理酷刑方法是剥夺（84.6％）。发现头部和面部疼痛与对头部和面部的酷刑密切相关（OR 3.89，95％CI 1.49-10.20）以及所遭受的物理酷刑方法的累积数量。背部疼痛与性折磨有关（OR 2.75，95％CI 1.07-7.12）。除了下肢跳动（OR 5.98，95％CI 2.47-14.48）之外，脚部疼痛的最强预测指标是全身的普遍滥用（OR 5.64，95％CI 1.93-16.45）。
结论：尽管有许多因素可能共同导致普遍的疼痛，但在发生酷刑之后数年，它仍表现为与特定的疼痛位点密切相关，具有广泛的影响和躯体化。

BACKGROUND & AIMS: :Chronic pain may result from hyperexcitability following activation of spinal NMDA receptors. A naturally-derived mammalian peptide, histogranin, may possess NMDA antagonist activity. This study explored the possibility that stable analog [Ser1]Histogranin (SHG) could reduce chronic pain. Neuropathic pain was induced using the chronic constriction injury model (CCI). Intrathecal injection of SHG markedly attenuated the hyperalgesia and allodynia resulting from CCI, nearly normalizing responses. These results suggest that the natural peptide histogranin may be a novel adjunct in neuropathic pain management.

背景与目标： ：慢性疼痛可能是由脊柱NMDA受体激活后的过度兴奋引起的。天然来源的哺乳动物多肽，组织颗粒蛋白可能具有NMDA拮抗剂活性。这项研究探讨了稳定的类似物[Ser1] Histogranin（SHG）可以减轻慢性疼痛的可能性。使用慢性收缩损伤模型（CCI）诱发神经性疼痛。鞘内注射SHG明显减轻了CCI引起的痛觉过敏和异常性疼痛，使反应趋于正常。这些结果表明，天然肽组织颗粒蛋白可能是神经性疼痛治疗的新辅助剂。

BACKGROUND & AIMS: :Peripheral neuropathic pain is a unique form of chronic pain that afflicts up to 50% of persons with AIDS. The purpose of this pilot study was to examine the effects of ice massage to reduce neuropathic pain and improve sleep quality and to determine the feasibility of a larger study. A repeated measures design was used. The three treatments consisted of ice massage, dry-towel massage, and presence. Consecutive sampling was used to select 33 persons with AIDS who had neuropathic pain. Although the results of the study were negative, there was a decrease in pain intensity over time with both the ice massage and towel massage, suggesting that the intervention has some clinical benefit.

背景与目标： ：周围神经性疼痛是慢性疼痛的一种独特形式，可折磨多达50％的艾滋病患者。这项初步研究的目的是检验冰按摩对减轻神经性疼痛和改善睡眠质量的作用，并确定一项更大研究的可行性。使用了重复测量设计。这三种治疗包括冰按摩，干毛巾按摩和临场感。连续抽样选择了33名患有神经性疼痛的艾滋病患者。尽管研究结果为阴性，但冰按摩和毛巾按摩的疼痛强度均随时间降低，表明该干预措施具有一定的临床益处。

BACKGROUND & AIMS: :Peroxisome proliferator-activated receptors (PPARs) are expressed on vascular tissue. To investigate the direct vasoprotective effects of PPARgamma and PPARalpha ligands, pioglitazone (3 mg/kg/day) and bezafibrate (10 mg/kg/day) were given by gavage to streptozotocin-induced diabetic rats for 4 weeks. Streptozotocin (65 mg/kg, i.p.) significantly increased NADPH oxidase, vascular call adhesion molecule-1 (VCAM-1), and osteopontin mRNA levels in the aorta, as determined by reverse transcription (RT)-polymerase chain reaction (PCR). Immunohistochemical analysis revealed that the expression of osteopontin protein was also enhanced in the streptozotocin-injected rat aorta. Pioglitazone or bezafibrate attenuated the streptozotocin-induced increase in the expression of NADPH oxidase and VCAM-1 mRNA. The enhanced expression of osteopontin gene and protein induced by streptozotocin was suppressed by pioglitazone, whereas treatment with bezafibrate had no effect on the expression of osteopontin. We also demonstrated that pioglitazone or bezafibrate prevented the streptozotocin-induced increase in angiotensin converting enzyme (ACE) gene and protein content, by the means of RT-PCR and Western blotting. On the other hand, the treatment of pioglitazone or bezafibrate in the present study did not affect glucose tolerance, serum insulin or lipid level in streptozotocin-induced diabetic rats. These results suggest that the direct anti-oxidant and anti-inflammatory effects of PPARs ligands in the aorta of streptozotocin-induced diabetic rats were not likely to have been mediated by the normalization of glucose or lipid metabolism, but instead these salutary effects appear to have been associated with the inhibition of the expression of ACE. In addition, pioglitazone appeared to be more effective on the suppression of osteopontin expression compared with bezafibrate.

背景与目标： ：过氧化物酶体增殖物激活受体（PPAR）在血管组织上表达。为了研究PPARγ和PPARα配体的直接血管保护作用，通过链饲法对链脲佐菌素诱导的糖尿病大鼠给予吡格列酮（3 mg / kg /天）和苯扎贝特（10 mg / kg /天）。通过逆转录（RT）-聚合酶链反应（PCR）确定，链脲佐菌素（65 mg / kg，腹膜内）显着增加主动脉中的NADPH氧化酶，血管调用粘附分子1（VCAM-1）和骨桥蛋白mRNA水平。免疫组织化学分析显示，在注射链脲佐菌素的大鼠主动脉中，骨桥蛋白的表达也得到了增强。吡格列酮或苯扎贝特减弱了链脲佐菌素诱导的NADPH氧化酶和VCAM-1 mRNA表达的增加。吡格列酮抑制了链脲佐菌素诱导的骨桥蛋白基因和蛋白质表达的增强，而苯扎贝特治疗对骨桥蛋白的表达没有影响。我们还证明了吡格列酮或苯扎贝特通过RT-PCR和Western印迹可以阻止链脲佐菌素诱导的血管紧张素转化酶（ACE）基因和蛋白质含量的增加。另一方面，本研究中吡格列酮或苯扎贝特的治疗并未影响链脲佐菌素诱发的糖尿病大鼠的葡萄糖耐量，血清胰岛素或血脂水平。这些结果表明，链脲佐菌素诱导的糖尿病大鼠主动脉中PPARs配体的直接抗氧化和抗炎作用不可能由葡萄糖或脂质代谢的正常化介导，但是这些有益的作用似乎具有与抑制ACE表达有关。此外，吡格列酮似乎比苯扎贝特对抑制骨桥蛋白的表达更有效。

BACKGROUND & AIMS: CONTEXT:Chronic pain in patients with advanced cancer poses a serious clinical challenge. The Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (U.S. Adopted Name, nabiximols; Sativex(®)) is a novel cannabinoid formulation currently undergoing investigation as an adjuvant therapy for this treatment group. OBJECTIVES:This follow-up study investigated the long-term safety and tolerability of THC/CBD spray and THC spray in relieving pain in patients with advanced cancer. METHODS:In total, 43 patients with cancer-related pain experiencing inadequate analgesia despite chronic opioid dosing, who had participated in a previous three-arm (THC/CBD spray, THC spray, or placebo), two-week parent randomized controlled trial, entered this open-label, multicenter, follow-up study. Patients self-titrated THC/CBD spray (n=39) or THC spray (n=4) to symptom relief or maximum dose and were regularly reviewed for safety, tolerability, and evidence of clinical benefit. RESULTS:The efficacy end point of change from baseline in mean Brief Pain Inventory-Short Form scores for "pain severity" and "worst pain" domains showed a decrease (i.e., improvement) at each visit in the THC/CBD spray patients. Similarly, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 scores showed a decrease (i.e., improvement) from baseline in the domains of insomnia, pain, and fatigue. No new safety concerns associated with the extended use of THC/CBD spray arose from this study. CONCLUSION:This study showed that the long-term use of THC/CBD spray was generally well tolerated, with no evidence of a loss of effect for the relief of cancer-related pain with long-term use. Furthermore, patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time, suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit.

背景与目标： 背景：晚期癌症患者的慢性疼痛提出了严峻的临床挑战。 Δ9-四氢大麻酚（THC）/大麻二酚（CBD）口腔粘膜喷雾剂（美国采用名称，nabiximols;Sativex®）是一种新型大麻素制剂，目前正在接受治疗，作为该治疗组的辅助疗法。
目的：这项随访研究调查了THC / CBD喷雾剂和THC喷雾剂在缓解晚期癌症患者的疼痛方面的长期安全性和耐受性。
方法：总共有43例癌症相关疼痛患者尽管使用了阿片类药物长期服用，但仍没有足够的镇痛作用，他们参加了先前的三组试验（THC / CBD喷雾剂，THC喷雾剂或安慰剂），为期两周的父母随机对照试验，参加了这项开放性，多中心的后续研究。患者自行滴定THC / CBD喷雾剂（n = 39）或THC喷雾剂（n = 4）以缓解症状或最大剂量，并定期检查其安全性，耐受性和临床获益证据。
结果：THC / CBD喷剂患者每次就诊时，“疼痛严重程度”和“最严重疼痛”域的平均简短疼痛清单-简表得分的基线变化的功效终点显示出降低（即改善）。同样，欧洲癌症生活质量研究和治疗组织问卷-C30的得分显示，失眠，疼痛和疲劳程度较基线水平有所降低（即有所改善）。这项研究没有引起与广泛使用THC / CBD喷雾剂相关的新安全隐患。
结论：这项研究表明，长期使用THC / CBD喷雾剂通常具有良好的耐受性，没有证据表明长期使用THC / CBD喷雾剂可减轻癌症相关疼痛。此外，继续使用研究药物的患者并未寻求随时间增加这种药物或其他缓解疼痛药物的剂量，这表明在与癌症相关的疼痛中辅助使用大麻素可提供有益的益处。

BACKGROUND & AIMS: OBJECTIVE:To compare magnetic resonance imaging-derived right ventricular (RV) dimensions and function between men with type 2 diabetes and healthy subjects, and to relate these parameters to left ventricular (LV) dimensions and function. RESEARCH DESIGN AND METHODS:RV and LV volumes and functions were assessed in 78 men with uncomplicated type 2 diabetes and 28 healthy men within the same range of age using magnetic resonance imaging. Steady-state free precession sequences were used to assess ventricular dimensions. Flow velocity mapping across the pulmonary valve and tricuspid valve was used to assess RV outflow and diastolic filling patterns, respectively. Univariate general linear models were used for statistical analyses. RESULTS:RV end-diastolic volume was significantly decreased in patients compared with healthy subjects after adjustment for BMI and pulse pressure (177 ± 28 mL vs. 197 ± 47 mL, P < 0.01). RV systolic function was impaired: peak ejection rate across the pulmonary valve was decreased (433 ± 54 mL/s vs. 463 ± 71 mL/s, P < 0.01) and pulmonary flow acceleration time was longer (124 ± 17 ms vs. 115 ± 25 ms, P < 0.05). Indexes of RV diastolic function were impaired: peak filling rate and peak deceleration gradient of the early filling phase were 315 ± 63 mL/s vs. 356 ± 90 mL/s (P < 0.01) and 2.3 ± 0.8 mL/s(2) × 10(-3) vs. 2.8 ± 0.8 mL/s(2) × 10(-3) (P < 0.01), respectively. All RV parameters were strongly associated with its corresponding LV parameter (P < 0.001). CONCLUSIONS:Diabetic cardiomyopathy affects the right ventricle, as demonstrated by RV remodeling and impaired systolic and diastolic functions in men with type 2 diabetes, in a similar manner as changes in LV dimensions and functions. These observations suggest that RV impairment might be a component of the diabetic cardiomyopathy phenotype.

背景与目标： 目的：比较2型糖尿病男性和健康受试者的磁共振成像得出的右心室（RV）尺寸和功能，并将这些参数与左心室（LV）尺寸和功能相关联。
研究设计和方法：使用磁共振成像技术评估了78例未合并2型糖尿病的男性和28例相同年龄范围内的健康男性的RV和LV容量及功能。稳态自由进动序列用于评估心室尺寸。跨肺动脉瓣和三尖瓣的流速映射分别用于评估RV流出和舒张期充盈模式。单变量一般线性模型用于统计分析。
结果：校正BMI和脉压后，与健康受试者相比，RV患者舒张末期容积显着降低（177±28 mL vs. 197±47 mL，P <0.01）。右室收缩功能受损：跨肺动脉瓣的峰值射血率降低（433±54 mL / s与463±71 mL / s，P <0.01），肺血流加速时间更长（124±17 ms与115） ±25毫秒，P <0.05）。 RV舒张功能指标受损：早期充盈期的峰值充盈率和峰值减速度梯度为315±63 mL / s，而356±90 mL / s（P <0.01）和2.3±0.8 mL / s（2） ×10（-3）与2.8±0.8 mL / s（2）×10（-3）（P <0.01）。所有RV参数均与其相应的LV参数密切相关（P <0.001）。
结论：糖尿病性心肌病会影响右心室，如右室重构和2型糖尿病男性收缩压和舒张功能受损所证实的，其方式与LV尺寸和功能的改变相似。这些观察结果表明，RV损伤可能是糖尿病性心肌病表型的一部分。

BACKGROUND & AIMS: :Nonhealing diabetic foot ulcers (DFUs) are a common and costly complication of diabetes. Microbial burden, or "bioburden," is believed to underlie delayed healing, although little is known of those clinical factors that may influence microbial load, diversity, and/or pathogenicity. We profiled the microbiomes of neuropathic nonischemic DFUs without clinical evidence of infection in 52 individuals using high-throughput sequencing of the bacterial 16S ribosomal RNA gene. Comparatively, wound cultures, the standard diagnostic in the clinic, vastly underrepresent microbial load, microbial diversity, and the presence of potential pathogens. DFU microbiomes were heterogeneous, even in our tightly restricted study population, but partitioned into three clusters distinguished primarily by dominant bacteria and diversity. Ulcer depth was associated with ulcer cluster, positively correlated with abundance of anaerobic bacteria, and negatively correlated with abundance of Staphylococcus. Ulcer duration was positively correlated with bacterial diversity, species richness, and relative abundance of Proteobacteria, but was negatively correlated with relative abundance of Staphylococcus. Finally, poor glycemic control was associated with ulcer cluster, with poorest median glycemic control concentrating to Staphylococcus-rich and Streptococcus-rich ulcer clusters. Analyses of microbial community membership and structure may provide the most useful metrics in prospective studies to delineate problematic bioburden from benign colonization that can then be used to drive clinical treatment.

背景与目标： ：非愈合性糖尿病足溃疡（DFU）是糖尿病的常见且代价高昂的并发症。尽管对影响微生物负荷，多样性和/或致病性的临床因素知之甚少，但是微生物负荷或“生物负荷”被认为是延迟愈合的基础。我们使用细菌16S核糖体RNA基因的高通量测序对52例无感染临床症状的神经性非缺血性DFU的微生物群进行了分析。相比之下，伤口培养物（临床上的标准诊断方法）在很大程度上代表了微生物负荷，微生物多样性以及潜在病原体的存在。即使在我们严格限制的研究人群中，DFU微生物群也是异质的，但被分为三类，主要以优势细菌和多样性为特征。溃疡深度与溃疡簇有关，与厌氧菌的数量呈正相关，与葡萄球菌的数量呈负相关。溃疡持续时间与细菌多样性，物种丰富度和变形杆菌相对丰度呈正相关，而与葡萄球菌相对丰度呈负相关。最后，血糖控制不佳与溃疡簇有关，最差的中位血糖控制集中于富含葡萄球菌和富含链球菌的溃疡簇。在前瞻性研究中，对微生物群落组成和结构的分析可能会提供最有用的指标，以从良性定殖中确定有问题的生物负荷，然后将其用于临床治疗。

BACKGROUND & AIMS: :The perception of visceral pain is a complex process involving the spinal cord and higher order brain structures. Increasing evidence implicates the gut microbiota as a key regulator of brain and behavior, yet it remains to be determined if gut bacteria play a role in visceral sensitivity. We used germ-free mice (GF) to assess visceral sensitivity, spinal cord gene expression and pain-related brain structures. GF mice displayed visceral hypersensitivity accompanied by increases in Toll-like receptor and cytokine gene expression in the spinal cord, which were normalized by postnatal colonization with microbiota from conventionally colonized (CC). In GF mice, the volumes of the anterior cingulate cortex (ACC) and periaqueductal grey, areas involved in pain processing, were decreased and enlarged, respectively, and dendritic changes in the ACC were evident. These findings indicate that the gut microbiota is required for the normal visceral pain sensation.

背景与目标： ：内脏痛的感觉是一个复杂的过程，涉及脊髓和高级大脑结构。越来越多的证据表明肠道菌群是大脑和行为的关键调节因子，但肠道细菌是否在内脏敏感性中起作用尚待确定。我们使用无菌小鼠（GF）评估内脏敏感性，脊髓基因表达和与疼痛相关的脑结构。 GF小鼠表现出内脏超敏反应，并伴随着脊髓Toll样受体和细胞因子基因表达的增加，这可以通过用常规定殖的（CC）菌群在出生后定植来实现。在GF小鼠中，前扣带回皮质（ACC）和导水管周围灰色的体积（参与疼痛处理的区域）分别减小和增大，并且ACC中的树突状变化是明显的。这些发现表明，肠道菌群是正常内脏痛感所必需的。

BACKGROUND & AIMS: BACKGROUND:Diabetes mellitus (DM) is associated with hyperglycemia, inflammatory disorders and abnormal lipid profiles, currently the extracts from leaves of cynara scolymus has been discovered to treat metabolic disorders and has been stated by multitudinous scientists according to a good source of polyphenols compounds. The present study aimed to evaluate the protective effect of the ethanol leaves extract of C. scolymus in alloxan induced stress oxidant, hepatic-kidney dysfunction and histological changes in liver, kidney and pancreas of different experimental groups of rats. METHODS:We determinate the antioxidant activity by ABTS .+ and antioxidant total capacity (TAC) of all extracts of C. scolymus leaves, the inhibition of α-amylase activity in vitro was also investigated. Forty male Wistar rats were induced to diabetes with a single dose intraperitoneal injection (i.p.) of alloxan (150 mg/kg body weight (b.w.)). Diabetic rats were orally and daily administrated of ethanol extract from C. scolymus at two doses (200-400 mg/kg, b.w) or (12 mg/kg, b.w) with anti-diabetic reference drug, Acarbose for one month. Ethanol extract of C. scolymus effect was confirmed by biochemical analysis, antioxidant activity and histological study. RESULTS:The results indicated that the ethanol extract from leaves of C. scolymus showed the highest antioxidant activity by ABTS .+ (499.43g± 39.72 Trolox/g dry extract) and (128.75 ± 8.45 mg VC /g dry extract) for TAC and endowed the powerful inhibition in vitro of α-amylase activity with IC50=72,22 ug/uL. In vivo, the results showed that ethanol extract from the leaves of C. scolymus (200-400 mg/kg) decreased significantly (p < 0.001) the α-amylase levels in serum of diabetic rats, respectively associated with significant reduction (p < 0.001) in blood glucose rate of 42,84% and 37,91% compared to diabetic groups after 28 days of treatment, a significant lowered of plasma total cholesterol (T-Ch) by 18,11% and triglyceride (TG) by 60,47%, significantly and low-density lipoproteins (LDL-C) by 37,77%, compared to diabetic rats, moreover, the administration of ethanol extract appears to exert anti-oxidative activity demonstrated by the increase of CAT, SOD and GSH activities in liver, kidney and pancreas of diabetic rats. This positive effect of the ethanol extract from C. scolymus was confirmed by histological study. CONCLUSION:These observed strongly suggest that ethanol extract from the leaves of C. scolymus has anti-hyperglycemic properties, at least partly mediated by antioxidant and hypolipidemic effects.

背景与目标： 背景：糖尿病（DM）与高血糖，炎性疾病和异常脂质状况相关，目前已发现粘虫c叶片的提取物可治疗代谢紊乱，许多科学家已经根据多酚化合物的良好来源进行了陈述。本研究旨在评价鳞球菌乙醇叶提取物对四氧嘧啶诱导的应激氧化剂，肝肾功能障碍以及不同实验组大鼠肝，肾和胰腺组织学变化的保护作用。
方法：我们通过ABTS测定抗氧化活性。鼠尾草叶片的所有提取物的抗氧化剂和总抗氧化剂（TAC），还研究了其对α-淀粉酶活性的体外抑制作用。通过单剂量腹膜内注射（i.p.）四氧嘧啶（150 mg / kg体重（b.w.））将40只雄性Wistar大鼠诱发为糖尿病。糖尿病大鼠口服和每天服用两种剂量（200-400 mg / kg，b.w）或（12 mg / kg，b.w）的鼠尾草乙醇提取物和抗糖尿病参考药物阿卡波糖（acarbose）。通过生化分析，抗氧化活性和组织学研究证实了粘液梭状芽胞杆菌的乙醇提取物作用。
结果：结果表明，ABTS从粘枝sco叶片中提取的乙醇具有最高的抗氧化活性。 （499.43g±39.72 Trolox / g干提取物）和（128.75±8.45 mg VC / g干提取物）用于TAC，并在体外有效抑制α-淀粉酶活性，IC50 = 72.22 ug / uL。在体内，结果显示，从粘液梭菌的叶子中提取乙醇（200-400 mg / kg）显着降低（p <0.001）糖尿病大鼠血清中的α-淀粉酶水平，分别与显着降低有关（p <0.001）。在治疗28天后，与糖尿病组相比，血糖比率分别为0.001、42.84％和37.91％，血浆总胆固醇（T-Ch）显着降低了18.11％，甘油三酸酯（TG）显着降低了60与糖尿病大鼠相比，低密度脂蛋白（LDL-C）降低了47.7％，低密度脂蛋白（LDL-C）降低了37.77％，此外，乙醇提取物的给药似乎表现出抗氧化活性，这是由于CAT，SOD和GSH的增加所证明的在糖尿病大鼠肝，肾和胰腺中的活性。组织学研究证实了粘液梭菌乙醇提取物的这种积极作用。
结论：这些观察结果强烈表明，从粘液梭菌的叶子中提取乙醇具有抗降血糖作用，至少部分是由抗氧化剂和降血脂作用介导的。

BACKGROUND & AIMS: :Objective To evaluate the etiologies for dense vitreous hemorrhage in adults with non-traumatic and reveal management of early vitrectomy for the disease. Methods Study included 105 eyes from 105 patients. Outcome measures were etiologies of vitreous hemorrhage, formation of retinal and/or disk neovascular membrane (NVM), incidence of retinal tear and detachment, visual acuity (VA) and postoperative complications. Results Mean time between presentation and surgery was 7.1 days. The most common etiologies were retinal vein occlusion (RVO) (58.1%), retinal tear (22.9%) and retinal vasculitis (10.4%). Most RVO (77.0%) and retinal vasculitis (72.7%) eyes were associated with retinal and/or disk NVM. Retinal tear and retinal detachment was found in 24 and 48 eyes, respectively. VA improved significantly from 1/70 to 0.6 following vitrectomy. The most common postoperative complication was cataract (28.6%). Conclusion RVO, retinal tear and retinal vasculitis were the most common causes of dense vitreous hemorrhage. Early vitrectomy has a good outcome with acceptable complication rates in this setting.

背景与目标： ：目的评估非创伤成人玻璃体大出血的病因，并揭示该疾病的早期玻璃体切除术的治疗方法。方法研究包括来自105名患者的105只眼睛。结果的措施是玻璃体出血，视网膜和/或盘状新血管膜（NVM）形成，视网膜撕裂和脱离的发生率，视力（VA）和术后并发症的病因。结果从就诊到手术的平均时间为7.1天。最常见的病因是视网膜静脉阻塞（RVO）（58.1％），视网膜撕裂（22.9％）和视网膜血管炎（10.4％）。大多数RVO（77.0％）和视网膜血管炎（72.7％）眼睛与视网膜和/或椎间盘NVM相关。分别在24和48只眼中发现了视网膜撕裂和视网膜脱离。玻璃体切除术后VA从1/70显着提高至0.6。最常见的术后并发症是白内障（28.6％）。结论RVO，视网膜撕裂和视网膜血管炎是玻璃体致密性出血的最常见原因。在这种情况下，早期玻璃体切除术的结果良好，并发症发生率可以接受。

BACKGROUND & AIMS: PURPOSE:The present study was aimed to evaluate the retinoprotective effects of Moringa oleifera (MO) in Streptozotocin-induced diabetic rats. METHODS:The study was continued for 24 weeks and evaluated for inflammatory (tumor necrosis factor [TNF]-α and interleukin [IL]-1β, angiogenic (vascular endothelial growth factor [VEGF] and protein kinase C [PKC]-β) and antioxidant (Glutathione, Superoxide dismutase, and Catalase) parameters. Retinal leakage was checked by Fluorescein angiography (FA) and fundus photographs were evaluated for retinal vessel caliber (arteriolar and venular). Transmission electron microscopy was done to determine basement membrane (BM) thickness. RESULTS:The results of the present study showed potential hypoglycemic and retinal antioxidant effects of MO. In the present study, a significant rise in the expression of retinal inflammatory (TNF-α and IL-1β) and angiogenic (VEGF and PKC-β) parameters was observed in diabetic retinae as compared to normal retinae. However, MO-treated retinae showed marked inhibition in the expression of inflammatory and angiogenic parameters. Further, in the present study, diabetic retinae showed dilated retinal vessels as compared to normal. However, MO-treated retinae showed marked prevention in the dilatation of retinal vessels. Fluorescein angiograms obtained from diabetic retinae showed leaky and diffused retinal vasculature. On the other hand, MO-treated retinae showed intact retinal vasculature. Further, results of the transmission electron microscopy study showed thickened capillary BM in the diabetic retina as compared to normal retinae. However, treatment with MO prevented thickening of capillary BM. CONCLUSION:Our result suggests that MO may be useful in preventing diabetes induced retinal dysfunction.

背景与目标： 目的：本研究旨在评估辣木（MO）对链脲佐菌素诱导的糖尿病大鼠的视网膜保护作用。
方法：研究持续了24周，并评估了炎症（肿瘤坏死因子[TNF]-α和白细胞介素[IL]-1β]，血管生成（血管内皮生长因子[VEGF]和蛋白激酶C [PKC]-β）和抗氧化剂（谷胱甘肽，超氧化物歧化酶和过氧化氢酶）参数，通过荧光素血管造影（FA）检查视网膜渗漏并评估眼底照片的视网膜血管口径（小动脉和小静脉），用透射电子显微镜确定基底膜（BM）的厚度。
结果：本研究结果显示了MO潜在的降血糖和视网膜抗氧化作用。在本研究中，与正常视网膜相比，在糖尿病视网膜中观察到了视网膜炎症表达（TNF-α和IL-1β）和血管生成（VEGF和PKC-β）参数的显着增加。然而，MO处理的视网膜在炎症和血管生成参数的表达中显示出明显的抑制作用。此外，在本研究中，与正常人相比，糖尿病视网膜显示出视网膜血管扩张。但是，MO处理的视网膜在视网膜血管扩张中显示出明显的预防作用。从糖尿病视网膜获得的荧光素血管造影照片显示渗漏和弥散性视网膜血管系统。另一方面，MO治疗的视网膜显示完整的视网膜脉管系统。此外，透射电子显微镜研究的结果表明与正常视网膜相比，糖尿病视网膜中的毛细血管BM增厚。但是，用MO处理可防止毛细血管BM增厚。
结论：我们的结果表明，MO可能有助于预防糖尿病引起的视网膜功能障碍。