单纯膝关节镜手术与联合术后放疗治疗弥漫性色素沉着绒毛结节性滑膜炎的临床研究

目的 探讨单纯膝关节镜手术与联合术后放疗治疗膝关节弥漫性色素绒毛结节性滑膜炎(DPVNS)的临床疗效和安全性。方法 武汉市中心医院及北京军区总医院于2009年1月至2014年1月收治的30例膝关节DPVNS患者,平均病程为35.6个月(4~121个月)。按患者治疗意愿分为手术联合术后放射治疗(联合治疗)组16例,单纯手术组14例。联合治疗组行关节镜下滑膜切除联合术后局部放射治疗,总剂量40 Gy,每次2 Gy。所有患者治疗后平均随访时间38.7个月(12~72个月),比较两组术后复发率、KSS临床评分和功能评分。结果 联合治疗组优良率(14/16)明显高于单纯手术组(11/14)(χ²=9.87,P<0.05),且复发率(1/16)明显低于单纯手术组(3/14)(χ²=1.83,P<0.05),治疗后KSS临床评分和功能评分改善明显优于单纯手术组(χ²=15.00、15.78,P<0.05)。放疗的不良反应为白细胞下降、肢体浮肿、皮肤出现色素沉着,联合治疗组患者均能较好地耐受。结论 关节镜术后放疗治疗膝关节DPVNS是一种安全有效的治疗手段,值得临床推广应用。     

Single molecule high-resolution colocalization of Cy3 and Cy5 attached to macromolecules measures intramolecular distances through time

Here we present a technique called single-molecule high-resolution colocalization (SHREC) of fluorescent dyes that allows the measurement of interfluorophore distances in macromolecules and macromolecular complexes with better than 10-nm resolution. By using two chromatically differing fluorescent molecules as probes, we are able to circumvent the Rayleigh criterion and measure distances much smaller than 250 nm. The probes are imaged separately and localized individually with high precision. The registration between the two imaging channels is measured by using fiduciary markers, and the centers of the two probes are mapped onto the same space. Multiple measurements can be made before the fluorophores photobleach, allowing intramolecular and intermolecular distances to be tracked through time. This technique's lower resolution limit lies at the upper resolution limit of single molecule FRET (smFRET) microscopy. The instrumentation and fluorophores used for SHREC can also be used for smFRET, allowing the two types of measurements to be made interchangeably, covering a wide range of interfluorophore distances. A dual-labeled duplex DNA molecule (30 bp) was used as a 10-nm molecular ruler to confirm the validity of the method. We also used SHREC to study the motion of myosin V. We directly observed myosin V's alternating heads while it walked hand-over-hand along an actin filament.     

磁共振成像对新生儿脑白质弥漫性高信号的诊断及预后评估

目的：探讨磁共振成像(magnetic resonance imaging,MRI)对新生儿脑白质弥漫性高信号(diffuse excessive high signal intensity,DEHSI)的诊断及预后评估的价值。材料与方法通过对比和随访不同类型DEHSI患儿常规MRI特征性表现、脑白质病灶演变过程及患儿神经心理发育结果,分析三者之间的内在联系。结果生后年龄、胎龄、头围与DEHSI评估之间呈显著负相关(r=－0.266、－0.303、－0.200,P均＜0.05)。DEHSI的严重程度与矫正年龄后5个月大的患儿的各项预后指标评分(ADQ、GMDQ、FMDQ、LDQ、PSDQ)呈负相关(r=－0.423、－0.499、－0.553、－0.317、－0.453,P均＜0.05)。结论宫外暴露时间可促进新生儿成熟;此外,胎龄越大,胎儿越成熟,DEHSI分级越低。MRI可区分不同分级的DEHSI及较好的评价预后,中重度DEHSI患儿预后较差,无或轻度DEHSI患儿预后较好。     

Assessment of Diffuse Thyroid Disease by Strain Ratio in Ultrasound Elastography

The goal of this study was to explore the value of strain ratio from real-time elastography in the semi-quantitative assessment of diffuse thyroid disease. Fifty-one patients with primary hyperthyroidism, 70 with Hashimoto's thyroiditis, 8 with subacute thyroiditis and 43 with normal healthy thyroids were recruited to measure the strain ratio (SR) of thyroid tissue and sternocleidomastoid muscle (on the same side of the thyroid). SR values of all groups were subjected to statistical analysis. The SRs (mean ± standard deviation) of patients with hyperthyroidism, Hashimoto's thyroiditis and subacute thyroiditis were 2.30 ± 1.08, 7.04 ± 7.74 and 24.09 ± 13.56, respectively. The SR of the control group was 1.76 ± 0.54. SR values ranked in ascending order were control group < hyperthyroidism group < Hashimoto's thyroiditis group < subacute thyroiditis group. There were statistically significant (p < 0.05) differences in thyroid hardness between groups with different diffuse thyroid diseases. SR values of the hyperthyroidism and control groups did not statistically differ (p > 0.05). It is feasible to assess diffuse thyroid disease with strain ratios obtained with ultrasound elastography.     

Role of Rab27 in synaptic transmission at the squid giant synapse

Small GTPase Rab is a member of a large family of Ras-related proteins, highly conserved in eukaryotic cells, and thought to regulate specific type(s) and/or specific step(s) in intracellular membrane trafficking. Given our interest in synaptic transmission, we addressed the possibility that Rab27 (a close isoform of Rab3) could be involved in cytosolic synaptic vesicle mobilization. Indeed, preterminal injection of a specific antibody against squid Rab27 (anti-sqRab27 antibody) combined with confocal microscopy demonstrated that Rab27 is present on squid synaptic vesicles. Electrophysiological study of injected synapses showed that the anti-sqRab27 antibody inhibited synaptic release in a stimulation-dependent manner without affecting presynaptic action potentials or inward Ca²⁺ current. This result was confirmed in in vitro synaptosomes by using total internal reflection fluorescence microscopy. Thus, synaptosomal Ca²⁺-stimulated release of FM1-43 dye was greatly impaired by intraterminal anti-sqRab27 antibody. Ultrastructural analysis of the injected giant preterminal further showed a reduced number of docked synaptic vesicles and an increase in nondocked vesicular profiles distant from the active zone. These results, taken together, indicate that Rab27 is primarily involved in the maturation of recycled vesicles and/or their transport to the presynaptic active zone in the squid giant synapse.     

Calcium signaling is implicated in the diffuse axonal injury of brain stem

Evaluating diffuse axonal injury (DAI) remains challenging in clinical sciences since the physiopathologic mechanism of DAI is still unclear. The calcium overload in the axoplasm is considered to be crucial for secondary axonal injury. The present study use calcium channel blocker, nimodipine, to explore the influence of Ca²⁺ in the pathogenesis of rat DAI. In the DAI group, the expressions of β-APP and NF-L in axons were increased from 12 to 72 h. The ultrastructural observation indicated the axon and vessel injury appeared at 12 h post-injury and severely aggravated from 24 to 72 h. The expression of vWF and brain water content was increased at 12 h after injury and further increased at 24 h. Nimodipine decreased the expression of β-APP, NF-L and vWF, and also attenuated the ultrastructural damage of vascular wall and axons. Furthermore, Ca-dependent enzyme, the calcineurin activity were increased in DAI and nimodipine suppressed the activity of calcineurins (CaN). However, the amount of CaN expression was not changed. Our results showed that disturbances of axonal calcium homeostasis play an important role in the secondary damage of the axon, neuron and capillary vessel which may be related with activating CaN during the acute phase of DAI. Nimodipine can alleviate the secondary damage by suppressing the calcineurin activity.     

Clinical outcomes of people living with human immunodeficiency virus (HIV) with diffuse large B-cell lymphoma (DLBCL) in Shanghai,China

Background:Numerous studies have focused on lymphoma among patients infected with human immunodeficiency virus (HIV). However, little is known about the treatment options and survival rate of lymphoma in the Chinese people living with HIV (PLHIV). Our study aimed to investigate the prognosis and compare outcome of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) with standard cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab(R-CHOP) as front line therapy for PLHIV with diffuse large B-cell lymphoma (DLBCL) receiving modern combined antiretroviral therapy (cART).Methods:A retrospective analysis evaluating PLHIV with DLBCL was performed in Shanghai Public Health Clinical Center from July 2012 to September 2019. The demographic and clinical data were collected, and overall survival (OS) and progression-free survival (PFS) analyses of patients receiving R-CHOP or DA-EPOCH-R therapy were performed by Kaplan-Meier analysis. Additionally, a Cox multiple regression model was constructed to identify related factors for OS.Results:A total of 54 eligible patients were included in the final analysis with a median follow-up of 14 months (interquartile range [IQR]: 8–29 months). The proportion of high international prognostic index (IPI) patients was much larger in the DA-EPOCH-R group (n = 29) than that in the R-CHOP group (n = 25). The CD4 cell counts and HIV RNA levels were not significantly different between the two groups. The 2-year OS for all patients was 73%. However, OS was not significantly different between the two groups, with a 2-year OS rate of 78% for the DA-EPOCH-R group and 66% for the R-CHOP group. Only an IPI greater than 3 was associated with a decrease in OS, with a hazard ratio of 5.0. The occurrence of grade 3 and 4 adverse events of chemotherapy was not significantly different between the two groups.Conclusions:Outcomes of R-CHOP therapy do not differ from those of DA-EPOCH-R therapy. No HIV-related factors were found to be associated with the OS of PLHIV in the modern cART era.     

Plasma Exchange Therapy to Reduce Mortality in Japanese Patients With Diffuse Alveolar Hemorrhage and Microscopic Polyangiitis

Diffuse alveolar hemorrhage (DAH) is well known as a serious complication of microscopic polyangiitis (MPA). We examined the effectiveness of plasma exchange (PLEX) therapy to reduce mortality in Japanese DAH patients with MPA. This retrospective, double‐center, observational cohort study included 20 DAH patients with MPA who were admitted to Juntendo University Hospital or Juntendo Koto Geriatric Medical Center between April 1998 and March 2018. The primary outcome was non–disease‐specific mortality. The 1‐year survival rate of patients with PLEX therapy (N = 4) was higher than that of patients with conventional therapy (N = 16, 75% and 13%, respectively, P = 0.037). Higher values of the 1996 Five‐Factor Score (FFS) and 2009 FFS were associated with increased mortality, with hazard ratios of 2.29 (P = 0.040) and 2.41 (P = 0.043), respectively, by Cox univariate analysis. We investigated PLEX therapy for reducing mortality in DAH patients with MPA, and the 1996 FFS and 2009 FFS were both independent prognostic factors.     

De-escalating therapy in gastric aggressive lymphoma

The treatment of primary gastric diffuse large B-cell lymphoma (DLBCL) has changed radically over the last 10–15 years, with the abandonment of routine gastrectomy in favor of more conservative therapies. Low-level evidence suggests that consolidation radiotherapy could be avoided in patients with limited-stage DLBCL of the stomach who achieve complete remission after rituximab-CHOP combination. Small, recent prospective trials suggest that selected patients with limited-stage Helicobacter pylori (H. pylori)-positive DLBCL of the stomach and favorable prognostic factors can be managed with antibiotics alone, with excellent disease control and cure rates, keeping chemo-radiotherapy for unresponsive patients. This recommendation should equally regard patients with mucosa-associated lymphoid tissue-related or de novo DLBCL. Future studies should be focused on the establishment of reliable variables able to distinguish the best candidates for exclusive treatment with H. pylori eradication from those who need for conventional chemo-immunotherapy.