桡骨短缩去旋转截骨皮下带蒂脂肪瓣填充治疗先天性尺桡骨融合

目的探讨桡骨短缩去旋转截骨钢板内固定局部皮下带蒂脂肪瓣填充分离融合区治疗先天性尺桡骨融合的疗效。方法回顾分析 2014 年 2 月—2018 年 6 月收治的 36 例（41 侧）先天性尺桡骨融合患儿，男 21 例，女 15 例；年龄 2.5～4.5 岁，平均 3.1 岁。前臂固定旋前位畸形 30°～90°，平均 71.6°；肘关节屈曲活动度 120°～135°，平均 128.2°。根据 Cleary-Omer 分型：Ⅱ型 8 侧，Ⅲ型 17 侧，Ⅳ型 16 侧。均采用桡骨近端短缩去旋转截骨钢板内固定局部皮下带蒂脂肪瓣填充分离融合区治疗。手术前后采用 Broberg 和 Morrey 肘关节评分标准对肘关节活动范围、肌力、关节稳定性、疼痛情况进行评分；采用 Failla 分级标准对患肢的日常生活能力进行评定。结果术后 3 例出现桡神经麻痹，2～4 周神经功能恢复。36 例患儿均获随访，随访时间 6～52 个月，平均 38 个月。截骨处均愈合，愈合时间 5～12 周，平均 6.3 周；取内固定物时可见带蒂脂肪瓣存活良好，位于尺桡骨之间。末次随访时，患肢肘关节屈曲活动度较术前未减少，前臂旋前和旋后活动度较术前改善。其中肘关节屈曲活动度为 125°～135°，平均 132.4°。前臂旋前活动度为 15°～45°，平均 30.1°；旋后活动度为 10°～40°，平均 22.6°。末次随访时 Broberg 和 Morrey 肘关节评分由术前（85.6±1.0）分提高至（91.8±1.8）分，差异有统计学意义（t=25.593，P=0.000）。根据 Failla 分级评定标准，术前良 3 侧、中 9 侧、差 29 侧，优良率 7.3%；末次随访时优 6 侧、良 28 侧、中 7 侧，优良率 82.9%；末次随访时较术前显著改善，差异有统计学意义（Z=−5.781，P=0.000）。 结论应用桡骨短缩去旋转截骨钢板内固定局部皮下带蒂脂肪瓣填充分离融合区，可以恢复前臂部分旋转功能，提高患儿生活质量，是治疗先天性尺桡骨融合的一种有效手术方法。     

Formosanin C promotes the curative efficacy of ultrasound-guided radiofrequency ablation in a mouse model of breast cancer

Breast cancer is the leading cause of tumor-associated death among women worldwide, and new therapeutic strategies are required to improve the post-surgery prognosis and quality of life of patients. Radiofrequency ablation (RFA) is a less invasive approach compared with traditional surgical resection to treat malignancies, and the combination of RFA and chemotherapeutic agents, including formosanin C (FC), can synergistically improve the curative effects against breast carcinoma. However, the detailed mechanisms remain unclear. In the present study, nude mice were used to identify the influence of FC on the therapeutic efficacy of RFA for breast cancer. Flow cytometry was performed to demonstrate the proportional alteration of CD8⁺ and CD45⁺ T cells with different biomarkers, including CD107a, IFNγ and TNFα. It was demonstrated that FC enhanced the therapeutic efficacy of RFA in breast cancer, while RFA combined with FC improved the proportion of IFNγ⁺ and TNFα⁺ CD8⁺ T cells and CD107a⁺ CD8⁺ T cells in tumor-infiltrating lymphocytes, thus increasing the immune responses caused by surgery and chemotherapy. The present study indicated that FC may promote the curative efficacy of ultrasound-guided RFA against breast tumor by regulating adaptive immune responses.     

Markers of inflammation are cross-sectionally associated with microvascular complications and cardiovascular disease in type 1 diabetes—the EURODIAB Prospective Complications Study

Aims/hypothesis The pathogenesis of vascular complications in type 1 diabetes is poorly understood, but may involve chronic, low-grade inflammation. We investigated the association of markers of inflammation with vascular complications in type 1 diabetes.Methods A cross-sectional nested case-control study of the follow-up data of the EURODIAB Prospective Complications Study. This study included 543 individuals (278 men) with type 1 diabetes diagnosed at <36 years of age. Cases (n=348) had complications of diabetes, controls (n=195) had no complications.Results C-reactive protein, interleukin-6 and tumour necrosis factor- levels, which were combined in an inflammatory marker Z-score, were associated with albuminuria, retinopathy and cardiovascular disease. Calculated means (95% confidence intervals) of the marker Z-score were –0.15 (–0.22 to –0.07), 0.10 (–0.05 to 0.25), and 0.28 (0.15 to 0.41), p for trend <0.0001, in individuals with normo-, micro- and macroalbuminuria; –0.23 (–0.33 to –0.13), 0.14 (0.02 to 0.25) and 0.20 (0.07 to 0.32), p for trend <0.0001, in individuals with no, non-proliferative and proliferative retinopathy; and –0.28 (–0.39 to –0.18) and 0.06 (–0.08 to 0.20), p<0.001, in individuals without and with cardiovascular disease. Per 1 SD increase of the inflammatory marker Z-score, GFR decreased by –4.6 (–6.6 to –2.6) ml per min per 1.73 m² (p<0.001).Conclusions/interpretation We have shown that markers of inflammation are strongly and independently associated with microvascular complications and cardiovascular disease in type 1 diabetes. These data suggest that strategies to decrease inflammatory activity may help to prevent the development of vascular complications in type 1 diabetes.     

中国北方汉族人HLA-Ⅰ、Ⅱ类基因与HBV水平感染及预后相关性研究

目的探讨人类白细胞抗原Ⅰ、Ⅱ类基因与乙型肝炎病毒(HBV)感染及其预后的相关性。方法采用PCR-SSP方法分别对102名慢性持续性HBV感染者(实验1组)、76名急性HBV感染者(实验2组)及1383名中华骨髓库山东分库无血缘关系自愿骨髓捐献者(对照组)作HLA-Ⅰ、Ⅱ类基因分型检测,将结果作统计学处理。结果HLA-DR9、DR12在实验组(实验1组+2组)中的分布频率较对照组明显增高(P<0.01);HLA-DR8在实验1组的分布频率明显高于实验2组(P<0.01);HLA-DR13,DR15在实验1组中的频率明显低于实验2组(P<0.01,P<0.05)。结论HLA-DR9可能有助于HBV对宿主的感染;HLA-DR8,DR12可能有助于HBV对宿主的持续感染,对HBV感染的慢性化有促进作用;HLA-DR13,DR15可能有助于宿主对HBV的清除,对HBV感染的慢性化有抑制作用。     

Effects of experimental potassium depletion on renal function and urinary prostanoid excretion in normal women during moderate anti-diuresis

Summary. The hypothesis that potassium depletion (KD) might play a role in stimulating the renal synthesis of prostanoids, and that these materials can contribute to hypokalaemic renal dysfunction, has been tested. Healthy women were studied either in normal potassium balance (N, n= 14), or in experimental KD. KD was induced by low dietary potassium intake (10 mmol day^-1) and natriuretic treatment, associated with replacement of net NaCl and water loss. By using different depletive patterns, two groups with estimated cumulative potassium deficits of 160 ± 43 mmol (KD1, n= 8) and 198±22 mmol (KD2, n= 6), respectively, were obtained. Renal function by the clearance (cl.) method and urinary PGE₂, 6-keto-PGF_lä, TxB₂ concentrations by the RIA method were measured during hypotonic polyuria (oral water load) and subsequent moderate antidiuresis induced by the infusion of low-dose lysine-8-vasopressin (LVP). Compared to the N group, only in the KD2 group do glomerular and tubular dysfunctions typical of hypokalaemia and reduced prostanoid excretions (significant for 6-keto-PGF_lä and TxB₂ but not for PGE₂) appear during polyuria besides the significant reductions of plasma potassium concentration, urinary potassium excretion and the significant increase in plasma renin activity. During LVP infusion the urinary prostanoid excretions were all significantly lower in absence of significant differences in urinary flow rate. Concerning its renal effects, LVP lost its ability to reduce the creatinine cl., while expressing a trend towards reduction in fractional chloride excretion. Indomethacin pretreatment restored the LVP effect on creatinine cl. and increased the antichloruretic LVP effect (although not significantly). To the extent that urinary prostanoid excretions reflect their intrarenal synthesis, our data demonstrate that KD inhibits this biosynthesis. A depressed production of prostanoids endowed with vasodilating and chloruretic activity probably played a role in attenuating the renal vascular hyporeactivity and the urinary chloride dispersion induced by KD.     

A skin-selective homing mechanism for human immune surveillance T cells

Effective immune surveillance is essential for maintaining protection and homeostasis of peripheral tissues. However, mechanisms controlling memory T cell migration to peripheral tissues such as the skin are poorly understood. Here, we show that the majority of human T cells in healthy skin express the chemokine receptor CCR8 and respond to its selective ligand I-309/CCL1. These CCR8(+) T cells are absent in small intestine and colon tissue, and are extremely rare in peripheral blood, suggesting healthy skin as their physiological target site. Cutaneous CCR8(+) T cells are preactivated and secrete proinflammatory cytokines such as tumor necrosis factor-alpha and interferon-gamma, but lack markers of cytolytic T cells. Secretion of interleukin (IL)-4, IL-10, and transforming growth factor-beta was low to undetectable, arguing against a strict association of CCR8 expression with either T helper cell 2 or regulatory T cell subsets. Potential precursors of skin surveillance T cells in peripheral blood may correspond to the minor subset of CCR8(+)CD25(-) T cells. Importantly, CCL1 is constitutively expressed at strategic cutaneous locations, including dermal microvessels and epidermal antigen-presenting cells. For the first time, these findings define a chemokine system for homeostatic T cell traffic in normal human skin.     

FBXO4 loss facilitates carcinogen induced papilloma development in mice

Cyclin D1 is frequently overexpressed in esophageal squamous cell carcinoma (ESCC) and is considered a key driver of this disease. Mutations in FBXO4, F-box specificity factor that directs SCF-mediated ubiquitylation of cyclin D1, occur in ESCC with concurrent overexpression of cyclin D1 suggesting a potential tumor suppressor role for FBXO4. To evaluate the contribution of FBXO4-dependent regulation cyclin D1 in esophageal squamous cell homeostasis, we exposed FBXO4 knockout mice to N-nitrosomethylbenzylamine (NMBA), an esophageal carcinogen. Our results revealed that loss of FBXO4 function facilitates NMBA induced papillomas in FBXO4 het (+/−) and null (−/−) mice both by numbers and sizes 11 months after single dose NMBA treatment at 2mg/kg by gavage when compared to that in wt (+/+) mice (P < 0.01). No significant difference was noted between heterozygous or nullizygous mice consistent with previous work. To assess cyclin D1/CDK4 dependence, mice were treated with the CDK4/6 specific inhibitor, PD0332991, for 4 weeks. PD0332991 treatment (150mg/kg daily), reduced tumor size and tumor number. Collectively, our data support a role for FBXO4 as a suppressor of esophageal tumorigenesis.     

Gastric cancer-derived mesenchymal stem cells prompt gastric cancer progression through secretion of interleukin-8

Background

Bone marrow mesenchymal stem cells (BM-MSCs) have been identified to be closely associated with tumor growth and progression. However, the roles of tumor-resident MSCs in cancer have not been thoroughly clarified. This study was to investigate the regulating effect of gastric cancer-derived MSCs (GC-MSCs) on gastric cancer and elucidate the underlying mechanism.

Methods

GC-MSCs were isolated from primary human gastric cancer tissues and characterized. The effect of GC-MSCs on gastric cancer cell proliferation was analyzed by MTT assay and colony formation assay. Transwell migration assay was performed to evaluate the influence of GC-MSCs in gastric cancer cell migration. The regulating effects of interactions between gastric cancer cells and GC-MSCs on their pro-angiogenic abilities were analyzed in a co-culture system, with the expression, and secretion of pro-angiogenic factors detected by RT-PCR and Luminex assay. Tube formation assay was used to further validate the angiogenic capability of gastric cancer cells or GC-MSCs. Cytokine profiles in the supernatant of GC-MSCs were screened by Luminex assay and neutralizing antibody was used to identify the key effective cytokines. The activations of Akt and Erk1/2 in gastric caner cells were detected by Western blot.

Results

GC-MSC treatment enhanced the proliferation and migration of BGC-823 and MKN-28 cells, which was more potently than MSCs from adjacent non-cancerous tissues (GCN-MSCs) or bone marrow (BM-MSCs). Higher expression levels of pro-angiogenic factors were detected in GC-MSCs than GCN-MSCs or BM-MSCs. After 10 % GC-MSC-CM treatment, BGC-823, and MKN-28 cells expressed increased levels of pro-angiogenic factors and facilitated tube formation more potently than cancer cells alone. Furthermore, GC-MSCs produced an extremely higher level of interleukin-8 (IL-8) than GCN-MSCs or BM-MSCs. Blockade of IL-8 by neutralizing antibody significantly attenuated the tumor-promoting effect of GC-MSCs. In addition, 10 % CM of IL-8-secreted GC-MSCs induced the activations of Akt or Erk1/2 pathway in BGC-823 and MKN-28 cells.

Conclusion

Tumor-resident GC-MSCs promote gastric cancer growth and progression more efficiently than GCN-MSCs or BM-MSCs through a considerable secretion of IL-8, which could be a possible target for gastric cancer therapy.