Endoplasmic reticulum stress is involved in ventilator-induced lung injury in mice via the IRE1α-TRAF2-NF-κB pathway

Inflammation plays a critical role in the development of ventilator-induced lung injury (VILI). Endoplasmic reticulum (ER) stress is associated with a variety of diseases through the modulation of inflammatory responses. However, little is known about how ER stress is implicated in VILI. In this study, murine mechanical ventilation models were constructed. Total protein and inflammatory cytokines were measured in bronchoalveolar lavage fluid (BALF), and lung tissue injury was assessed by histology. Our data revealed that mice subjected to high tidal ventilation (TV) for 4 h showed more severe pulmonary edema and inflammation than those of mice with spontaneous breathing and low TV-treatment. In addition, the high TV-treated animals upregulated the ER stress markers GRP78, CHOP, p-IRE1α, TRAF2, and p-NF-κB expression at both the mRNA and protein levels in lung tissue. Administration of thapsigargin exacerbated the histological changes, inflammation and expression of GRP78 and CHOP after high TV, but treatment with ER stress and IRE1α kinase inhibitors attenuated the pathological damage and downregulated the high expression of GRP78, CHOP, p-IRE1α, TRAF2, and p-NF-κB, suggesting that ER stress is involved in VILI though the IRE1α/TRAF2/NF-κB signaling pathway in mice.     

Consensus on the use and monitoring of anti‐TNF‐α therapies for rheumatic diseases in Hong Kong 2005

The development and use of the tumour necrosis factor (TNF) antagonists is a major breakthrough in the treatment of many rheumatic diseases. Although these novel agents are undoubtedly superior to conventional therapeutic modalities, their costs and potential adverse effects are of concern. The current consensus statements were developed in early 2005 to help practicing rheumatologists identify which adult patients may benefit from anti‐TNF therapies and highlight their potential toxicities. The Hong Kong Society of Rheumatology has developed a registry on the use of the biologics in our local patients with chronic rheumatic disorders. Because the indications and novel data regarding the TNF inhibitors are ever changing, this consensus will be updated regularly.     

新化合物 A-失碳-17β-羟基-17α-乙炔基-Δ3(5),9(10)-雌甾二烯-2-酮的合成

报道新化合物A-失碳-17β-羟基-17α-乙炔基-Δ^3(5),9(10)-雌甾二烯-2-酮2的合成。文中探讨了用炔钾粗品对A-失碳-Δ^3(5),9(10)-雌甾二烯-2，17-二酮１和Ａ-失碳-６β，１９-环氧-Δ³-雄甾-2，17-二酮3的选择性炔化，分别得标题化合物2（44%）及Ａ-失碳-17β-羟基-17α-乙炔基-６β，１９-环氧-Δ³雄甾-2-酮４（６５％），４经还原性破开环氧、去羟甲基和去醋酰氧基合成了标题化合物２。四步总收率为３４％。     

体外短波热疗联合前列腺灸及哈乐治疗非细菌性前列腺炎和前列腺痛疗效观察

目的 探讨慢性非细菌性前列腺炎（CNP）和前列腺痛（PD）的治疗方法。方法 应用体外短波热疗联合前列腺灸及α1A-肾上腺素能受体阻滞剂哈乐治疗CNP和PD患者26例，疗程8周。观察治疗前后前列腺炎症状评分（CPSI）与最大尿流率（MFR）变化。结果 有效率为80．8％。治疗前后CPSI和MFR均有显著改善（P〈0．05）。结论 体外短波热疗联合前列腺灸及哈乐治疗CNP和PD安全有效。     

血清α—L-岩藻糖苷酶（AFU）对原发性肝癌（PHC）的诊断意义

目的研究血清α-L-岩藻糖苷酶（AFU）对原发性肝癌的诊断意义。方法分别测定20例正常对照者、45例慢性乙型肝炎、40例肝硬化、50例转移性肝癌及35例原发性肝癌患者的血清AFU。结果原发性肝癌组的血清AFU浓度和阳性率显著高手其他各组。结论血清AFU对原发性肝癌的诊断有重要价值。     

Circulating adipocytokines in non-diabetic and Type 1 diabetic children: relationship to insulin therapy, glycaemic control and pubertal development.

AIM: To determine the influence of Type 1 diabetes mellitus on circulating adipocytokines in children. METHODS: The circulating concentrations of leptin, adiponectin, resistin and tumour necrosis factor (TNF)-alpha were measured in 91 children, aged 11.1 +/- 2.7 years, with Type 1 diabetes mellitus (T1DM). Ninety-one healthy children were selected as control subjects. RESULTS: Body mass index-adjusted leptin concentrations were higher in the pubertal diabetic children compared with the control children. There was a significant positive correlation between leptin and daily insulin dose in the diabetic group. Circulating adiponectin concentrations were higher in the prepubertal diabetic children and were positively associated with HbA(1c). Resistin concentrations were lower in the prepubertal non-diabetic subjects compared with the pubertal non-diabetic children, whose values were higher than those of the diabetic children. TNF-alpha concentrations were similar in non-diabetic and diabetic children. CONCLUSIONS: Circulating concentrations of adipocytokines are abnormal in Type 1 diabetic children, although the direction of change differs by cytokine. Pubertal development, in addition to insulin treatment and glycaemic control, also influences the concentrations.     

Inadequate Erythropoietin Response to Anaemia in HIV Patients: Relationship to Serum Levels of Tumour Necrosis Factor-Alpha, Interleukin-6 and Their Soluble receptors

Severe anaemia is a frequent complication in advanced HIV infection. In our study we investigated the interaction between cytokine network, HIV infection and erythropoietin (Epo) response with increasing anaemia levels. No correlations could be established between circulating tumour necrosis factor (TNF)-alpha and any of the examined parameters. However, a negative correlation was found between haemoglobin values and soluble TNF receptor levels (sTNF-R-I: r  = −0.54; P  < 0.001; sTNF-R II: r  = −0.47; P  < 0.001) as well as interleukin-6 levels ( r  = −0.29; P  < 0.001). In contrast, no significant increase in log[Epo], counterbalancing haemoglobin decline and paralleling the rise in sTNF receptors, was found. In patients classified as stage III, according to the Centers for Disease Control (CDC) classification, the erythropoietin response was significantly more impaired than in patients from CDC groups I and II ( P  < 0.001). The results of this study suggest that similar to its action in vitro , activation of the TNF/TNF-R system may impair erythropoietin production in HIV-associated anaemia. Due to the brief half-life of TNF-α, this activation is particularly reflected by elevations of soluble TNF receptor levels.     

当归多糖及其中性组分对巨噬细胞分泌TNF-α的影响

目的 :观察当归多糖 (ASP)及其中性组分 (ASP 1)在体内外对小鼠腹腔巨噬细胞 (MФ)分泌TNF α的影响。方法 :直接制取小鼠腹腔MФ ,与ASP及ASP 1共同培养 16h ;ASP及ASP 112 5、2 5 0mg kg经口灌胃给药 7d ,于第 7d制取MФ ,体外培养 16h ,分别观察ASP及ASP 1在体外均可显著增强MФ对TNF α的分泌。ASP及ASP 1体内给药无直接诱导MФ分泌TNF α的功能。结论 :ASP及ASP 1在体内外均可增强小鼠腹腔MФ分泌TNF α的功能。