通气侧肺前列腺素E1雾化吸入对单肺通气患者氧合的影响

目的 探讨通气侧肺前列腺素E₁(PGE₁)雾化吸入预给药对食管癌患者FiO₂ 50%单肺通气(OLV)期间机体氧合的影响。方法 选择拟行左剖胸食管癌根治术的患者113例,男92例,女21例,年龄18～79岁,BMI<30 kg/m²,ASAⅡ或Ⅲ级。采用随机数字表法将患者分为四组：PGE₁ 0.1μg/kg组(P1组,n=29)、PGE₁ 0.2μg/kg组(P2组,n=29)、PGE₁ 0.3μg/kg组(P3组,n=30)和生理盐水对照组(C组,n=25)。麻醉平稳改右侧卧位后,P1组、P2组和P3组分别给予右侧肺PGE₁ 0.1、0.2和0.3μg/kg(以生理盐水稀释至10 ml)雾化吸入,C组给予右侧肺生理盐水10 ml雾化吸入,雾化吸入时间均为10 min。记录术前PaO₂、手术时间、OLV时间、术中出血量、尿量、输液量。分别于全麻后右侧卧位时(T₀)...     

Is GSN significant for hip BMD in female Caucasians?

Low bone mineral density (BMD) is a risk factor for osteoporosis. Osteoporosis is more prevalent in females than in males. So far, the pathophysiological mechanisms underlying osteoporosis are unclear. Peripheral blood monocytes (PBMs) are precursors of bone-resorbing osteoclasts. This study aims to identify PBM-expressed proteins (genes) influencing hip BMD in humans.We utilized three independent study cohorts (N = 34, 29, 40), including premenopausal Caucasians with discordant hip BMD. We studied PBM proteome-wide protein expression profiles in cohort 1 and identified 57 differentially expressed proteins (DEPs) between low vs. high BMD subjects. One protein gelsolin (GSN), after validation by Western blotting, was subject to follow-up. We compared GSN mRNA level in PBM between low vs. high BMD subjects in cohorts 2 and 3. We genotyped SNPs across GSN in 2286 unrelated Caucasians (cohort 4) and 1627 Chinese (cohort 5) and tested their association with hip BMD in females and males, respectively.We discovered and validated that GSN protein expression level in PBM was down-regulated 3.0-fold in low vs. high BMD subjects (P < 0.05). Down-regulation of GSN in PBM in low BMD subjects was also observed at mRNA level in both cohort 2 and cohort 3. We identified that SNP rs767770 was significantly associated with hip BMD in female Caucasians (P = 0.0003) only. Integrating analyses of the datasets at DNA, RNA, and protein levels from female Caucasians substantiated that GSN is highly significant for hip BMD (P = 0.0001).We conclude that GSN is a significant gene influencing hip BMD in female Caucasians.     

Grafts of Genetically Modified Schwann Cells to the Spinal Cord: Survival,Axon Growth,and Myelination

Schwann cells naturally support axonal regeneration after injury in the peripheral nervous system, and have also shown a significant, albeit limited, ability to support axonal growth and remyelination after grafting to the central nervous system (CNS). It is possible that Schwann cell-induced axonal growth in the CNS could be substantially increased by genetic manipulation to secrete augmented amounts of neurotrophic factors. To test this hypothesis, cultured primary adult rat Schwann cells were genetically modified using retroviral vectors to produce and secrete high levels of human nerve growth factor (NGF). These cells were then grafted to the midthoracic spinal cords of adult rats. Findings were compared to animals that received grafts of nontransduced Schwann cells. Spinal cord lesions were not placed prior to grafting because the primary aim of this study was to examine features of grafted Schwann cell survival, growth, and effects on host axons. In vitro prior to grafting, Schwann cells secreted 1.5 ± 0.1 ng human NGF/ml/10⁶ cells/day. Schwann cell transplants readily survived for 2 wk to 1 yr after in vivo placement. Some NGF-transduced grafts slowly increased in size over time compared to nontransduced grafts; the latter remained stable in size. NGF-transduced transplants were densely penetrated by primary sensory nociceptive axons originating from the dorsolateral fasciculus of the spinal cord, whereas control grafts showed significantly fewer penetrating sensory axons. Over time, Schwann cell grafts also became penetrated by TH- and DBH-labeled axons of putative coerulospinal origin, unlike control cell grafts. Ultrastructurally, axons in both graft types were extensively myelinated by Schwann cells. Grafted animals showed no changes in gross locomotor function. In vivo expression of the human NGF transgene was demonstrated for periods of at least 6 m. These findings demonstrate that primary adult Schwann cells 1) can be transduced to secrete augmented levels of neurotrophic factors, 2) survive grafting to the CNS for prolonged time periods, 3) elicit robust growth of host neurotrophin-responsive axons, 4) myelinate CNS axons, and 5) express the transgene for prolonged time periods in vivo. Some grafts slowly enlarge over time, a feature that may be attributable to the propensity of Schwann cells to immortalize after multiple passages. Transduced Schwann cells merit further study as tools for promoting CNS regeneration.     

A study from The Mayo Clinic evaluated long-term outcomes of kidney transplantation in patients with immunoglobulin light chain amyloidosis

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Differential Expression of the Transcription Factor GATA3 Specifies Lineage and Functions of Innate Lymphoid Cells

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Curcumin induces apoptosis involving bax/bcl-2 in human hepatoma SMMC-7721 cells

Curcumin is a major active component of Curcuma aromatica salisb, which has been shown to inhibit proliferation of a wide variety of tumor cells. In this study, the molecular mechanisms of curcumin inducing apoptosis in human hepatoma SMMC-7721 cells were examined. We find that curcumin inhibits the growth of SMMC-7721 cells significantly in a concentration-depenent manner, with typical apoptotic morphological changes of cellular nuclei. Annexin-V/PI double staining detected by flow cytometry and expression of the relative apoptotic proteins (Bax, Bcl-2 and caspase-3) revealed a strong apoptosis-inducing competent of curcumin in SMMC-7721 cells. Curcumin increased the expression of bax protein while decreasing that of bc1-2 protein significantly. The results suggest that curcumin induction of apoptosis involves modulation of bax/bcl-2 in SMMC-7721 cells and provide a molecular basis for the development of naturally compounds as novel anticancer agents for human hepatomas.     

JWA T723G多态性与胃癌易感性

目的探讨JWAT723G多态性与胃癌易感性之间的关系。方法采用多聚酶链反应(polymerase chain reaction,PCR)和变性高效液相色谱法(denaturing high performance liquid chromatography,DHPLC)检测107例胃癌患者和200例同龄健康人群的JWAT723G多态性并进行分析。结果病例组和对照组JWAT723G基因分布频度无显著差异(χ2=2.290,P=0.318)。在调整了性别和年龄后,与T/T基因型相比,T/G基因型发生胃癌的危险性上升到1.21(95%CI:0.94～1.57),G/G基因型发生胃癌的危险性上升到1.49(95%CI:0.45～4.96)。合并T/G和G/G基因型分析显示G等位基因发生胃癌的危险性上升到1.21(95%CI:0.95～1.55),JWAT723G多态性与胃癌的易感性无相关性(P=0.1316)。结论 JWAT723G多态性与胃癌易感性不相关。     

Phase II Trial of Weekly Nanoparticle Albumin-Bound Paclitaxel With Carboplatin and Trastuzumab as First-line Therapy for Women With HER2-Overexpressing Metastatic Breast Cancer

PurposeThis multicenter phase II trial evaluated the efficacy and safety of weekly nanoparticle albumin-bound paclitaxel with carboplatin and weekly trastuzumab as first-line therapy for women with HER2-overexpressing metastatic breast cancer (MBC).Patients and MethodsWe treated 32 patients who had measurable MBC that was HER2-positive defined by an immunohistochemical staining score of 3+ or gene amplification by fluorescence in situ hybridization, required for those with an IHC of 2+. Patients were treated with albumin-bound paclitaxel 100 mg/m² and carboplatin at area under the curve (AUC) = 2 on days 1, 8, and 15 of a 28-day cycle. Trastuzumab was administered at 2 mg/kg weekly after a loading dose of 4 mg/kg. Because of hypersensitivity reactions occurring during carboplatin infusion numbers 6–8 in 4 of the first 13 patients with this premedication-free regimen, the protocol was amended for carboplatin and dosed at AUC = 6 day 1 each 28-day cycle, in lieu of introducing steroid prophylaxis. Patients were treated with 6 cycles and allowed to continue with all 3 drugs or trastuzumab alone if free of progression and unacceptable toxicity after 6 cycles.ResultsThe overall response rate (ORR) was 62.5% (95% CI, 45.7%–79.3%) with 3 confirmed complete responders (CRs; 9%) and 17 confirmed partial responses (PRs; 53%). An additional 6 patients (19%) had stable disease (SD) for greater than 16 weeks for a clinical benefit rate (ORR + SD > 16 weeks) of 81%. As of April 16, 2009, 20 patients (63%) had progressed with a median progression-free survival (PFS) of 16.6 months (95% CI, 7.5-26.5 months). Antitumor activity was similar for patients treated with weekly carboplatin and every-4-week carboplatin (ORR, 65% vs. 67%, respectively). Hematologic toxicities were the only grade 4 toxicities noted and were infrequent with grade 4 neutropenia in 3 patients (9%) and 1 febrile neutropenia. Grade 2/3 peripheral neuropathy was uncommon (13%/3%).ConclusionWeekly albumin-bound paclitaxel with carboplatin and trastuzumab is highly active in HER2-overexpressing MBC. In the absence of corticosteroid premedication, which we avoided with albumin-bound paclitaxel, carboplatin seems best dosed every 4 weeks rather than weekly because of carboplatin-associated hypersensitivity reactions. The regimen was very well tolerated with few grade 3 and 4 nonhematologic toxicities experienced, and severe hematologic toxicity and peripheral neuropathy were infrequent.     

Thalidomide Combined with Chemotherapy in Treating Patients with Advanced lung Cancer

Objectives: To evaluate efficacy and toxicity in patients with advanced lung cancer, including non-small cell and small cell variants (NSCLC and SCLC), treated with thalidomide plus chemotherapy. Methods: Fourteen patients with advanced lung cancer were scheduled to receive chemotherapy combined with thalidomide. All patients in this study received thalidomide (100 mg orally per night before sleeping, produced by Changzhou Pharmaceutical Factory Co.Ltd) after the start of chemotherapy for at least 14 days. Chemotherapy was administered according to the condition of patients. After at least 14 days of treatment, efficacy and toxicity were evaluated. Results: There were 6 female and 8 male patients with advanced lung cancer recruited into this study, including 2 with SCLC and 12 with NSCLC. The median age was 56.7 (44-65) years. Progressive disease was observed in 12 patients (12/14), and stable disease in 2 (2/14). Grade 1 to 2 myelosuppression was observed in 4/14 patients, and Grade 1 to 2 elevation of hepatic enzymes was recorded in 5/14 patients. Adverse effects on the gastrointestinal tract were documented in 2/14 patients, all beingGrade 1. No Grade 3-4 toxicity was recorded. No treatment related deaths occurred. Conclusions: Our results demonstrate that thalidomide combined with chemotherapy is mildly effective and safe for treating patients with advanced lung cancer. However, further evaluation of this combination is warranted.