补肾化瘀解毒方药对肺癌耐药细胞的耐药逆转及机制研究

目的 :探讨补肾化瘀解毒方对肺癌耐药细胞的耐药逆转和逆转机制。方法 :选择人肺腺癌 A5 4 9、A5 4 9/DDP细胞株 ,采用细胞毒试验 (MTT)和流式细胞仪法 (FCM) ,分别观察补肾化瘀解毒方荷瘤动物血清对A5 4 9/DDP细胞的细胞毒和耐药逆转作用 ,以及对 A 5 4 9/DDP细胞肺耐药蛋白 L RP- 5 6的表达、耐药细胞内游离Ca2 +浓度等指标的影响。结果 :补肾化瘀解毒方含药血清对肺癌 A5 4 9/DDP耐药细胞有细胞毒作用和增强A5 4 9/DD对顺铂 (DDP)的敏感性 ,并能显著抑制肺耐药蛋白 L RP的表达 (P<0 .0 1) ,降低细胞内 Ca2 +浓度(P<0 .0 0 1)。结论 :补肾化瘀解毒方药物血清对化疗药物具有增敏和化疗耐药逆转作用 ,其机制与抑制肺癌耐药细胞耐药基因表达 ,阻止肺癌耐药细胞内 ca2 +的内流或释放有密切的关系     

Hypertension and diabetes synergistically strengthen the association with cataracts among Chinese

AIM: To examine the relationship between age-related cataracts (ARC) and comorbid hypertension and diabetes. METHODS: We analyzed the administrative records of 6,467 patients aged 50 years and older admitted to the ophthalmological department of a tertiary hospital from January 1st, 2011 to May 20th, 2017. With either eye considered, an ARC (n=3,343) was defined as the presence of lens opacity or previous cataract surgery without evidence of trauma, congenital anomalies or using certain medications. Patients admitted to the same department during the same period due to ocular traumas without clinical evidence of cataracts (n=379) were recruited as the cataract-free controls. Unconditional logistic regressions were obtained the odds ratio (OR) of hypertension and diabetes among ARC patients adjusted for age, sex and health care accessibility. RESULTS: Hypertension was diagnosed in 29.54% of men with any type of cataracts, in 30.12% of men with an ARC, and 10.82% of men of cataract-free controls. Diabetes was diagnosed in 16.64% of men with any type of cataracts, in 16.48% of men with ARC and 4.22% of men of cataract-free controls. Similar patterns were observed among women. After adjusting for age, sex, and health care accessibility, hypertension was weakly [OR=1.83 (95%CI: 1.23, 2.74)] and diabetes was strongly [3.38 (1.86, 6.15)] associated with ARCs. The adjusted OR of comorbid hypertension and diabetes among adults with ARC was 18.20 (4.38, 75.59). CONCLUSION: Hypertension and diabetes were independently associated with ARC. Hypertension and diabetes, if co-existing, multiplicatively strengthened the association with ARC.     

Heparanase expression increases throughout the endometrial hyperplasia-cancer sequence.

OBJECTIVE: To assess the expression of heparanase in the different stages leading to endometrial cancer. METHODS: The 38 examined specimens included adenocarcinoma, hyperplasia, and normal endometrium specimens. Heparanase, estrogen, and progesterone receptor expressions were analyzed immunohistochemically and the intensity was scored. RESULTS: Secretory normal endometrium and simple hyperplasia specimens expressed the lowest mean values of expression (1.00 and 0.63, respectively); the complex hyperplasia specimens and G2 endometrioid adenocarcinoma showed the highest values of expression (2.33 and 2.71, respectively). A linear trend (P=0.005) of heparanase expression was observed when comparing the normal endometrium and simple hyperplasia group with the complex hyperplasia+G1 carcinoma group and the G2+G3 carcinoma group. Evaluation of atrophic and inactive endometrium compared with papillary serous carcinomas yielded no significant differences. We found no significant correlation between heparanase expression and estrogen receptor or progesterone receptor expression. CONCLUSION: Heparanase expression was tightly regulated in endometrial tumorigenesis.     

Elucidating the mechanism of nucleation inhibition of pathology crystallization of gout based on the evidence from amorphous form and in solution

The first gout attack in a hyperuricaemic patient may be regarded as a nucleation event which is caused by monosodium urate monohydrate (MSUM) deposition in the synovial fluid. The effect of Tailor-Made Inhibition (TMI) may be effective as drugs for the prevention of aberrant nucleation and crystallization. Therefore, the understanding of the underlying mechanisms in inhibiting the MSUM nucleation by TMI has proven to be of great significance. Yet most of the published studies about nucleation inhibition have tended to focus on simpler molecular models with a hydrogen-bonded acceptor and donor, which may be not suitable for the uric acid molecule with multiple hydrogen-bonded acceptors and donors under physiological conditions. Herein, the mechanisms of nucleation inhibition of MSUM were explored in a simulated biological environment (0.15 M Na⁺ and pH 7.40) in the presence and absence of TMI. And the evidence of nucleation inhibition by TMI in solution and the amorphous form of MSUM was investigated by HNMR, IR, Raman, PXRD, Dynamic light scattering (DLS), induction time measurements, and density functional theory (DFT) calculations. Results showed that the inhibition comes from a combination of kinetic and thermodynamic effects, with an impact of kinetics as the TMI inhibition effects far exceeded what could be accounted for by changes in usual factors of classical nucleation theory. The data demonstrated that the complex between urate and TMI disturbed the formation of two-dimensional sheets of sodion and purine rings parallel to the (011) plane and further impeded the formation of a three-dimensional structure with aromatic stacking interactions in solution. To our knowledge, the nucleation inhibition of TMI is achieved by suppressing interplanar stacking, which is a mechanism proposed for the first time.

Xanthine, a tailor-made inhibitor, could suppress nucleation in the crystallization of gout pathology by blocking the dominant interplanar accumulation in a solution.     

基于化学指纹图谱-生物热活性图谱关联检测的注射用双黄连冻干粉针质量控制方法的初步研究

为了建立包括生物热活性检测在内的中药注射剂质量控制方法, 本文以注射用双黄连冻干粉针为模式药, 建立HPLC-ELSD特征图谱, 进行相似度评价; 采用微量量热法, 建立生物热活性图谱, 并提取相关生物热动力学参数 (达峰时间  T²_m ,  T_j和抑制率I%), 以相关系数法进行相似度评价。结果表明, HPLC-ELSD特征图谱不易区分不同贮藏条件下样品之间的微小差异, 特别是对生物污染样品基本无法辨识; 生物热活性图谱可以区别高温处理样品及污染变质样品, 并可以全面反映模型生物的热生物学信息, 提供了专属性较强的二维信息, 可作为化学特征图谱的有益补充。本文从质量均一性出发, 通过HPLC-ELSD特征图谱和生物热活性图谱关联检测对注射用双黄连冻干粉针进行质量控制, 为实现对中药注射剂质量变化的早期快速筛查, 预警其不良反应提供了技术参考。     

肩痛颗粒治疗肩周炎的临床观察

目的:初步观察和评价肩痛颗粒治疗肩痹(肩周炎)属风寒湿痹证者的疗效和安全性。方法:采用随机双盲、双模拟、平行阳性药对照的临床试验方法,将72例肩周炎(风寒湿痹证)患者,随机分为试验组(肩痛颗粒组)和对照组(祛痹肩安丸组),两组每次服用颗粒剂和丸剂各1袋,一日3次,疗程为4周。按照症状、体征分级量化标准,对治疗前及用药后每周进行疗效评价;并对患者进行用药前后的三大常规、心、肝、肾功能等安全性检查,观察以上安全性指标的变化。结果:疗效性结果:肩痛颗粒组的愈显率为29.63%,总有效率为92.59%;而祛痹肩安丸组分别为16.67%和83.33%。两组差别无统计学。每周证候总积分:试验组患者用药后21、28d中医证候总积分下降值和下降率均高于对照组,但差别无统计学意义。安全性结果:治疗前后患者的指标差异值无临床意义,未观察到药物引起的不良反应和不良事件。结论:肩痛颗粒在目前的口服剂量疗程范围内,治疗证属风寒湿痹的肩周炎疗效确切,安全,无毒副作用,是一种治疗肩周炎安全、有效的中药新药。     

姬松茸多糖与OVA共同免疫改善E.G7-OVA荷瘤小鼠免疫功能的研究

目的通过小鼠体内免疫的方法,观察姬松茸多糖与模型肿瘤抗原卵清白蛋白(OVA)共同免疫对E.G7-OVA荷瘤小鼠免疫功能的影响。方法姬松茸多糖(高、中、低剂量)与OVA共同免疫E.G7-OVA荷瘤小鼠,观察其对EG7荷瘤小鼠脾指数、胸腺指数以及小鼠外周血中T淋巴细胞亚群CD4+和CD8+比例的影响。结果姬松茸多糖(高、中剂量)与OVA共同免疫组小鼠的脾指数、胸腺指数明显大于单独使用OVA组,外周血中CD4+/CD8+T细胞比值也有明显升高。结论姬松茸多糖能够辅助OVA改善EG7-OVA荷瘤小鼠的免疫功能状态,姬松茸多糖可能作为免疫佐剂用于肿瘤的预防与治疗。     

杨积武教授益气活血方治疗冠心病不稳定心绞痛气虚血瘀型临床观察

目的：探讨杨积武教授在治疗气虚血瘀型冠心病的经验方，验证其临床疗效。方法：按诊断标准选取42例患者并分为2组。2组患者除每天静点硝酸酯类药物外，治疗组每天服用益气活血方汤荆；对照组每天服用脂必妥片。观察期间禁止使用除硝酸甘油外其他治疗冠心病心绞痛的中西药物，共18天。结果：治疗组的心绞痛症状和硝酸甘油停减率总有效率均明显高于对照组。心电图疗效指标中，两组的总有效率无统计学意义。各例患者治疗后检查肝肾功能，均无明显变化。结论：本经验方与脂必妥之间除心电图疗效无明显差异外，其它指标均优于对照药。临床中可以随时根据患者的各种兼症加减应用，灵活多变，对肝功肾功也无明显的损害。     

The challenges of androgen insensitivity syndrome

Androgen insensitivity syndrome (AIS) is an X-linked recessive genetic syndrome that occurs as result of an androgen receptor mutation; it affects the normal masculinization process in chromosomal male patients. More than 900 androgen receptor mutations that can lead to AIS have been identified. The complete androgen insensitivity is characterized by a total lack of response to androgens, usually in patients with 46XY karyotype but with feminine phenotype. Primary amenorrhoea and inguinal swellings in female patients are the main signs that could raise suspicion for this syndrome. Patients with partial androgen insensitivity have ambiguous genitalia at birth and gynecomastia during puberty, whereas those with mild androgen insensitivity present a normal male phenotype but altered spermatogenesis during adulthood and pubertal gynecomastia. The diagnosis of AIS often proves to be a challenge; its management is complex and requires a multidisciplinary approach to meet decision-making challenges in sex assignment, fertility and timing of gonadectomy, psychological outcomes and genetic counselling.