何首乌致药物性肝损伤的病理学特点

目的了解何首乌致药物性肝损伤(Polygonum multiflorum-associated drug induce liver injury,PM-DILI)的临床病理学特点。方法收集2019年3月1日至2021年3月1日深圳市第三人民医院收治的8例PM-DILI患者临床资料。肝穿组织进行苏木素-伊红染色、网状纤维染色、Masson三色染色、铁、铜特殊染色和免疫组织化学染色,显微镜下观察分析。结果8例PM-DILI患者男女比为1∶1,平均年龄43岁,其中6例为急性PM-DILI,2例慢性为PM-DILI。入院血清学检查异常主要包括转氨酶升高和淤胆均为7例。主要组织病理学改变为点灶状坏死8例、界面炎5例、融合坏死4例,融合坏死以肝腺泡3带为主,不伴或伴少数炎细胞浸润;胆汁淤积5例,为肝腺泡3带的肝细胞、毛细胆管内淤胆,不伴或伴少数炎细胞浸润;中央静脉炎3例;病程长者可发生肝纤维化,甚至肝硬化2例。结论肝腺泡3带为主的急性淤胆和肝细胞坏死是PM-DILI主要组织学表现,严重者可发生静脉炎等血管损伤。     

Confounded association between proton pump inhibitor use and risk of biliary tract cancer: Result from three cohorts

Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes.     

肥胖型PCOS患者的生物学特征和临床特征

多囊卵巢综合征（polycystic ovary syndrome,PCOS）是一种内分泌代谢紊乱综合征,临床表现高度异质性。肥胖是PCOS异质性临床表现之一,超过50%的PCOS患者超重或肥胖。肥胖型PCOS主要表现为高雄激素血症、中心型肥胖和糖脂代谢紊乱,非肥胖型PCOS主要表现为黄体生成激素（luteinizing hormone,LH）水平异常升高。尽管肥胖型和非肥胖型PCOS均存在内分泌代谢异常,然而肥胖可加重PCOS糖脂代谢紊乱;肥胖型PCOS还表现脂肪代谢的异常。综述肥胖型PCOS患者的临床特征、性激素水平、糖脂代谢特征,旨在为肥胖型和非肥胖型PCOS患者新的分型诊治提供参考。     

癫痫发作后状态及其临床意义

癫痫发作后状态(PIS)是指癫痫发作停止到恢复至发病前水平的异常状态,包括认知、运动、感觉、自主神经和精神行为等异常,症状多样,严重程度不一,持续数秒至数天不等,对患者的健康和生活质量产生很大影响。然而,目前国内外相关的研究较少,临床医生对此缺乏正确认识,容易误诊误治。本文将从PIS的定义、病理生理机制、临床表现、诊断和鉴别诊断、临床意义以及干预策略等进行综述,以提高临床医生的认识,并为今后临床研究提供参考。     

Recent advances with cyclin-dependent kinase inhibitors: therapeutic agents for breast cancer and their role in immuno-oncology

Introduction: Collaborative interactions between several diverse biological processes govern the onset and progression of breast cancer. These processes include alterations in cellular metabolism, anti-tumor immune responses, DNA damage repair, proliferation, anti-apoptotic signals, autophagy, epithelial-mesenchymal transition, components of the non-coding genome or onco-mIRs, cancer stem cells and cellular invasiveness. The last two decades have revealed that each of these processes are also directly regulated by a component of the cell cycle apparatus, cyclin D1.

Area covered: The current review is provided to update recent developments in the clinical application of cyclin/CDK inhibitors to breast cancer with a focus on the anti-tumor immune response.

Expert opinion: The cyclin D1 gene encodes the regulatory subunit of a proline-directed serine-threonine kinase that phosphorylates several substrates. CDKs possess phosphorylation site selectivity, with the phosphate-acceptor residue preceding a proline. Several important proteins are substrates including all three retinoblastoma proteins, NRF1, GCN5, and FOXM1. Over 280 cyclin D3/CDK6 substrates have b\een identified. Given the diversity of substrates for cyclin/CDKs, and the altered thresholds for substrate phosphorylation that occurs during the cell cycle, it is exciting that small molecular inhibitors targeting cyclin D/CDK activity have encouraging results in specific tumors.     

Subacute posttraumatic ascending myelopathy (SPAM): A potential complication of subarachnoid shunt for syringomyelia?

Context: Treatment of primary spinal syringomyelia is still controversial. Among others, shunting syrinx fluid to the subarachnoid, peritoneal or pleural space has been utilized with varying success. Shunt obstruction, migration, and infection represent the most common complications of these procedures.

Findings: The authors present the case of an 81-year-old woman who developed an unusual neurological deterioration resembling a subacute posttraumatic ascending myelopathy (SPAM) after the insertion of a syringosubarachnoid shunt for the treatment of slow-growing D10 syringomyelia.

Conclusion/Clinical Relevance: To date, no cases of SPAM secondary to the insertion of a syringosubarachnoid shunt for the treatment of syringomyelia have been reported. The potential pathogenesis related to this phenomenon is discussed.     

糖尿病黄斑水肿患者病变程度与脉络膜厚度的关系

目的　利用频域光学相干断层扫描深度增强（enhanced depth imaging spectral domain optical coherence tomography，EDI SD-OCT）观察糖尿病黄斑水肿（diabetic macular edema，DME）患者脉络膜厚度（choroidal thickness，CT）的变化及结构特点，探讨DME病变程度与CT的关系。方法　纳入2型糖尿病患者共123例204眼，其中69眼诊断为DME（DME组），135眼无黄斑水肿为对照组。DME眼依据OCT形态学特点进一步分为视网膜弥漫性增厚（diffuse retinal thickness，DRT）型（34眼）、黄斑囊样水肿（cystoid macular edema，CME）型（19眼）和浆液性视网膜脱离（serous retinal detachment，SRD）型（16眼），利用EDI-OCT分别测量黄斑中心凹下CT和以黄斑为中心上、下、鼻、颞500 μm、1000 μm、1500 μm、2000 μm处CT。结果　DME组黄斑中心凹下CT为（326.72±90.15）μm，对照组为（320.17±106.46）μm，两组之间无统计学差异，但黄斑中心凹下CT与视网膜厚度间具有明显正相关关系（r=0.270，P=0.025）。DME亚型CT分别为:DRT型（303.94±81.47）μm、CME型（304.42±73.98）μm和SRD型（401.63±88.80）μm，SRD型CT明显高于其他亚型（P<0.05），此外，SRD型的周边CT同样呈现均匀一致的增厚；鼻侧CT从500 μm至2000 μm呈距离敏感性降低（P<0.05），但SRD型鼻侧CT降低幅度明显变缓（P=0.195）。结论　SRD型黄斑水肿患者CT在中心凹下及周边部均显著增厚，CT与DME病变程度之间有一定相关性。