Biomarkers on patient T cells diagnose active tuberculosis and monitor treatment response

BACKGROUND. The identification and treatment of individuals with tuberculosis (TB) is a global public health priority. Accurate diagnosis of pulmonary active TB (ATB) disease remains challenging and relies on extensive medical evaluation and detection of Mycobacterium tuberculosis (Mtb) in the patient’s sputum. Further, the response to treatment is monitored by sputum culture conversion, which takes several weeks for results. Here, we sought to identify blood-based host biomarkers associated with ATB and hypothesized that immune activation markers on Mtb-specific CD4⁺ T cells would be associated with Mtb load in vivo and could thus provide a gauge of Mtb infection.METHODS. Using polychromatic flow cytometry, we evaluated the expression of immune activation markers on Mtb-specific CD4⁺ T cells from individuals with asymptomatic latent Mtb infection (LTBI) and ATB as well as from ATB patients undergoing anti-TB treatment.RESULTS. Frequencies of Mtb-specific IFN-γ⁺CD4⁺ T cells that expressed immune activation markers CD38 and HLA-DR as well as intracellular proliferation marker Ki-67 were substantially higher in subjects with ATB compared with those with LTBI. These markers accurately classified ATB and LTBI status, with cutoff values of 18%, 60%, and 5% for CD38⁺IFN-γ⁺, HLA-DR⁺IFN-γ⁺, and Ki-67⁺IFN-γ⁺, respectively, with 100% specificity and greater than 96% sensitivity. These markers also distinguished individuals with untreated ATB from those who had successfully completed anti-TB treatment and correlated with decreasing mycobacterial loads during treatment.CONCLUSION. We have identified host blood-based biomarkers on Mtb-specific CD4⁺ T cells that discriminate between ATB and LTBI and provide a set of tools for monitoring treatment response and cure.TRIAL REGISTRATION. Registration is not required for observational studies.FUNDING. This study was funded by Emory University, the NIH, and the Yerkes National Primate Center.     

张宁教授“固本泻浊法”治疗肾病综合征经验浅谈

肾病综合征是儿童和成人常见的肾脏疾病之一，激素治疗常不能达到满意的效果，并会出现多种不良反应。张宁教授运用中医治疗肾病综合征经验丰富，认为肾病综合征病性虚实夹杂，脾肾亏虚为本，肝失疏泄、湿热内阻、瘀血停滞为标。标实的病理因素由本虚引起及加重。治以“固本泻浊法”，健脾益肾，兼以调肝养血、清热化湿、活血化瘀，提高了临床疗效，减少了不良反应。     

自噬在前列腺癌发生发展和治疗中的研究进展

自噬是真核细胞通过溶酶体对其自身生物大分子和细胞器回收再利用的过程，其在维持细胞稳态中发挥重要作用，并参与多种病理生理过程。在肿瘤的发病过程中，自噬发挥“双面作用”，既可以抗癌也能促癌。前列腺癌是老年男性最常见的恶性肿瘤，研究表明前列腺癌的发生发展与自噬作用密切相关，放化疗、内分泌治疗等对肿瘤细胞造成的应激可通过自噬得以缓解，抵抗治疗，因而自噬抑制剂对于放化疗等具有协同促进作用。本文就自噬在前列腺癌中发病和治疗进行综述，以期为前列腺癌的诊治提供一些新的思路。     

经典名方中木通与通草的本草考证

通过查阅历代本草、医籍、方书等古代资料,结合近现代文献,对经典名方中所用木通及通草药材的名称、基原、产地、品质、采收加工及炮制等不同方面进行了本草考证,厘清古今关系,为涉及该类药材的经典名方开发与利用提供参考与依据。唐代之前历代本草中仅有"通草"之名,唐代出现"木通"别名,其药材基原均为木通科木通Akebia quinata(Thunb.)Decne.。宋代木通、通草名实发生混淆,民间多以五加科通脱木Tetrapanax papyrifer(Hook.)K. Koch.作通草用,而将前代本草中的通草唤作"木通",来源为木通科、毛茛科等植物。元代正式将木通与通草分称。明代木通药材主流来源为木通科植物,通草来源则为五加科通脱木,陈嘉谟、李时珍等曾试图对两者名实进行纠正。清代本草中木通、通草分类逐渐清晰,木通基原多为毛茛科植物,木通科木通的使用逐渐减少。近代出现关木通、川木通、小通草等药材,而关木通自马兜铃事件后被禁用。自2005年版《中华人民共和国药典》起收载木通、川木通2类,而通草亦分成通草与小通草2类。据记载,木通药材古代以江淮为道地产区,现代以江西、湖北资丘产者为最,农历正月、二月采枝、阴干,切粗片或剉细用,品质以色黄白而细者为佳。通草产地记载多为江南地区,秋季采茎,取出髓部,切片。     

MicroRNA‐375‐3p enhances chemosensitivity to 5‐fluorouracil by targeting thymidylate synthase in colorectal cancer

Resistance to chemotherapy is a major challenge for the treatment of patients with colorectal cancer (CRC). Previous studies have found that microRNAs (miRNAs) play key roles in drug resistance; however, the role of miRNA‐373‐3p (miR‐375‐3p) in CRC remains unclear. The current study aimed to explore the potential function of miR‐375‐3p in 5‐fluorouracil (5‐FU) resistance. MicroRNA‐375‐3p was found to be widely downregulated in human CRC cell lines and tissues and to promote the sensitivity of CRC cells to 5‐FU by inducing colon cancer cell apoptosis and cycle arrest and by inhibiting cell growth, migration, and invasion in vitro. Thymidylate synthase (TYMS) was found to be a direct target of miR‐375‐3p, and TYMS knockdown exerted similar effects as miR‐375‐3p overexpression on the CRC cellular response to 5‐FU. Lipid‐coated calcium carbonate nanoparticles (NPs) were designed to cotransport 5‐FU and miR‐375‐3p into cells efficiently and rapidly and to release the drugs in a weakly acidic tumor microenvironment. The therapeutic effect of combined miR‐375 + 5‐FU/NPs was significantly higher than that of the individual treatments in mouse s.c. xenografts derived from HCT116 cells. Our results suggest that restoring miR‐375‐3p levels could be a future novel therapeutic strategy to enhance chemosensitivity to 5‐FU.     

eIF4EBP3 was downregulated by methylation and acted as a tumor suppressor by targeting eIF4E/β-catenin in gastric cancer

Gastric Cancer - Epigenetic aberrations of tumor suppressor genes (TSGs), particularly DNA methylation, are frequently involved in the pathogenesis of gastric cancer (GC). Through a methylome...     

“龙虎交战”针法针刺八脉交会穴对偏头痛患者头痛天数及血清CGRP表达的影响＊

目的 观察“龙虎交战”针法针刺八脉交会穴对无先兆偏头痛（Migraine without aura，MO）患者头痛天数及外周血降钙素基因相关肽（Calcitonin gene related peptide，CGRP）表达水平的影响。方法 按照头痛程度将90例MO受试者区层随机分为治疗Ⅰ组、治疗Ⅱ组和对照组各30例。治疗Ⅰ组施以“龙虎交战”针法针刺八脉交会穴（外关和足临泣），治疗Ⅱ组施以平补平泻针法针刺八脉交会穴（外关和足临泣），对照组施以平补平泻针法针刺非经非穴点，每次留针30分钟，5次/周，共治疗20次。于治疗前、治疗结束4周后的随访分别记录三组患者头痛天数的变化情况以判定疗效，并采集患者治疗前、治疗结束4周后随访的肘部静脉血用ELISA法检测血清中的CGRP含量的变化。结果 ①各组治疗前患者的头痛天数无显著差异（Ｐ > 0.05），治疗Ⅰ组、治疗Ⅱ组和对照组治疗结束4周后随访的头痛天数较治疗前均显著降低（Ｐ < 0.05）；治疗Ⅰ组头痛天数的降低显著优于治疗Ⅱ组和对照组（Ｐ < 0.001），治疗Ⅱ组头痛天数的降低显著优于对照组（Ｐ < 0.05）；②3组治疗前CGRP的表达无显著差异，治疗Ⅰ组、治疗Ⅱ组治疗结束4周后随访CGRP的表达较治疗前均显著下降（Ｐ < 0.001），对照组治疗结束4周后随访CGRP的表达较治疗前差异无显著性（Ｐ > 0.05）；治疗Ⅰ组CGRP治疗结束4周随访的表达较治疗Ⅱ组和对照组均显著下降（Ｐ < 0.01），治疗Ⅱ组CGRP的表达较对照组显著下降（P < 0.01）。结论 ①八脉交会穴施以“龙虎交战”针法针刺能明显改善MO患者的头痛天数，同时降低MO患者血清CGRP的表达水平，这可能是针刺八脉交会穴治疗MO的机制之一；②非经非穴点的针刺效应无持续性，而八脉交会穴的针刺效应具有持续性；③八脉交会穴可以充分发挥复式针刺手法的治疗效应，提示我们在临床上治疗疾病时不仅要注意腧穴配伍，恰当的针刺手法更是提高临床疗效、事半功倍的关键。