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BackgroundPrevious studies examining associations between subclinical hypothyroidism (SCH) with in vitro fertilization (IVF) outcome indicate some benefits of levothyroxine (LT4) treatment. But IVF outcomes in treated SCH women whose serum Thyroid Stimulating Hormone (TSH) concentration did and did not exceed 2.5 mIU/L before the IVF cycle has not been studied thoroughly.MethodsIn this study, we performed a prospective cohort study with 270 treated subclinical hypothyroidism patients undergoing their first IVF retrieval cycle at a single cite.ResultsSCH in women receiving LT4 replacement with a basal TSH level between 0.2-2.5mIU/L displayed a similar rate of clinical pregnancy (47.4% vs 38.7%, P = .436), miscarriage (7.4% vs 16.7%, P = .379) and live birth (43.9% vs 32.3%, P = .288) compared to women with a basal TSH level between 2.5-4.2 mIU/L.ConclusionStrictly controlled TSH (less than 2.5 mIU/L) before IVF may have no effect on the pregnancy rate in LT4 treated SCH women.

In asthma, mucus hypersecretion is thought to be a prominent pathological feature associated with widespread mucus plugging. However, the current treatments for mucus hypersecretion are often ineffective or temporary. The potential therapeutic targets of mucus hypersecretion in asthma remain unknown. Here, we show that Lyn is a central effector of endoplasmic reticulum stress (ER stress) and mucous hypersecretion in asthma. In Lyn-transgenic mice (Lyn-TG) and wild-type (WT) C57BL/6J mice exposed to ovalbumin (OVA), Lyn overexpression attenuates mucus hypersecretion and ER stress. Interleukin 13 (IL-13) induced MUC5AC expression by enhancing ER stress in vitro. Lyn serves as a negative regulator of IL-13-induced ER stress and MUC5AC expression. We further find that an inhibitor of ER stress, which is likely involved in the PI3K p85α/Akt pathway and NFκB activity, blocked MUC5AC expression in Lyn-knockdown cells. Furthermore, PI3K/Akt signaling is required for IL-13-induced ER stress and MUC5AC expression in airway epithelial cells. The ER stress regulation of MUC5AC expression depends on NFκB in Lyn-knockdown airway epithelial cells. Our studies indicate not only a concept of mucus hypersecretion in asthma that involves Lyn kinase but also an important therapeutic candidate for asthma.

Kimura’s disease (KD) is a rare chronic inflammatory or allergic disease. Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign vascular neoplasm. Their relationship has always been debated. This article reports two rare cases, one of each disease. One patient was a 48-year-old female that presented with a mass on her right mandible. She also had oedema erythema and wheals on her lower limbs. She was diagnosed with Kimura’s disease complicated with chronic urticaria. The second patient was a 23-year-old female that presented with multiple nodules of unequal size on the scalp. She was diagnosed with angiolymphoid hyperplasia with eosinophilia. The first patient recovered after being treated with surgical resection, glucocorticosteroids, cyclophosphamide and radiotherapy. The second patient underwent the first stage of surgical excision and is currently being followed-up. Comparison of the clinical and histopathological features of these two cases supports the theory that KD and ALHE are two separate disease entities.

Functions and mechanisms of microRNA (miRNA) involved in colorectal cancer (CRC) metastasis are largely unknown. Here, a miRNA microarray analysis was performed in CRC primary tissues and metastatic hepatic tissues to disclose crucial miRNA involved in CRC metastasis. MiR-133b was decreased and negatively correlated with metastasis in CRC. Overexpression of miR-133b significantly suppressed metastasis of CRC in vitro and in vivo. HOXA9 was identified as a direct and functional target of miR-133b. In addition, HOXA9 was negatively correlated with miR-133b and promoted CRC malignant progress. Moreover, miR-133b decreased HOXA9 expression, and subsequently downregulated ZEB1 and upregulated E-cadherin expression. Intriguingly, lower miR-133b and higher HOXA9 expression significantly contributed to poorer outcomes in CRC patients. Multivariate analysis indicated that miR-133b was an independent and significant predictor of CRC patient overall survival. In conclusion, we newly determined that miR-133b targeted the HOXA9/ZEB1 pathway to promote tumor metastasis in CRC cells. This axis provided insights into the mechanism underlying miRNA regulation of CRC metastasis and a novel therapeutic target for CRC treatment.

Due to the risk of waitlist dropout from tumor progression, liver transplant candidates with hepatocellular carcinoma (HCC) within Milan criteria (MC) receive standardized exception points. An expansion of this process to candidates with HCC beyond MC has been proposed, though it remains controversial. This study sought to better define the utilization of exception points in candidates with HCC beyond MC and the associated outcomes. We reviewed all nonstandardized HCC applications that underwent formal regional review board evaluation between January 1, 2005 and March 2, 2011; 2184 initial HCC exception point applications were submitted. Of these, 41.9% fulfilled MC, 26.6% fulfilled University of California-San Francisco (UCSF) criteria and 17.6% exceeded UCSF criteria. The majority of applications were accepted: 89.8% within UCSF and 71.2% beyond UCSF. There was a significantly (p < 0.001) higher risk of death on the waitlist or within 90 days of waitlist removal for candidates within UCSF (12.4%) or beyond UCSF (13.0%) criteria, compared to candidates with HCC within MC (6.0%). However, posttransplant outcomes were similar. While these results suggest increasing access to candidates with HCC beyond MC, comprehensive documentation of tumor characteristics and of successful downstaging is needed to ensure priority is restricted to those with the highest likelihood of favorable posttransplant outcome.

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