社区综合治疗老年慢性阻塞性肺病的疗效观察

目的:分析社区综合治疗对老年慢性阻塞性肺病的疗效.方法:以2015年1月至2016年6月在我院诊治的120例老年慢性阻塞性肺病患者为研究对象,被随机分为观察组(63例)和对照组(57例).观察组患者接受药物、家庭氧疗、社区恢复训练及心理干预等综合治疗;对照组患者仅接受药物治疗.持续治疗2周后比较两组的疗效、动脉氧分压(PaO2)、以及动脉二氧化碳分压(PaCO2).结果:观察组的治疗总有效率为96.8%(61/63),显著高于对照组77.2%(44/57,P<0.01);观察组PaO2及PaCO2的改善也显著优于对照组(P<0.01).结论:社区综合治疗能提高老年慢性阻塞性肺病的临床疗效.     

Light Emitting Diodes Irradiation Regulates miRNA-877-3p to Promote Cardiomyocyte Proliferation

Mammalian cardiomyocytes (CMs) maintain a low capacity for self-renewal in adulthood, therefore the induction of CMs cycle re-entry is an important approach to promote myocardial repair after injury. Recently, photobiomodulation (PBM) has been used to manipulate physiological activities of various tissues and organs by non-invasive means. Here, we demonstrate that conditioned PBM using light-emitting diodes with a wavelength of 630 nm (LED-Red) was capable of promoting the proliferation of neonatal CMs. Further studies showed that low-power LED-Red affected the expression of miR-877-3p and promoted the proliferation of CMs. In contrast, silencing of miR-877-3p partially abolished the pro-proliferative actions of LED-Red irradiation on CMs. Mechanistically, GADD45g was identified as a downstream target gene of miR-877-3p. Conditioned LED-Red irradiation also inhibited the expression of GADD45g in neonatal CMs. Moreover, GADD45g siRNA reversed the positive effect of LED-Red on the proliferation of neonatal CMs. Taken together, conditioned LED-Red irradiation increased miR-877-3p expression and promoted the proliferation of neonatal CMs by targeting GADD45g. This finding provides a new insight into the role of LED-Red irradiation in neonatal CMs biology and suggests its potential application in myocardial injury repair.     

Hippo pathway monomerizes STAT3 to regulate prostate cancer growth

Prostate cancer ranks among the most commonly diagnosed malignancies for men and has become a non‐negligible threat for public health. Interplay between inflammatory factors and cancer cells renders inflammatory tissue environment as a predisposing condition for cancer development. The Hippo pathway is a conserved signaling pathway across multiple species during evolution that regulates tissue homeostasis and organ development. Nevertheless, whether Hippo pathway regulates cancer‐related inflammatory factors remains elusive. Here, we show that high cell density–mediated activation of the Hippo pathway blunts STAT3 activity in prostate cancer cells. Hippo pathway component MST2 kinase phosphorylates STAT3 at T622, which is located in the SH2 domain of STAT3. This phosphorylation blocks the SH2 domain in one STAT3 molecule to bind with the phosphorylated Y705 site in another STAT3 molecule, which further counteracts IL6‐induced STAT3 dimerization and activation. Expression of a nonphosphorylatable STAT3 T622A mutant enhances STAT3 activity and IL6 expression at high cell density and promotes tumor growth in a mice xenograft model. Our findings demonstrate that STAT3 is a novel phosphorylation substrate for MST2 and thereby highlight a regulatory cascade underlying the crosstalk between inflammation and the Hippo pathway in prostate cancer cells.     

IFN‐α/β‐mediated NK2R expression is related to the malignancy of colon cancer cells

Neurokinin 2 receptor (NK2R), a G protein‐coupled receptor for neurokinin A (NKA), a tachykinin family member, regulates various physiological functions including pain response, relaxation of smooth muscle, dilation of blood vessels, and vascular permeability. However, the precise role and regulation of NK2R expression in cancer cells have not been fully elucidated. In this study, we found that high NK2R gene expression was correlated with the poor survival of colorectal cancer patients, and Interferon (IFN‐α/β) stimulation significantly enhanced NK2R gene expression level of colon cancer cells in a Janus kinas 1/2 (JAK 1/2)‐dependent manner. NKA stimulation augmented viability/proliferation and phosphorylation of Extracellular‐signal‐regulated kinase 1/2 (ERK1/2) levels of IFN‐α/β‐treated colon cancer cells and NK2R blockade by using a selective antagonist reduced the proliferation in vitro. Administration of an NK2R antagonist alone or combined with polyinosinic‐polycytidylic acid, a synthetic analog of double‐stranded RNA, to CT26‐bearing mice significantly suppressed tumorigenesis. NK2R‐overexpressing CT26 cells showed enhanced tumorigenesis and metastatic colonization in both lung and liver after the inoculation into mice. These findings indicate that IFN‐α/β‐mediated NK2R expression is related to the malignancy of colon cancer cells, suggesting that NK2R blockade may be a promising strategy for colon cancers.     

HPV circulating tumor DNA to monitor the efficacy of anti‐PD‐1 therapy in metastatic squamous cell carcinoma of the anal canal: A case report

Squamous cell carcinoma of the anal canal (SCCA) is a rare HPV‐associated cancer with limited sensitivity to standard chemotherapy. In a phase 2 study, nivolumab, an anti PD‐1 immune checkpoint inhibitor, demonstrated significant efficacy as single‐agent therapy in metastatic SCCA patients. Nevertheless, imaging assessment by standard RECIST criteria of the efficacy of immune therapy can be difficult in some patients due to tumor immune cell infiltration, and biomarkers of treatment efficacy are needed. We have previously developed a quantitative droplet digital PCR (ddPCR) technique to detect HPV circulating tumor DNA (HPV ctDNA), with excellent sensitivity and specificity. Here, we report, for the first time, the kinetics of HPV ctDNA during therapy in a patient with metastatic SCCA, who obtained sustained partial response to single‐agent nivolumab. We observed an early and very significant decrease of HPV ctDNA during therapy from the baseline level of 3713 copies/ml plasma to 564 copies/ml plasma at 4 weeks, and 156 copies/ml at 6 weeks, followed by a plateau. This observation provides proof‐of‐concept that HPV ctDNA can be used as a noninvasive early dynamic biomarker to monitor the efficacy of new immunotherapy agents.     

Timely follow‐up of positive cancer screening results: A systematic review and recommendations from the PROSPR Consortium

Timely follow‐up for positive cancer screening results remains suboptimal, and the evidence base to inform decisions on optimizing the timeliness of diagnostic testing is unclear. This systematic review evaluated published studies regarding time to follow‐up after a positive screening for breast, cervical, colorectal, and lung cancers. The quality of available evidence was very low or low across cancers, with potential attenuated or reversed associations from confounding by indication in most studies. Overall, evidence suggested that the risk for poorer cancer outcomes rises with longer wait times that vary within and across cancer types, which supports performing diagnostic testing as soon as feasible after the positive result, but evidence for specific time targets is limited. Within these limitations, we provide our opinion on cancer‐specific recommendations for times to follow‐up and how existing guidelines relate to the current evidence. Thresholds set should consider patient worry, potential for loss to follow‐up with prolonged wait times, and available resources. Research is needed to better guide the timeliness of diagnostic follow‐up, including considerations for patient preferences and existing barriers, while addressing methodological weaknesses. Research is also needed to identify effective interventions for reducing wait times for diagnostic testing, particularly in underserved or low‐resource settings. CA Cancer J Clin 2018;68:199–216 . © 2018 American Cancer Society .     

Two BRM promoter polymorphisms predict poor survival in patients with hepatocellular carcinoma

Polymorphisms in the promoter of the BRM gene, a critical subunit of the chromatin remodeling SWI/SNF complex, have previously been implicated in risk and prognosis in Caucasian‐predominant lung, head and neck, esophageal, and pancreatic cancers, and in hepatocellular cancers in Asians. We investigated the role of these polymorphisms in hepatocellular carcinoma (HCC) risk and prognosis. HCC cases were recruited in a comprehensive cancer center while the matched controls were recruited from family practice units from the same catchment area. For risk analyses, unconditional logistic regression analyses were performed in HCC patients and matched healthy controls. Overall survival analyses were performed using Cox proportional hazard models, Kaplan‐Meier curves, and log‐rank tests. In 266 HCC cases and 536 controls, no association between either BRM promoter polymorphism (BRM‐741 or BRM‐1321) and risk of HCC was identified (P > 0.10 for all comparisons). There was significant worsening of overall survival as the number of variant alleles increased: BRM‐741 per variant allele adjusted hazards ratio (aHR) 5.77, 95% confidence interval (CI) 2.89‐11.54 and BRM‐1321 per variant allele aHR 4.09, 95%CI 2.22‐7.51. The effects of these two polymorphisms were at least additive, where individuals who were double homozygotes for the variant alleles had a 45‐fold increase in risk of death when compared to those who were double wild‐type for the two polymorphisms. Two BRM promoter polymorphisms were strongly associated with HCC prognosis but were not associated with increased HCC susceptibility. The association was strongest in double homozygotes for the allele variants.     

Normalizing GDNF expression in the spinal cord alleviates cutaneous hyperalgesia but not ongoing pain in a rat model of bone cancer pain

Bone cancer pain (BCP) is the most common complication in patients with bone cancer. Glial cell line‐derived neurotrophic factor (GDNF) is believed to be involved in chronic pain conditions. In this article, the expression and roles of GDNF were studied in a rat model of BCP induced by tibia injection of Walker 256 rat mammary gland carcinoma cells. Significant mechanical and thermal hyperalgesia and ongoing pain were observed beginning as early as day 5 post injection. The expression level of GDNF protein examined on day 16 after tibia injection was decreased in the L3 dorsal root ganglion (DRG) and lumbar spinal cord, but not in other spinal levels or the anterior cingulate cortex. Phosphorylation of Ret, the receptor for GDNF family ligands, was also decreased. Furthermore, normalizing GDNF expression with lentiviral vector constructs in the spinal cord significantly reduced mechanical and thermal hyperalgesia, spinal glial activation, and pERK induction induced by tibia injection, but did not affect ongoing pain. Together these findings provide new evidence for the use of GDNF as a therapeutic treatment for bone cancer pain states.