竹叶石膏汤合清气化痰丸加减治疗急性加重期慢性阻塞性肺疾病分析

目的:分析竹叶石膏汤合清气化痰丸加减治疗急性加重期慢性阻塞性肺疾病(Acute Exacerbations of Chronic Obstructive Pulmonary Disease,AECOPD)疗效。方法:以2017年1月-2019年1月收治的AECOPD患者80例,随机分为两组,各40例。对照组采用常规西药治疗,观察组在对照组基础上采用竹叶石膏汤合清气化痰丸加减治疗。比较两组治疗前后肺功能指标[第1秒用力呼气容积占预计值百分比(Forced Expiratory Volume,FEV1%)、第一秒用力呼气肺容积(Forced Expiratory Volume,FEV1)]、改良版英国医学研究委员会呼吸问卷(mMRC)、慢阻肺患者自我评估测试问卷(CAT)等评分变化以及疗效。结果:在FEV1%、FEV1等肺功能指标上,两组治疗前对比无统计学差异(P>0.05);而观察组治疗后均高于对照组,二者差异存在统计学意义(P<0.05)。在mMRC、CAT等评分上,两组治疗前差异对比无统计学意义(P>0.05);而观察组治疗后均低于对照组,二者差异存在统计学意义(P<0.05)。在治疗有效率上,对照组总体为82.5%(33/40),观察组总体为95.0%(38/40),二者差异对比存在统计学意义(P<0.05)。结论:竹叶石膏汤合清气化痰丸加减治疗AECOPD的疗效确切,即可有效改善患者肺功能和临床症状,且利于其预后康复,因此值得应用推广。     

The FABP12/PPARγ pathway promotes metastatic transformation by inducing epithelial‐to‐mesenchymal transition and lipid‐derived energy production in prostate cancer cells

Early stage localized prostate cancer (PCa) has an excellent prognosis; however, patient survival drops dramatically when PCa metastasizes. The molecular mechanisms underlying PCa metastasis are complex and remain unclear. Here, we examine the role of a new member of the fatty acid‐binding protein (FABP) family, FABP12, in PCa progression. FABP12 is preferentially amplified and/or overexpressed in metastatic compared to primary tumors from both PCa patients and xenograft animal models. We show that FABP12 concurrently triggers metastatic phenotypes (induced epithelial‐to‐mesenchymal transition (EMT) leading to increased cell motility and invasion) and lipid bioenergetics (increased fatty acid uptake and accumulation, increased ATP production from fatty acid β‐oxidation) in PCa cells, supporting increased reliance on fatty acids for energy production. Mechanistically, we show that FABP12 is a driver of PPARγ activation which, in turn, regulates FABP12''s role in lipid metabolism and PCa progression. Our results point to a novel role for a FABP‐PPAR pathway in promoting PCa metastasis through induction of EMT and lipid bioenergetics.

Abbreviations

AR

androgen receptor

ATP

adenosine triphosphate

CN

copy number

CPT1

carnitine palmitoyltransferase I

CS

citrate synthase

EMT

epithelial–mesenchymal transition

ET

electron transfer‐state

FABP

fatty acid‐binding protein

LD

lipid droplet

OA

oleic acid

PCa

prostate cancer

PPAR

peroxisome proliferator‐activated receptor

PPRE

peroxisome proliferator‐activated receptor response element

TZD

thiazolidinediones

     

A Novel Algorithm to Differentiate Between Multiple Primary Lung Cancers and Intrapulmonary Metastasis in Multiple Lung Cancers With Multiple Pulmonary Sites of Involvement

IntroductionDifferentiating between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IPM) is critical for developing a therapeutic strategy to treat multiple lung cancers with multiple pulmonary sites of involvement.MethodsWe retrospectively included 252 lesions (126 pairs) from 126 patients with surgically resected multiple lung adenocarcinomas. Each pair was classified as MPLC or IPM based on histopathologic findings as the reference standard. A novel algorithm was established with four sequential decision steps based on the combination of computed tomography (CT) lesion types (step 1), CT lesion morphology (step 2), difference of maximal standardized uptake values on positron-emission tomography/CT (step 3), and presence of N2/3 lymph node metastasis or distant metastasis (step 4). The diagnostic accuracy of the algorithm was analyzed. Performances of 11 observers were assessed without and with knowledge of algorithm.ResultsAmong 126 pairs, 90 (71.4%) were classified as MPLCs and 36 (28.6%) as IPMs. On applying the diagnostic algorithm, the overall accuracy for diagnosis of IPM among conclusive cases up to step 4 was 88.9%, and 65 and 44 pairs were correctly diagnosed based on step 1 and step 2, respectively. Specificity and positive predictive value for diagnosis of IPM increased significantly in all observers compared with reading rounds without the algorithm.ConclusionsApplication of the algorithm based on comprehensive information on clinical and imaging variables can allow differentiation between MPLCs and IPMs. When both of two suspected malignant lesions appear as solid predominant lesions without spiculation or air-bronchogram on CT, IPM should be considered.     

Cost-Effectiveness of Follow-Up for Subsolid Pulmonary Nodules in High-Risk Patients

ObjectiveTo evaluate the cost-effectiveness of a number of follow-up guidelines and variants for subsolid pulmonary nodules.MethodsWe used a simulation model informed by data from the literature and the National Lung Screening Trial to simulate patients with ground-glass nodules (GGNs) detected at baseline computed tomography undergoing follow-up. The nodules were allowed to grow and develop solid components over time. We tested the guidelines generated by varying follow-up recommendations for low-risk nodules, that is, pure GGNs or those stable over time. For each guideline, we computed average US costs and quality-adjusted life-years (QALYs) gained per patient and identified the incremental cost-effectiveness ratios of those on the efficient frontier. In addition, we compared the costs and effects of the most recently released version of the Lung Computed Tomography Screening Reporting and Data System (Lung-RADS), version 1.1, with those of the previous version, 1.0. Finally, we performed sensitivity analyses of our results by varying several relevant parameters.ResultsRelative to the no follow-up scenario, the follow-up guideline system that was cost-effective at a willingness-to-pay of $100,000/QALY and had the greatest QALY assigned low-risk nodules a 2-year follow-up interval and stopped follow-up after 2 years for GGNs and after 5 years for part-solid nodules; this strategy yielded an incremental cost-effectiveness ratio of $99,970. Lung-RADS version 1.1 was found to be less costly but no less effective than Lung-RADS version 1.0. These findings were essentially stable under a range of sensitivity analyses.ConclusionsCeasing follow-up for low-risk subsolid nodules after 2 to 5 years of stability is more cost-effective than perpetual follow-up. Lung-RADS version 1.1 was cheaper but similarly effective to version 1.0.     

Proposal of a novel subclassification of pN3b for improvement the prognostic discrimination ability of gastric cancer patients

IntroductionIn the recent edition of TNM staging system, pN3b gastric cancer were separated into the staging system for better prognosis accuracy. The definition of pN3b contains a large range of metastasis lymph nodes (mLNs). However, few studies have evaluated the prognosis of pN3b patients and it remains unknown whether these patients were reasonably assigned into the same substage.Materials and methodsA total of 642 pN3b patients from a multi-institutional cohort in China were included. Disease-specific survival (DSS) was estimated using the Kaplan-Meier method and the Cox proportional hazards regression analysis was used to identify the independent prognostic factors. Restricted cubic spine model was used to specify the association between the continuous variables and the logarithm Hazard ratios (HRs). The optimal cut-off value of mLNs for DSS was identified using the X-tile software.ResultsThe 5-year DSS rate of total pN3b cohort was 15.4%. The smooth curves showed a non-linear association between the mLNs and the logarithm HRs. All pN3b gastric cancer patients were divided into two subclassifications (pN3b1: 16-24 mLNs, pN3b2: ≥25 mLNs). Significant survival difference was observed between two subclassifications (P = 0.048). Additionally, more LNs examined could decrease the death risk of pN3b patients and bring survival benefit only in pN3b1 patients, but not in pN3b2 patients.ConclusionsWe proposed a novel subclassification of pN3b patients, which assigned patients into two subclassifications with significant survival difference. Future study should explore the prognosis value based on this novel subclassification in TNM staging system.     

The prognostic value of lymph node ratio in Medullary thyroid carcinoma: A multi-center study

IntroductionThe lymph node ratio (LNR), which represents the proportion of metastatic lymph nodes resected, has been found to be a prognostic variable in several cancers, but data for Medullary thyroid carcinoma (MTC) are sparse. The aim of this study was to determine the value of the LNR in predicting outcome in patients with MTC.Materials and methodsA retrospective multicenter study design of 107 patients with MTC who underwent total thyroidectomy with neck dissection between 1984 and 2016. The association of LNR with patient and tumor characteristics and prognostic factors was evaluated.ResultsStudy population consisted of 53.3% female, mean age at diagnosis was 50.3 ± 18.4 years; 16.8% had inherited MTC. LNR was positively correlated with tumor size (p = 0.018) and inversely correlated with age at diagnosis (p = 0.024). A higher LNR was associated with extrathyroidal extension (p < 0.001), multifocality (p = 0.001), bilateral tumor (p = 0.002), distant metastases (p < 0.001), and tumor recurrence (OR = 14.7, p < 0.001). LNR was also correlated to postoperative calcitonin levels (p < 0.001) and carcinoembryonic antigen (p = 0.011). LNR >0.1 was associated with shorter disease-specific survival in patients at risk: tumor larger than 20 mm at diagnosis (p = 0.013), sporadic MTC (p = 0.01), and age above 40 years at diagnosis (p = 0.004). Cox multivariate survival analysis revealed LNR as the only significant independent factor for disease free survival (p = 0.005).ConclusionsThis study showed that LNR correlates well with patient and tumor characteristics and prognostic variables. We suggest that LNR should be considered an important parameter for predicting outcome in MTC.     

Intracellular claudin‐1 at the invasive front of tongue squamous cell carcinoma is associated with lymph node metastasis

Claudins are the major component of tight junctions, which form a primary barrier to paracellular diffusion and maintain cell polarity in normal epithelia and endothelia. In cancer cells, claudins play additional roles besides serving as components of the tight junctions, and participate in anoikis or invasion. Among the claudin family proteins, claudin‐1 has the most promising potential, both diagnostically and prognostically, in many types of cancers, including oral, gastric, liver, and colon cancers. However, conflicting results have been reported in relation to the degree of claudin‐1 expression and the prognosis, suggesting that the expression level of claudin‐1 alone is not sufficient to analyze the relationship between claudin‐1 and cancer progression. As endocytic trafficking of claudin‐1 has been reported in several epithelial cell types in vitro, we aimed to determine whether intracellular localization of claudin‐1 is the missing aspect between claudin‐1 and cancer. We investigated the expression of claudin‐1 in 83 tongue squamous cell carcinoma (TSCC) pathological specimens. Although the expression level of claudin‐1 based on immunohistochemistry was not associated with TSCC progression, within the high claudin‐1 expression group, the incidence of intracellular localization of claudin‐1 was correlated with cervical lymph node metastasis. In an in vitro experiment, claudin‐1 was constitutively internalized in TSCC‐derived cells. Motility of TSCC‐derived cells was increased by deficiency of claudin‐1, suggesting that the decrease in cell‐surface claudin‐1 promoted the cell migration. Therefore, intracellular localization of claudin‐1 at the invasion front may represent a promising diagnostic marker of TSCC.     

Risk factors of rib metastases in nasopharyngeal carcinoma patients with rib 99mTc- MDP foci on whole-body bone scansCSCD

Objective To investigate the correlation of rib 99mTc-MDP foci on whole-body bone scan with clinical variables and rib metastases in nasopharyngeal carcinoma(NPC) patients, and to screen the risk factors of rib metastases. Methods We retrospectively reviewed 312 NPC patients with rib 99mTc-MDP foci on wholebody bone scan. Chi-square test and logistic regression were performed to evaluate the correlation between clinical variables and rib metastases. Results In all 312 NPC patients, rib metastases were associated with T stage, skull base bone invasion, other bone metastasis, number of rib foci, lateral localization on rib and foci type (P<0.01), and the risk factors of rib metastasis included skull base bone invasion, other bone metastases, lateral localization on rib and foci type (P<0.05). In 176 patients with pure rib foci, rib metastases were closely related to T stage, skull base bone invasion, other bone metastasis, number of rib foci and lateral localization on rib (P<0.05), while only lobar distribution (P=0.029) was the effective risk factor. In 198 patients with single rib focus, rib metastases were affected by skull base bone invasion and foci type (P<0.01), while only foci type (P=0.000) was the effective risk factor. In all 566 rib foci, uptake level and localization on rib were the effective risk factors of rib metastases(P<0.01). Conclusion In NPC patients with rib foci on whole body bone scan, the effective risk factors of rib metastases include skull base bone invasion, other bone metastases, lateral localization on rib, foci type, uptake level and anterior and posterior localization on rib. Follow up should be the main way for the pure rib foci on unilateral ribs. For multiples rib foci on bilateral ribs or single rib focus combined with other bones foci, additional image modalities should be required to exclude bone metastasis. © 2020, CHINA RESEARCH ON PREVENTION AND TREATMENT. All rights reserved.