高分辨率CT定量在慢性阻塞性肺疾病评估中的应用价值

慢性阻塞性肺疾病（COPD）是常见的呼吸系统疾病之一,其表现为持续的、进行性的气流阻塞,是全球发病率和死亡率的主要原因,经济和社会负担巨大。随着科学技术的不断进步和发展,胸部高分辨率计算机断层扫描（HRCT）检查在COPD患者诊断和评估中具有重要应用价值。本文就HRCT定量参数在COPD患者的诊断、急性加重及并发症评估的相关研究进展进行综述。     

Proxalutamide in metastatic castration-resistant prostate cancer: Primary analysis of a multicenter,randomized, open-label,phase 2 trial

We aim to assess the safety and efficacy of proxalutamide, a novel androgen receptor antagonist, for men with metastatic castration-resistant prostate cancer (mCRPC) in a multicenter, randomized, open-label, phase 2 trial. In our study, the enrolled mCRPC patients were randomized to 100, 200 and 300 mg dose groups at 1:1:1. The primary efficacy endpoint was prostate-specific antigen (PSA) response rate. The secondary endpoints included objective response rate (ORR), disease control rate (DCR) and time to PSA and radiographic progression. Safety and pharmacokinetics were also assessed. Finally, there were 108 patients from 17 centers being enrolled. By week 16, there were 13 (35.1%), 12 (36.4%) and 15 (42.9%) patients with confirmed 50% or greater PSA decline in 100 mg (n = 37), 200 mg (n = 33) and 300 mg (n = 35) groups, respectively. Among the 19 patients with target lesions at study entry, three (15.8%) had a partial response and 12 (63.2%) had stable disease. The ORRs of 20.0%, 22.2%, 0% and DCRs of 80.0%, 88.9%, 60.0% were, respectively, achieved in 100, 200 and 300 mg groups. By the maximum follow-up time of 24 weeks, there were 42.6% and 10.2% of cases experiencing PSA progression and radiographic progression, respectively. Overall, adverse events (AEs) were experienced by 94.4% of patients, most of which were mild or moderate. There were 28 patients experiencing ≥grade 3 AEs. The most common AEs were fatigue (17.6%), anemia (14.8%), elevated AST (14.8%) and ALT (13.0%), decreased appetite (13.0%). These findings preliminarily showed the promising antitumor activity of proxalutamide in patients with mCRPC with a manageable safety profile. The proxalutamide dose of 200 mg daily is recommended for future phase 3 trial (Clinical trial registration no. CTR20170177).     

Survival among Breast Cancer Patients: Comparison of the U.S. Military Health System with the Surveillance,Epidemiology and End Results Program

IntroductionAccessibility to health care is important to cancer survival. The U.S. military health system (MHS) provides universal health care access. However, whether the universal care has been translated into improved cancer survival is unknown. We compared survival of patients with breast cancer in the MHS with that in the U.S. general population and assessed the differences in cancer stage at diagnosis and treatment receipt between the two populations.MethodsThe MHS patients (n = 31,548) were identified from the Department of Defense's (DoD) Automated Central Tumor Registry (ACTUR). Patients in the U.S. general population (n = 63,096) were identified from the Surveillance, Epidemiology, and End Results (SEER) program. The two populations were matched on age, race, and diagnosis year. Multivariable Cox regression hazard modeling was used to estimate hazard ratios (HRs) comparing ACTUR with SEER. Multivariable logistic regression was used to estimate odds ratios (ORs) comparing stage and treatment receipt.ResultsACTUR patients exhibited a 24% lower overall mortality than the SEER patients (HR = 0.76, 95% CI, 0.71-0.80). They were less likely to present with later stage compared to the SEER patients (OR = 0.61, 95% CI, 0.55-0.67 for stage IV tumors). The ACTUR patients with stages I-III tumors were more likely to receive surgery (OR = 1.35, 95% CI, 1.20-1.52) but less likely to receive radiation (OR = 0.91, 95% CI, 0.88-0.94). The survival advantage of ACTUR patients remained regardless of surgery or radiation receipt.ConclusionsBreast cancer patients with universal health care access had improved survival compared to patients in the general population.     

Aprepitant exerts anti-fibrotic effect via inhibition of TGF-β/Smad3 pathway in bleomycin-induced pulmonary fibrosis in rats

Bleomycin is a well-recognized antineoplastic drug. However, pulmonary fibrosis (PF) is considered to be the principal drawback that greatly limits its use. Here, we sought to investigate ability of the neurokinin receptor 1 blocker, aprepitant, to prevent PF caused by bleomycin. Male adult Wistar rat groups were given a single intratracheal injection of bleomycin, either alone or in combination with aprepitant therapy for 3 or 14 days. Collagen deposition and a rise in transforming growth factor beta (TGF-β) immunoreactivity in lung tissue serve as evidence of bleomycin-induced PF. The serum levels of lactate dehydrogenase, alkaline phosphatase, and total antioxidant improved after aprepitant therapy.Additionally, it reduced the protein expressions of interferon alpha, tumor necrosis factor alpha, and lung lipid peroxidation. Moreover, aprepitant treatment led to an increase in the antioxidant indices glutathione, glutathione peroxidase, and catalase. Aprepitant is postulated to protect against bleomycin-induced PF by decreasing TGF-β, phosphorylating Smad3, and increasing interleukin 37, an anti-fibrotic cytokine, and G Protein-coupled Receptor Kinase 2. Aprepitant for 14 days considerably exceeded aprepitant for 3 days in terms of improving lung damage and having an anti-fibrotic impact. In conclusion, aprepitant treatment for 14 days may be used as an adjuvant to bleomycin therapy to prevent PF, mostly through inhibiting the TGF-/p-Smad3 fibrotic pathway.     

Ochratoxin A induced differentiation nephrotoxicity in renal tubule and glomeruli via autophagy differential regulation

Ochratoxin A (OTA) is a mycotoxin that mainly causes nephrotoxicity. The single nephrotoxicity of OTA exposure on glomeruli or renal tubule had been well documented, however, the comparison toxicity between it is still unclear. Here, C57BL/6 mice and two types of nephrocyte were treated with concentration-gradient OTA to explore its differentiation nephrotoxicity. Results showed that OTA induced nephrotoxicity in vivo and in vitro, manifested as the deteriorative kidney function in mice and the cut-down cell viability in nephrocyte. Besides, results of murine kidney pathological section and IC₅₀ of two types nephrocyte indicated that OTA-induced toxicity in renal tubule was higher than its in glomeruli. In addition, OTA exposure induced autophagy signaling differentiation expression. It revealed that autophagy was implicated in OTA-induced differential nephrotoxicity in glomeruli and renal tubule. Altogether, we proved that OTA induces a differentiation nephrotoxicity in glomeruli and renal tubule, and it is related to autophagy differential regulation.     

Hypothermic Machine Perfusion with Hydrogen Gas Reduces Focal Injury in Rat Livers but Fails to Restore Organ Function

BackgroundWe have previously reported the efficacy of post-reperfusion H₂ gas treatment in cold storage (CS) and subsequent reperfusion of the rat liver. The present study aimed to evaluate the effect of H₂ gas treatment during hypothermic machine perfusion (HMP) in rat livers retrieved from donation after circulatory death (DCD) and elucidate the mechanism of action of H₂ gas.MethodsLiver grafts were procured from rats after 30 min of cardiopulmonary arrest. The graft was subjected to HMP for 3 hours at 7°C using Belzer MPS with or without dissolved H₂ gas. The graft was reperfused using an isolated perfused rat liver apparatus at 37°C for 90 minutes. Perfusion kinetics, liver damage, function, apoptosis, and ultrastructure were evaluated.ResultsPortal venous resistance, bile production, and oxygen consumption rates were identical in the CS, MP, and MP-H₂ groups. Liver enzyme leakage was suppressed by MP (vs control), whereas H₂ treatment did not show a combination effect. Histopathology revealed poorly stained areas with a structural deformity just below the liver surface in the CS and MP groups, whereas these findings disappeared in the MP-H₂ group. The apoptotic index in the CS and MP groups was high but decreased in the MP-H₂ group. Mitochondrial cristae were damaged in the CS group but preserved in the MP and MP-H₂ groups.ConclusionsIn conclusion, HMP and H₂ gas treatment are partly effective in DCD rat livers but insufficient. Hypothermic machine perfusion can improve focal microcirculation and preserve mitochondrial ultrastructure.     

Lycium Barbarum polysaccharides ameliorates hyperglycemia-exacerbated cerebral ischemia/reperfusion injury via protecting blood-brain barrier

BackgroundHyperglycemia exacerbates brain damage in cerebral ischemia/reperfusion injury. Previous study found that Lycium barbarum polysaccharides (LBP) has a neuroprotective effect on hyperglycemia-aggravated ischemic brain injury, which raising the possibility for treatment of neurodegenerative diseases. However, the underlying mechanism of LBP-induced protection by ameliorating hyperglycemia-aggravated ischemia/reperfusion injury needs to be tested. This study aimed to investigate the effects of LBP on blood–brain barrier (BBB) integrity with a hyperglycemia-aggravated cerebral ischemia/reperfusion injury model.MethodsSprague-Dawley male rats were randomly divided into three groups: normoglycemic (NG), hyperglycemic (HG), and LBP-pretreated hyperglycemic (HG + LBP). Animals underwent middle cerebral artery occlusion (MCAO) for 30 min, followed by 1-, 3-, and 7-day of reperfusion.ResultsOur results showed that the neurological deficit, infarct volume, cell apoptosis, and IgG leakage in the HG group significantly increased separately, compared with that of the NG group, (p < 0.05). Pre-treatment with LBP reversed these injury indicators (p < 0.05). And much more severe degree of swelling endothelium, swollen astrocyte, and decreased tight junctions in the micro-vessel were detected in the HG group comparing to that of the NG group. In addition, increased degree of basement membrane degradation, dissociation between the astrocyte endfeet and basement membrane, and tight junction's protein degradation was found in the HG group compared with the NG group (p < 0.05). However, when exposure to LBP therapy could reverse the above alterations (p < 0.05).ConclusionsThese results demonstrated that LBP could ameliorate hyperglycemia-exacerbated cerebral ischemia/reperfusion injury via protecting the blood-brain barrier.     

Inhibition of microRNA-19a-3p alleviates the neuropathic pain (NP) in rats after chronic constriction injury (CCI) via targeting KLF7

Background/purposeNeuropathic pain(NP) is derived from the dysfunctions of nerve system. The current research is to explore the impact and mechanism of miR-19a-3p in neuropathic pain in rats.MethodsThe NP was induced through the chronic constriction injury (CCI) surgery in rats. The pro-inflammatory factors (IL-1β, IL-6, TNF-α) in spinal cord tissues from rats were measured using Elisa kits. Moreover, the different levels of thermal hyperalgesia and mechanical allodynia in rats were examined through paw withdrawal latency (PWL) and paw withdrawal threshold (PWT). To investigate into the role of miR-19a-3p and KLF7 in NP of rats, the knockdown of miR-19a-3p alone or along with KLF7 downregulation in rats were achieved through lentivirus injection. The miR-19a-3p and KLF7 expression in spinal cord of rats on Day 3,7,14 after CCI were detected using RT-qPCR. The protein expression of KLF7 were measured by Western blot. Bioinformatics and luciferase assays were used for the prediction and verification of bindings between KLF7 and miR-19a-3p.ResultsCCI surgery caused neuropathic pain in rats with the levels of inflammatory cytokines increased and PWL and PWT decreased. Moreover, miR-19a-3p expression was increased while the protein and mRNA levels were decreased in spinal cord tissues in rats after CCI surgery. In rat microglial cells, miR-19a-3p downregulation could promote the KLF7 in both mRNA and protein expression. In spinal cord tissues of rats, the inhibition of miR-19a-3p enhanced the KLF7 expression. Furthermore, miR-19a-3p downregulation suppressed the IL-1β, IL-6 and TNF-α concentrations, and could decrease the NP but inhibition of KLF7 could partially reverse this in CCI rats.ConclusionmiR-19a-3p inhibition may alleviate NP via KLF7 in CCI rats.     

A multicenter,randomized trial comparing efficacy and safety of paclitaxel/capecitabine and cisplatin/capecitabine in advanced gastric cancer

Background

We compared efficacy and safety of paclitaxel/capecitabine therapy followed by capecitabine for maintenance (PACX) versus cisplatin/capecitabine therapy (XP) in advanced gastric cancer.

Methods

Multicenter, randomized, phase III trial was conducted in China (December 2009–February 2014). Adults (n = 320) with histologically confirmed, untreated metastatic/unresectable gastric or gastroesophageal junction adenocarcinoma; with ≥ 1 measureable lesions according to Response Evaluation Criteria in Solid Tumors 1.0 criteria; Karnofsky performance score ≥ 70 and life expectancy ≥ 3 months were randomized (1:1) to PACX or XP. PACX group received paclitaxel 80 mg/m² intravenous on days 1 and 8; capecitabine 1000 mg/m² orally BD on days 1–14, followed by a 7-day rest interval for 4 cycles, followed by maintenance capecitabine at same dosage/schedule until disease progression, unendurable adverse events or death. XP group received cisplatin intravenous 80 mg/m² on day 1 and capecitabine at same dosage/schedule as PACX group per cycle for 6 cycles.

Results

Median progression-free survival (5.0 versus 5.3 months; hazard ratio [95% CI]: 0.906; 0.706–1.164; p = 0.44) and overall survival (12.5 versus 11.8 months; hazard ratio: 0.878 [0.685–1.125]; p = 0.30) were not significantly different between PACX and XP groups. Objective response rate was significantly higher (43.1 versus 28.8%; p = 0.012) and disease control rate was similar (77.5 versus 72.5%; p = 0.75) in PACX versus XP, respectively. Quality of life was significantly improved in PACX versus XP after three treatment cycles. Many treatment-related adverse events were significantly lesser in PACX than XP.

Conclusions

First-line chemotherapy with PACX is effective with milder toxicities in advanced gastric cancer, but could not replace XP.