Objective To assess the clinical efficacy and adverse effect of pemetrexed-based chemotherapy as first-line treatment in elderly patients with advanced non-squamous non-small-cell lung cancer (NSCLC).Methods A total of 40 elderly patients with advanced non-squamous NSCLC confirmed by pathology were retrospective analyzed in the study,who received pemetrexed plus cisplatin (group A,n =18) or pemetrexed plus carboplatin (group B,n =22) as the first-line treatment.RECIST was used to assess the efficacy of the treatment and NCI-CTC AE version was used to describe adverse events.Results In the 40 patients,no one received complete response (CR),17 patients showed partial response (PR),16 had stable disease (SD),7 had progress disease (PD),the objective response rate (ORR) was 42.5 ％ (17/40) and the disease control rate (DCR) was 82.5 ％ (33/40).The median progression-free survival (PFS) time was 5.3 months.1 year suvival rate was 63.2 ％ (24/38).In further subgroup analyses,the ORR,DCR,PFS and 1 year suvival rate in group A were higher than those in group B,but they had no statistically significant difference (P ＞ 0.05).The drug-related adverse events were myelosuppression,gastrointestinal response,most of which were grade 1 to 2.Conclusion Pemetrexed combined with cisplatin or carboplatin may be recommended as first-line chemotherapy for elderly patients with advanced non-squamous NSCLC because of its safety and efficacy.

Objective To value the clinical efficacy and toxicity of S-1 compared to gemcitabine combined with S-1 in treatment of patients with advanced pancreatic cancer.Methods From January 2011 to December 2013,the data of 46 patients with advanced pancreatic cancer were analyzed retrospectively,including 24 patients receiving S-1 alone (group A) and 22 patients who received gemcitabine combined with S-1 (group B).The results were evaluated by objective response rate (ORR),disease control rate (DCR),survival time and safety.Results In group A the ORR was 20.8 ％ (5/24),DCR was 66.7 ％ (16/24),median progression-free survival was 4.8 months,median overall survival was 9.6 months,and 1 year survival was 12.5 ％.In group B the ORR was 27.3 ％ (6/22),DCR was 72.7 ％ (16/22),median progression-free survival was 5.9 months,median overall survival was 10.3 months,and 1 year survival was 22.7 ％.There was no significant difference between the two groups (P ＞ 0.05).The incidence rates of leukopenia,neutropenia and thrombopenia in group A were significantly lower than those in group B (P ＜ 0.05).Conclusion S-1 alone and gemcitabine combined with S-1 have similar effects in the treatment of advanced pancreatic cancer,but the toxicity of S-1 is mild and tolerable.

Objective To evaluate the association between CYP1A1 polymorphism and colorectal cancer risk.Methods PubMed,Embase and Web of Science databases were searched using the search terms as ‘Cytochrome P4501Al’,‘CYP1A1’,‘polymorphism’ and ‘colorectal cancer’.A meta-analysis was performed by STATA 10.0 software to assess the data included.Results By using 6768 cases and 7973 controls from 15 studies,significantly elevated colorectal cancer risks were associated with CYP1A1 2454A＞G in the following models (G vs A:pooled OR =1.19,95 ％ CI =1.03-1.37; GG vs AA:OR =1.40,95 ％ CI =1.12-1.75; GG vs AG+AA:OR =1.43,95 ％ CI =1.15-1.78).Conclusion CYP1A1 2454A＞G may cause an increased risk of colorectal cancer.

Heparinase III is an enzyme that specifically cleaves certain sequences of heparan sulfate. Previous reports showed that this enzyme expressed in Escherichia coli was highly prone to aggregation in inclusion bodies and lacks detectable biological activity. In this paper, we fused a glutathione-S-transferase (GST) tag to the N-terminus of heparinase III gene and expressed the fusion protein in Escherichia coli to develop an expression system of soluble heparinase III. As a result, approximately 80% of the fusion protein was soluble. The protein was then purified to near homogeneity via one-step affinity chromatography. A 199.4-fold purification was achieved and the purified enzyme had a specific activity of 101.7 IU/mg protein. This represented 32.3% recovery of the total activity of recombinant GST-heparinase III. The maximum enzyme production was achieved when bacteria were induced with 0.5 mmol/L isopropyl-beta-D-thiogalactoside at 15 degrees C for 12 h. The enzyme showed maximum activity at 30 degrees C and pH 7.5. And the enzyme activity was stimulated by 1 mmol/L Ca2+ and 150 mmol/L NaCl.
Escherichia coli ; genetics ; metabolism ; Flavobacterium ; enzymology ; genetics ; growth & development ; Glutathione Transferase ; biosynthesis ; genetics ; Heparin Lyase ; biosynthesis ; genetics ; isolation & purification ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; isolation & purification

Objective To study doctor-patient interest demands satisfaction and its influencing factors of the payment system reform of the new rural cooperative medical care scheme to provide reference for the reform. Methods Cross-sectional survey was conducted from September 2016 to February 2017. Multi-stage stratified random sampling was used in six counties of three provinces in the eastern, middle and western regions of China, and mathematical statistics was applied to analyze the data. Results The doctor-patient overall interest demands satisfaction was high, but the satisfaction was lower both with the income and ability improvement of medical staff and with the benefits of farmers. The influencing factors of the satisfaction of managers in medical institutions included the type of payment, educational level and work unit (P＜0.05). The influencing factors of medical staff's satisfaction included the type of payment, work unit, and working years among others(P＜0.05). The influencing factors of farmers'satisfaction included the type of payment and the average annual income, etc(P＜0.05). Conclusions The core interest demands of both doctors and patients should be valued to enhance their satisfaction. Diseases related groups should be promoted and applied scientifically, and appropriately integrated with other methods of payment. Both doctors and patients'understanding of the payment reform should be improved by propaganda and training, to get their support and cooperation.

OBJECTIVE: To investigate the relationship between Toll-like receptor 4 (TLR4) and collateral circulation in patients with acute cerebral infarction (AIS) after thrombolytic therapy. METHODS: This retrospective, observational cohort study was conducted among 65 patients with AIS receiving thrombolytic therapy, who were divided according to findings by computed tomographic angiography (CTA) into good collateral circulation (group A, = 34) and poor collateral circulation (group B, = 31). Serum samples were collected from all the patients and the levels of TLR4 were measured with ELISA. RESULTS: The patients in group A had significantly better outcomes than those in group B. The NIHSS scores at 24 h and 30 days after thrombolytic therapy, mRS scores at 90 days and serum TLR4 levels were significantly lower in group A than in group B ( < 0.05); the percentages of patients with symptomatic intracerebral hemorrhage were comparable between the two groups. The serum levels of TLR4 were negatively correlated with the rMLC score ( < 0.05). Multivariate logistic regression analysis showed that a high level of TLR4 was associated with a poor collateral circulation after thrombolysis. CONCLUSIONS Good collateral circulation can increase the benefit of intravenous thrombolysis in patients with ACI, and the level of TLR4 is a predictive factor for the compensation of collateral circulation following ACI.
Biomarkers ; Brain Ischemia ; Cerebral Infarction ; Cerebrovascular Circulation ; Cohort Studies ; Collateral Circulation ; Fibrinolytic Agents ; Humans ; Retrospective Studies ; Stroke ; metabolism ; therapy ; Thrombolytic Therapy ; Toll-Like Receptor 4 ; metabolism ; Treatment Outcome

The treatment strategy for colon cancer with liver metastasis has always been a great challenge for clinical surgeons.Single treatment method such as surgical resection or systemic chemotherapy can no longer meet the treatment needs of such patients.With the extensive development of the multi-disciplinary team(MDT)for colorectal cancer based on surgery,more and more patients with advanced colorectal cancer have obtained better treatment effects and survival benefits.A case of descending colon cancer with huge hepatic metastasis diagnosed and treated by a multi-disciplinary team was reported,aiming to provide reference for clinical practice.

Stage T4 colon cancer is divided into two categories:tumor penetrating the visceral peritoneum(T4a)and tumor directly invading or attaching to adjacent organs or structures(T4b).Treatment of T4 colon cancer requires technically demanding surgical procedures,including total resection of adjacent infiltrating organs or structures,and is characterized by a high incidence of postoperative complications and a high rate of positive surgical margin microscopy.It has been found that taking laparoscopic surgery for T4 colon cancer may decrease long-term survival and increase the rate of peritoneal metastasis,but taking laparoscopic surgery for colon cancer also has the potential advantages in increasing perioperative benefits and improving the prognosis.With the upgrade of laparoscopic equipment and the improvement of surgeons'surgical skills,more and more surgeons have adopted laparoscopic surgery to treat T4 colon cancer.Currently,the oncologic safety of laparoscopic surgery for T4 colon cancer has not been effectively evaluated.Therefore,this article reviews the advantages,risks,and the choice of treatment strategies for laparoscopic surgery for T4 colon cancer,taking into account the current status and progress of domestic and international studies.

OBJECTIVE： To provide scientific evidence for establishing perfect rationality evaluation indicator system of antibiotics. METHODS： On the basis of literature research， Delphi method was used to conduct several rounds of consultations on 30 experts in related fields with E-mail and questionnaire field investigation. After several rounds of consultations， rationality evaluation index system for antibiotics was determined. The effective recovery rate of expert consultation questionnaire was used to express the positive coefficient of experts； the authoritative coefficient was used to express the authoritative degree of experts； the index importance assignment and the full score ratio were used to reflect the concentration degree of experts’ opinions； the coefficient of variation and the coefficient of coordination were used to express the coordination degree of experts’ opinions. RESULTS & CONCLUSIONS： After two rounds of consultations， response rates of the questionnaire in two rounds of surveys were 100％ and 96.67％， indicating experts were highly motivated. The authoritative coefficients were 0.91 and 0.88， indicating experts had a high degree of authority. Finally， an evaluation index system for rationality of antibiotics was established， which included four first-level indicators （indications， drug selection， medication process， management indicators） and 35 second-level indicators. Among them， the mean value of importance scoring of first-level indicators ranged from 4.28 to 5.00， the full score ratio from 0.93 to 1.00， the coefficient of variation from 0.00 to 0.15 and the coefficient of coordination was 0.446 （P＜0.001）. While， the mean value of importance scoring of second-level indicators ranged from 3.83 to 4.79； the full score ratio from 0.67 to 1.00； variation coefficient from 0.10 to 0.26 and the coefficient of coordination was 0.115 （P＜0.001）， which indicating the system was reliable.

Sympathetic cues via the adrenergic signaling critically regulate bone homeostasis and contribute to neurostress-induced bone loss, but the mechanisms and therapeutics remain incompletely elucidated. Here, we reveal an osteoclastogenesis-centered functionally important osteopenic pathogenesis under sympatho-adrenergic activation with characterized microRNA response and efficient therapeutics. We discovered that osteoclastic miR-21 was tightly regulated by sympatho-adrenergic cues downstream the β2-adrenergic receptor (β₂AR) signaling, critically modulated osteoclastogenesis in vivo by inhibiting programmed cell death 4 (Pdcd4), and mediated detrimental effects of both isoproterenol (ISO) and chronic variable stress (CVS) on bone. Intriguingly, without affecting osteoblastic bone formation, bone protection against ISO and CVS was sufficiently achieved by a (D-Asp₈)-lipid nanoparticle-mediated targeted inhibition of osteoclastic miR-21 or by clinically relevant drugs to suppress osteoclastogenesis. Collectively, these results unravel a previously underdetermined molecular and functional paradigm that osteoclastogenesis crucially contributes to sympatho-adrenergic regulation of bone and establish multiple targeted therapeutic strategies to counteract osteopenias under stresses.
Adrenergic Agents/pharmacology* ; Apoptosis Regulatory Proteins/pharmacology* ; Bone Diseases, Metabolic/metabolism* ; Humans ; Liposomes ; MicroRNAs/genetics* ; Nanoparticles ; Osteoclasts ; Osteogenesis/physiology* ; RNA-Binding Proteins/pharmacology*