Objective To explore the influence of arsenous acid on hepatic and colonic cancer cell lines BEL-7402 and HT-29 .The effect of bortezomib combined with chemotherapeutic medicine and the optimal combination plan of them were also investigated .Methods We detected cell proliferation by MTT to get the inhi-bition rate of two cell lines and further to determine IC 50 ( inhibitory concentration50%) of 5-Fu,oxaliplatin or arsenous acid;preincubated cancer cells for 2 h、4 h or 8 h by bortezomib .Chemotheraputic medicine were com-bined respectively .The cell proliferation and apoptosis were analysed by MTT ,TUNEL and Annexin V -PI.Re-sult s The 24 h inhibition rate of arsenous acid to BEL -7402 and HT-29 was:0.59 ±0.09、0.71 ±0.12 re-spectively;the IC50 of 5 -Fu,Oxaliplatin or arsenous acid to BEL -7402 was:5.33 ±0.07 mg/L,28.73 ± 0.72 mg/L,25.93 ±4.05 mg/L, while to HT -29 was:7.33 ±1.13 mg/L、53.94 ±1.23 mg/L,21.93 ± 2.05 mg/L.Both inhibition rate and apoptosis rate were enhanced when chemotheraputic medicine was combined with bortezomib .Co nclusion Arsenous acid can inhibit the growth of cancer cells obviously;the susceptibility of each chemotherapy medicine can be strengthened significantly when it is combined with bortezomib ,P<0.05.

Background and purpose:For patients with advanced lung adenocarcinoma harboring an activating EGFR gene mutation, the current standard of care is EGFR-TKI alone. This study aimed to compare efficacy and safety of gefitinib plus chemotherapy with gefitinib or chemotherapy alone for treating advanced lung adenocarcinoma with an activatingEGFR gene mutation.Methods:This study included 61 patients with lung adenocarcinoma harboring an acti-vatingEGFR gene mutation (19 exons deletion and exon 21 L858R mutations) whose ECOG performance status was 0 or 1. Patients were randomly divided into 3 groups. Group A (n=20) were given carboplatin/pemetrexed of a 4-week cycle, six cycles at most, plus gefitinib (pemetrexed 500 mg/m2, d1; carboplatin AUC 5, d1; gefitinib 250 mg/d, d 5-21), and then re-ceived pemetrexed of a 4-week cycle plus gefitinib as maintenance therapy; Group B (n=20) were given carboplatin/peme-trexed of a 4-week cycle, six cycles at most (pemetrexed 500 mg/m2, d1; carboplatin AUC 5, d1), then received pemetrexed as maintenance therapy; Group C (n=21) were given gefitinib (gefitinib 250 mg/d). Patients continued to receive therapy until disease progression or unacceptable toxicity or death. The primary end point was middle PFS and 12 months PFS rate. The secondary end points included objective response rate and adverse events.Results:Groups A and C both lost 1 case during follow-up. Median PFS for patients was 20.1 months (95%CI:18.0-22.2) in group A, 5.5 months (95%CI:3.9-7.2) in group B, and 9.8 months (95%CI:6.8-12.8) in group C. PFS rates of 12 months for groups A, B and C were 78.9%, 15.0% and 40.0%, respectively. The overall objective response rates for groups A, B and C were 84.2%, 35.0% and 65.0%, respectively. Serious adverse events were reported by 36.8% for group A, 30.0% for group B, and 5.0% for group C. The most common grade 3/4 adverse events were neutropenia (3 cases in group A, 4 cases in group B), fatigue (2 cases in group A, 2 cases in group B) and liver function impairment (2 cases in group A, 1 case in group C).Conclusion:Among patients withEGFR mutant lung adenocarcinoma, combination of chemotherapy with gefitinib as first-line treatment demonstrates an improvement in PFS. Long-term survival results will be further followed up.

ObjectiveTo investigate the status of benefit finding in diabetic patients,and mediating effect of resilience between family support and benefit finding in diabetic patients.MethodsFive hundred and thirteen diabetic patients from a hospital of Harbin were recruited as investigative subjects from September 2015 to June 2016.The resilience scale,family adaptability,cohesion scale and benefit finding scale were used in the study.ResultsThe scores of benefit finding,resilience and family adaptability and cohesion were 55.67±12.87,70.65±10.39 and 104.25±15.38,separately.The total score of family adaptability and cohesion was positively related to the total score of benefit finding(r=0.389,P<0.05).The total score of resilience was positively related to the total score of benefit finding(r=0.155,P<0.05).The total score of family adaptability and cohesion was positively related to the total score of resilience(r=0.112,P<0.05).Benefit finding as the dependent variable,the results of hierarchical regression analysis indicated that family adaptability and cohesion (β=0.382,P<0.01),resilience(β=0.098,P<0.01)entered the regression equation.There was a partial mediating effect of resilience between family support and benefit finding in diabetic patients.The mediating effect was 0.011,accounted for 2.8% of the total effect.The resilience was the important protective factor for benefit finding.ConclusionFamily support has a direct influence on benefit finding and an indirect effect mediated by resilience on benefit finding.

Objective To assess the anti-arrhythmic activity and cardioprotective effects of Wenxin Granula, a traditional Chinese formula (consisting of Salviae Miltiorrhizae Radix, Polygonati Rhizoma, Notoginseng Radix et Rhizoma, Nardostachyos Radix et Rhizoma, Angelicae Sinensis Radix, and Succinum), on heart in ischemic-induced myocardial infarction (MI) rats and compare with those of Amiodarone which have been demonstrated in clinic. Methods Rats were randomly divided into Sham-operated (control), Ml + Amiodarone [5 mg/(kg·d)] (MI), and MI + Wenxin Granula [10 mg/(kg·d)] groups and left anterior descending coronary artery was occluded in each group. After left anterior descending for 12 h, standard lead Ⅱ of administration electrocardiogram was recorded in order to analyze the occurrence of arrhythmia. After one month, the size of the infarct area of heart was evaluated by TTC staining method and haemodynamic function was assessed to detect the heart function. Laser scanning confocal microscope and the technique of patch clamp were used to detect the intracellular Ca2+ ([Ca2+]j) and L-type calcium current (ICa-L), respectively. Results Both Wenxin Granula [10 mg/(kg·d)] and Amiodarone [5 mg/(kg·d)] could markedly decrease the incidence of arrhythmia in heart of rats which were subjected to ischemic injury. After one month, Wenxin Granula could significantly decrease mortality to 22.22% and reduce the infarct area (P < 0.05), but Amiodarone did not. The mechanism may involve that Wenxin Granula attenuated [Ca2+]j decreasing in MI rats. Additionally, Wenxin Granula could obviously ameliorate the impaired heart function of MI rats by decreasing the elevated left ventricular end-diastolic pressure and increasing the attenuated maximum change velocity of left ventricular pressure in the isovolumic contraction or relaxation period. On the other hand, electrophysiological experiment results revealed that Wenxin Granula administration one month later also increased the reduced ICa-L density in rat ventricular myocytes in MI rats. The results of LSCM showed that Wenxin Granula could recover the amplitude of [Ca2+]j decreased by heart failure during long term. Conclusion Wenxin Granula could not only inhibit the incidence of arrhythmia but also decrease the mortality, which was accompanied by recovering the amplitude of [Ca2+]j. This protective effect of Wenxin Granula may partially be mediated through changing ICa-L.as well as increasing [Ca2+]j.

Objective The objective of this study was to investigate the role and molecular mechanism of AtractylenolideⅠin the progression of lung cancer. Methods qRT-qPCR and immunohistochemistry were used to detect the expression of TLR4 and MyD88 at levels of mRNA and protein in lung cancer and adjacent tissues. Transwell and MTT assays were used to detect effects of at-ractylenolide I(100 μM)on the invasion,migration and proliferation of A549 cells. Western blot was also used to detect the effect of atractylenolide I on the expression of TLR4 and MyD88 proteins. Results The expression of TLR4 and MyD88 at levels of mRNA and protein was highly expressed in lung cancer tissues when compared to adjacent tissues(P<0. 05). Compared with the control group,the invasion ability of A549 cells in the Atractylenolide I group was significantly decreased,and the proliferative activity was in-hibited(P<0. 05). Atractylenolide I inhibited the expression of TLR4 and MyD88 protein in A549 cells( P<0. 05). Conclusion

BACKGROUND:Our previous studies found that adding barium sulfate could improve the mechanical and radiopaque properties of calcium phosphate cement.However,with the degradation of calcium phosphate,the remaining radiopaque agent is difficult to degrade,and the space-occupying and osteoclast effects at the implantation site affect the bone repair process.Therefore,it is necessary to develop a new biodegradable radiopaque material. OBJECTIVE:To discuss the radiopaque ability of bioactive degradable material strontium polyphosphate(SrPP)and its impact on the physicochemical properties and osteogenic effect of calcium phosphate cement. METHODS:(1)Calcium phosphate cement(CPC),starch modified calcium phosphate cement(CPS)and starch modified calcium phosphate cement(20%SrPP-CPN)containing SrPP(20%mass fraction of bone cement powder)were prepared respectively,and the physicochemical properties of the three groups of bone cements were characterized.(2)The three groups of bone cement extracts were co-cultured with rat bone marrow mesenchymal stem cells,respectively,to detect cell proliferation,energy metabolism,and osteogenic differentiation.(3)Bone defects with a diameter of 5 mm were made on each side of the top of the skull of 24 SD rats,and they were randomly divided into control group(without any intervention),CPC group,CPS group,and 20%SrPP-CPN group for intervention,with 6 rats in each group.Relevant tests were performed after 4 and 12 weeks of intervention. RESULTS AND CONCLUSION:(1)Compared with the other two groups of bone cement,20%SrPP-CPN had enhanced radiopaque ability,increased compressive strength and degradation rate,and prolonged curing time,and 20%SrPP-CPN could release Sr2+ stably during degradation.(2)CCK-8 assay showed that 20%SrPP-CPN did not affect the proliferation of bone marrow mesenchymal stem cells.Cell starvation test(serum-free culture)showed that 20%SrPP-CPN could promote the proliferation of bone marrow mesenchymal stem cells compared with the other two groups of bone cement.Compared with the other two groups of bone cements,20%SrPP-CPN increased adenosine triphosphate concentration in bone marrow mesenchymal stem cells.Alkaline phosphatase and alizarin red staining showed that 20%SrPP-CPN could promote osteogenic differentiation of bone marrow mesenchymal stem cells compared with the other two groups of bone cement.(3)In the rat skull defect experiment,Micro-CT scanning and histological observation(hematoxylin-eosin and Masson stainings)showed that bone cement in 20%SrPP-CPN group was significantly degraded compared with that in CPC and CPS groups,and a large number of new bone tissues were dispersed in degraded bone cement.Immunohistochemical staining showed that Runx2 protein expression was increased in 20%SrPP-CPN group compared with CPC group and CPS group(P＜0.01).(4)These results show that 20%SrPP-CPN has good radiopaque ability and osteogenic properties.

Objective To design a kind of customized insole with zonal gradient hardness for people with high arch foot in need of plantar decompression. Methods A functional gradient structure was designed and applied to the customized insole. Porous elements with corresponding elastic modulus were used in different areas of insole. The relationship between structural element parameters and modulus was studied through mechanical tests. The foot geometry and plantar pressure distribution data of volunteers were collected, and the plantar region was divided according to the pressure contour line, so as to assemble the structural unit. Four kinds of customized insoles were designed: ordinary flat insole, optimized flat insole, ordinary full contact insole and optimized full contact insole. Through plantar pressure test experiment, the optimization design of sub region was verified. Results The designed insole could reduce the peak pressure of high arch foot by 52.8% in static standing state and 18.43% in gait condition. Conclusions This method can be used to design customized insoles, such as functional insoles for patients with diabetes and high arch feet, by providing better decompression function. The research findings provide references for conservative treatment of foot diseases with decompression needs.

OBJECTIVE To explore the effects of 5，10-methylenetetetrahydrofolate reductase （MTHFR） gene polymorphism on the adverse reactions in patients with osteosarcoma after the first high-dose methotrexate （HD-MTX） treatment. METHODS A prospective study was conducted to include 53 patients with osteosarcoma treated with HD-MTX at the first admission in General Hospital of Eastern Theater Command. The dose of MTX was evaluated according to the polymorphism of rs1801133 in the METHFR gene and demographic factors， then whole pharmaceutical monitoring was conducted. The data on liver toxicity， renal toxicity， hematological toxicity， and gastrointestinal reaction were collected after the first chemotherapy cycle. Single factor analysis and binary Logistic regression analysis were used to analyze the correlation between MTX dose， 24 h blood drug concentration， and rs1801133 locus genotype with four adverse reactions. RESULTS The MTX dosage in patients with CC wild type was significantly higher than that in TT mutant type （7.97 g/m2 vs. 6.98 g/m2， P＝0.030）， but this difference did not affect the 0 h and 24 h blood drug concentrations of MTX. The above four adverse reactions were not related to the dose of MTX. The results of binary Logistic regression analysis showed that carrying one T allele increased the risk of developing hematological toxicity by 4.13 times（95% confidence interval：1.35-12.62，P＝0.013）. When 24 h plasma concentration threshold of MTX was set to 2.65 µmol/L， the sensitivity and specificity of predicting liver function damage were 53.33% and 86.96%， respectively； when the threshold was set to 7.28 μmol/L， the sensitivity and specificity of predicting renal damage were 100% and 81.63%. CONCLUSIONS The polymorphism of the rs1801133 in the MTHFR gene is associated with hematological toxicity of MTX. Patients who take HD-MTX for the first time and carry the T allele have a high risk of hematological toxicity. The 24 h plasma concentration of MTX is related to liver toxicity and renal toxicity. In addition， monitoring the 24 h blood drug concentration can predict liver and renal toxicity， and take early intervention.

Objective: To evaluate the feasibility and safety percutaneous pulmonary vein intervention in patients with severe pulmonary vein stenosis (PVS) caused by fibrosing mediastinitis(FM). Methods: This retrospective analysis included 5 FM patients (2 male, 3 female, 54-77 years old) confirmed by clinical presentation and chest computed tomography (CT) scan from January to June 2018 who were from Gansu Provincial Hospital and Shanghai Chest Hospital. CT pulmonary angiography (CTPA) further revealed severe PVS caused by fibrotic tissue compression in mediastinum. After selective pulmonary vein angiography, gradually balloon angioplasty was used to expand the pulmonary vein and then stents were implanted in the pre-dilated stenotic pulmonary veins. Evaluation of therapeutic effect was made at 6 months after the procedure. Results: All of 11 serious compression PVS were treated with stent implantation (diameter: 7-10 mm, length: 17-27 mm). After stenting, degree of pulmonary vein stenosis decreased from (83±16)% to (12±4)% (P<0.01). The minimal diameter of the stenotic pulmonary vein was significantly increased from (0.8±0.5)mm to (7.5±0.8)mm (P<0.01). Trans-stenotic gradient decreased from (27.0±15.1)mmHg (1 mmHg=0.133 kPa) to (2.50±0.58)mmHg (P<0.05). Mean pulmonary pressure measured by cardiac catheter decreased from (45.0±9.0)mmHg to (38.7±8.4)mmHg (P<0.05). One patient experienced cardiac arrest due to vagal nerve reflex during big sizing balloon stent dilation and recovered after cardiopulmonary resuscitation. There were no other serious procedure related complications. During the follow-up, severe stenosis at end of proximal stent was evidenced in 1 patient due to fibrotic compression, and another patient developed in-stent thrombosis due to discontinuation of prescribed anticoagulant. Conclusion Percutaneous intervention for severe pulmonary vein stenosis caused by FM is feasible and safe, and can improve hemodynamic caused by the compression of mediastinal vascular structures in these carefully selected patients.

【Objective】 To investigate the relationship of miRNA gene polymorphisms with blood pressure (BP) responses to the sodium and potassium diet intervention. 【Methods】 In 2004, we recruited 514 participants from 124 families in seven villages of Baoji, Shaanxi Province, China. All subjects were given a three-day normal diet, followed by a seven-day low-salt diet, a seven-day high-salt diet, and finally a seven-day high-salt and potassium supplementation. A total of 19 miRNA single nucleotide polymorphisms (SNPs) were selected for analysis. 【Results】 Throughout the sodium-potassium dietary intervention, the BP of the subjects fluctuated across all phases, showing a decrease during the low-salt period and an increase during the high-salt period, followed by a reduction in BP subsequent to potassium supplementation during the high-salt diet. MiR-210-3p SNP rs12364149 was significantly associated with systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) responses to low-salt diet. MiR-4638-3p SNP rs6601178 was significantly associated with SBP while miR-26b-3p SNP rs115254818 was significantly associated with MAP responses to low-salt intervention. In addition, miR-26b-3p SNP rs115254818 was significantly correlated with SBP, DBP and MAP responses to high-salt intervention. MiR-1307-5p SNPs rs11191676 and rs2292807 were associated with SBP and MAP responses to high-salt diet. MiR-4638-3p SNP rs6601178, miR-210-3p SNP rs12364149, miR-382-5p SNP rs4906032 and rs4143957 were significantly associated with SBP response to high-salt diet. In addition, miR-26b-3p SNP rs115254818 was significantly associated with SBP, DBP and MAP responses to potassium supplementation. MiR-1307-5p SNPs rs11191676, rs2292807, and miR-19a-3p SNP rs4284505 were significantly associated with SBP responses to high-salt and potassium supplementation. 【Conclusion】 miRNA gene polymorphisms are associated with BP response to sodium and potassium, suggesting that miRNA genes may be involved in the pathophysiological process of salt sensitivity and potassium sensitivity.