Objective To make the cost-effectiveness analysis of pembrolizumab and platinum chemotherapy as the first-line treatment for advanced non-small cell lung cancer(NSCLC)in the population with tumor proportion score(TPS)≥1%of PD-L1,and provide some reference for the clinical use and future price negotiation of pembrolizumab.Methods Based on Pubmed database,the published RCT literatures of pembrolizumab were analyzed,and the survival data were extracted,combined with the treatment plan of a tertiary hospital,the Markov model were established to simulate the cost and health effectiveness of patients for twenty years,and the stability of the model was tested by one-way sensitivity analysis and probability sensitivity analysis.Results Twenty years later,the cost-effectiveness ratio of pembrolizumab group and chemotherapy group was ￥58 517.60/quality adjusted life month(QALM)and ￥41 213.08/QALM.Compared with the chemotherapy group,the incremental cost effective ratio(ICER)was ￥104 485.36/QALM.Conclusion When the willingness to pay(WTP)value was ￥30 902/QALM,the pembrolizumab therapy was not more cost-effective advantages than platinum chemotherapy,and the sensitivity analysis showed that the results of the model were relatively stable.

Objective·To detect the effects of propofol sedation on cognitive function in rats and its mechanism. Methods?·?Forty-eight SD rats were randomly divided into three groups, i.e. control group, 100?mg/kg group and 300?mg/kg group. Rats were administrated intraperitoneally with propofol (10?mg/mL, 100?mg/kg or 300?mg/kg). The mRNA levels of brain derived neurotropic factor (BDNF)-TrkB/p75 signal molecules in rat hippocampus were evaluated by realtime PCR 45 min after propofol treatment. Learning and memory ability was examined by inhibitory avoidance (IA) test after propofol treatment. Results?·?The mRNA levels of BDNF in the hippocampal tissue were (1.20±0.13) fold (P=0.002) and (88±12) % (P=0.044) of that in control group, respectively, in 100?mg/kg group and 300?mg/kg group after injection of propofol. The mRNA levels of TrkB were (1.01±0.11) fold ( P=0.982) and (86±11) % (P=0.018) of that in control group, respectively, in 100?mg/kg group and 300?mg/kg group. The mRNA levels of p75 were (1.02±0.10) fold (P=0.778) and (1.59±0.18) fold (P=0.000) of that in control group, respectively, in 100?mg/kg group and 300?mg/kg group. There was no significant difference of the 24 h IA memory retention latency between 100?mg/kg group and control group. The 24 h IA memory retention latency in 300?mg/kg group was significantly decreased compared with control group (P=0.028) and 100?mg/kg group (P=0.020). Conclusion?·?Propofol dose-dependently regulates the expression of BDNF-TrkB/p75 signal molecules, and high dose propofol may reduce cognitive function via BDNF-TrkB/p75 signal.

BACKGROUNDParoxysmal kinesigenic dyskinesia (PKD) is a rare movement disorder characterized by recurrent dystonic or choreoathetoid attacks triggered by sudden voluntary movements. Under the condition of psychological burden, some patients' attacks may get worsened with longer duration and higher frequency. This study aimed to assess nonmotor symptoms and quality of life of patients with PKD in a large population.

METHODSWe performed a cross-sectional survey in 165 primary PKD patients from August 2008 to October 2016 in Rui Jin Hospital, using Symptom Check List-90-Revised (SCL-90-R), World Health Organization Quality of Life-100 (WHOQoL-100), Self-Rating Depression Scale, and Self-Rating Anxiety Scale. We evaluated the differences of SCL-90-R and WHOQOL-100 scores in patients and Chinese normative data (taken from literature) by using the unpaired Student's t-test. We applied multivariate linear regression to analyze the relationships between motor manifestations, mental health, and quality of life among PKD patients.

RESULTSCompared with Chinese normative data taken from literature, patients with PKD exhibited significantly higher (worse) scores across all SCL-90-R subscales (somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism; P= 0.000 for all) and significantly lower (worse) scores of five domains in WHOQoL-100 (physical domain, psychological domain, independence domain, social relationship domain, and general quality of life; P= 0.000 for all). Nonremission of dyskinesia episodes (P = 0.011) and higher depression score (P = 0.000) were significantly associated with lower levels of quality of life. The rates of depression and anxiety in patients with PKD were 41.2% (68/165) and 26.7% (44/165), respectively.

CONCLUSIONSDepression, anxiety, and low levels of quality of life were prevalent in patients with PKD. Co-occurrence of depression and anxiety was common among these patients. Regular mental health interventions could set depression and anxiety as intervention targets. Considering that the motor episodes could be elicited by voluntary movements and sometimes also by emotional stress, and that symptoms may get worsened with longer duration and higher frequency when patients are stressed out, intervention or treatment of depression and anxiety might improve the motor symptoms and overall quality of life in PKD patients.

Exons ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Membrane Proteins ; genetics ; Middle Aged ; Mutation ; Pedigree ; Spastic Paraplegia, Hereditary ; etiology ; genetics

In the 1960s, modern science began involving the essence of heat syndrome, but there have still no in-depth systematic studies on pathological mechanisms of heat syndrome and action mechanisms of cold and cool herbs. In this study, the animal model with heat syndrome was set up by feeding herbs with hot property, and then cold and cool herbs was applied in the experimental therapy. The two-dimensional electrophoresis and mass spectrometry technologies were adopted to compare the liver mitochondria proteome of the rats of the heat syndrome model and the ones treated with cold and cool herbs, so as to discover specificity-related proteins after heat syndrome and treatment with cold and cool herbs.
Animals ; Carbohydrate Metabolism ; drug effects ; Cold Temperature ; Drugs, Chinese Herbal ; pharmacology ; Energy Metabolism ; drug effects ; Hot Temperature ; Lipid Metabolism ; drug effects ; Male ; Mitochondria, Liver ; drug effects ; metabolism ; Proteome ; metabolism ; Rats ; Rats, Sprague-Dawley

[Introduction] To explore the gene-based logistic kemel-machine regression model and its application in genome-wide association study (GWAS).Using the simulated genome-wide singlenucleotide polymorphism (SNPs) genotypes data,we proposed a practical statistical analysis strategynamed ‘ the logistic kernel-machine regression model',based on the gene levels to assess the association between genetic variations and complex diseases.The results from simulation showed that the P value of genes in related diseases was the smallest among all the genes.The results of simulation indicated that not only it could borrow information from different SNPs that were grouped in genes and reducing the degree of freedom through hypothesis testing,but could also incorporate the covariate effects and the complex SNPs interactions.The gene-based logistic kernel-machine regression model seemed to have certain statistical power for testing the association between genetic genes and diseases in GWAS.

To explore the gene-based principal component logistic regression model and its application in genome-wide association study.Using the simulated genome-wide single nucleotide polymorphism (SNPs) genotypes data,we proposed a practical statistical analysis strategy-'the principal component logistic regression model',based on the gene levels to assess the association between genetic variations and complex diseases.The simulation results showed that the P value of genes in related diseases was the smallest among the results from all the genes.The results of simulation indicated that not only it could reduce the degree of freedom through hypothesis testing but could also better understand the correlations between SNPs.The gene-based principal component logistic regression model seemed to have certain statistical power for testing the association between genetic genes and diseases in the genome-wide association studies.

OBJECTIVETo analyze the relation between recurrent miscarriage and routine semen parameters.

METHODSWe compared the semen parameters of normal healthy men with those of the spouses of recurrent miscarriage women through 1: 1 age-matched case-control study.

RESULTSCompared with the healthy controls, the men of the case group showed a significantly lower mean semen volume ([1.95 +/- 1.11] ml vs [2.74 +/- 1.43] ml), sperm concentration ([48.68 +/- 20.07] x 10(6)/ml vs [59.26 +/- 25.35] x 10(6)/ml), percentage of grade b sperm ([12.07 +/- 3.34] % vs [16.18 +/- 6.74] %), fruit-sugar content ([1.73 +/- 0.64] g/L vs [2.21 +/- 0.75] g/L), acrosomal enzyme activity ([84.34 +/- 26.69] U/mg prot vs [94.20 +/- 26.35] U/mg prot), alpha-glucuronidase (alpha-GLU) content ([36.28 +/- 15.98] U/ml vs [44.45 +/- 12. 54] U/ml), and acid phosphatase (ACP) content ([68.55 +/- 35.45] U/ml vs [84.78 +/- 51. 10] U/ml) (P < 0.05), but remarkably higher percentages of head teratospermia ([47.36 +/- 4.59] % vs [46.50 +/- 6.32] %) and tail teratospermia ([7.56 +/- 2.27] % vs [7.28 +/- 3.10] %), and elastase content ([885.64 +/- 1 272.30] ng/ml vs [661.08 +/- 764.64] ng/ml) (P < 0.05). Based on the results of discriminant analysis, the semen volume, percentages of grade b sperm and combined teratospermia, and contents of fruit-sugar, alpha-GLU and ACP could be used to evaluate the semen and sperm quality of the spouses of recurrent miscarriage women.

CONCLUSIONRoutine semen and sperm tests might help evaluate the seminal factors of recurrent miscarriage, but they lack specificity and need comprehensive analysis. Poorer semen quality is associated with higher incidence of recurrent miscarriage.

Abortion, Habitual ; etiology ; Adult ; Case-Control Studies ; Female ; Humans ; Male ; Pregnancy ; Semen ; Sperm Count ; Sperm Motility ; Spermatozoa

Objective To investigate the depressing effect of antigene peptide nucleic acid (AGPNA)on the k-ras gene expression of human pancreatic cancer Patu8988 cells, the inducing apoptosis effect on Patu8988 cells, and the biodistribution characteristics in nude mice bearing xenografts using 188Re-k-ras-AGPNA.Methods The expression level of k-ras mRNA and the expression ratio of k-ras protein in Patu8988 cells transfected with AGPNA was measured by RT-PCR and flow cytometry ,respectively. The degree of cellular apoptosis 3 to 5 d after treating Patu8988 cells with 188Re-k-ras-AGPNA or 188ReO4- was determined by flow cytometry. For biodistribution study, 58 nude mice bearing Patu8988 cell xenografts were divided into two groups: intratumoral injection of 188Re-k-ras-AGPNA (Group A) and 188ReO4- (Group B). At different time points, the mice were sacrificed and organs of interest were excised, weighted and counted by a gamma counter. The organ uptake was calculated as a % ID/g and the absorbed doses of organs were calculated. One-way analysis of variance was used. Results After transfected with 1 nmol/ml AGPNA, the k-ras mRNA gray scale ratio and the expression ratio of k-ras protein were 1.00 ± 0.39 and (15.05 ± 5.07)%, respectively. They were significantly lower than those of the control group with 1.86 ± 0.07 and (24. 38 ± 5.40) % (F = 2. 545, 5. 327, P<0. 05). At 4 and 5 d after treatment in Group A, float cells' apoptosis ratios were (26.30 ± 7.45) % and (27.90 ± 10. 38) %, respectively. Tumors were the major distribution site in Group A with uptake of (37.47 ±21.31), (35.96 ±7.80) and (15.46 ±4.93) %lD/g at 1 h, 1 d and 7 d after intra-tumor injection, respectively. The absorbed dose of tumor was 15 569 mGy/MBq. Condusions Transfection with k-ras-AGPNA on Patu8988 cells may inhibit k-ras expression at mRNA and protein expression level, and 188Re-k-ras-AGPNA can induce apoptosis of Patu8988 cells.Tumor is the major distribution site in nude mice bearing human pancreatic cancer xenografts after intratumoral injection of 188Re-k-ras-AGPNA.

Objective Some major procedures for DeBakey type Ⅰ aortic dissection used to be performed with deep hypothermic circulatory arrest, which had been associated with more complications than seen with standard extracorporeal circulation. We reviewed the cases who received the treatment for DeBakey type Ⅰ aortic dissection by hybrid procedure without deep hypothermic circulatory arrest. The procedure consisted of ascending aorta replacement, ascending aorta-aortic arch branch vascular bypass reconstruction and endovascular graft exclusion. Methods From January 2009 to June 2010, 39 patients [mean age (55 ±16) years] who had DeBakey Ⅰ aortic dissection underwent hybrid procedure without deep hypothermic circulatory arrest. The femoral artery and right axillary artery were cannulated for perfusion. The ascending aorta and/or aortic valves were replaced under conventional extracorporeal circulation with Bentall procedure or Wheat procedure. The aortic arch branch vessels were dissected and the proximal part was sealed. Then the ascending aorta-aortic arch branch vascular bypasses were constructed with 4-bifurcation vascular grafts, Y-shape bifurcated vascular grafts or artificial vessels. Finally the endovascular grafts were deployed via the femoral incisions monitored dynamically with DSA, or via the ascending aortic bifurcated vessels monitored with transesophageal echocardiography. Results The operation succeeded in all 39 patients. Eight patients underwent ascending aorta replacement without aortic valve replacement or prosthesis, 20 patients underwent Bentall procedure ( Carbrol procedure were used in 11 cases), and 11 underwent Wheat procedure. For ascending aorta-aortic branch vascular bypass reconstruction, sequential anastomoses were performed in 8, Y-shaped bifurcated grafts were used in 15, and 4-bifurcated grafts were employed in 16 patients. The endovascular stent grafts were deployed via the former femoral incisions in 36 patients and via ascending aortic bifurcated vessels in 3. The cardiopulmonary bypass time was (61 ±22) minutes, the aortic crossclamp time was (48 ±18) minutes, and the post-operative intubation time was (30 ±9) hours. The thoracic drainage from each patient was less than 300 ml in 24 hours. No complication, such as hemiplegia, paraplegia, severe infections, renal failure or coagulation disorder, was observed. The duration of hospitalization was (21 ±6) days. No hospital death occurred. Follow-up was performed 1 to 15 months [mean (8.4 ±7.2) months] postoperatively. All patients survived without any organ dysfunction at follow up. The CTA examination 3 months after operation revealed that the false lumens had been closed in 91.2% of the patients. Conclusion Our findings indicated that the hybrid procedure, which combining ascending aorta replacement,ascending aorta-aortic arch branch vascular bypass reconstruction and endovascular graft exclusion under conventional extracorporeal circulation, may be an option for avoiding the possible complications associated with profound hypothermic circulatory arrest. The novel hybrid operation may improve the surgical outcomes and provide a simplified surgical approach for the treatment of DeBakey Ⅰ aortic dissection.