ABSTRACT
Purpose@#Triple-negative breast cancer (TNBC) is highly malignant and has poor prognosis and a high mortality rate. The lack of effective therapy has spurred our investigation of new targets for treating this malignant cancer. Here, we identified RON (macrophage-stimulating 1 receptor) and MET (MET proto-oncogene, receptor tyrosine kinase) as a prognostic biomarker and therapeutic targets for potential TNBC treatment. @*Materials and Methods@#We analyzed RON and MET expression in 187 primary TNBC clinical samples with immunohistochemistry. We validated the targeted therapeutic effects of RON and MET in TNBC using three tyrosine kinase inhibitors (TKIs): BMS-777607, INCB28060, and tivantinib. The preclinical therapeutic efficacy of the TKIs was mainly estimated using a TNBC xenograft model. @*Results@#Patients with TNBC had widespread, abnormal expression of RON and MET. There was RON overexpression, MET overexpression, and RON and MET co-overexpression in 63 (33.7%), 63 (33.7%), and 43 cases (23.0%), respectively, which had poor prognosis and short survival. In vivo, the TKI targeting RON ant MET inhibited the activation of the downstream signaling molecules, inhibited TNBC cell migration and proliferation, and increased TNBC cell apoptosis; in the xenograft model, they significantly inhibited tumor growth and shrank tumor volumes. The TKI targeting RON and Met, such as BMS-777607 and tivantinib, yielded stronger anti-tumor effects than INCB28060. @*Conclusion@#RON and MET co-overexpression can be significant pathological characteristics in TNBC for poor prognosis. TKIs targeting RON and MET have stronger drug development potential for treating TNBC.
ABSTRACT
Objective To estimate the health-adjusted life expectancy (HALE) of adults in Zhejiang province and evaluate the health status of the adults.Methods This study was based on the mortality data collected from Zhejiang Chronic Disease Surveillance Information and Management System,and mortality rates from the underreporting survey and self-reported health data in 2016.Hierarchical Ordered Probit (HOPIT) model was used to estimate the severity-weighted prevalence of disability.Sullivan's method was used to calculate the HALE.Results After adjustment by HOPIT model,the severity-weighted prevalence of disability increased significantly with age (x2=5 795.81,P＜0.001),and it was higher in females than in males (x2=5 353.27,P＜0.001).The life expectancy and self-evaluated HALE were 59.08 years and 48.68 years,respectively,in those aged ≥20 years,the difference was 10.40 years due to disability.The proportion of HALE loss due to disability in the total life expectancy was 17.61％,and it increased with age.HALE was higher in males than in females (49.21 years vs.48.14 years),and in urban residents than in rural residents (49.92 years vs.47.43 years).Conclusion The proportion of loss of HALE in the total life expectancy in adults was high in Zhejiang,and it higher in males than in females,in urban residents than rural residents.Programs on improving health care in women and rural residents should be promoted.
ABSTRACT
Objective To estimate the health-adjusted life expectancy (HALE) of adults in Zhejiang province and evaluate the health status of the adults.Methods This study was based on the mortality data collected from Zhejiang Chronic Disease Surveillance Information and Management System,and mortality rates from the underreporting survey and self-reported health data in 2016.Hierarchical Ordered Probit (HOPIT) model was used to estimate the severity-weighted prevalence of disability.Sullivan's method was used to calculate the HALE.Results After adjustment by HOPIT model,the severity-weighted prevalence of disability increased significantly with age (x2=5 795.81,P＜0.001),and it was higher in females than in males (x2=5 353.27,P＜0.001).The life expectancy and self-evaluated HALE were 59.08 years and 48.68 years,respectively,in those aged ≥20 years,the difference was 10.40 years due to disability.The proportion of HALE loss due to disability in the total life expectancy was 17.61％,and it increased with age.HALE was higher in males than in females (49.21 years vs.48.14 years),and in urban residents than in rural residents (49.92 years vs.47.43 years).Conclusion The proportion of loss of HALE in the total life expectancy in adults was high in Zhejiang,and it higher in males than in females,in urban residents than rural residents.Programs on improving health care in women and rural residents should be promoted.
ABSTRACT
Objective To investigate the effect of clopidogrel on platelet function and inflammation factor in treatment of severe carotid artery stenosis after stent-assisted angioplasty.Methods Patients (120 cases) with severe carotid artery stenosis after stent-assisted angioplasty were chosen and divided into two groups,the control group were given atorvastatin combined with aspirin,and the observation group were given atorvastatin combined with chlorine.The serum coagulants DD level,FIB level,inflammation factor P-chosen element level and restenosis event incidence of two groups were observed.Results D-double polymer of two groups had no significant difference;After surgery,the D-double polymer and FIB level of two groups were all higher (P ＜ 0.05).After surgery for 24 h,the D-double polymer and FIB level of observation group were higher,after 3 months of surgery,the D-double polymer and FIB level had no significant differences compared with before surgery,which were all in normal level.After 24 h,1 month,3 months of surgery,the D-double polymer and FIB level of observation group were all lower than control group (P ＜ 0.05).Before treatment,the P-chosen selectin of two groups had no significant differences,which were all decreased after surgery,and the observation group was lower than control group (P ＜ 0.05);The restenosis event of observation group was lower than control group (P ＜ 0.05).Conclusion Clopidogrel could control the platelet aggregation of severe carotid stenosis after surgery to prevent the thrombogenesis and decrease the restriction incidence,while control the inflammation factor expression to prevent the atherosclerosis.
ABSTRACT
Objective To investigate the effect of clopidogrel on platelet function and inflammation factor in treatment of severe carotid artery stenosis after stent-assisted angioplasty.Methods Patients (120 cases) with severe carotid artery stenosis after stent-assisted angioplasty were chosen and divided into two groups,the control group were given atorvastatin combined with aspirin,and the observation group were given atorvastatin combined with chlorine.The serum coagulants DD level,FIB level,inflammation factor P-chosen element level and restenosis event incidence of two groups were observed.Results D-double polymer of two groups had no significant difference;After surgery,the D-double polymer and FIB level of two groups were all higher (P ＜ 0.05).After surgery for 24 h,the D-double polymer and FIB level of observation group were higher,after 3 months of surgery,the D-double polymer and FIB level had no significant differences compared with before surgery,which were all in normal level.After 24 h,1 month,3 months of surgery,the D-double polymer and FIB level of observation group were all lower than control group (P ＜ 0.05).Before treatment,the P-chosen selectin of two groups had no significant differences,which were all decreased after surgery,and the observation group was lower than control group (P ＜ 0.05);The restenosis event of observation group was lower than control group (P ＜ 0.05).Conclusion Clopidogrel could control the platelet aggregation of severe carotid stenosis after surgery to prevent the thrombogenesis and decrease the restriction incidence,while control the inflammation factor expression to prevent the atherosclerosis.
ABSTRACT
Objective To explore the effect of the combination of Tuina and treadmill training on nerve regeneration after sciatic nerve transection.Methods A total of 60 Sprague-Dawley rats were randomly divided into control group,model group and treatment group equal-ly.The sciatic nerve was transected in the latter two groups and the epineurium suture was delayed four days.Then the treatment group ac-cepted Tuina and treadmill training once a day.The motor conduction velocity(MCV)of sciatic nerve was measured one and two months af-ter intervention in ten rats respectively,while the number of regenerated axons and Schwann cells was counted,and structures of sciatic nev-er were observed under electron microscopy. Results Compared with the model group, the MCV accelerated in the treatment group (P<0.05),the number of axons was not significantly different(P>0.05),and the number of Schwann cells increased two months after modeling (P<0.05),with less injury under electron microscopy.Conclusion Tuina combined with treadmill training can promote the regeneration of the injured peripheral nerve.
ABSTRACT
Objective To improve the diagnosis and treatment of type Ⅰ autoimmune pancreatitis, a study was carried out to summarize the epidemiological characteristics, clinical manifestations and diagnosis of autoimmune pancreatitis (AIP).Methods This study retrospectively analyzed the clinical data of all the patients diagnosed with AIP from January 1998 to December 2016 in the ward of Peking union medical college hospital.Results 194 type 1 AIP patients were enrolled in this study.The M/F ratio of the disease was 3.51/1,with an average age of 57±15 years.The most common symptom is jaundice, abdominal pain and weight loss.The most common diseases of the pancreas are sclerosing cholangitis, salivary glands, IgG4 nephropathy.There are 36.68 percent of AIP patients with diabetes mellitus.IgG4, ANA, ESR, c-reactive protein and CA199 are all contribute to disease diagnosis and follow-up.Pathology, pet-CT and hormone therapy response all contribute to the diagnosis of AIP.Conclusions As a systemic disease, the type 1 AIP has special clinical features and laboratory profiles.The diagnosis of AIP can be applied in many ways.
ABSTRACT
Objective To evaluate the effect for stroke(cerebral infarction)at acute stage intervened by traditional Chinese medicine(TCM) clinical pathway. Methods A retrospective analysis was carried out in the patients before and after intervention by TCM clinical pathway during the year of 2013-2016. The outcomes included the entrance rate,completion percentage,aberration rate,severity,hospitalization time,and hospitalization fee as well as functional prognosis 30 d after discharge. Results A total of 792 cases was included,241 cases admitted in the year of 2013, 191 in the year of 2014, 135 in the year of 2015, and 225 in the year of 2016. In the year of 2014-2016,the entrance rate,completion percentage,hospitalization time,hospitalization fee,critical case percentage,and gender constituent ratio were steadily(P > 0.05). Modified Rankin Scale(mRS)for short-term functional prognosis mRS 0 ~ 2 percentage and aberration rate in the year of 2016 were superior to those in the year of 2014 and 2015(P < 0.05). Functional improvement on discharge day 30 in the year of 2014-2016 was superior to that in the year of 2013(P < 0.05). The hospitalization time and hospitalization fee in the year of 2014-2016 were a liffle higher than those in the year of 2013(P < 0.05), showing no obvious increase. Conclusion The application of TCM clinical pathway can make the diagnosis and treatment procedure of stroke at acute stage standardized,enhance the therapeutic effect,achieve or even exceed the goal of manage scheme.
ABSTRACT
Objective To determine the susceptibility genes and resistance genes in HLA-DRB1 alleles in Tibetan patients with cystic and alveolar hydatid diseases,so as to provide the references for the research of the genetic characteristics and infec-tion mechanism of Tibetan hydatid diseases. Methods The case control method was applied. The Tibetan patients with cystic and alveolar hydatid diseases(63 and 73 cases respectively)in Yushu and Guoluo Tibetan Autonomous Prefecture,and unrelat-ed healthy people(60 cases)in this area were selected as the study subjects. The polymerase chain reaction-sequence based typ-ing(PCR-SBT)technique was applied for genotyping of HLA-DRB1,and the comparison of the gene frequency. Results The frequency of HLA-DRB1*04 in the alveolar/cystic echinococcosis group was lower than that in the control group(χ2 =4.71, 4.31,both P<0.05). Conclusion HLA-DRB1*04 genotypes may be associated with the resistance of cystic and alveolar echi-nococcosis and its resistance genes.
ABSTRACT
Objective To improve vibration resistance of conventional blood transportation kits and mitigate hemolysis during transportation.Methods The structure of a blood transportation kit was modified.We installed a suspension brac-kets within the kit,added buffer material between the brackets,and tested the vibration-suppressing effect compared with the conventional blood transportation kit.Results Rubber and plastic materials between brackets were added,and double membrane suspension brackets were installed.After 4 and 6 min of vibration,free hemoglobin(FHb)[(1559.7 ±1038.5) and(1886.2 ±1023.8)mg/L],lactic dehydrogenase levels[(135.3 ±67.7)and(195.7 ±123.6)U/L]and hemolysis rate[(0.35 ±0.34)%and(0.42 ±0.38)%]in the conventional transportation kit were significantly higher than in the vibration-suppressing kit.K+did not change significantly,and was comparable in both groups at each time point.After 4 and 6 min of vibration, FHb in the conventional transportation kit exceeded the standard.However, after 12 min of vibration,FHb[(560.1 ±342.3)mg/L]in the vibration-suppressing kit were within the standard range.No bacterial growth was detected in either group.Conclusion The vibration-suppressing kit under research shows a better 1986vibration-suppressing effect,which could improve blood support capability in case of emergency.
ABSTRACT
The restoration of motor function after spinal cord injury is a major problem in the medical field,in which axonal regenera-tion is the basis and goal of motor and neurological recovery.Researches showed that electroacupuncture was effective on axonal regenera-tion after spinal cord injury.In this paper,the mechanisms were summarized from the aspects of the formation of glial scar,the role of axon growth inhibitory factor,the secretion of neurotrophic factor and the growth status of neurons.
ABSTRACT
Identifying a target molecule that is crucially involved in pancreatic tumor growth and metastasis is necessary in developing an effective treatment. The study aimed to investigate the role of the eukaryotic translation initiation factor 3a (eIF3a) in the cell proliferation and motility in pancreatic cancer. Our data showed that the expression of eIF3a was upregulated in pancreatic ductal adenocarcinoma as compared with its expression in normal pancreatic tissues. Knockdown of eIF3a by a specific shRNA caused significant decreases in cell proliferation and clonogenic abilities in pancreatic cancer SW1990 and Capan-1 cells. Consistently, the pancreatic cancer cell growth rates were also impaired in xenotransplanted mice. Moreover, wound-healing assay showed that depletion of eIF3a significantly slowed down the wound recovery processes in SW1990 and Capan-1 cells. Transwell migration and invasion assays further showed that cell migration and invasion abilities were significantly inhibited by knockdown of eIF3a in SW1990 and Capan-1 cells. Statistical analysis of eIF3a expression in 140 cases of pancreatic ductal adenocarcinoma samples revealed that eIF3a expression was significantly associated with tumor metastasis and TNM staging. These analyses suggest that eIF3a contributes to cell proliferation and motility in pancreatic ductal adenocarcinoma.
Subject(s)
Animals , Mice , Adenocarcinoma , Cell Movement , Cell Proliferation , Neoplasm Metastasis , Neoplasm Staging , Pancreatic Ducts , Pancreatic Neoplasms , Peptide Initiation Factors , RNA, Small Interfering , Wounds and InjuriesABSTRACT
<p><b>BACKGROUND</b>Although the use of hepatitis B immunoglobulin (HBIG) may lead to a significant reduction in recurrent hepatitis B virus (HBV) infection and improve the survival of patients who have undergone liver transplantation (LT) for hepatitis B-related diseases, the recurrence of the disease still remains at a lower level. Different clinical curative effects were observed in patients with the same HBV-related diseases and the same therapy. This study was undertaken to investigate whether the efficacy of HBIG is associated with FCGR3A gene polymorphisms in Chinese liver transplant patients.</p><p><b>METHODS</b>Altogether 77 patients who had received liver transplantation for hepatitis B-related diseases with more than one-year survival after surgery were studied. The recurrence of HBV was characterized by the appearance of HBsAg in serum after the operation. The FCGR3A genotyping was performed using genomic DNA sequencing (ABI 3037). Single nucleotide polymorphism at nucleotide 559 was detected by Polyphred.</p><p><b>RESULTS</b>Of the 77 patients, 14 were complicated with HBV recurrence post-transplant. The FCGR3A at nucleotide 559 TT was observed in 35 (45.5%) subjects, whereas TG in 31 (40.3%) and GG in 11 (14.3%). In the 559G carrier group (n = 42, 54.5%), the risk of HBV recurrence was 9.5%, and 1- and 2-year recurrence-free survival rates were 95.2% and 88.7%, respectively. In the 559G noncarrier group (n = 35, 45.5%), the risk of HBV recurrence was 28.6%, and 1- and 2-year recurrence-free survival rates were 74.3% and 69.3%, respectively. The risk of HBV recurrence and the recurrence-free survival rate were both statistically different between the 559G carrier and noncarrier groups (P < 0.05).</p><p><b>CONCLUSIONS</b>A single nucleotide polymorphism (T/G) at position 559 of the FCGR3A gene was found in Chinese patients. The efficacy of HBIG in prophylaxis of HBV recurrence after LT is associated with the gene polymorphism, so detecting FCGR3A genotypes can be a clinical reference of the HBIG administration.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Genotype , Hepatitis B , Immunoglobulins , Therapeutic Uses , Liver Transplantation , Polymorphism, Genetic , Prognosis , Receptors, IgG , Genetics , RecurrenceABSTRACT
<p><b>BACKGROUND</b>SARS-CoV is the causative agent of severe acute respiratory syndrome (SARS) which has been associated with outbreaks of SARS in Guangdong, Hong Kong and Beijing of China, and other regions worldwide. SARS-CoV from human has shown some variations but its origin is still unknown. The genotyping and phylogeny of SARS-CoV were analyzed and reported in this paper.</p><p><b>METHODS</b>Full or partial genomes of 44 SARS-CoV strains were collected from GenBank. The genotype, single nucleotide polymorphism and phylogeny of these SARS-CoV strains were analyzed by molecular biological, bioinformatic and epidemiological methods.</p><p><b>RESULTS</b>There were 188 point mutations in the 33 virus full genomes with the counts of mutation mounting to 297. Further analysis was carried out among 36 of 188 loci with more than two times of mutation. All the 36 mutation loci occurred in coding sequences and 22 loci were non-synonymous. The gene mutation rates of replicase 1AB, S2 domain of spike glycoprotein and nucleocapsid protein were lower (0.079% - 0.103%). There were 4 mutation loci in S1 domain of spike glycoprotein. The gene mutation rate of ORF10 was the highest (3.333%) with 4 mutation loci in this small domain (120 bp) and 3 of 4 loci related to deletion mutation. By bioinformatics processing and analysis, the nucleotides at 7 loci of genome (T:T:A:G:T:C:T/C:G:G:A:C:T:C) can classify SARS-CoV into two types. Therefore a novel definition is put forward that according to these 7 loci of mutation, 40 strains of SARS-CoV in GenBank can be grouped into two genotypes, T:T:A:G:T:C:T and C:G:G:A:C:T:C, and named as SARS-CoV Yexin genotype and Xiaohong genotype. The two genotypes can be further divided into some sub-genotypes. These genotypes can also be approved by phylogenetic tree of three levels of 44 loci of mutation, spike glycoprotein gene and complete genome sequence. Compared to various strains among SARS-CoV Yexin genotype and Xiaohong genotype, GD01 strain of Yexin genotype is more closely related to SARS-CoV like-virus from animals.</p><p><b>CONCLUSION</b>The results mentioned above suggest that SARS-CoV is responding to host immunological pressures and experiencing variation which provide clues, information and evidence of molecular biology for the clinical pathology, vaccine developing and epidemic investigation.</p>