ABSTRACT
Objective:To investigate the correlation between time within the glucose target range(TIR) and hyperuricemia(HUA) in patients with type 2 diabetes mellitus(T2DM).Methods:A total of 215 patients with T2DM in the First Affiliated Hospital of Bengbu Medical College from June 2021 to May 2022 were selected and divided into HUA group and non-HUA group according to serum uric acid level. The clinical characteristics and biochemical indicators of the patients were collected. The association of 72 h glucose monitoring system(FGMS) related indicators TIR, mean blood glucose fluctuation range(MAGE), blood glucose variability(CV), blood glucose standard deviation(SDBG), and mean blood glucose(MBG) with serum uric acid level was analyzed. The influencing factors of T2DM combined with HUA were analyzed with binary logistic regression, and receiver operating characteristic(ROC) curve was drawn to evaluate their predictive values.Results:TIR of HUA group was significantly decreased compared with non-HUA group, while HbA 1C, MAGE, CV, SDBG, and MBG were increased( P<0.001). Spearman correlation analysis showed that serum uric acid levels were negatively correlated with TIR, but positively correlated with MAGE, CV, SDBG, and MBG( P<0.001). After dichotomous logistic regression analysis, TIR was found to be an independent protective factor for T2DM with HUA. The ROC curve results showed that the area under the curve(AUC) of TIR for predicting HUA in T2DM was 0.856(95% CI 0.803-0.909, P<0.001), with the best cut-off value being 64.5%, the sensitivity being 76.8%, and the specificity being 90.3%. Conclusion:TIR in patients with T2DM combined with HUA was significantly decreased. TIR is an independent protective factor for T2DM combined with HUA, and TIR shows a certain predictive value for T2DM combined with HUA.
ABSTRACT
The triple-negative breast cancer has a relatively poor prognosis with limited therapeutic options. This subtype is highly immunogenetic and exhibits rich tumor infiltrated lymphocytes in the tumor microenvironment. However, immunotherapy alone is less effective as compared with the doublet of chemotherapy and immunotherapy in TNBC. The efficacy in early recurrence settings of mTNBC exceeds that in heavily treated subgroups. Meanwhile, other combinations including anti-angiogenesis, immune modulators, and PARPi elicit a promising effect. Herein, this paper reviews the progress of efficacy, safety, and the outlook in the immunotherapy of TNBC disease.
ABSTRACT
s Triple-negative breast cancer (TNBC), a heterogeneous tumor that lacks the expression of estrogen receptor (ER), proges-terone receptor (PR), and human epidermal growth factor receptor 2 (HER2), is more aggressive and tends to recur or metastasize. In contrast to other breast cancer subtypes, no approved endocrine or targeted treatments exist for TNBC. Therefore, identification of the prognosis characteristisics and potential therapeutic targets of TNBC could facilitate early personalized treatment. Owing to the rapid development of various technologies, researchers are increasingly focusing on the integration of "big data" and biological sys-tems, which is referred to "omics," as means of resolving it . Here, we review the recent progress in transcriptomics and proteomics re-search on TNBC.
ABSTRACT
To explore the immobilization of target proteins for screening libraries of ligand mixtures, magnetic submicron particles (MSP) functionalized with Ni²⁺-NTA and carboxyl were compared for the immobilization of Mycobacterium tuberculosis dihydrofolate reductase (MtDHFR). MtDHFR fused with 6×His was expressed, purified and characterized for kinetics. MtDHFR was immobilized on Ni²⁺-NTA-functionalized MSP directly and carboxyl-functionalized MSP upon activation. The immobilization capacity, residual activity, thermostability and affinities for putative inhibitors were characterized. MtDHFR immobilized on Ni²⁺-NTA-functionalized MSP retained about 32% activity of the free one with the immobilization capacity of (93±12) mg/g of MSP (n=3). Ni²⁺ and EDTA synergistically inhibited MtDHFR activity, while Fe³⁺ had no obvious interference. MtDHFR immobilized on carboxyl-functionalized MSP retained (87±4)% activity of the free one with the immobilization capacity of (8.6±0.6) mg/g MSP (n=3). In 100 mmol/L HEPES (pH 7.0) containing 50 mmol/L KCl, there was no significant loss of the activities of the free and immobilized MtDHFR after storage at 0 °C for 16 h, but nearly 60% and 35% loss of their activities after storage at 25 °C for 16 h, respectively. The inhibition effects of methotrexate on the immobilized and free MtDHFR were consistent (P>0.05). The immobilization of MtDHFR on carboxyl-functionalized MSP was thus favorable for higher retained activity and better thermostability, with promise for rapid screening of its ligand mixtures.
Subject(s)
Enzyme Stability , Enzymes, Immobilized , Hydrogen-Ion Concentration , Kinetics , Ligands , Magnetite Nanoparticles , Mycobacterium tuberculosis , Temperature , Tetrahydrofolate DehydrogenaseABSTRACT
Objective To analyze the drug resistance phenotype and genetic background of New Delhi metallo-β-lactamase (NDM)-producing bacterial strains in Lishui area of Zhejiang province.Methods The imipenem-resistant Enterobacteriaceae strains were isolated from January 2012 to December 2016 in Lishui Municipal Central Hospital of Zhejiang Province.Mrieux Vitek 2 Compact system was used to identified strains and PCR was used to screen for blaNDMgene.Susceptibility was detected by K-B method and MICs were obtained by Vitek 2 with GN13 cards.Plasmids typing was carried out by DNA sequencing of the replication initiator with the transconjugates as templates.The blaNDMgenetic contexts were detected by PCR and complete genome sequencing.Results A total of 102 strains of carbapenem-resistant enterobacteria (CRE), mainly Escherichia coli and Enterobacter cloacae, were isolated, of which 15 were positive for blaNDMwith a positive detection rate of 14.7%.The resistance rate to β-lactam antibiotics was 100%, and the resistance rates to aztreonam, compound sulfamethoxazole , tobramycin and gentamicin were all ＞80%;and the resistance rate to quinolones was ＞50%.Among the 15 NDM-producing strains , 12 strains were positive for Hodge test, and 2 strains of Enterobacter cloacae and 1 strain of Escherichia coli were negative. There were 11 strains of blaNDM-1and 4 strains of blaNDM-1.A variety of plasmid types such as IncX 3, IncFIIγ and IncA/C were detected, and 4 blaNDM-5genes were located in the IncX3 plasmid.Four blaNDMsurrounding gene structures were found, of which 8 blaNDM-1genes were located in ISAb125-hyp-blaNDM-1-bleMBL-TrpF-DsbC-IS26, while blaNDM-5was located in IS3000-IS5-blaNDM-5-bleMBL-TrpF-DsbC-IS26 structure, and the former was reported for the first time in China.Conclusion NDM-producing bacterial strains in Lishui area are prevalent at a low level and have high sensitivity to fosfomycin and polymyxin .The blaNDMgene may have multiple sources, but IncX3 plasmid is still the main source for gene transfer.Some new types of blaNDM-1 gene structure have been also found in this study.
ABSTRACT
Objective To investigate whether MT1-MMP is involved in the inhibition effect of curcumin on the proliferation and invasion of breast cancer cell and the mechanism . Methods Firstly, MCF-7 cell lines transfected by MT1-MMP eukaryotic expression vector was established. We divided all cells into 3 groups,including null vector transfection group, non-transfected and transfected group with different concentrations of curcumin. The expression of MT1-MMP protein, the proliferation and invasion ability were respectively analyzed by western blot, transwell method, and cell counting kit-8 (CCK-8). Results The expression of MT1-MMP was inhibited by curcumin. Transwell and CCK-8 experiment indicated the proliferation and invasion abilities of MT1-MMP transfected MCF-7 cells were inhibited by curcumin in a concentration dependent manner. Conclusion The inhibition value of curcumin on proliferation and invasion is probably due to its ability to inhibit the expression of MT1-MMP.
ABSTRACT
Objective To explore how clinical pharmacists participate in clinical drug practice.Methods Clinical pharmacists involved in the treatment of one lymphocytic hyophysitis case with glucocorticoid and provided patient with medication education to ensure the safe and effective treatment.Results Pharmacists offered an effective and feasible treatment program for doctors and the patient.Conclusion Clinical pharmacists participated actively in the clinical treatment programs to ensure the effective development of clinical diagnosis and treatment and improve the medication therapy results.
ABSTRACT
<p><b>OBJECTIVE</b>To examine the expression pattern of membrane type-1 matrix metalloproteinase (MT1-MMP) in breast carcinomas.</p><p><b>METHODS</b>Forty-three breast cancer tissues were collected and examined for MT1-MMP protein and mRNA expressions using immunohistochemistry, semi-quantitative RT-PCR and in situ hybridization.</p><p><b>RESULTS</b>Immunohistochemistry of the breast cancer specimens showed MT1-MMP immunoreactivity on the cancer cell membrane. MT1-MMP mRNA was located in the stromal cells surrounding the breast cancer nest as shown by in situ hybridization. MT1-MMP mRNA expression was detected in all of the carcinomas, but its level was significantly lower in immunohistochemically negative specimens than in positive ones (0.547=0.0886 vs 0.759=0.0802, Plt;0.01).</p><p><b>CONCLUSION</b>MT1-MMP is very likely produced by stromal cells surrounding the breast cancer nest and anchored on the cell membrane after activation.</p>
Subject(s)
Female , Humans , Breast Neoplasms , Genetics , Metabolism , Immunohistochemistry , In Situ Hybridization , Matrix Metalloproteinase 14 , Genetics , Metabolism , RNA, Messenger , Genetics , Metabolism , Tumor Cells, CulturedABSTRACT
An auxiliary training system was explored for the development of creativity of long-termsystem medical undergraduates through scientific researches in spare time.In practice,professionals from research groups of different disciplines were recruited for developing wide-scope theoretical and technical bases of the undergraduates through training among these research groups followed by focused researches on topics of the running projects of these professionals.The undergraduates were engaged in a serial of research activities,including the discovery of problems for reasoning out scientific research projects,the writing of their project proposals,the summary of their data and the writing of reports,to develop their creativity and their qualification for scientific researches.
ABSTRACT
Objective To identify the association of thyroid stimulating hormone receptor ( TSHR ) gene intron 1 susceptible loci and 4p14 susceptible locus rs6832151 polymorphisms with Graves’ disease ( GD) in Han Chinese population in Bengbu, Anhui, China. The gene-gene interaction among TSHR intron 1 susceptible loci and 4p14 susceptible locus rs6832151 was also investigated. Methods The genotypes of the single-nucleotide polymorphisms ( SNPs) were analyzed by Taqman probe technique on Fluidigm EP1 platform in 611 patients with GD and 555 control subjects, and linkage analysis, correlation analysis, haplotype analysis, and epistasis analysis with them were performed. Results Six SNPs in two candidate genes(rs12101261, rs4903964,rs179247, rs2284722 and rs17111394 in TSHR, rs6832151 in 4p14) were associated with GD (all P<0. 05). The frequency distributions of haplotypes of SNPs in TSHR intron 1 ( AGTA, GGCG, AATA, and CC) were significantly different between GD and control groups(all P<0. 01). There existed the interactions between rs179247 and rs12101261 in TSHR(P=0. 001) and among rs179247(TSHR),rs4903964(TSHR) and rs6832151(4p14) (P=0. 001). Conclusions rs683215 in 14p14 and rs12101261, rs4903964, rs179247, rs2284722 and rs17111394 in TSHR intron 1 were susceptible loci of GD in the Chinese Han population from Bengbu. The haplotypes in TSHR intron 1 were associated with GD. There exists the interaction between the SNPs in TSHR and 4p14,which may change the risk of GD.
ABSTRACT
Objective To evaluate the clinical value of early intervention of second-line treatment for advanced breast cancer patients who experienced elevated tumor marker without any evidence for progress on imaging after effective first-line treatment. Methods We recruited 42 metastatic breast cancer patients experiencing elevated tumor marker (CEA or CA-153) meanwhile, who had merely increased tumor markers again in regular review after effective first-line treatment. Patients were divided into two groups: 20 patients in treatment group were given second-line treatment (palliative chemotherapy); 22 patients in observation group insisted on regular follow-up without any changing of treatment strategy. We mainly evaluated PFSmarker , which was defined as the time between tumor markers increase and disease progression. Results CEA and CA-153 in patients with advanced breast cancer showed a tendency to decrease after first-line chemotherapy , which can be reduced again by second-line treatment while increased in regular review , and the observation group continued to rise until disease progressed. The PFSmarker in treatment group was 13.65 (6 ~ 24) months while that of the observation group was 8.18 (3 ~ 15) months. The difference of PFS between these two groups was statistically significant (P < 0.05) and the median time to disease progression in treatment group was significantly longer than that in observation group. Conclusions Early intervention of second-line treatment for advanced breast cancer patients who only experienced elevated tumor marker after effective first-line treatment could slow down disease progression and improve the quality of life.
ABSTRACT
Diabetes is a kind of metabolic syndrome, always hap-pening in the case of insufficient secretion of insulin or insulin resistance, inducing the increase of blood glucose. While, dia-betic osteoporosis is a kind of chronic diabetic complications, which happens when insulin secretion is absolutely or relatively insufficient and then the insufficiency induces imbalance of hor-mone, calcium phosphorus metabolic disorders, thus leading to the decline of bone mineral density and change of bone micro-structure. The overnutrition, less exercise and the environment change lead to the increased incidence of diabetes. For all the diabetes, type 2 diabetes accounts for about 90%. Patients with type 2 diabetes show the increasing risk of fracture. This review summarizes the recent advances in the influence of type 2 diabe-tes on bones.
ABSTRACT
Cardiovascular and cerebrovascular diseases have be-come a great health threat.Increasing evidence has shown that both asymmetric dimethylarginine (ADMA)and symmetric dim-ethylarginine (SDMA)play important and independent roles in the development of cardiovascular and cerebrovascular diseases as well as in the prediction of cardiovascular and cerebrovascular events.Alanine-glyoxylate aminotransferase 2 (AGXT2 )is re-cently observed to be involved in ADMA metabolism.Deficiency in the expression and activity of AGXT2 may thus play a role in the development of cardiovascular and cerebrovascular diseases by affecting ADMA levels in vivo.Several single-nucleotide poly-morphisms at AGXT2 locus are observed to be associated with plasma SDMA level.This review summarizes recent advances in AGXT2 and its role in ADMA metabolism and the clinical rele-vance.
ABSTRACT
As a tubulin stabilizer, taxanes are widely used in the treatment of breast cancer, ovarian cancer, non-small-cell lung cancer (NSCLC),and part of head and neck malignant tumors, and were confirmed to be significantly effective.However, taxanes-induced peripheral neuropathy(TIPN) still affects the quality of life and psychological status of patients to varying degrees, severe cases can lead to dose reduction, and even chemotherapy interruption.In this paper, we summarize the pathogenesis, risk factors, clinical assessment, the progress of prevention and treatment of TIPN, to provide the basis for the prediction and early prevention of TIPN in the clinical administration, thus we can improve patients’ quality of life while extending their survival.
ABSTRACT
Breast cancer is one of the most common malignancies in women. Over these years, the morbidity of metabolic syndrome (MS) has also been increasing in China, probably due to changes in economies and lifestyles. As a result, the association to between these two diseases has at tracted much attention. Results demonstrated the presence of MS was associated with breast cancer risk, and the risk became higher when more MS components were present compared to no components. Moreover, a specific association was indicated between MS and breast cancer recurrence and metastasis to some extent as well. Further, for breast cancer patients, being diagnosed with MS can increase the mortality and lead to poor prognosis. The mechanisms underlying the association is not clear yet, but several factors are speculated to be the possible causes, including the elevated level of insulin, insulin like growth factor-1, leptin and pro-inflammatory cytokines, the decreased level of adiponectin as well as the interaction between DBC1 and SIRT1. The prognosis of patients with breast cancer combined MS can be improved by means of changing diet habits, increasing physical activities and drug-intervention. Although the specific mechanisms underlying the association are still need to be elucidated, better understanding of the association must help us with new strategies for the prevention and treatment of breast cancer.
Subject(s)
Humans , Adiponectin , Breast Neoplasms , Insulin , Metabolic Syndrome , PrognosisABSTRACT
<p><b>OBJECTIVE</b>To screen differentially expressed genes and identify potential signaling pathway in Asian people with breast cancer.</p><p><b>METHODS</b>Five gene microarray datasets of Asian people with breast cancer, GSE6367, GSE9309, GSE15852, GSE33447 and GSE45255, were downloaded from GEO. Microarrays with 318 breast cancer and 60 normal breast tissues were used for analysis of differentially expressed genes and pathway. 32 pairs of breast cancer patients' specimens were used to validate the differentially expressed genes by real-time PCR.</p><p><b>RESULTS</b>Analysis of the large sample of microarray data identified 436 differentially expressed genes in breast cancer tissues, while 259 of these genes were up-regulated and the other 177 down-regulated. Pathway analysis showed that metabolism-related signaling pathway may be involved in the development of breast cancer in Asian people. The expressions of KRT19, ADIPOQ, CFD, RBP4, LPL, ABCA8 and CD36 genes were confirmed by real-time PCR.</p><p><b>CONCLUSION</b>This study shows differential gene expression profile and potential signaling pathway in Asian people with breast cancer. CD36 gene may be closely related to the Asian breast cancer. ABCA8 gene may be a new disease gene in Asian breast cancer.</p>
Subject(s)
Female , Humans , Asian People , Breast Neoplasms , Genetics , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Oligonucleotide Array Sequence Analysis , Real-Time Polymerase Chain Reaction , Signal Transduction , TranscriptomeABSTRACT
Objective:To identify BSG single nucleotide polymorphisms (SNPs) in Chinese Han population. Methods:Peripheral blood samples were collected from 48 unrelated healthy Chinese Han subjects. Sequences at the BSG locus, including the promoter region, all exons and exon-intron boundaries were ampliifed, sequenced and followed by Hardy-Weinberg equilibrium test and linkage disequilibrium (LD) analysis. Results:A total of 19 SNPs were identiifed, 2 of which two were novel. Genotype distributions of all SNPs were consistent with Hardy-Weinberg equilibrium. Four haplotype blocks were constructed throughout the gene locus, and 9 haplotype tag SNPs (htSNPs) were inferred. Distribution of SNPs was in accordance with the neutrality theory in Chinese Han population. Conclusion:For the ifrst time, systematic identiifcation of BSG SNPs in the Chinese Han population has been done, and 9 htSNPs are identified. Our study has provided basis for further genetic association studies for related diseases as wel as pharmacogenetics study for drug response in Chinese Han population.
ABSTRACT
ObjectiveTo evaluate the impact of compliance with antihypertensive therapy in pailents with essential hypertension on risk for their first-ever cerebral infarction.MethotisQuestionnaire survey and auxiliary examinations were conducted in 114 patients with essential hypertension hospitalized for acute cerebral infaretion at the First Hospihal Affiliated to Harbin Medical University during December 2006 to December 2007,as well as in another 114 patients with essential hypertensive without history of cerebral infarction as controls during the sanle period.Univariate and multivariate 10gistic regression analyses were performed to study the relationship between first-ever cerebral infarction and compliance with antihypertensive agents and other relevant factors.ResultsAntihypertensive agents compliance,course of hypertension,and history of smoking and alcohol drinking could significantly affect their first occurrence of cerebral infarction in patients with essential hypertension(P＜0.05),with odds ratios(OR)of 0.429(95%C10.186-0.993) and 2.142(95% CI 1.052-4.364)for good and poor compliance with antihypertensive agents,respectively,as compared to those without antihypertensive treatmenL Mild drinking was a protective factor for cerebral infarction with an OR of 0.494(95%CI 0.252-0.968).kngth of hypertension with 10-19-years and more than or equal to 20 years.as compared to those with le88 than five years of hypertension,was also a risk factor for it,with an OR of 2.118(95% CI 1.075-4.174).ConclusionsCompliance of essential hypertensive patients with antihypertensive therapy was an important factor that affect their contracting first-ever cerebral infarction.Good compliance could obviously refrain them from it.Patients with poor-compliance or without treatment prone to contract cerebral infarction more easily than those with good compliance.It is necessary to improve compliance with antihypertensive agents in patients with essential hypertension as soon as possible.as well as quitting smoking and limiting alcohol drinking for prevention and control for their first-ever cerebral infarction.
ABSTRACT
Real-time fluorescent quantitative PCR was used to examine PGC-1α mRNA expression in brown adipose tissue and skeletal muscle of rats. The results showed that the expression levels of PGC-1α mRNA in brown adipose tissue and skeletal muscle of obese rats were lower than those of the normal ones (all P<0.01). After high dose glucocorticoid treatment, the levels of PGC-1α mRNA expression in brown adipose tissue and skeletal muscle, both in normal and obese rats, were decreased significantly.
ABSTRACT
Thymosin ?1 is a multiple peptide of hormone and protein isolated from thymus gland,and it has many biological functions.It has been reported that it plays an important role in immune response,neuroendocrine modulation and gene expression.The article is to review the progress of thymosin ?1 and its mechanisms.