ABSTRACT
As the main carrier of oxygen delivery in the blood circulation system, hemoglobin (Hb) plays a key role in the adaptation of animals to high altitude hypoxia.In this paper, we combined analysis of genome, transcriptome, molecular evolution, homology modeling and molecular dynamics simulation, and explored the molecular mechanisms of increased blood oxygen affinity of Pseudopodoces humilis.Our results showed that the prenatal expressed p gene was highly expressed in the adult Pseudopodoces humilis (RPKM = 32.22) compared to Parus major (RPKM = 0), and this may result in the presence of two additional p-type Hbs with high oxygen affinity in the blood of P.humilis, i.e.(al>p)2 and (aAp)2.The PA25G-A and pA55L-I mutations may increase the van der Waals force between the B and D helices, which might eventually make the entire Pv subunit more compact and finally reduce the number of hydrogen bonds between a dimers, hence the transition from T state to R state is prone to occur.The two mutations of (3a43A-S and pA44S-N could change the conformation and polarity of the heme pocket opening, thus making the solution easier to flow into/out of the heme pocket and therefore facilitating the gas exchange.The pA90E-K mutation in P.humilis has undergone strong positive selection, which could increase the basicity of pA-type Hb, thereby offsetting the decrease in Hb-02 affinity caused by the Bohr effect.In addition, we also found that aA44P-S and pA43A-S mutations may increase the hydrophilicity of otA and pv type Hbs, which is beneficial to the accumulation of Hb to a higher concentration in red blood cells.Collectively, the prenatal Hb genes highly expressed in the adult together with the genetic based changes in intrinsic 0, affinity and physicochemical property of aA and pA Hb could be the main causes for the increase in blood oxygen affinity of P.humilus.
ABSTRACT
BACKGROUND AND PURPOSE: It is essential to develop a reliable predictive serum biomarker for Parkinson's disease (PD). The accumulation of alpha-synuclein (αSyn) and up-regulated expression of Rab35 participate in the etiology of PD. The purpose of this investigation was to determine whether the combined assessment of serum αSyn and Rab35 is a useful predictive biomarker for PD. METHODS: Serum levels of αSyn or Rab35 were determined in serum samples from 59 sporadic PD patients, 19 progressive supranuclear palsy (PSP) patients, 20 multiple system atrophy (MSA) patients, and 60 normal controls (NC). Receiver operating characteristics (ROC) curves were calculated to determine the diagnostic accuracy of αSyn or/and Rab35 in discriminating PD patients from NC or atypical parkinsonian patients. RESULTS: The levels of αSyn and Rab35 were increased in PD patients. The serum level of Rab35 was positively correlated with that of αSyn in PD patients. Compared to analyzing αSyn or Rab35 alone, the combined analysis of αSyn and Rab35 produced a larger area under the ROC curve and performed better in discriminating PD patients from NC, MSA patients, or PSP patients. When age was dichotomized at 55, 60, 65, or 70 years, the combined assessment of αSyn and Rab35 for classifying PD was better in the group below the cutoff age than in the group above the cutoff age. CONCLUSIONS: Combined assessment of serum αSyn and Rab35 is a better biomarker for discriminating PD patients from NC or atypical parkinsonian patients, and is a useful predictive biomarker for younger sporadic PD patients.
Subject(s)
Humans , alpha-Synuclein , Multiple System Atrophy , Parkinson Disease , ROC Curve , Supranuclear Palsy, ProgressiveABSTRACT
Uterine leiomyoma is a common benign tumour in women of childbearing age,with an incidence of 25%-30%.Uterine myoma can cause infertility,as well as abortion,premature delivery,placental abruption and postpartum hemorrhage and other adverse pregnancy outcomes,which increases the cesarean section rate.The influence of uterine leiomyoma on fertility is closely related to its location and size.The treatment should be individualized,considering the size,location and fertility of the myoma.
ABSTRACT
Objective To investigate the distribution and drug resistance of pathogenic bacteria associated with ventilator associated infection in Intensive Care Unit (ICU) patients with severe tumor in Chengdu area. Methods 846 patients with severe and critical tumors who underwent mechanical ventilation in ICU from Jan-uary 2013 to December 2016 in Chengdu area were enrolled in the study.84 sputum specimens from patients with ventilator associated infection were collected ,bacteria were isolated and identified ,Gram-negative bacteria drug sensitivity test was carried out by GN201 method ,Gram-positive bacteria drug sensitivity test was carried out by GP method ,and drug sensitivity test was carried out by paper diffusion method.Results There were 80 strains of pathogenic bacteria in the sputum specimens from 84 patients with infection related infection ,inclu-ding 54 Gram-negative bacteria (67.50%) ,21 Gram-positive bacteria (26.25%) ,and 5 fungi (6.25%).The resistance rates of major Gram-negative bacteria to ceftazidime and cefepime were higher ,and the resistance rates of Pseudomonas aeruginosa to ceftazidime and cefepime were 94.74% and 89.47%,respectively ,the re-sistance rates of K lebsiella pneumoniae to ceftazidime and cefepime were 87.50% and 93.75%,respectively , and the resistance rates of Acinetobacter Bauman to ceftazidime and cefimidime were 100.00% and 83.33%, respectively ;the resistance rates of the main Gram-positive bacteria to penicillin and erythromycin were high-er ,and the resistance rates of Staphylococcus aureus to penicillin and erythromycin were 80.00% and 90.00%respectively ,the resistance rates of Staphylococcus hemolytic to penicillin and erythromycin were 87.50% and 75.00% respectively.Conclusion The pathogenic bacteria of ventilator associated infection in ICU patients with severe tumor in Chengdu area were mainly Gram-negative bacteria ,which should be paid attention to ,and effective monitoring and prevention measures should be taken for the relevant factors.
ABSTRACT
Objective To observe the impairment effect of retinol binding protein 4(RBP4) on neurocognitive function in diabetic nephropathy(DN) patients with silent cerebral infarction(SCI) and to explore its mechanism.Methods Sixty patients with newly diagnosed DN and 30 healthy volunteers were selected as the study subjects and the DN cases were divided into the complicating SCI group(SCI,n=30) and non-complicating SCI group(NSCI,n=30) according to the imaging results.The degrees of neurological function deficit and Montreal cognitive assessment(MoCA) were evaluated.Serum RBP4 level was determined by ELISA and expressions of Lp-PLA2 and C-X-C chemokine receptor type 4(CXCR4) were determined by Western blot.Results Compared with the NSCI group,the neurocognitive function in the SCI group was subsided,the expression levels of RBP4,Lp-PLA2 and CXCR4 were increased(P＜0.05).The RBP4 level was positively correlated with the neurocognitive function impairment in SCI patients,moreover,there existed a regression correlation between them.Conclusion Serum RBP4 may serve as the predictive factor of DN complicating SCI and is positively correlated with neurocognitive dysfunction.Lp-PLA2/CXCR4 pathway activation may be one of its pathogenesis.
ABSTRACT
BACKGROUND AND PURPOSE: The effects of high-intensity cycling as an adjuvant therapy for early-stage Parkinson's disease (PD) were highlighted recently. However, patients experience difficulties in maintaining these cycling training programs. The present study investigated the efficacy of cycling at a mild-to-moderate intensity in early-stage PD. METHODS: Thirteen PD patients were enrolled for 16 serial cycling sessions over a 2-month period. Motor function was assessed using the Unified Parkinson's Disease Rating Scale part III (UPDRS III) and Timed Up and Go (TUG) test as primary outcomes. The Montreal Cognitive Assessment (MoCA), modified Hoehn and Yahr Stage (mHYS), total UPDRS, Falls Efficacy Scale, New Freezing of Gait Questionnaire, Schwab and England Activities of Daily Living, 39-item Parkinson's Disease Questionnaire, Patient Global Impression of Change, and gait performance were assessed as secondary outcomes. RESULTS: The age and the age at onset were 59.67±7.24 and 53.23±10.26 years (mean±SD), respectively. The cycling cadence was 53.27±8.92 revolutions per minute. The UPDRS III score improved significantly after 8 training sessions (p=0.011) and 16 training sessions (T2) (p=0.001) in the off-state, and at T2 (p=0.004) in the on-state compared to pretraining (T0). The TUG duration was significantly shorter at T2 than at T0 (p < 0.05). The findings of MoCA, total UPDRS, double limb support time, and mHYS (in both the off- and on-states) also improved significantly at T2. CONCLUSIONS: Our pioneer study has demonstrated that a low-intensity progressive cycling exercise can improve motor function in PD, especially akinesia. The beneficial effects were similar to those of high-intensity rehabilitation programs.
Subject(s)
Humans , Accidental Falls , Activities of Daily Living , Age of Onset , Education , England , Extremities , Freezing , Gait , Methylenebis(chloroaniline) , Parkinson Disease , RehabilitationABSTRACT
Severe acute pancreatitis (SAP) is accompanied with complex pathogenic course and high mortality. The imbalance of immune response is an important cause which leads the SAP patients to the severe situation and even death. The immunomodulatory therapy can regulate the imbalance of inflammation, alleviate SAP-associated organ injury, and improve the prognosis of patients. Previous immunomodulatory therapy had some problems, such as single-object and simple-method. In recent years, some new methods of immunomodulatory therapy, such as regulating the apoptosis and mature of immune cells, applying of mesenchymal stem cells (MSCs) and multi-regulation methods, provide some new ideas and hopes for SAP therapy. This paper reviewed the history and recent research progresses of SAP immunomodulatory therapy.
ABSTRACT
Severe acute pancreatitis (SAP) is accompanied with complex pathogenic course and high mortality. The imbalance of immune response is an important cause which leads the SAP patients to the severe situation and even death. The immunomodulatory therapy can regulate the imbalance of inflammation, alleviate SAP-associated organ injury, and improve the prognosis of patients. Previous immunomodulatory therapy had some problems, such as single-object and simple-method. In recent years, some new methods of immunomodulatory therapy, such as regulating the apoptosis and mature of immune cells, applying of mesenchymal stem cells (MSCs) and multi-regulation methods, provide some new ideas and hopes for SAP therapy. This paper reviewed the history and recent research progresses of SAP immunomodulatory therapy.
ABSTRACT
Objective To investigate the effects of 1 ,25-dihydroxyvitamin D3 on the expression of urinary Nephrin in patients with diabetic nephropathy .Methods According to albumin excretion rate ,40 type-2 diabetic nephropathy patients were divided into 2 groups ,10 healthy volunteers served as control .The treatment groups received 1 ,25-dihydroxyvitamin D3 0 .25 μg/d for 12 weeks .The levels of blood calcium ,phosphorus ,serum creatinine ,24-hour urinary protein excretion were detected .Enzyme-linked immunosorbent assay was used to detect urinary Nephrin in different groups .Results The expressions of urinary Nephrin were sta-tistically different among NC group ,DN1 group and DN2 group .1 ,25-dihydroxyvitamin D3 treatment significantly decreased the ex-pression of urinary Nephrin in DN1 patients ,whereas no statistically changes were observed in DN2 group .Conclusion In diabetic nephropathy patients ,urinary Nephrin is supposed to be effective an marker of disease progression .1 ,25-dihydroxyvitamin D3 may be effective to prevent podocyte injury in early-stage diabetic nephropathy .
ABSTRACT
<p><b>OBJECTIVE</b>Calibrated Automated Thrombogram(CAT) is a test to monitor the generation of thrombin. It can be described by four parameters: lag time, peak thrombin, endogenous thrombin potential (ETP) and time to peak (ttPeak). This study aims to determine the normal ranges of CAT parameters in Chinese, and evaluate whether thrombin generation is correlated with the concentration of heparin/low molecular weight heparin.</p><p><b>METHODS</b>Plasma from 120 healthy subjects were collected to determine the normal rangea of CAT parameters in Chinese. Normal plasma pool (NPP, n=25) spiked with different concentrations of heparin or enoxaparin were used to detecte CAT parameters. The overall and age specific normal ranges of CAT parameters were calculated using descriptive statistics method with mean±2SD. The correlation between CAT parameters and age or concentrations of heparin, enoxaparin were analyzed with linear regression model.</p><p><b>RESULTS</b>The normal ranges for lag time, peak thrombin, ETP, ttPeak in the subjects were 3.648±2.465 min, 367.39±151.93 nmol/L, 2277±1030 nmol/L•min and 6.372±4.280 min respectively. Age was linearly correlated with lag time (r=-0.6583, P<0.0001), peak thrombin (r=0.4863, P<0.0001), ETP (r=0.3608, P<0.0014) and ttPeak (r=-0.6313, P<0.0001). The values of ETP/peak ratio were linearly correlated with concentrations of heparin.</p><p><b>CONCLUSION</b>The normal ranges of four CAT parameters for Chinese were determined. CAT parameters are associated with age. ETP/peak ratio could be used to monitor the process of anticoagulation therapy.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Aging , Blood , Asian People , Blood Coagulation Tests , Reference Standards , China , Healthy Volunteers , Heparin , Reference Values , ThrombinABSTRACT
Objective: To optimize the infiltration process of Pericarpium Citri Reticulatae (PCR) in Huoxiang Zhengqi Liquid (HZL). Methods: Using the dissolution content of hesperidin as indicator, the infiltration process parameters for PCR such as soaking time, fineness of grind, degree of compaction, infiltration rate, and medicinal infiltration or not were studied, and considering the actual production efficiency, the optimal process conditions were determined. Results: The optimal infiltration process conditions were as follows: PCR was loaded into the extraction tank without soaking (there was no difference between 24 and 48 h of soaking time), spread evenly and compacted properly; The crude medicine fineness was about 0.5 cm × 0.5 cm; The infiltration solvent was 60% ethanol; The infiltration solvent was added to the extraction tank of crude medicines, the volume of solvent can not be too much, just inundating crude medicines; Adding solvent speed and infiltration speed were basically identical; The primary infiltration speed was 1 mL/(min·kg) and the continued infiltration speed was 2 mL/(min·kg). Conclusion: The optimal PCR infiltration process conditions of HZL are determined by evaluating the dissolution content of hesperidin.
ABSTRACT
<p><b>OBJECTIVE</b>To study the effects of environmental multi-media lead pollution on blood lead and sex hormone levels among lead exposed males engaged in E-waste dismantling, and the correlation between confounding factors and sex hormone levels.</p><p><b>METHODS</b>An E-waste dismantling area in Taizhou of Zhejiang Province was selected as the research site. One hundred and fifty two samples were collected from the groundwater, soil, rice, corn, chicken, and pork in the dismantling area. The effects of the multi-media lead pollution on the male blood lead and sex hormone levels of FSH, LH, and T, as well as the correlation with confounding factors, were studied.</p><p><b>RESULTS</b>The blood lead concentrations in the males aged under 31, from 31 to 45 and from 46 to 60 were 98.55, 100.23, and 101.45 μg/L, respectively. Of all the environmental media lead exposures, the groundwater, rice and soil were main contributing factors to the lead accumulation in humans. FSH and LH levels increased with the age while the T levels decreased with the age instead. There was a significant correlation between the FSH and LH levels and wearing masks.</p><p><b>CONCLUSION</b>There was correlation between the FSH, LH, and T levels, and the mean values of lead concentrations in environmental media, and the sex hormone levels were correlated with the confounding factor of wearing masks.</p>
Subject(s)
Adult , Humans , Male , Middle Aged , Electronic Waste , Environmental Monitoring , Environmental Pollutants , Blood , Chemistry , Follicle Stimulating Hormone , Blood , Gonadal Steroid Hormones , Blood , Lead , Blood , Chemistry , Luteinizing Hormone , Blood , Occupational Exposure , Refuse Disposal , Methods , Testosterone , BloodABSTRACT
<p><b>BACKGROUND</b>Rh blood group system is the most complex and immunogenetic blood group system. Prevalent RHD alleles varied in different populations. The purpose of this study is to determine the molecular basis of weak D and DEL phenotype in Anhui Chinese Han population.</p><p><b>METHODS</b>The D antigen was determined with IgM monoclonal anti-D conformed to the guidelines for donor testing in China. Weak D samples were identified by an indirect antiglobulin test. DEL phenotype was determined by adsorption and elution test. All the RHD 10 exons were screened by PCR with sequence-specific priming or sequenced for the first-time donors who typed weak D, DEL or D negative by serologic test.</p><p><b>RESULTS</b>Of all the 30 799 blood donors, 155 blood samples were found D negative with IgM anti-D; 34 blood samples were found D positive by indirect antiglobulin test or absorption elution test. RHD alleles were identified by nucleotide sequencing. Total 4 RHD alleles were found including two new. One hundred and twenty of 155 (77.4%) of the serologically D negative samples lacked the RHD gene. One D negative was RHD(615del2). Thirty-two of 155 (20.6%) carried RHD(K409K) among them one carrying 1227G > A and 845G > A. Two of 155 (1.3%) was weak D type 15.</p><p><b>CONCLUSIONS</b>In this study at the molecular level, all DEL phenotype is RHD(K409K); weak D type 15 is the prevalent weak D allele in Anhui Chinese Han population. Additionally, an improved more efficient method was adopted to amplify all the RHD exons in one PCR program. Our study added to the understanding of molecular mechanisms underlying D antigen expression in Anhui Han population and provided useful information for adopting suitable genotyping strategies in routine use.</p>
Subject(s)
Humans , Alleles , China , Exons , Genetics , Immunoglobulin M , Blood , Multiplex Polymerase Chain Reaction , Phenotype , Polymerase Chain Reaction , Rh-Hr Blood-Group System , GeneticsABSTRACT
<p><b>BACKGROUND</b>Recent studies have discovered that nuclear translocation of nerve growth factor (NGF) and its receptor fragments function differently from the traditional model. This study aimed to uncover the nuclear expression of NGF in astrocytoma and its biological significance.</p><p><b>METHODS</b>Ninety-four paraffin-embedded astrocytoma specimens were subjected to immunohistochemical (IHC) and hemotoxylin & eosin (HE) staining. Preoperative cerebrospinal fluid (CSF) specimens and intraoperative snap-frozen astrocytoma tissues were assayed for NGF expression by ELISA and Western blotting. The outcome of patients who contributed samples was tracked. Each ten tissue samples from patients with traumatic brain injury who had received decompression surgery and CSF samples from patients undergoing spinal anesthesia but with no history of nervous system disease were taken as control.</p><p><b>RESULTS</b>NGF-positive immunoreactive products were distributed in both the cytoplasm and nucleus of astrocytoma, but were only located in the cytoplasm of traumatic brain injury (TBI) tissue. NGF nuclear-positive rate (NPR) of grades III - IV astrocytomas (70.0%) was higher than that of grades I - II astrocytoma (28.6%, P < 0.05). NGF-NP expression positively correlated with the NGF concentration in cerebrospinal fluid (CSF) (r = 0.755, P < 0.01). Kaplan-Meier survival analysis indicated that the median survival time was 25 months for NGF-NP astrocytoma grade I - II patients and 42 months in NGF nuclear negative (NGF-NN) astrocytoma grade I - II patients (P < 0.05). In astrocytoma III - IV patients, the median survival was 7 months for NGF-NP patients and 24 months for NGF-NN patients (P < 0.01). Two types of NGF with molecular weights of 13 and 36 kDa were present in astrocytoma, but only the 36 kDa NGF was found in the CSF. NGF expression elevated as the malignancy increased.</p><p><b>CONCLUSIONS</b>NGF-NP expression and NGF level in CSF were significant prognostic factors in astrocytoma patients. Because of the easy access of CSF, it may be developed as an index for early diagnosis and surveillance of astrocytoma.</p>
Subject(s)
Female , Humans , Male , Middle Aged , Astrocytoma , Metabolism , Biomarkers , Metabolism , Blotting, Western , Cerebrospinal Fluid , Metabolism , Enzyme-Linked Immunosorbent Assay , Immunohistochemistry , Nerve Growth Factor , Metabolism , PrognosisABSTRACT
<p><b>BACKGROUND</b>Seroma formation is one of the most common complications after breast cancer surgery. Various risk factors have been evaluated for their associations with the development of seromas in Western populations. However, similar data are not available in Chinese series. Therefore, we sought to investigate the potential risk factors for Chinese breast cancer patients.</p><p><b>METHODS</b>A prospective study of female breast cancer patients undergoing surgery was carried out in Cancer Hospital of Fudan University, Shanghai, China. Univariate analyses were performed by chi-square test or Student's t test or Mann-Whitney test and multivariate analyses by stepwise Logistic regression. The logistic model included age (years), total serum protein concentration (g/L), drainage volume on postoperative day 3 (POD 3; ml) and time to daily drainage volume not more than 30 ml (TTV30; days).</p><p><b>RESULTS</b>A total of 158 patients with breast cancer were studied. The mean age at diagnosis was (52.14 ± 10.77) years (range 25 - 92). During the follow-up period, 24 (15.2%) patients developed seromas. Calculated as continuous variables in the stepwise Logistic regression, age (OR = 1.090, 95%CI 1.028 - 1.155, P = 0.004), total serum protein concentration (OR = 0.886, 95%CI 0.791 - 0.992, P = 0.036), drainage volume on POD3 (OR = 1.013, 95%CI 1.002 - 1.023, P = 0.017) and TTV30 (OR = 1.273, 95%CI 1.039 - 1.561, P = 0.020) were independent risk factors for seroma formation. Additionally, significant difference in daily drainage volume was substantiated in the analysis by seroma formation (P = 0.034) rather than by type of surgery (P = 0.713).</p><p><b>CONCLUSIONS</b>Although the pathogenesis of seroma remains controversial, such risk factors as age, nutritional status, drainage volume on POD3 and TTV30 should be considered for prediction and prevention of seroma formation in Chinese breast cancer patients.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Asian People , Breast Neoplasms , General Surgery , Postoperative Complications , Prospective Studies , Risk Factors , SeromaABSTRACT
<p><b>OBJECTIVE</b>To summarize the clinical experience of trastuzumab treatment in neoadjuvant, adjuvant, metastatic setting of Chinese patients with Her-2 positive breast cancer and evaluate the efficacy of trastuzumab in combination with chemotherapy.</p><p><b>METHODS</b>From January 2004 to December 2008, 141 outpatients with breast cancer treated with trastuzumab were investigated retrospectively. The follow-up time ranged from 3 to 319 months. The disease free survival time (DFS) of metastatic setting was calculated. The overall survival time (OS), time to treatment failure (TTF) and clinical response rate (CRR, including complete response, partial response and stable disease) of adjuvant, first-line, second-line therapy were analyzed statistically.</p><p><b>RESULTS</b>In the neoadjuvant regimen, paclitaxel plus carboplatin in combination with trastuzumab accounted for 66.7%, which achieved pathological complete response in 10 of 16 patients. In the adjuvant regimen, anthracycline or anthracycline followed by taxane accounted for 53.9%. The median DFS of 57 cases with metastatic diseases was 17 months. The CRR of first-line trastuzumab use in metastatic setting was 84.5%, compared with 44.4% of second-line use. The median TTF of first-line treatment was 24 months compared with 5 months of second-line treatment. Statistically significant differences were observed.</p><p><b>CONCLUSION</b>The regimen of paclitaxel plus carboplatin in combination with trastuzumab deserves wide clinical use. In metastatic setting, first-line treatment of trastuzumab plus chemotherapy can achieve a higher response rate than second-line treatment. Continued trastuzumab therapy combined with different chemotherapy treatment after disease progression may obtain additive clinical advantage.</p>
Subject(s)
Adult , Female , Humans , Middle Aged , Anthracyclines , Antibodies, Monoclonal, Humanized , Therapeutic Uses , Antineoplastic Agents , Therapeutic Uses , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Breast Neoplasms , Drug Therapy , Metabolism , Pathology , Bridged-Ring Compounds , Carboplatin , Chemotherapy, Adjuvant , Disease-Free Survival , Follow-Up Studies , Neoadjuvant Therapy , Neoplasm Metastasis , Neoplasm Recurrence, Local , Paclitaxel , Receptor, ErbB-2 , Metabolism , Retrospective Studies , Survival Rate , Taxoids , Trastuzumab , Treatment FailureABSTRACT
<p><b>OBJECTIVE</b>To identify predictive markers of the long-term outcome for neo-adjuvant chemotherapy (NC) in locally advanced breast cancer (LABC) treated with intravenous vinorelbine (V) and epirubicin (E) combination regimen.</p><p><b>METHODS</b>One hundred and nineteen patients with LABC were treated from September 2001 to May 2006. All patients were diagnosed as invasive breast cancer by 14G core needle biopsy and treated with three cycles of VE regimen before the operation. The patients were subjected to surgery and subsequently were given other three cycles of VE or cyclophosphamide+epirubicin+fluorouracil (CEF) regimen according to the clinical responses. Local-regional radiotherapy was applied to all patients after the chemotherapy and followed by hormone-therapy according to hormone receptor status. The impact of clinical, pathological, and immunohistochemical features on disease free survival (DFS) and overall survival (OS) was evaluated.</p><p><b>RESULTS</b>All patients were evaluable for responses: clinical complete response was documented in 27 patients (22.7%), 78 patients (65.5%) obtained partial clinical response. The pathological complete response was found in 22 cases (18.5%). Of the patients, 115 cases (96.6%) were followed-up for a median time of 63.4 months (range, 9-76 months), the 5-year DFS rate and OS rate was 58.7% and 71.3%, respectively. On multivariate analysis, high pre-Ki-67 (P=0.012) and post-Ki-67 expression (P=0.045), no pathological complete response after NC (P=0.034) were associated with the higher risk of disease relapse; high pre-Ki-67 (P=0.017) and post-Ki-67 expression (P=0.001), negative pre-ER (P=0.002) and no pathological complete response after NC (P=0.034) were associated with a shorter survival.</p><p><b>CONCLUSION</b>Pathological response in primary tumor, pre-Ki-67 and post-Ki-67 expression, pre-ER expression are important predictors of long-term outcome for LABC patients with three cycles of VE regimen before operation.</p>
Subject(s)
Adult , Aged , Female , Humans , Middle Aged , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Breast Neoplasms , Drug Therapy , Pathology , General Surgery , Chemotherapy, Adjuvant , Epirubicin , Follow-Up Studies , Lymphatic Metastasis , Prognosis , Retrospective Studies , Treatment Outcome , VinblastineABSTRACT
<p><b>OBJECTIVE</b>To explore the therapeutic effects of amiodarone and metoprolol, either alone or in combination, on chronic heart failure (CHF) complicated by ventricular arrhythmia.</p><p><b>METHODS</b>A total of 110 NYHA class II-III patients with CHF complicated by ventricular arrhythmia were randomly divided into amiodarone group, metoprolol group and amiodarone + metoprolol group. The therapeutic effects was evaluated at the end of the 1-year follow-up.</p><p><b>RESULTS</b>Amiodarone, metoprolol and their combination produced statistically different therapeutic effects (P<0.05). Compared with amiodarone and metoprolol used alone, amiodarone combined with metoprolol resulted in significant cardiac function improvement (P<0.05) and ventricular arrhythmia control (P<0.01). During the 1-year follow-up, the readmission rate and cardiac event rate in the amiodarone + metoprolol group were significantly lower than those in amiodarone group (P<0.01) and metoprolol group (P<0.05). The adverse reaction rates in the 3 groups were similar (P>0.05).</p><p><b>CONCLUSION</b>The combination of amiodarone and metoprolol produces better effect than amiodarone or metoprolol alone in the treatment of CHF complicated by ventricular arrhythmia.</p>
Subject(s)
Adult , Female , Humans , Male , Adrenergic beta-Antagonists , Therapeutic Uses , Amiodarone , Therapeutic Uses , Anti-Arrhythmia Agents , Therapeutic Uses , Chronic Disease , Drug Therapy, Combination , Heart Failure , Drug Therapy , Metoprolol , Therapeutic Uses , Tachycardia, Ventricular , Drug Therapy , Treatment Outcome , Ventricular Premature Complexes , Drug TherapyABSTRACT
<p><b>OBJECTIVE</b>To study the "hot spot" of BRCA1/2 gene mutations in Chinese mainland breast cancer population.</p><p><b>METHODS</b>The known BRCA1/2 gene mutations in author's previous studies were reanalyzed by denaturing high performance liquid chromatography and DNA sequencing method in 177 patients with early onset breast cancer or affected relatives and 426 sporadic breast cancer patients from four breast cancer centers in China.</p><p><b>RESULTS</b>Three cases were found with BRCA1 5589del8 mutation out of 247 hereditary-predisposing breast cancer patients (70 patients in previous study and 177 patients in current study) and 2 cases with BRCA1 5589del8 mutation out of 426 sporadic breast cancer patients. They had similar even same haplotype.</p><p><b>CONCLUSION</b>BRCA1 5589del8 mutation is likely to be the "founder mutation" in Chinese population, but it should be confirmed by further studies.</p>
Subject(s)
Adult , Female , Humans , Asian People , Genetics , BRCA1 Protein , Genetics , Base Sequence , Breast Neoplasms , Ethnology , Genetics , China , Chromatography, High Pressure Liquid , DNA Mutational Analysis , Genetic Predisposition to Disease , Genetics , MutationABSTRACT
<p><b>OBJECTIVE</b>To evaluate the available surgical treatment modalities so as to explore the optimal strategy of managing early breast cancer.</p><p><b>METHODS</b>The clinical data of 2173 consecutive early-stage breast cancer patients treated by surgery treatments were retrospectively reviewed in order to clarify the indications and contraindications of different modalities. Therapeutic outcome of different surgical treatment modes were compared in terms of recurrence-free survival ( RFS) , disease-free survival ( DFS) , overall survival (OS). The cosmetic results of breast conservation and reconstruction were also evaluated .</p><p><b>RESULTS</b>The median age of these patients was 51 years ranging from 18 to 91. Of 2173 patients, 547 had stage 0- I lesions and 1626 stage II , and 1155 (53. 2% ) premenopausal. The proportion of patients who received radical surgery, breast conservation and reconstruction after mastectomy was 83. 6% (1817/2173), 10. 5% (229/2173) and 2. 5% (55/2173) , respectively. Younger and premenopausal patients prefer conservative and reconstructive surgeries, which are reasonable for stage 0-I and non-invasive breast cancer patients. Conservative surgery was not suitable for Paget's disease of breast (P = 0. 004) , mastectomy followed by reconstruction in this type of cancer was up to 38. 5%. The recurrence and metastasis rate of conservation or mastectomy were similar with a comparable 3-year RFS of 97. 4% and 95. 4% , respectively; there were also no significant differences in RFS(P =0. 2435) , DFS( P =0. 1395) and OS(P =0. 9406) after having been followed for 3 to 64 months. Similarly, immediate reconstruction did not show any negative effects with only 1 recurrence and 1 metastasis. Aesthetic outcomes were assessed as excellent or good in 90. 0% of breast conservation surgery, and the acceptability of reconstruction was 94. 5%.</p><p><b>CONCLUSION</b>Breast conserving surgery not only has comparable survival as mastectomy, but also has better cosmetic outcomes. Immediate breast reconstruction can be a suitable option without compromising survival. It is very important in the management for early breast cancer by selecting the most suitable surgery mode for every individual patient not only to cure her disease but also to satisfy the patient psychologically. Conservation should be preferred prior to reconstruction whenever possible.</p>