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1.
Clin Mol Hepatol ; 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38600872

ABSTRACT

Background/Aims: The performance of machine-learning (ML) in predicting the outcomes of patients with hepatocellular carcinoma (HCC) remains uncertain. We aimed to develop risk scores using conventional methods and ML to categorize early-stage HCC patients into distinct prognostic groups. Methods: The study retrospectively enrolled 1411 consecutive treatment-naïve patients with the Barcelona Clinic Liver Cancer (BCLC) stage 0 to A HCC from 2012 to 2021. The patients were randomly divided into a training cohort (n=988) and validation cohort (n=423). Two risk scores (CATS-IF and CATS-INF) were developed to predict overall survival (OS) in the training cohort using the conventional methods (Cox proportional hazards model) and ML-based methods (LASSO Cox regression), respectively. They were then validated and compared in the validation cohort. Results: In the training cohort, factors for the CATS-IF score were selected by the conventional method, including age, curative treatment, single large HCC, serum creatinine and alpha-fetoprotein levels, fibrosis-4 score, lymphocyte-to-monocyte ratio, and albumin bilirubin grade. The CATS-INF score, determined by ML-based methods, included the above factors and two additional ones (aspartate aminotransferase and prognostic nutritional index). In the validation cohort, both CATS-IF score and CATS-INF score outperformed other modern prognostic scores in predicting OS, with the CATS-INF score having the lowest Akaike information criterion value. A calibration plot exhibited good correlation between predicted and observed outcomes for both scores. Conclusions: Both the conventional Cox-based CATS-IF score and ML-based CATS-INF score effectively stratified patients with early-stage HCC into distinct prognostic groups, with the CATS-INF score showing slightly superior performance.

2.
Mol Cell Proteomics ; 23(4): 100748, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38493954

ABSTRACT

The molecular mechanisms underlying muscular adaptations to concentric (CON) and eccentric (ECC) exercise training have been extensively explored. However, most previous studies have focused on specifically selected proteins, thus, unable to provide a comprehensive protein profile and potentially missing the crucial mechanisms underlying muscular adaptation to exercise training. We herein aimed to investigate proteomic profiles of human skeletal muscle in response to short-term resistance training. Twenty young males were randomly and evenly assigned to two groups to complete a 4-week either ECC or CON training program. Measurements of body composition and physiological function of the quadriceps femoris were conducted both before and after the training. Muscle biopsies from the vastus lateralis of randomly selected participants (five in ECC and four in CON) of both before and after the training were analyzed using the liquid-chromatography tandem mass spectrometry in combination with bioinformatics analysis. Neither group presented a significant difference in body composition or leg muscle mass; however, muscle peak torque, total work, and maximal voluntary contraction were significantly increased after the training in both groups. Proteomics analysis revealed 122 differentially abundant proteins (DAPs; p value < 0.05 & fold change >1.5 or <0.67) in ECC, of which the increased DAPs were mainly related to skeletal muscle contraction and cytoskeleton and enriched specifically in the pentose phosphate pathway, extracellular matrix-receptor interaction, and PI3K-Akt signaling pathway, whereas the decreased DAPs were associated with the mitochondrial respiratory chain. One hundred one DAPs were identified in CON, of which the increased DAPs were primarily involved in translation/protein synthesis and the mitochondria respiratory, whereas the decreased DAPs were related to metabolic processes, cytoskeleton, and de-ubiquitination. In conclusion, the 4-week CON and ECC training resulted in distinctly different proteomic profiles, especially in proteins related to muscular structure and metabolism.


Subject(s)
Adaptation, Physiological , Exercise , Muscle, Skeletal , Proteomics , Resistance Training , Humans , Male , Proteomics/methods , Young Adult , Muscle, Skeletal/metabolism , Exercise/physiology , Muscle Proteins/metabolism , Body Composition , Adult , Muscle Contraction , Proteome/metabolism
3.
Sci Total Environ ; 896: 165053, 2023 Oct 20.
Article in English | MEDLINE | ID: mdl-37348732

ABSTRACT

Large amounts of waste isopropanol (IPA) are generated in industry, rendering the recovery of IPA highly desirable due to the economic and environmental benefits. Because it forms an azeotropic mixture with water, IPA is difficult to separate from the waste stream. In the present work, a novel CO2-switchable monoethanolamine-butanol deep eutectic solvent (DES) ([MEA][BuOH]) was identified as a superior medium for separating IPA and water at ambient temperature by forming butanol-IPA mixtures. The switchable solvent system combines the advantages of homogeneous and heterogeneous systems, i.e., rapid mixing due to the low mass transfer limitations and facile product separation, respectively. The low viscosity of [MEA][BuOH], the similar physical features (polarity, dipole moment, and dielectric constant) of butanol and IPA, and the H-bonding interactions of [BuOH] with IPA are thought to enable effective IPA capture from water by the butanol. Recovery of the IPA and formation of a butanol-IPA mixture is appealing because the resultant mixture could serve as an additive or substitute for alternative fuels. The results suggest that the developed process will provide a low-cost, energy-saving, effective, and environmentally benign route to recycling and repurposing waste IPA, an environmental hazard, as a potential alternative fuel.

4.
Am J Obstet Gynecol MFM ; 5(7): 100978, 2023 07.
Article in English | MEDLINE | ID: mdl-37094635

ABSTRACT

OBJECTIVE: Various prophylactic antibiotic regimens are used in the management of preterm premature rupture of membranes. We investigated the efficacy and safety of these regimens in terms of maternal and neonatal outcomes. DATA SOURCES: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to July 20, 2021. STUDY ELIGIBILITY CRITERIA: We included randomized controlled trials involving pregnant women with preterm premature rupture of membranes before 37 weeks of gestation and a comparison of ≥2 of the following 10 antibiotic regimens: control/placebo, erythromycin, clindamycin, clindamycin plus gentamicin, penicillins, cephalosporins, co-amoxiclav, co-amoxiclav plus erythromycin, aminopenicillins plus macrolides, and cephalosporins plus macrolides. METHODS: Two investigators independently extracted published data and assessed the risk of bias with a standard procedure following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Network meta-analysis was conducted using the random-effects model. RESULTS: A total of 23 studies that recruited a total of 7671 pregnant women were included. Only penicillins (odds ratio, 0.46; 95% confidence interval, 0.27-0.77) had significantly superior effectiveness for maternal chorioamnionitis. Clindamycin plus gentamicin reduced the risk of clinical chorioamnionitis, with borderline significance (odds ratio, 0.16; 95% confidence interval, 0.03-1.00). By contrast, clindamycin alone increased the risk of maternal infection. For cesarean delivery, no significant differences were noted among these regimens. CONCLUSION: Penicillins remain the recommended antibiotic regimen for reducing maternal clinical chorioamnionitis. The alternative regimen includes clindamycin plus gentamicin. Clindamycin should not be used alone.


Subject(s)
Chorioamnionitis , Premature Birth , Infant, Newborn , Pregnancy , Female , Humans , Clindamycin/adverse effects , Chorioamnionitis/diagnosis , Chorioamnionitis/epidemiology , Chorioamnionitis/prevention & control , Amoxicillin-Potassium Clavulanate Combination , Network Meta-Analysis , Anti-Bacterial Agents/adverse effects , Premature Birth/prevention & control , Erythromycin/adverse effects , Macrolides/therapeutic use , Gentamicins/adverse effects , Cephalosporins
5.
Front Physiol ; 13: 947749, 2022.
Article in English | MEDLINE | ID: mdl-35991169

ABSTRACT

Duchenne muscular dystrophy (DMD) is an X-linked recessive fatal muscular disease. Gene therapy, cell therapy, and drug therapy are currently the most widely used treatments for DMD. However, many experiments on animals and humans suggested that appropriate exercise could improve the effectiveness of such precision medicine treatment, thereby improving patient's muscle quality and function. Due to the striated muscle damage of DMD individuals, there are still many debates about whether DMD animals or patients can exercise, how to exercise, when to exercise best, and how to exercise effectively. The purpose of this review is to summarize and investigate the scientific basis and efficacy of exercise as an adjuvant therapy for DMD gene therapy, cell therapy and drug therapy, as well as to present the theoretical framework and optional strategies of "exercise + X″″ combination therapy.

6.
Sci Rep ; 12(1): 8343, 2022 05 18.
Article in English | MEDLINE | ID: mdl-35585167

ABSTRACT

We investigated the outcomes of patients with ruptured hepatocellular carcinoma (HCC) and identified the optimal treatment modality for such patients. We retrospectively enrolled 91 patients with treatment-naive HCC and tumor rupture at diagnosis, including 38 patients who underwent surgical resection (SR) alone, 28 patients who were treated with transarterial chemoembolization (TACE) only, 20 patients who had a sequential combination therapy of TACE and SR, and 5 patients who received best supportive care. After a median follow-up of 13.1 months, 54 patients died. The cumulative 5 years overall survival (OS) rates were 55.1% and 0% in the SR group and non-SR group, respectively (p < 0.001). Non-SR therapy was associated with poorer OS according to a multivariate analysis with a hazard ratio of 6.649 (95% confidence interval 3.581-12.344, p < 0.001). Moreover, whether patients received TACE or not did not impact the OS in both the SR group and the non-SR group. In conclusion, for patients with HCC and tumor rupture at the time of diagnosis, SR could lead to better prognoses than non-surgery treatment modalities. Moreover, a sequential combination of TACE and SR had similar clinical outcomes when compared to SR alone.


Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Combined Modality Therapy , Hepatectomy , Humans , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Retrospective Studies , Treatment Outcome
7.
Orthop Surg ; 14(5): 911-918, 2022 May.
Article in English | MEDLINE | ID: mdl-35445587

ABSTRACT

OBJECTIVE: To investigate the outcomes of open reduction and internal fixation combined with medial buttress plate (MBP) and allograft bone-assisted cannulated screw (CS) fixation for patients with unstable femoral neck fracture with comminuted posteromedial cortex. METHODS: In a retrospective study of patients operated on for unstable femoral neck fractures with comminuted posteromedial cortex from March 2016 to August 2020, the clinical and radiographic outcomes of 48 patients treated with CS + MBP were compared with the outcomes of 54 patients treated with CS only. All patients in the CS + MBP group were fixed by three CS and MBP (one-third tubular plates or reconstructive plates) with bone allografts. The surgery-related outcomes and complications were evaluated, including operative time, blood loss, union time, femoral head necrosis, femoral neck shortening, and other complications after the operation. The Harris score was evaluated at 12 months after the operation. RESULTS: All patients were followed up for 12-40 months. The average age of patients in the CS-only group (54 cases, 22 females) and CS + MBP group (48 cases, 20 females) was 48.46 ± 7.26 and 48.73 ± 6.38 years, respectively. More intraoperative blood loss was observed in the CS + MBP group than that of patients in CS-only group (153.45 ± 64.27 vs 21.86 ± 18.19 ml, t = 4.058, P = 0.015). The average operative time for patients in the CS + MBP group (75.35 ± 27.67 min) was almost double than that of patients in the CS-only group (36.87 ± 15.39 min) (t = 2.455, P < 0.001). The Garden alignment index of patients treated by CS + MBP from type I to type IV was 79%, 19%, 2%, and 0%, respectively. On the contrary, they were 31%, 43%, 24% and 2% for those in the CS-only group, respectively. The average healing times for the CS-only and CS + MBP groups were 4.34 ± 1.46 and 3.65 ± 1.85 months (t = 1.650, P = 0.102), respectively. Femoral neck shortening was better in the CS + MBP group (1.40 ± 1.73 mm, 9/19) than that in the CS-only group (4.33 ± 3.32 mm, 24/44). Significantly higher hip function was found in the CS + MBP group (85.60 ± 4.36 vs 82.47 ± 6.33, t = 1.899, P = 0.06). There was no statistical difference between femoral head necrosis (4% vs 11%, χ2  = 1.695, P = 0.193) and nonunion (6% vs 9%, χ2  = 0.318, P = 0.719). CONCLUSION: For unstable femoral neck fractures with comminuted posteromedial cortex, additional MBP combined with bone allografts showed better reduction quality and neck length control than CS fixation only, with longer operative time and more blood loss.


Subject(s)
Femoral Neck Fractures , Femur Head Necrosis , Fractures, Comminuted , Adult , Allografts , Bone Screws , Female , Femoral Neck Fractures/etiology , Femoral Neck Fractures/surgery , Femur Head Necrosis/etiology , Fracture Fixation, Internal/adverse effects , Fractures, Comminuted/surgery , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
8.
J Chin Med Assoc ; 85(5): 554-565, 2022 05 01.
Article in English | MEDLINE | ID: mdl-35385417

ABSTRACT

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) is significantly higher in men than women. Nonetheless, the impact of sex disparities on HCC outcomes remains unclear. We aimed to compare the clinical manifestations and prognoses between male and female patients with HCC. METHODS: This retrospective study enrolled 5337 consecutive patients (3976 men, 1361 women) who were diagnosed with HCC from 2007 to 2020. The prognostic factors were identified by the Cox proportional hazards model. RESULTS: Male patients were younger upon HCC diagnosis (median age 64 vs 69 years; p < 0.001) with more favorable hepatic functional reserves (39.0% vs 35.1% albumin-bilirubin grade 1; p = 0.025) but had greater tumor burdens than the female patients. Furthermore, fewer male patients underwent curative therapies for HCC compared with the female patients (49.0% vs 57.0%; p < 0.001). After a median follow-up of 20.1 months (interquartile range, 5.8-47.3 months), 3133 patients died. The cumulative 5-year overall survival rates were 37.1% and 41.9% for male and female patients, respectively (p < 0.001). From the multivariate analysis, male sex was not an independent factor predictive of poor overall survival in all patients and in the subgroup analysis stratified by treatment modalities. When stratified by age, the female sex was an independent factor associated with lower mortality in younger (≤50 years) patients but not in older patients with HCC. CONCLUSION: Sex was not an independent predictor of the outcome of patients with HCC, especially for those aged more than 50 years.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Aged , Bilirubin , Carcinoma, Hepatocellular/pathology , Female , Humans , Liver Neoplasms/pathology , Male , Middle Aged , Prognosis , Retrospective Studies
9.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 35(11): 1434-1439, 2021 Nov 15.
Article in Chinese | MEDLINE | ID: mdl-34779170

ABSTRACT

OBJECTIVE: To evaluate the effectiveness of unstable femoral neck fracture with posteromedial comminutations treated by cannulated screws and medial bracing plate combined with bone allograft. METHODS: The clinical data of 18 patients with unstable femoral neck fracture with posteromedial comminutations treated by cannulated screws and medial bracing plate combined with bone allograft between July 2016 and March 2020 were retrospectively analyzed. The age ranged from 22 to 64 years, with a median age of 43 years. The causes of injury included 11 cases of falling injury, 3 cases of traffic accident injury, and 4 cases of fall from height injury. According to Garden classification, the femoral neck fracture was classified as type Ⅲ in 3 cases, type Ⅳ in 15 cases, and all patients were type Ⅲ according to Pauwels classification. The time from injury to operation was 1-5 days, with an average of 2.3 days. The fracture healing time and complications were recorded. The quality of fracture reduction was evaluated by Garden index immediately after operation; at last follow-up, the degree of femoral neck shortening was determined by Zlowodzki method, Harris score was used to evaluate hip function. RESULTS: The operation time was 62-98 minutes (mean, 75 minutes); intraoperative blood loss was 101-220 mL (mean, 153 mL). Cannulated screws guide wire was inserted 3-5 times (mean, 4 times). Intraoperative fluoroscopy was performed 9-21 times (mean, 15 times). The hospital stay was 5-11 days (mean, 7.2 days). All the patients were followed up 12-40 months with an average of 17.3 months. There was no postoperative complication such as accumulated pneumonia, lower extremity deep venous thrombosis, nail cutting, nail withdrawal, internal fixation fracture, and so on. There was no fracture nonunion and osteonecrosis of the femoral head during the follow-up; the fracture healing time was 7-15 weeks, with an average of 12.1 weeks. The quality of fracture reduction was evaluated immediately after operation, the results were grade Ⅰ in 15 cases and grade Ⅱ in 3 cases. At last follow-up, there were 2 cases with femoral neck shortening less than 5 mm and 1 case with 5-10 mm. The incidence of femoral neck shortening was 16.7%. The Harris score of hip joint was 73-97, with an average of 93.5; among them, 12 cases were rated as excellent, 3 cases as good, and 3 cases as fair, with an excellent and good rate of 83.3%. CONCLUSION: For the treatment of unstable femoral neck fracture with posteromedial comminutations, cannulated screws and medial bracing plate combined with bone allograft are dramatically effective due to earlier weight bearing, faster fracture healing, and better hip function recovery.


Subject(s)
Femoral Neck Fractures , Adult , Allografts , Bone Screws , Femoral Neck Fractures/surgery , Fracture Fixation, Internal , Humans , Middle Aged , Retrospective Studies , Treatment Outcome , Young Adult
10.
J Chin Med Assoc ; 84(2): 136-143, 2021 Feb 01.
Article in English | MEDLINE | ID: mdl-33433133

ABSTRACT

BACKGROUND: Patients with hepatocellular carcinoma (HCC) and with a single tumor <2 cm in size are classified as having Barcelona Clinic Liver Cancer (BCLC) stage 0 HCC. We aimed to investigate the role of the albumin-bilirubin (ALBI) grade in predicting outcomes in patients with BCLC stage 0 HCC. METHODS: We retrospectively enrolled patients with BCLC stage 0 HCC in Taipei Veterans General Hospital from 2007 to 2015. Prognostic factors were analyzed using a Cox proportional hazards model and propensity score matching (PSM) analysis. RESULTS: There were 420 patients enrolled, including 207 with ALBI grade 1, and 213 with ALBI grade 2 or 3. After a median follow-up of 60.0 months (interquartile range, 37.2-84.6 months), 179 patients died. The cumulative 5-year overall survival (OS) rates were 80.6% in patients with ALBI grade 1 and 53.7% in those with ALBI grade 2 or 3, respectively (p < 0.001). Multivariate analysis showed that age >65 years, negative hepatitis B surface in serum, creatinine >1.0 mg/dL, platelet count ≤105/mm3, tumor size >1.5 cm, nonsurgical resection (SR) therapy, and higher ALBI grade were independent risk factors related to poor OS. Patients who underwent SR had a better OS and recurrence-free survival than those who received radiofrequency ablation, which was confirmed by a multivariate analysis and PSM analysis. CONCLUSION: The ALBI grade can determine OS for patients with BCLC stage 0 HCC. SR can also provide a better outcome than nonsurgical treatment.


Subject(s)
Bilirubin/blood , Bilirubin/metabolism , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Outcome Assessment, Health Care , Serum Albumin/analysis , Serum Albumin/metabolism , Aged , Female , Humans , Male , Middle Aged , Proportional Hazards Models , Prospective Studies , Retrospective Studies , Taiwan
11.
Sci Rep ; 10(1): 17259, 2020 10 14.
Article in English | MEDLINE | ID: mdl-33057213

ABSTRACT

There has been insufficient investigation of the differences in long-term outcomes between surgical resection (SR) and radiofrequency ablation (RFA) among patients with hepatocellular carcinoma (HCC) and esophagogastric varices (EGV). We retrospectively enrolled 251 patients with treatment-naïve HCC and EGV who underwent SR or RFA as a first-line treatment. Prognostic factors were analyzed using a Cox proportional hazards model. A total of 68 patients underwent SR, and the remaining 183 patients received RFA. Patients who underwent SR were younger, had better liver functional reserves, and had larger tumors. After a median follow-up duration of 45.1 months, 151 patients died. The cumulative 5-year overall survival (OS) rate was significantly higher among patients who underwent SR than those treated with RFA (66.7% vs. 36.8%, p < 0.001). Multivariate analysis showed that age > 65 years, multiple tumors, RFA, albumin bilirubin grade > 1, and the occurrence of major peri-procedural morbidity were the independent risk factors that are predictive of poor OS. In conclusion, SR could be recommended as a first-line treatment modality for HCC patients with EGV if the patients are carefully selected and liver function is well preserved.


Subject(s)
Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/surgery , Esophageal and Gastric Varices/surgery , Liver Neoplasms/mortality , Liver Neoplasms/surgery , Aged , Female , Humans , Male , Middle Aged , Prognosis , Proportional Hazards Models , Radiofrequency Ablation , Retrospective Studies , Survival Rate
12.
Ann Transl Med ; 8(5): 238, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32309385

ABSTRACT

BACKGROUND: For patients with solitary huge (>10 cm in size) hepatocellular carcinoma (HCC) and without major vascular invasion, the treatment efficacy between surgical resection (SR) and transarterial chemoembolization (TACE) is not well studied. We aimed to compare the prognoses between SR and TACE for patients with solitary huge HCC. METHODS: We enrolled 143 patients with treatment-naïve, solitary HCC (>10 cm) who had received either SR or TACE treatment between 2007-2016. Factors of overall survival (OS) were analyzed by multivariate analysis. Propensity scores matching (PSM) method was adopted to adjust baseline demographic differences for further analysis. RESULTS: Ninety patients underwent SR and 53 patients received TACE. After a median follow-up of 17.0 (interquartile range 7.7-45.6) months, 83 patients had died. The cumulative 5-year OS rate was 44.7% and 11.7% for the SR group and the TACE group, respectively (P<0.001). A multivariate analysis showed that TACE [hazard ratio (HR): 3.515, 95% confidence interval (CI): 2.202-5.610, P<0.001], and albumin-bilirubin (ALBI) grade >1 (HR: 2.181, 95% CI: 1.343-3.543, P=0.002) were the independent risk factors associated with poorer OS. After PSM, 37 pairs of matched patients were selected from each treatment arm. After matching, patients who underwent SR still evinced a significantly higher OS than did those who underwent TACE (P=0.010). CONCLUSIONS: SR provided a better OS than did TACE for patients with solitary huge (≥10 cm) HCC. As such, SR is recommended as the therapeutic priority for these patients.

13.
J Biomed Opt ; 19(7): 77002, 2014.
Article in English | MEDLINE | ID: mdl-25027003

ABSTRACT

We are reporting on an experimental investigation of a movable diffuse reflectance spectroscopy system to extract diagnostically relevant optical properties of two-layered tissue phantoms simulating mucosae that are covered with stratified squamous epithelium. The reflectance spectra were measured at multiple sourcedetector separations using two imaging fiber bundles in contact with the phantoms, one with its optical axis perpendicular to the sample surface (perpendicular probe) and the other with its distal end beveled and optical axis tilted at 45 deg (oblique probe). Polystyrene microspheres and purified human hemoglobin were used to make tissue phantoms whose scattering and absorption properties could be well controlled and theoretically predicted. Monte Carlo simulations were used to predict the reflectance spectra for system calibration and an iterative curve fitting that simultaneously extracted the top layer reduced scattering coefficient, thickness, bottom layer reduced scattering coefficient, and hemoglobin concentration of the phantoms. The errors of the recovered parameters ranged from 7% to 20%. The oblique probe showed higher accuracy in the extracted top layer reduced scattering coefficient and thickness than the perpendicular probe. The developed system and data analysis methods provide a feasible tool to quantify the optical properties in vivo.


Subject(s)
Models, Biological , Phantoms, Imaging , Spectrum Analysis/instrumentation , Spectrum Analysis/methods , Epithelium/chemistry , Hemoglobins/chemistry , Humans , Microspheres , Monte Carlo Method , Mucous Membrane/chemistry , Polystyrenes
14.
Mitochondrion ; 12(6): 630-9, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23006892

ABSTRACT

We investigated the biogenesis and mitochondrial antioxidant capacity of cytochrome c oxidase (COX) within the skeletal muscle under the treatments of p53 inhibitors (pifithrin, PFTα and PFTµ). Significantly, PFTµ increased mtDNA content and COX biogenesis. These changes coincided with increases in the activity and expression of manganese superoxide dismutase (MnSOD), the key antioxidant enzyme in mitochondria. Conversely, PFTα caused muscle loss, increased oxidative damage and decreased MnSOD activity in intermyofibrillar (IMF) mitochondria. Mechanically, PFTµ inhibited p53 translocation to mitochondria and thus increased its transcriptional activity for expression of synthesis of cytochrome c oxidase 2 (SCO2), an important assembly protein for COX. This study provides in vivo evidence that PFTµ, superior to PFTα, preserves muscle mass and increases mitochondrial antioxidant activity.


Subject(s)
Electron Transport Complex IV/biosynthesis , Muscle, Skeletal/drug effects , Sulfonamides/metabolism , Superoxide Dismutase/metabolism , Animals , Benzothiazoles/metabolism , DNA, Mitochondrial/metabolism , Mice , Protein Transport/drug effects , Toluene/analogs & derivatives , Toluene/metabolism , Tumor Suppressor Protein p53/metabolism
15.
Arch Surg ; 147(2): 137-44, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22006855

ABSTRACT

OBJECTIVE: The effect of age on the clinicopathologic manifestations of hepatocellular carcinoma (HCC) and on the survival rate in patients with HCC after resection surgery remains controversial. We aim to compare the clinicopathological features and prognoses between younger and older patients with HCC undergoing resection. DESIGN: Retrospective review. SETTING: A tertiary medical center. PATIENTS: We enrolled 1074 consecutive patients with HCC who were undergoing a partial hepatectomy. Patients who were 55 years of age or younger were defined as the younger group (n = 374), and patients who were older than 55 years of age were defined as the older group (n = 700). MAIN OUTCOME MEASURES: The postoperative prognoses of the younger and older groups using multivariate analysis and propensity score matching analysis. RESULTS: The younger patients had better liver functional reserve but more aggressive tumor factors than did the older patients. After a median follow-up of 41.0 months, 543 patients died. The cumulative 10-year survival rates were 41.3% in younger patients and 28.8% in the older patients (P = .02). However, using both multivariate analysis and propensity score matching analysis, we failed to demonstrate that age was an independent risk factor associated with overall survival. Besides, there were 643 patients with tumor recurrence after surgery. Using both multivariate analysis and propensity score matching analysis, we found that the incidence of tumor recurrence in younger patients was comparable to that in the older patients. CONCLUSIONS: Age is not a risk factor to determine the prognosis of patients with HCC who underwent resection. Older patients with HCC who have good liver functional reserve are encouraged to receive resection surgery.


Subject(s)
Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/surgery , Hepatectomy/mortality , Liver Neoplasms/mortality , Liver Neoplasms/surgery , Propensity Score , Aged , Carcinoma, Hepatocellular/pathology , Female , Humans , Liver Neoplasms/pathology , Male , Middle Aged , Multivariate Analysis , Neoplasm Recurrence, Local/epidemiology , Risk Factors
16.
PLoS One ; 6(7): e21140, 2011.
Article in English | MEDLINE | ID: mdl-21750704

ABSTRACT

The purpose of this study was to outline the timelines of mitochondrial function, oxidative stress and cytochrome c oxidase complex (COX) biogenesis in cardiac muscle with age, and to evaluate whether and how these age-related changes were attenuated by exercise. ICR/CD-1 mice were treated with pifithrin-µ (PFTµ), sacrificed and studied at different ages; ICR/CD-1 mice at younger or older ages were randomized to endurance treadmill running and sedentary conditions. The results showed that mRNA expression of p53 and its protein levels in mitochondria increased with age in cardiac muscle, accompanied by increased mitochondrial oxidative stress, reduced expression of COX subunits and assembly proteins, and decreased expression of most markers in mitochondrial biogenesis. Most of these age-related changes including p53 activity targeting cytochrome oxidase deficient homolog 2 (SCO2), p53 translocation to mitochondria and COX biogenesis were attenuated by exercise in older mice. PFTµ, an inhibitor blocking p53 translocation to mitochondria, increased COX biogenesis in older mice, but not in young mice. Our data suggest that physical exercise attenuates age-related changes in mitochondrial COX biogenesis and p53 activity targeting SCO2 and mitochondria, and thereby induces antisenescent and protective effects in cardiac muscle.


Subject(s)
Electron Transport Complex IV/metabolism , Mitochondrial Proteins/metabolism , Myocardium/metabolism , Physical Conditioning, Animal , Tumor Suppressor Protein p53/metabolism , Aging , Animals , Blotting, Western , DNA, Mitochondrial/genetics , DNA, Mitochondrial/metabolism , Electron Transport Complex IV/genetics , Gene Expression Profiling , Male , Mice , Mice, Inbred ICR , Mitochondria, Heart/genetics , Mitochondria, Heart/metabolism , Mitochondrial Proteins/genetics , Molecular Chaperones , Protein Subunits/genetics , Protein Subunits/metabolism , Protein Transport/drug effects , Random Allocation , Reactive Oxygen Species/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Sulfonamides/pharmacology , Time Factors , Tumor Suppressor Protein p53/genetics
17.
Clin Gastroenterol Hepatol ; 9(1): 79-86, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20831902

ABSTRACT

BACKGROUND & AIMS: Differences in efficacy of radiofrequency ablation (RFA) and surgical resection (SR) are not clear for patients with hepatocellular carcinoma (HCC). METHODS: From 2002 to 2007, 419 patients with HCCs ≤5 cm were enrolled consecutively in the study. Among these patients, 190 and 229 patients received RFA and SR, respectively, as their first treatment. Factors were analyzed in terms of overall survival and recurrence by multivariate analysis and propensity score matching analysis. RESULTS: The SR group had younger age, a higher male-to-female ratio, higher prevalence of hepatitis B virus, lower prevalence of hepatitis C virus, better liver function reserve, and larger tumor size than the RFA group. The cumulative 5-year overall survival rates were 79.3% in the SR group and 67.4% in the RFA group. During the follow-up period, tumors recurred in 244 patients in a median time of 14.5 ± 15.7 months. Before propensity-score matching, the RFA group had shorter overall survival time (P = .009) and higher tumor recurrence rate (P < .001) than the SR group. After matching, RFA was comparable to SR in overall survival time (P = .519), but the RFA group still had a greater incidence of tumor recurrence (P < .001). In patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 HCC, RFA was as effective as SR for overall survival time and recurrence. CONCLUSIONS: Patients with small HCCs have a higher rate of tumor recurrence following RFA than surgery, but overall survival rates are comparable between therapies. RFA is as effective as surgery in patients with BCLC stage 0 HCC.


Subject(s)
Ablation Techniques , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/mortality , Liver Neoplasms/surgery , Aged , Female , Humans , Male , Middle Aged , Recurrence , Survival Analysis , Treatment Outcome
19.
J Plant Res ; 120(2): 323-8, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17122901

ABSTRACT

Two Ty1/copia-like retrotransposons, RTvr1 and RTvr2, were isolated from mung bean (Vigna radiata (L.) Wilczek) genomic DNA and are the first complete elements of this kind to be reported in this legume. Nucleotide sequence analyses revealed that both elements are AT-rich (60% and 61%, respectively) and are flanked by a target-site duplication of 5 bp. The structures of RTvr1 and RTvr2 are those of typical long terminal repeat retrotransposons. Both transposons were able to produce putative proteins with the domain order of Gag-protease-integrase-reverse transcriptase-RNase H, indicating that RTvr1 and RTvr2 belong to the Ty1/copia-like retrotransposons. Except for a 2,500-bp insertion region in RTvr2, the overall similarity between RTvr1 and RTvr2 is 92%. Dot blots showed that these two retroelements were present at a copy number of 120 per mung bean haploid genome. Multiple sequence alignments showed that the conserved motifs of the aspartic proteases, integrase, reverse transcriptase, and the RNase H in the Ty1/copia-like group all exist in RTvr1 and RTvr2.


Subject(s)
DNA, Plant/isolation & purification , Fabaceae/genetics , Retroelements/genetics , Amino Acid Sequence , Base Sequence , Gene Dosage , Molecular Sequence Data , Phylogeny , Plant Proteins/chemistry
20.
Article in English | MEDLINE | ID: mdl-16321577

ABSTRACT

A simple and selective micellar electrokinetic chromatography (MEKC) is described for determination of indomethacin in plasma. Plasma proteins are precipitated by acetonitrile. An aliquot of supernatant was evaporated and reconstituted with Tris buffer for MEKC analysis. The separation of indomethacin was performed at 25 degrees C using a background electrolyte consisting of Tris buffer (30 mM; pH 8.0) with 100 mM sodium octanesulfonate (SOS) as an anionic surfactant. Under this condition, a good separation with high efficiency and short analysis time is achieved. Several parameters affecting the separation of indomethacin were studied, including pH and concentrations of the Tris buffer and SOS. The linear range of the method for the determination of indomethacin was over 0.3-10.0 microg/mL; the detection limit (signal-to-noise ratio=3; injection 0.5 psi 5s) was 0.1 microg/mL. The proposed method for determination of indomethacin in premature infants with patent ducts arteriosus has been demonstrated.


Subject(s)
Chromatography, Micellar Electrokinetic Capillary/methods , Ductus Arteriosus, Patent/blood , Indomethacin/blood , Administration, Oral , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/blood , Calibration , Chromatography, Micellar Electrokinetic Capillary/instrumentation , Ductus Arteriosus, Patent/drug therapy , Humans , Indomethacin/administration & dosage , Indomethacin/standards , Infant, Newborn , Infant, Premature , Reference Standards , Reproducibility of Results , Spectrophotometry, Ultraviolet/methods
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