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OBJECTIVES@#To investigate the genotypes and biochemical phenotypes of neonates with abnormal metabolism of butyrylcarnitine (C4).@*METHODS@#One hundred and twenty neonates with increased C4 levels detected by tandem mass spectrometry in the neonatal screening at Children's Hospital, Zhejiang University School of Medicine from January 2018 to June 2023 were included. The initial screening data and recalled data of C4 and C4/C3 were collected and converted into multiples of C4 reference range. Next generation sequencing was performed and the exons with adjacent 50 bp regions of ACAD8 and ACADS genes were captured by liquid phase capture technique. Variant information was obtained by bioinformatic analysis and the pathogenicity were classified according to the American College of Medical Genetics and Genomics criteria. The Wilcoxon rank sum test was used to analyze the differences in C4 levels among neonates with different variation types.@*RESULTS@#In total, 32 variants in ACAD8 gene were detected, of which 7 variants were reported for the first time; while 41 variants of ACADS gene were detected, of which 17 variants have not been previously reported. There were 39 cases with ACAD8 biallelic variations and 3 cases with ACAD8 monoallelic variations; 34 cases with ACADS biallelic variations and 36 cases with ACADS monoallelic variations. Furthermore, 5 cases were detected with both ACAD8 and ACADS gene variations. Inter group comparison showed that the multiples of C4 reference range in initial screening and re-examination of the ACAD8 biallelic variations and ACADS biallelic variations groups were significantly higher than those of the ACADS monoallelic variations group (all P<0.01), while the multiples in the ACAD8 biallelic variations group were significantly higher than those in the ACADS biallelic variations group (all P<0.01). The multiples of C4 reference range in the initial screening greater than 1.5 times were observed in all neonates carrying ACAD8 or ACADS biallelic variations, while only 25% (9/36) in neonates carrying ACADS monoallelic variations.@*CONCLUSIONS@#ACAD8 and/or ACADS gene variants are the main genetic causes for elevated C4 in newborns in Zhejiang region with high genotypic heterogeneity. The C4 levels of neonates with biallelic variations are significantly higher than those of neonates with monoallelic variations. The cut-off value for C4 level could be modestly elevated, which could reduce the false positive rate in tandem mass spectrometry neonatal screening.
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Child , Humans , Infant, Newborn , Acyl-CoA Dehydrogenase/genetics , Genotype , Phenotype , Carnitine/metabolism , MutationABSTRACT
Objective: To systematically evaluate the impact of acupuncture on exercise-induced fatigue (EIF). Methods: Scopus, Springer Link, Web of Science, PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Academic Journal Full-text Database (Wanfang), Chongqing VIP Database (CQVIP), and China Biology Medicine Disc (CBM) were systematically searched to identify randomized controlled trials (RCTs) studying acupuncture treatment of EIF from the inception till August 2020. The risk of bias in the included studies was assessed using the Cochrane handbook. RevMan 5.3 was used to conduct statistical analysis on the extracted data. Results: A total of 11 RCTs were included for meta-analysis, involving 531 patients. It was revealed that acupuncture produced more significant effects in alleviating subjective fatigue [standardized mean difference (SMD)=-3.08, 95％ confidence interval (CI) (-4.35, -1.81), P<0.001], increasing the hemoglobin content [weighted mean difference (WMD)=3.89, 95％CI (1.37, 6.42), P=0.003], reducing the lactate dehydrogenase content [WMD=-10.63, 95％CI (-17.67, -3.59), P=0.003], reducing the blood lactic acid content [SMD=-2.65, 95％CI (-4.47, -0.83), P=0.004], and down-regulating the levels of serum creatine kinase [SMD=-0.79, 95％CI (-1.10, -0.48), P<0.001] and blood urea nitrogen [WMD=-1.47, 95％CI (-1.84, -1.11), P<0.001] than the control groups. Conclusion: Based on the existing evidence, acupuncture can be recognized as effective in improving EIF and is worthy of promotion in clinical settings.
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Objective:The clinical features, laboratory indices, and imaging data of patients with Pneumocystis jirovecii pneumonia (PJP) were described and analyzed, aiming to provide helpful information for the diagnosis and treatment of PJP. Methods:A retrospective study were conducted with data from 154 PJP patients who visited China-Japan Friendship Hospital from May 2017 to August 2020. Their clinical characteristics, laboratory and imaging data, and clinical outcomes were collected for analysis. The patients were further divided into the death group (51 cases) and the survival group(103 cases). The differences between the groups were compared by using t-test, nonparametric test, and chi-square test. Results:Of the 154 PJP patients, there were 89 males and 65 females, with a mean age of (53.7±14.8) years. Among them, 85.7% (132/154) were on immunosuppressive/glucocorticoids agents within the past month. Besides, 27.9% (43/154) and 33.1% (51/154) had kidney diseases and connective tissue diseases, respectively. The major clinical manifestations in these patients involved fever 82.9% (126/154), cough 59.7% (92/154), and dyspnea 52.6% (81/154). For the laboratory data, the lactate dehydrogenase (LDH) was 561.0 (434.3, 749.0) IU/L and the value increased in 91.3% (95/104) of the patients. The CD4+T-cell lymphocytes in 88.0% (95/108) and 57.4% (62/108) of patients were lower than 400/μl and 200/μl, respectively. Furthermore, (1, 3)-β-D glucan (BG) increased in 74.4% (67/90) of PJP patients (≥100.0 ng/L). For the imaging results, chest computed tomography (CT) showed diffuse ground-glass shadows/grid shadows in 90% (117/130) patients. Compared with the survival group, higher LDH [690.5 (528.8, 932.3) IU/L vs 502.5 (381.8, 657.0) IU/L, Z=-3.375, P=0.001], white blood cell count (WBC) [9.8 (5.8, 12.6) ×10 9/L vs 7.3 (5.0, 10.1) ×10 9/L, Z=-2.392, P=0.017], and age [(69.8±14.5) years vs (50.6±14.0) years, t=-3.756, P=0.001] were found in the death group. Lower lymphocyte ratio [5.3 (3.2, 9.3) % vs 9.6 (5.6, 17.2) %, Z=?3.262, P=0.001] and oxygen partial pressure (PaO 2) levels [(73.2±20.5) mmHg vs (64.8±17.7) mmHg (1 mmHg=0.133 kPa), t=2.345, P=0.021] were also observed in the death group. Furthermore, in the death group, the bacterial and fungal infection rate was higher than the rates in the survival group [55.1% (27/51) vs 21.5% (22/103), χ 2=15.372, P=0.001]. Conclusions:Long-term use of immunosuppressive agents or glucocorticoids predispose to PJP. CD4+T-lymphocytes, LDH, and BG might be used as important auxiliary examinations for PJP patients. Age, LDH, WBC, lymphocyte ratio, PaO 2 and possible combinations with bacterial or fungal infections are more closely related to the prognostic of PJP patients.
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Objective:To explore the factors influencing complete remission in patients with diffuse large B-cell lymphoma (DLBCL), and to explore the effect of the interaction of Karnofsky performance status scale (KPS) scores and the level of lactate dehydrogenases (LDH) on whether patients with DLBCL are completely relieved.Methods:The clinical data of 373 DLBCL patients admitted to Shanxi Province Cancer Hospital from January 2014 to December 2020 were retrospectively analyzed. SPSS 25.0 logistic regression model and Cox proportional risk regression models were used to explore the factors affecting complete remission in patients with DLBCL and to explore whether there was a multiplicative interaction between the factors. For factors with multiplicative interactions, the Matrix package, epiR package, and survival package in R 4.2.0 software were used to analyze whether there was an additive interaction. The relative excess risk of interaction (RERI), attributable proportion due to interaction (AP), and the synergy index (S) were used to evaluate the presence of additive interactions.Results:Elevated β 2 macroglobulin (β 2-MG), KPS scores below 80, and elevated LDH were risk factors for incomplete remission in patients with DLBCL (all P < 0.05). The risk of incomplete remission in patients with elevated β 2-MG, KPS scores below 80 and LDH was 1.971 times ( OR = 1.971, 95% CI 1.161-3.346), 2.056 times ( OR = 2.056, 95% CI 1.057-4.000) and 3.351 times ( OR = 3.351, 95% CI 1.783-6.300) higher than those in patients with normal β 2-MG, KPS scores above 80 and non-elevated LDH, respectively. There was a negative multiplicative interaction between the two risk factors of KPS scores below 80 and elevated LDH ( OR = 0.317, 95% CI 0.126-0.785). The estimated value of RERI, AP and S was -2.07 (95% CI -4.79-0.64),0.50 (95% CI -1.68-0.32),0.50 (95% CI 0.22-1.13), respectively; and there was no additive interaction among them. Conclusions:Elevated β 2-MG, KPS scores below 80, and elevated LDH are risk factors influencing incomplete remission for patients with DLBCL. The combined effect in patients with the combination of elevated LDH and KPS scores below 80 is lower than the single effect of the multiple of the both. There is a negative multiplicative interaction and no additive interaction in DLBCL patients with KPS scores below 80 and elevated LDH level.
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As a new hepatocyte-specific lipid droplet-related protein, 17β-hydroxysteroid dehydrogenase 13 (HSD17B13) is involved in hepatocyte lipid synthesis. Recent studies have shown that an insertion-deletion variant of the HSD17B13 gene is associated with a reduced risk of chronic liver diseases; however, the specific biological function of HSD17B13 and its involvement in the pathogenesis of liver diseases remain unclear. This article elaborates on the biological function of HSD17B13, its mechanism of action in alcohol-related liver, and the research advances in clinical application.
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Objective To investigate the clinical significance of cellular immune function, inflammatory factors and myocardial enzyme detection in evaluation of prognosis of septic shock,so as to provide a reference for clinical diagnosis and treatment of septic shock.Methods From June 2015 to June 2018,73 patients with septic shock treated in the First People＇s Hospital of Yongkang were selected as the research subjects.According to the 28d prognosis after the patients entered the ICU,the patients were divided into the death group and the survival group. Another 67 cases of health examination from June 2015 to June 2018 were selected as control group.The changes of T lymphocyte subsets includingCD3,CD4 and CD8 were measured by BD FACSCanto I I flow cytometry,the content of procalcitonin(PCT) was determined by immunoluminescence assay,the content of C -reactive protein(CRP) was determined by immunoturbidimetry,and the content of creatine kinase MB(CK-MB),cardiac troponin I(cTnI) and lactate dehydrogenase(LDH) was determined by enzymatic kinetics. Results The APACHE Ⅱ score and MODS score of the survival group and the death group were higher than those of the control group [(2.20 ± 0.61)points and (4.86 ± 1. 29 ) points]. The APACHE Ⅱ score and MODS score of death group [(16. 45 ± 4. 28) points and (27.63 ± 4.97)points] were higher than those of survival group [(9.84 ± 2.45)points and (19.84 ± 3.28)points] (all P＜0.05).The CD+3 ,CD+4 and CD+4 /CD+8 in the survival group and the death group were significantly lower than those in the control group[(71.32 ± 6.96)%,(42.63 ± 4.26)%,(1.67 ± 0.31)%] ( all P＜0.05).The contents of PCT and CRP in the survival group and the death group were higher than those in the control group [(0.19 ± 0.03) ng/mL and (2.19 ± 0.76)mg/L],and the contents of PCT [(15.93 ± 3.26) ng/mL] and CRP [(184.32 ± 29.80)mg/L] in the death group were higher than those in the survival group [(6.87 ± 1.94)ng/mL and (69.49 ± 17.42)mg/L] (all P＜0.05).The CK-MB content in the survival group and the death group of septic shock was lower than that in the control group [(1.97 ± 0.21)μg/L],and the cTnI and LDH contents were higher than that in the control group [(0.03 ± 0.01)μg/L and (168.93 ± 16.52) U/L],the content of CK-MB [(0.68 ± 0.10)μg/L] in the death group was lower than that in the survival group [(1.27 ± 0.13)μg/L],while the contents of cTnI [(0.39 ± 0.06)μg/L] and LDH [(384.52 ± 39.89)U/L] in the death group were lower than those in the survival group [(0.17 ± 0.04) μg/L and (257.18 ± 25.47) U/L] ( P ＜0.05). Conclusion The immune function of the patients with septic shock is obviously reduced,there are obvious inflammatory reactions and abnormal myocardial enzymes, and the detection of cellular immune function, inflammatory factors and myocardial enzymes can be used as an effective index to judge the shock of septic shock.
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Objective To investigate the diagnostic value of lactate dehydrogenase (LDH) isoenzymes in children with refractory mycoplasma pneumoniae pneumonia (RMPP). Methods One hundred and forty-seven children with mycoplasma pneumoniae pneumonia (MPP) in Children′s Medical Center, Dongfeng Hospital Affiliated to Hubei University of Medicine from July 2016 to July 2018 were selected. Among them, RMPP was in 54 cases (RMPP group), and non-RMPP was in 93 cases (non-RMPP group). The white blood cell count (WBC), C- reactive protein (CRP), erythrocyte sedimentation rate (ESR), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK) were detected; meanwhile, the serum levels of total LDH and LDH isoenzymes (LDH1, LDH2, LDH3, LDH4 and LDH5) were measured by radioimmunoassay. Results The ESR, AST, ALT, LDH1, LDH2, LDH4, LDH5 and total LDH in RMPP group were significantly higher than those in non-RMPP group:(23.15 ± 3.62) mm/h vs. (19.45 ± 3.04) mm/h, (37.20 ± 6.82) U/L vs. (31.49 ± 4.70) U/L, (35.48 ± 5.72) U/L vs. (27.31 ± 7.22) U/L, (89.77 ± 5.26) U/L vs. (85.01 ± 7.65) U/L, (154.60 ± 22.30) U/L vs. (133.17 ± 32.82) U/L, (61.51 ± 10.09) U/L vs. (47.74 ± 11.22) U/L, (78.99 ± 12.86) U/L vs. (64.98 ± 7.14) U/L and (511.49 ± 38.90) U/L vs. (450.19 ± 47.63) U/L, and there were statistical differences (P＜0.05); there were no statistical differences in WBC, CRP, CK and LDH3 between 2 groups (P＞0.05). Logistic regression analysis result showed that the ESR, AST, ALT, LDH1, LDH4 and LDH5 were the risk factors of RMPP ( OR=0.618, 0.735, 0.785, 0.769, 0.866, 0.880; 95% CI 0.430 to 0.888, 0.596 to 0.906, 0.665 to 0.926, 0.646 to 0.917, 0.781 to 0.961, 0.803 to 0.965; P<0.01). Receiver operating characteristic curve analysis result showed that the area under curve (AUC) of RMPP predicted by LDH5 was the largest (0.857), and then by LDH4 (0.819). The critical values were 70.74 and 53.14 U/L respectively; the AUC of RMPP predicted by LDH4 combined with LDH5 was 0.914, and the critical values was 130.10 U/L, with a sensitivity of 83.3% and a specificity of 92.5% , 95% CI 0.856 to 0.954. Conclusions Serum levels of LDH4 and LDH5 are significantly increased in children with RMPP. LDH4 combine with LDH5 detection might be useful in predicting the occurrence of RMPP.
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Objective@#To investigate the clinical significance of cellular immune function, inflammatory factors and myocardial enzyme detection in evaluation of prognosis of septic shock, so as to provide a reference for clinical diagnosis and treatment of septic shock.@*Methods@#From June 2015 to June 2018, 73 patients with septic shock treated in the First People's Hospital of Yongkang were selected as the research subjects.According to the 28d prognosis after the patients entered the ICU, the patients were divided into the death group and the survival group.Another 67 cases of health examination from June 2015 to June 2018 were selected as control group.The changes of T lymphocyte subsets includingCD3, CD4 and CD8 were measured by BD FACSCanto I I flow cytometry, the content of procalcitonin(PCT) was determined by immunoluminescence assay, the content of C-reactive protein(CRP) was determined by immunoturbidimetry, and the content of creatine kinase MB(CK-MB), cardiac troponin I(cTnI) and lactate dehydrogenase(LDH) was determined by enzymatic kinetics.@*Results@#The APACHE Ⅱ score and MODS score of the survival group and the death group were higher than those of the control group [(2.20±0.61)points and (4.86±1.29)points]. The APACHE Ⅱ score and MODS score of death group [(16.45±4.28)points and (27.63±4.97)points] were higher than those of survival group [(9.84±2.45)points and (19.84±3.28)points](all P<0.05). The CD3+, CD4+ and CD4+/CD8+ in the survival group and the death group were significantly lower than those in the control group[(71.32±6.96)%, (42.63±4.26)%, (1.67±0.31)%](all P<0.05). The contents of PCT and CRP in the survival group and the death group were higher than those in the control group [(0.19±0.03)ng/mL and (2.19±0.76)mg/L], and the contents of PCT [(15.93±3.26)ng/mL] and CRP [(184.32±29.80)mg/L] in the death group were higher than those in the survival group [(6.87±1.94)ng/mL and (69.49±17.42)mg/L] (all P<0.05). The CK-MB content in the survival group and the death group of septic shock was lower than that in the control group [(1.97±0.21)μg/L], and the cTnI and LDH contents were higher than that in the control group [(0.03±0.01)μg/L and (168.93±16.52)U/L], the content of CK-MB [(0.68±0.10)μg/L] in the death group was lower than that in the survival group [(1.27±0.13)μg/L], while the contents of cTnI [(0.39±0.06)μg/L] and LDH [(384.52±39.89)U/L] in the death group were lower than those in the survival group [(0.17±0.04)μg/L and (257.18±25.47)U/L] (P<0.05).@*Conclusion@#The immune function of the patients with septic shock is obviously reduced, there are obvious inflammatory reactions and abnormal myocardial enzymes, and the detection of cellular immune function, inflammatory factors and myocardial enzymes can be used as an effective index to judge the shock of septic shock.
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Objective@#To investigate the levels of matrix metalloproteinases-3 (MMP-3), adenosine deaminase (ADA) and lactate dehydrogenase (LDH) in the hydrothorax and ascites, and to approach the diagnostic value of three combined indexes in benign and malignant hydrothorax and ascites.@*Methods@#Case-control study. A total of 278 patients with hydrothorax and ascites were enrolled in this study who were hospitalized in the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine from August 2018 to July 2019 to detect the levels of MMP-3, ADA and LDH in the hydrothorax and ascites. The benign group (208 patients) and malignant group (70 patients) were compared with MMP-3, ADA, LDH, receiver operating characteristic (ROC) curve, sensitivity and specificity in the hydrothorax and ascites, and the results were compared comprehensively.@*Results@#(1)The MMP-3 level in the benign hydrothorax group was 89.21±61.93 ng/mL, the ADA level was (9.08±8.89) U/L, the LDH level was (143.34±68.63) U/L, and the MMP-3 level in the malignant hydrothorax group was (205.63±98.16) ng/mL, he ADA level was (10.96±5.04) U/L, the LDH level was (243.44±131.20) U/L. The MMP-3 level in the benign ascites group was (84.91±73.48) ng/mL, the ADA level was (3.48±2.80) U/L, the LDH level was (99.48±69.53) U/L, and the MMP-3 level in the malignant ascites group was (174.89±82.48) ng/mL, the ADA level was (6.31±4.42) U/L, the LDH level was (191.86±94.52) U/L. The levels of MMP-3, ADA and LDH in the hydrothorax and ascites of the malignant group were higher than those in the benign group, and the difference was statistically significant (Z1 values were 5.215, 2.549, 3.212, respectively, and Z2 values were 6.188, 4.524, 6.38, respectively, P1 and P2 were <0.05). (2)The area under the curve (AUC) of MMP-3 for diagnosis of hydrothorax, liver cancer ascites and gastric cancer ascites was 0.853, 0.826, and 0.763, respectively. The sensitivity was 76%, 96.9%, and 92.3%, respectively, and the specificity was 80%, 64.5%, 61.6%. The diagnostic efficacy of MMP-3 in lung cancer hydrothorax and liver cancer ascites was higher than ADA (AUC were 0.672, 0.691,respectively) and LDH (AUC were 0.717, 0.804, respectively), and the diagnostic efficacy of gastric cancer ascites was lower than ADA (AUC is 0.808) and LDH (AUC is 0.849), and LDH was the best. (3)The AUC of MMP-3, ADA and LDH combined diagnosis of lung cancer hydrothorax, liver cancer ascites and gastric cancer ascites were 0.861, 0.842, and 0.879, respectively. The sensitivities were 64%, 96.9%, and 84.6%, respectively, and the specificities were 92.9%, 63.8%, and 80.4%, respectively. In the lung cancer hydrothorax, liver cancer ascites and gastric cancer ascites, the combined efficacy of the three combined tests was better than the combined detection of MMP-3 and LDH (AUC were 0.86, 0.839, 0.872, respectively), combined detection of MMP-3 and ADA (AUC were 0.845, 0.831, 0.855, respectively), LDH and ADA combined detection (AUC were 0.713, 0.791, 0.846, respectively).@*Conclusions@#MMP-3 is important for the differential diagnosis of benign and malignant hydrothorax and ascites, and may be one of the important indicators for the differential diagnosis of benign and malignant hydrothorax and ascites. The diagnostic efficacy of MMP-3 combined with ADA and LDH and three combined detection is better than single index, which has certain clinical value for differential diagnosis of benign and malignant hydrothorax and ascites.
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Objective To investigate the levels of matrix metalloproteinases-3 (MMP-3), adenosine deaminase (ADA) and lactate dehydrogenase (LDH) in the hydrothorax and ascites, and to approach the diagnostic value of three combined indexes in benign and malignant hydrothorax and ascites. Methods Case-control study. A total of 278 patients with hydrothorax and ascites were enrolled in this study who were hospitalized in the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine from August 2018 to July 2019 to detect the levels of MMP-3, ADA and LDH in the hydrothorax and ascites. The benign group (208 patients) and malignant group (70 patients) were compared with MMP-3, ADA, LDH, receiver operating characteristic (ROC) curve, sensitivity and specificity in the hydrothorax and ascites, and the results were compared comprehensively. Results (1)The MMP-3 level in the benign hydrothorax group was 89.21±61.93 ng/mL, the ADA level was (9.08±8.89) U/L, the LDH level was (143.34± 68.63) U/L, and the MMP-3 level in the malignant hydrothorax group was (205.63 ± 98.16) ng/mL, he ADA level was (10.96±5.04) U/L, the LDH level was (243.44±131.20) U/L. The MMP-3 level in the benign ascites group was (84.91±73.48) ng/mL, the ADA level was (3.48±2.80) U/L, the LDH level was (99.48±69.53) U/L, and the MMP-3 level in the malignant ascites group was (174.89 ± 82.48) ng/mL, the ADA level was (6.31 ± 4.42) U/L, the LDH level was (191.86±94.52) U/L. The levels of MMP-3, ADA and LDH in the hydrothorax and ascites of the malignant group were higher than those in the benign group, and the difference was statistically significant (Z1 values were 5.215, 2.549, 3.212, respectively, and Z2 values were 6.188, 4.524, 6.38, respectively, P1 and P2 were <0.05). (2)The area under the curve (AUC) of MMP-3 for diagnosis of hydrothorax, liver cancer ascites and gastric cancer ascites was 0.853, 0.826, and 0.763, respectively. The sensitivity was 76％, 96.9％, and 92.3％, respectively, and the specificity was 80％, 64.5％, 61.6％. The diagnostic efficacy of MMP-3 in lung cancer hydrothorax and liver cancer ascites was higher than ADA (AUC were 0.672, 0.691, respectively) and LDH (AUC were 0.717, 0.804, respectively), and the diagnostic efficacy of gastric cancer ascites was lower than ADA (AUC is 0.808) and LDH (AUC is 0.849), and LDH was the best. (3)The AUC of MMP-3, ADA and LDH combined diagnosis of lung cancer hydrothorax, liver cancer ascites and gastric cancer ascites were 0.861, 0.842, and 0.879, respectively. The sensitivities were 64％, 96.9％, and 84.6％, respectively, and the specificities were 92.9％, 63.8％, and 80.4％, respectively. In the lung cancer hydrothorax, liver cancer ascites and gastric cancer ascites, the combined efficacy of the three combined tests was better than the combined detection of MMP-3 and LDH (AUC were 0.86, 0.839, 0.872, respectively), combined detection of MMP-3 and ADA (AUC were 0.845, 0.831, 0.855, respectively), LDH and ADA combined detection (AUC were 0.713, 0.791, 0.846, respectively). Conclusions MMP-3 is important for the differential diagnosis of benign and malignant hydrothorax and ascites, and may be one of the important indicators for the differential diagnosis of benign and malignant hydrothorax and ascites. The diagnostic efficacy of MMP-3 combined with ADA and LDH and three combined detection is better than single index, which has certain clinical value for differential diagnosis of benign and malignant hydrothorax and ascites.
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Adipose tissue inflammation is considered a major contributing factor in the development of obesity-associated insulin resistance and cardiovascular diseases. However, the cause of adipose tissue inflammation is presently unclear. The role of mitochondria in white adipocytes has long been neglected because of their low abundance. However, recent evidence suggests that mitochondria are essential for maintaining metabolic homeostasis in white adipocytes. In a series of recent studies, we found that mitochondrial function in white adipocytes is essential to the synthesis of adiponectin, which is the most abundant adipokine synthesized from adipocytes, with many favorable effects on metabolism, including improvement of insulin sensitivity and reduction of atherosclerotic processes and systemic inflammation. From these results, we propose a new hypothesis that mitochondrial dysfunction in adipocytes is a primary cause of adipose tissue inflammation and compared this hypothesis with a prevailing concept that “adipose tissue hypoxia” may underlie adipose tissue dysfunction in obesity. Recent studies have emphasized the role of the mitochondrial quality control mechanism in maintaining mitochondrial function. Future studies are warranted to test whether an inadequate mitochondrial quality control mechanism is responsible for mitochondrial dysfunction in adipocytes and adipose tissue inflammation.
Subject(s)
11-beta-Hydroxysteroid Dehydrogenases , Adipocytes , Adipocytes, White , Adipokines , Adiponectin , Adipose Tissue , Hypoxia , Cardiovascular Diseases , Homeostasis , Inflammation , Insulin Resistance , Metabolism , Mitochondria , Nitric Oxide , Obesity , Quality ControlABSTRACT
Objective To evaluate the protective effect of WSY6 (a caffeic acid derivative) on hydrogen peroxide (H2O2)-induced oxidative stress injury in melanocytes,and to explore its potential molecular mechanism.Methods In vitro cultured human primary melanocytes were divided into 5 groups:control group receiving no treatment,H2O2 group treated with 1 mmol/L H2O2,6.25,12.5,25 μmol/L WSY6 groups pretreated with 6.25,12.5,25 μmol/L WSY6 respectively followed by 1-hour treatment with 1 mmol/L H2O2.After 24-hour treatment,MTS assay was performed to determine the survival rate of melanocytes,and the lactate dehydrogenase (LDH)kit was used to detect the LDH leakage level.Some melanocytes were divided into 2 groups:inhibitor group pretreated with the p38 inhibitor for 1 hour followed by 1-hour treatment with 1 mmol/L H2O2,and H2O2 group treated with 1 mmol/L H2O2 for 1 hour.After 24-hour treatment,the LDH kit was used to detect the LDH leakage level.Some other melanocytes were pretreated with 25 μmol/L WSY6 for 1,2,4 hours separately,followed by 1-hour treatment with H2O2.Then,flow cytometry was conducted to detect the level of intracellular reactive oxygen species (ROS).Some melanocytes were treated with 6.25,12.5,25 μmol/L WSY6 separately for 1 hour,followed by 1-hour treatment with H2O2.Then,Western bolt analysis was performed to determine the protein expression of cytochrome c (cyto-c),caspase-3,caspase-9,phosphorylated (p)-p38 MAPK,p-ERK and p-JNK.Results Compared with the control group,the H2O2 group showed significantly decreased survival rate of melanocytes (29.22％ ± 1.31％,P ＜ 0.05),but significantly increased intracellular LDH leakage level (47.19％ ± 4.85％,P ＜ 0.05),elevated intracellular ROS level (18.37 ± 1.59,P ＜ 0.05),and increased expression of caspase-3 and caspase-9.Compared with the H2O2 group,the 6.25,12.5,25 μmol/L WSY6 groups showed significantly increased cell survival rate (52.48％ ± 1.17％,60.21％ ± 0.25％,78.32％ ± 1.73％,P ＜ 0.05),but significantly decreased LDH leakage level (21.99％ ± 0.22％,15.38％ ± 0.45％,13.18％ ± 0.38％,P ＜ 0.05),and the intracellular ROS level was significantly decreased in the 25 μmol/L WSY6 group after 1,2,4 hours of treatment (7.59 ± 1.00,6.22 ± 0.52,5.1 ± 0.48,P ＜ 0.05).The LDH leakage level in melanocytes was significantly lower in the p38 inhibitor group than in the H2O2 group (P ＜ 0.05).Western blot analysis revealed that after the pretreatment with 6.25,12.5,25 μmol/L WSY6 separately,the WSY6 groups all showed obviously decreased expression of caspase-3,caspase-9 and p-p38 compared with the H2O2 group.However,there was no obvious difference in the expression of p-ERK and p-JNK between the WSY6 groups and the H2O2 group.Besides,the WSY6 groups showed decreased expression of p-p53 (a downstream product of p38 MAPK),which decreased along with the increase in the concentration of WSY6.Conclusion WSY6 shows a markedly protective effect on H2O2-induced oxidative stress injury in melanocytes,likely through the p38 MAPK pathway.
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The growth of tumour cells is closely related to cancer-associated fibroblasts (CAFs)present within their microenvironment. CAFs, the most abundant cells in tumour stroma, secretegrowth factors that play pivotal roles in tumour cell proliferation, metabolism, angiogenesis andmetastasis. Tumour cells adapt to rapid environmental changes from normoxia to hypoxia throughmetabolic interplay with CAFs. In this mini review, we discuss the role of lactate dehydrogenases(LDHs) and monocarboxylate transporters (MCTs) on the metabolic interplay between tumourcells and CAFs under hypoxia compared to normoxia. The LDHs catalyse the interchange oflactate and pyruvate, whereas MCTs facilitate the influx and efflux of monocarboxylates, especiallylactate and pyruvate. To sum up, tumour cells switch their metabolic state between glycolysis andoxidative phosphorylation through metabolic interplay with CAFs, which exhibit the Warburgeffect under hypoxia and reverse Warburg effect under normoxia.
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ObjectiveTo investigate the expression of D-bifunctional protein (DBP) in hepatocellular carcinoma (HCC) tissue and its correlation with serum tumor markers alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9), as well as the clinical value of DBP in early diagnosis and prognostic evaluation of HCC. MethodsA total of 20 patients who underwent hepatectomy for liver cancer in Tangshan Maternal and Child Health Hospital and Tangshan People’s Hospital from June 2015 to May 2017 were enrolled as experimental group, and 20 healthy subjects who underwent physical examination in these two hospital during the same period of time were enrolled as control group. Chemiluminescence was used to measure the expression of AFP and CA19-9, and immunohistochemistry was used to measure the expression of DBP, which was expressed as integrated optical density (IOD), in HCC tissue and adjacent tissue. The t-test was used for comparison of continuous data between groups, and the Pearson correlation analysis was used to investigate correlation between indices. ResultsThe IOD value of DBP in HCC tissue was significantly higher than that in adjacent tissues (220.52±101.30 vs 40.49±1932, t=-7.00, P＜0.01). The expression of DBP was positively correlated with that of AFP (r2=0.868, P＜0.01) and CA19-9 (r2=0.814, P＜0.01). ConclusionThe expression of DBP increases in HCC patients, which is closely associated with the development and progression of HCC. Therefore, it provides a new target for the diagnosis of HCC.
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Objective: To evaluate the application value of fluorine-18-fludeoxyglucose (18F-FDG) PET/CT maximal standard uptake (SUVmax) in the diagnosis of lymphoma. Methods: A total of 103 patients with lymphoma which confirmed by pathological diagnosis in Gansu Provincial Hospital from January 2011 to December 2016 were collected. All patients underwent a whole body simultaneous18F-FDG PET/CT and had complete clinical data. The possible relationships of SUVmax with the different pathological subtypes, clinical stages and risk grades of lymphoma were analyzed. The correlations of SUVmax value with Ki-67 index, lactate dehydrogenase (LDH) and erythrocyte sedimentation rate (ESR) were analyzed. Results: There was no significant difference in SUVmax between Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) (P > 0.05). The SUVmax in patients with strongly invasive diffuse large B-cell lymphoma (DLBCL), T-lymphoblastic lymphoma (T-LBL), anaplastic large cell lymphoma (ALCL) and natural killer (NK)/T cell lymphoma was higher than that in patients with relatively weakly invasive mantle cell lymphoma (MCL), peripheral T-cell lymphoma (PTCL), small lymphocytic lymphoma (SLL), follicular lymphoma (FL) (grade 1-2) and marginal zone lymphoma (MZL) (P 0.05). The SUVmax had no significant difference between stage -Ⅱ and III- in the patients with lymphoma (P > 0.05). The SUVmax in the patients with high-risk NHL was higher than that in the patients with intermediate- and low-risk NHL (both P 0.05). Conclusion:18F-FDG PET/CT SUVmax can be used as a reference indicator for evaluating the invasive degree of lymphoma, predicting Ki-67 index, and judging the risk classification of NHL.
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Objective: To explore the relationship of 11β-hydroxysteroid dehydrogenases (11β-HSDs) expression in the ovarian granulosa cells and cortisol regeneration in the ovary of polycystic ovary syndrome (PCOS). Methods: In accordance with the revised Rotterdam inclusion/exclusion criteria (2003), 24 patients in the PCOS group were included, meanwhile 21 patients in the control group were included. Follicular fluid and luteinized granulosa cells were collected from patients underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) in the Center for Reproductive Medicine of Renji Hospital. Enzyme linked immunosorbent assay (ELISA) was used to detect the cortisol concentration and the cortisone levels of follicular fluid. Real-time quantitative PCR (RT-qPCR) was used to measure 11β-HSDs abundance in the luteinized granulosa cells. The expression of 11β-HSD1 and 11β-HSD2 in the luteinized granulosa cells were verified by immunofluorescence. The correlation of local cortisol level in the ovary with 11β-HSDs expression in the luteinized granulosa cells was further analyzed. Results: Compared with the control group, the cortisol level in the follicular fluid was elevated in the PCOS group [(477.3±35.3) nmol/L vs (292.0±36.4) nmol/L, P=0.014], while no change was observed in the cortisone levels in two groups. Both 11β-HSD1 and 11β-HSD2 were detected in the luteinized granulosa cells. Compared with the control group, the 11β-HSD1 mRNA abundance (P=0.033) and reductase activity (P=0.006) were increased significantly in the PCOS group, and there was no significant difference in the 11β-HSD2 expression and oxidase activity between two groups. Consistently, Pearson correlation analysis showed that the 11β-HSD1 but not 11β-HSD2 mRNA levels in the luteinized granulosa cells was correlated with the cortisol level in the follicular fluid (r2=0.347 6, P=0.001). Conclusion: Elevation of local cortisol in the ovary of PCOS patients may be related to the increased expression of 11β-HSD1 and reductase activity in the ovarian granulosa cells.
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Objective To explore the clinical significance of serum myocardial enzyme detection in infants with rotavirus (RV) enteritis.Methods One hundred and two infants with enteritis were selected as study objects .52 cases diagnosed as RV enteritis were selected as observation group ,while the other 50 cases with negative RV were selected as control groups .The fasting serum myocardial enzyme levels of the two groups were detected .Results The serum myocardial enzyme levels including AST ,ALT,LDH,CK,CK-MB,α-HBD in the observation group were (46.54 ±3.27)U/L,(28.32 ±12.90)U/L,(395.61 ±38.75)U/L,(148.43 ±18.22)U/L,(62.98 ±4.17)U/L, (271.28 ±22.64) U/L,respectively,which were significantly higher than those in the control group [(34.02 ± 8.93)U/L,(22.27 ±11.42) U/L,(295.84 ±56.36) U/L,(119.74 ±20.06) U/L,(42.85 ±9.73) U/L, (235.30 ±19.18) U/L] (t =26.765,24.572,38.337,31.329,25.453,56.832,all P <0.05).Conclusion Infants with RV enteritis are more likely to have myocardial injury than simple RV negative enteritis ,it is important to monitor ECG and serum myocardial enzyme levels ,which can help to diagnose and improve prognosis .
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Objective To observe the relationship between the dynamic changes of Epstein-Barr virus (EBV) and the clinical efficacy of lymphoma. Methods The retrospective study was performed on 51 lymphoma patients with EBV-positive in Anhui Provincial Cancer Hospital from September 2015 to August 2017. The treatment effect of lymphoma was evaluated by the changes of EBV DNA, lactic dehydrogenase (LDH) and lymph nodes. Results Among the 51 lymphoma patients, EBV DNA elevated in 18 patients when the LDH was elevated, 23 cases presented with EBV DNA decrease and the LDH also decreased. EBV DNA decreased in 2 patients when the LDH was elevated. Eight patients were elevated when LDH was reduced. The quantification of EBV DNA and LDH had high consistency (κ = 0.609, P= 0.000). Among the 51 lymphoma patients, 20 patients with elevated EBV DNA were elevated with lymph nodeen largement, the lymph nodes in 22 cases with EBV DNA decrease were also decreased. EBV DNA decreased in 3 patients when the lymph nodes were enlarged. Six patients were elevated when lymph nodes were reduced. The quantification of EBV and lymph nodes had high consistency (κ = 0.648, P= 0.000). Patients with elevated EBV DNA during the course of treatment showed an increase in the mean value of LDH, and the patients with reduced EBV DNA during treatment also had lower average LDH. LDH levels were positively correlated with EBV DNA in patients with EBV-positive lymphoma (r= 0.627, P= 0.000). Conclusion Dynamic detection of EBV DNA and LDH can be used as the evaluation index of therapeutic effect and follow-up in patients with EBV-positive lymphoma.
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Objective@#To investigate the expression and clinicopathological significance of hypoxia-inducible factor 1 alpha (HIF-1α), glucose transporter 1(GLUT-1) and lactate dehydrogenase(LDH)-5 in colorectal cancer.@*Methods@#The expression levels of HIF-1α, GLUT-1 and LDH-5 were detected by immunohistochemical staining in 142 specimens of human carcinoma in comparison with adjacent normal tissues.@*Results@#The expression levels of HIF-1α(78.2%, 111/142), GLUT-1(75.4%, 107/142) and LDH-5(68.3%, 97/142) were higher in tumor tissues than in adjacent normal tissues(14.8%, 21/142; 11.3%, 16/142; 7.0%, 10/142; P<0.01 for all three proteins), and such over-expression was significantly associated with lymphovascular invasion, tumor grade and pathological stages(all P<0.01). Additional studies showed that HIF-1α, GLUT-1 and LDH-5 were positively associated with each other(r<0.3, P<0.05 for all three proteins).@*Conclusion@#The data suggest that HIF-1α, GLUT-1 and LDH-5 expression may serve as prognostic indicators for colorectal cancer patients.
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Objective To evaluate the effects of sub-acute alcoholism on cardiac structure and function, and investigate the mechanisms of aldehyde dehydrogenases-2 (ALDH2)alleviating the damage of heart caused by acute myocardial infarction.Methods The wild mice with ALDH2 (+/+) (WT group) and mice with knockout type ALDH2 (-/-) genotypes (KO group) were raised and then divided into four groups according to the presence or absence of sub-acute alcoholism: WT group (n=10), KO group (n=16), WT+alcoholism group(WT+E,n=10) and KO+alcoholism group(KO+E,n=10).The mice of WT+E group and KO+E group were fed with high-dose of ethanol(2 g/kg per day for 8 days), while the mice of WT group and KO group were treated with equal amount of saline instead.Acute myocardial infarction models were established in all mice after ethanol administration,and blood ethanol concentration, cardiac function, myocardial infarct size, the activity of ALDH2, and the key molecules of PI3K/Akt signal pathway and caspase-3 mRNA were detected one week after modeling.Statistical analysis was performed using SPSS 17.0.Differences in levels of detected biomarkers between groups were assessed using Chi-squared or One way ANOVA, and P<0.05 was considered to be statistically significant.Results (1) The mortality rates of WT group, KO group, WT+E group and KO+E group were 20.0%, 30.0%, 31.3% and 37.5%, respectively.(2)Compared with WT group and KO group, the blood ethanol concentration was higher and the damage of liver was more severe in WT+E group and KO+E group(P<0.05).(3)The fraction shortening of short axis of left ventricle(FS) and left ventricular ejection fraction were higher in WT group and WT+E group compared with KO group and KO+E group(P<0.05).(4) The area of myocardial infarction was largest in KO+E group, followed by KO group, WT+E group, and WT group (all P<0.05).(5) The activity of ALDH2 in WT group was higher than that in other groups, and the ALDH2 activity in KO+E group was lower than that in KO group (P<0.05).(6) There was no significant difference in expressions of PI3K among four groups.The level of p-Akt was highest in WT group, followed by WT+E group, KO group, and KO+E group (all P<0.05).The levels of caspase-3 mRNA was highest in KO+E group, followed by KO group, WT+E group, and WT group (all P<0.05).Conclusions Myocardial damage caused by acute myocardial infarction can be aggravated by sub-acute alcoholism, while ALDH2 protection can effectively alleviate the damage effects of sub-acute alcoholism on myocardial infarction.The mechanism of protective effects of ALDH2 on acute myocardial infarction may be related to attenuation of cardiocytes apoptosis mediated by PI3K/Akt signal pathway.