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ObjectivePeriprosthetic joint infections （PJI） are currently the most calamitous complication after arthroplasty. Although achievements have been made in many markers for the diagnosis of PJI， the lack of a gold standard remains a great obstacle for early diagnosis. This study aimed to investigate the association between coagulation markers and the development of PJI in patients undergoing revision total joint arthroplasty （TJA）. MethodsWe conducted a retrospective cohort study with a total of 2 517 patients who underwent hip or knee arthroplasties from January 2011 to January 2022 （2 394 with primary TJA， 87 with aseptic revision and 36 with PJI）. We applied univariate analysis and multivariate logistic regression to analyze differences of coagulation factors between primary TJA and aseptic revision or PJI group. Receiver operating characteristic （ROC） curve and area under the curve （AUC） were used to measure the diagnostic value of coagulation factors in predicting PJI. ResultsCoagulation factors and their ratios including plasma fibrinogen （FBG）， prothrombin time （PT）， thrombin time （TT）， activated partial thromboplastin time （APTT）， platelet （PLT）， mean platelet volume （MPV）， platelet distribution width （PDW）， plateletcrit （PCT）， PLT / MPV， PLT / PDW and PLT / PCT were included in this study. High FGB level was strongly correlated with the risk of PJI compared to other coagulation factors. The optimal threshold value of FBG was 4.53 g/L with a sensitivity of 47.22%， a specificity of 93.07% （Primary TJA group vs. PJI group）. Similarly， the optimal threshold value of FBG was 4.44 g/L with a sensitivity of 47.22%， a specificity of 95.40% between the other two groups （Aseptic revision group vs. PJI group）. ROC curve analysis demonstrated moderate diagnostic performance of FBG （AUC value）， indicating a potential to be a diagnostic marker for PJI. ConclusionsFBG is significantly correlated with PJI and it can be used as a potential non-invasive marker for early detection. It may serve as a safe and cost-effective tool for assessing PJI in clinical work.
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Aldolase B (ALDOB), a glycolytic enzyme, is uniformly depleted in clear cell renal cell carcinoma (ccRCC) tissues. We previously showed that ALDOB inhibited proliferation through a mechanism independent of its enzymatic activity in ccRCC, but the mechanism was not unequivocally identified. We showed that the corepressor C-terminal-binding protein 2 (CtBP2) is a novel ALDOB-interacting protein in ccRCC. The CtBP2-to-ALDOB expression ratio in clinical samples was correlated with the expression of CtBP2 target genes and was associated with shorter survival. ALDOB inhibited CtBP2-mediated repression of multiple cell cycle inhibitor, proapoptotic, and epithelial marker genes. Furthermore, ALDOB overexpression decreased the proliferation and migration of ccRCC cells in an ALDOB-CtBP2 interaction-dependent manner. Mechanistically, our findings showed that ALDOB recruited acireductone dioxygenase 1, which catalyzes the synthesis of an endogenous inhibitor of CtBP2, 4-methylthio 2-oxobutyric acid. ALDOB functions as a scaffold to bring acireductone dioxygenase and CtBP2 in close proximity to potentiate acireductone dioxygenase-mediated inhibition of CtBP2, and this scaffolding effect was independent of ALDOB enzymatic activity. Moreover, increased ALDOB expression inhibited tumor growth in a xenograft model and decreased lung metastasis in vivo. Our findings reveal that ALDOB is a negative regulator of CtBP2 and inhibits tumor growth and metastasis in ccRCC.
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Humans , Carcinoma, Renal Cell/genetics , Fructose-Bisphosphate Aldolase/metabolism , Co-Repressor Proteins/metabolism , Transcription Factors/genetics , Kidney Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, NeoplasticABSTRACT
The outbreak of COVID-19 as an acute communicable disease has also changed the epidemiological status of diabetes mellitus and other noncommunicable chronic diseases. During the COVID-19 epidemic period, it was observed that there were increased morbidity of diabetes, difficulties in blood sugar control and increased acute complications for diabetic patients. This may be attributed to lifestyle changes during the epidemics, such as the reduced exercise time and increased sedentary time, more snacks and sugary food intake, as well as anxiety and depression. However, it is not known the long-term impact of COVID-19 epidemic on the management of diabetic patients, so it is necessary to closely monitor the exposed diabetic patients in the future.
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Objective:To explore the relationship between soft markers found in the first trimester (11-13 + 6 gestational weeks) ultrasound screening and fetal adverse pregnancy outcomes. Methods:Single pregnancy fetuses were selected from the Multicenter Clinical Study of First Trimester Screening in China during August 2017 to August 2020. The types and detection rate of soft markers during the first trimester were compared. The correlation between positive soft markers and adverse pregnancy outcomes was analyzed by binary Logistics regression.Results:A total of 16 625 fetuses with complete follow-up outcomes were included in the group. Six hundred and seven ultrasonic soft markers were detected in 556 fetuses with positive soft markers during the first trimester, and the first four most frequently occurred were increased nuchal translucency (NT) (2.08%, 345/16 625), echogenic intracardiac focus (EIF) (0.94%, 156/16 625), hypoplasia of fetal nasal bone (0.20%, 34/16 625), single umbilical artery (SUA) (0.19%, 31/16 625). Among 556 fetuses, the incidence of adverse pregnancy outcome in fetuses with two or more positive soft markers was 32.50% (13/40), which was significantly higher than fetuses with single positive soft marker (11.05%, 57/516), and the difference was statistically significant (χ 2=5.055, P<0.001). The incidence of adverse pregnancy outcome in positive soft markers fetus associated with structural abnormalities was 80.77% (21/26), which was significantly higher than fetuses with isolated positive soft marker (12.08%, 64/530), and the difference was statistically significant (χ 2=90.310, P<0.001). Binary logistic regression analysis showed choroid plexus cyst (CPC), SUA, echogenic bowel (EB), absent/reversed a-wave of ductus venosus, hypoplasia of fetal nasal bone, increased NT, and EIF were closely related to the adverse pregnancy outcomes (all P<0.05). However, there were no significant correlations between tricuspid regurgitation (TR), pyelectasis (PYE) and fetal adverse pregnancy outcomes (all P>0.05). Conclusions:The ultrasonic soft markers during the first trimester are of great significance in predicting fetal adverse pregnancy outcomes. For multiple positive soft markers or positive soft markers combined with structural abnormalities, more attention should be paid to them and comprehensive evaluation is required to be carried out.
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Objective:To examine the reliability and validity of the theory of planned behavior psychological help-seeking questionnaire (TPB-PHSQ) in Chinese adults.Methods:A total of 979 Chinese adults were recruited through convenient sampling method.The final scale was determined by item analysis and exploratory factor analysis.Then, the TPB-PHSQ was examined for reliability and validity.Results:The theory of planned behavior psychological help-seeking scale included 14 items in four sections: attitude, subjective norm, perceived behavioral control and help-seeking intention.The internal consistency reliability of the TPB-PHSQ were 0.893, 0.711, 0.869, 0.918, and the retest reliability were 0.798, 0.713, 0.712, 0.729 for the 4 sections.The confirmatory factor analysis met the fit criteria for each indicator ( χ2/ df= 2.585, RMSEA=0.063, SRMR= 0.067, NFI=0.934, RFI=0.912, IFI=0.958, TLI=0.944, CFI=0.958). TPB-PHSQ was significantly correlated with validated variable, which the correlation coefficients of attitude, perceived behavioral control and the score of the attitude toward professional psychological help-short form were 0.474, 0.357, and the correlation coefficients of subjective norm, help-seeking intention and the score of intention of seeking counseling inventory were 0.432, 0.415 ( all P<0.01). Conclusion:The TPB-PHSQ has good reliability and validity, which can be used for relevant research and application.
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Objective To explore the isolation, culture and identification of mouse amniotic fluid-derived mesenchymal stem cell (AF-MSC). Methods The uteruses of pregnant mice were obtained under sterile conditions. The amniotic fluid was collected, filtered and centrifuged, and the precipitated cell mass was cultured and passaged. The morphology of AF-MSC was observed and the proliferation characteristics of AF-MSC were analyzed. The surface markers of AF-MSC were identified by flow cytometry. The osteogenic, chondrogenic and adipogenic differentiation capability of AF-MSC and cell vitality after cryopreservation and resuscitation were evaluated. Results The mouse AF-MSC was seen in typical spindle shape, and vortex structure could be observed when the cell confluency exceeded 80%. No evident latency was noted in the passage and culture of mouse AF-MSC. After 2-3 d culture, AF-MSC proliferated in the logarithmic growth stage with the fastest growth rate, which was slowed down and entered into the plateau period. AF-MSC expressed stem cell antigen (Sca)-1, CD29 and CD44 rather than CD34 and CD45. After the osteogenic differentiation of mouse AF-MSC, the mineralized crystals were stained in dark red spots by Alizarin red S staining. After chondrogenic differentiation, the secreted acid mucopolysaccharide was stained in light blue by Alcian blue. After adipogenic differentiation, cytoplasmic lipid droplets were stained in red by oil red O staining. After cryopreservation and resuscitation, the survival rate of AF-MSC exceeded 95%, and the growth status was excellent. The proliferation ability at 6 d was significantly better than that before cryopreservation (P < 0.05), and the proliferation ability at other time points did not significantly differ from that before cryopreservation (all P > 0.05). Conclusions Mouse AF-MSC may be successfully isolated with convenient procedure and the low cost. In addition, the isolated AF-MSC may be purified along with the increasing times of passage. Cryopreservation does not affect the proliferation ability of AF-MSC.
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Objective:To analyze changes in nutritional status and immune function of elderly men receiving regular physical examinations, and to investigate the effects of aging on the nutritional status and immune function among elderly men.Methods:A total of 209 elderly men aged 60-101(72.9±11.5)years and receiving regular physical check-ups were enrolled.All research subjects were subjected to nutritional risk screening(NRS2002)and monitoring of nutrition and immune-related indicators, including routine blood work, blood biochemistry, immunoglobulin and T lymphocyte subsets.Results:Body weight, body mass index, hemoglobin, total protein, albumin and serum iron of elderly men decreased with age( F=21.754, 6.257, 47.528, 12.285, 18.397, 18.667, all P<0.001), with those aged 80 and above showing more significant decline and a greater proportion with malnutrition( χ2=77.134, P<0.001). The B lymphocyte counts of elderly men aged 80 and above were significantly lower( P<0.05)while serum IgA and IgG levels were significantly higher( F=3.110, 3.866, P=0.047, 0.022)than those of the 70-79 year old group.In addition, the B lymphocyte count and B lymphocyte ratio in malnourished elderly men were significantly lower( t=2.512, 2.874, P=0.013, 0.005), and IgA was significantly increased( t=2.513, P=0.017), compared with those with normal nutrition. Conclusions:The risk of malnutrition and reduced immune function among elderly men aged 80 years and above is significantly increased, and assessment and screening of the risk of malnutrition in the elderly should be stressed.
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Elderly patients with diabetes often have multiple co-morbidities, comprehensive geriatric health assessment and highly individualized management should be emphasized for them. In recent years, with the emerging of new hypoglycemic drugs the treatment for elderly diabetic patients has advanced, which offers new options and challenges in the management and treatment of elderly diabetic patients with multiple comorbidities.
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Physical fitness is the basic ability necessary to meet daily living activities,including walking, running, jumping, throwing, climbing, and so on. Adequate physical fitness is essential for the prevention and management of metabolic diseases. Impaired physical fitness is common in patients with diabetes mellitus and its chronic complications. This article reviews the impact of diabetes and its complications on physical fitness, current methods for assessment and management to provide a reference for comprehensive prevention and treatment of diabetic patients.
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Diabetes mellitus is a chronic metabolic disease, in which the abnormality of glucose and lipid metabolism may cause multisystem damage. Sodium-glucose synergistic transporter 2 (SGLT2) inhibitors are a novel type of hypoglycemic drug that can lower blood sugar level by inhibiting the absorption of glucose through renal tubules. Studies have shown that SGLT2 inhibitors also have a lowering effect on blood pressure, but the mechanism is not fully elucidated. In this article the hypotensive effects of SGLT2 inhibitors and possible mechanisms are reviewed.
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The importance of glucose measurement in the treatment of diabetes can not be overstated. However, the compliance with blood glucose measurement is low because most of the measurement of blood glucose monitor are invasive or minimal invasive. Non-invasive technology can reduce discomfort, improve adherence of blood glucose monitor by the guidelines, facilitate glycemic control, and subsequently lower the prevalence of acute and chronic complications. It is expected that large-scale clinical application will be possible in the future if accurate data can be obtained and costs can be controlled in the non-invasive measurement of blood glucose. This review overviewed the current technology accuracy, advantages, disadvantages, and potential limitations of non-invasive blood glucose measurement.
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Objective:The aim of the present study was to observe the effects of liralutide on body composition and muscle function in adult obese patients with type 2 diabetes.Method:A total of 63 adult obese type 2 diabetic patients who were (52.6±9.7) years of age and with body mass index (BMI) of ≥28 kg/m 2 were enrolled. The patients were randomly assigned into two groups. On the basis of maintaining the original hypoglycemic regimen, patients in the control group ( n=24) were given dietary guidance only, and those in the treatment group ( n=39) were injected with liraglutide. All patients were followed up for a period of 12 weeks. Blood glucose, glycosylated hemoglobin(HbA1c) and insulin levels, liver and kidney function, body composition assessed with electrical impedance methods, and grip strength measured by a grip meter for muscle function were detected at the baseline and the end of the study. Results:Compared with those in the control group, the reductions in HbA1c [(-1.54±2.10) % vs.(-0.53±0.84) %], body weight [(-3.46±4.2) kg vs.(-0.34±3.66) kg], body fat mass [(-1.97±2.98) kg vs.(-0.01±2.16) kg] and visceral fat area [(-0.01±2.16) cm 2 vs.(0.34±6.39) cm 2] were more pronouced in liraglutide treated group (all P<0.05). However, no changes could be observed in muscle mass and grip strength after liraglutide treatment. Conclusions:In addition to reducing blood glucose, body weight and fat mass, treatment with lilaluptide had no impact on muscle mass and muscle function. Therefore, liralutide is suitable for obese patients with type 2 diabetes, especially for weight management patients who are at risk of muscle loss.
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Elderly diabetic patients in China accounts for one fourth of the total number of elderly diabetic patients in the world, ranking the first worldwide. In 2021, National Center of Gerontology, Chinese Society of Geriatrics and Diabetes Professional Committee of Chinese Aging Well Association issued China′s first guideline on elderly diabetic patients——Guideline for the management of diabetes mellitus in the elderly in China (2021 edition). The present article interprets parts of the important recommendations of the guideline, aiming to facilitate its implementation in clinical practice effectively and improve the clinical prognosis of elderly diabetic patients in our country.
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Objective:To study the influence of patients' ages on average medical expenses under the diagnosis related group and prospective payment system(DRG-PPS)model.Methods:Medical records of 52 987 selected patients at a third-tier general hospital in Beijing were collected from January 1 to December 31, 2019, and were then divided into three age groups based on age, the elderly group, the middle-aged group and the young group, and one-way ANOVA was used to determine differences in medical expenses between the same DRG group and different age groups.Related-sample nonparametric tests and linear regression were carried out for the three age groups to estimate the influence of the age factor on the medical expenses of different DRG groups.Results:First, the data of the three age groups in the same DRG group were analyzed by one-way ANOVA.The P values of the DRG groups were less than 0.05, except for the cb39 crystal surgery DRG group; Then, the data of the three age groups in different DRG groups were analyzed with the nonparametric test( P=0.021, less than 0.05); Finally, linear regression analysis was also used to analyze the case data of the three age groups.The p value was less than 0.05, and the standardized influence coefficient was 0.173, suggesting age was positively correlated with hospitalization expenses. Conclusions:Age affects average hospitalization expenses.After the implementation of the DRG-PPS model, the payment of DRG patients should be standardized with the inclusion of the age factor.
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Objective:To explore the clinical value of prenatal ultrasound in diagnosis of fetal cleft lip and palate during first-trimester (11-13 + 6 gestational weeks). Methods:Ultrasonographic images were retrospectively selected from those fetuses who underwent first trimester scanning during July 2017 to June 2020 in the Affiliated Suzhou Hospital of Nanjing Medical University. Fetal facial mid-sagittal section and the retronasal triangle (RNT) section were combined together to evaluate whether the fetuses had cleft lip and palate (CLP) or not. All fetuses were followed up to birth or induced abortion.Results:A total of 5 520 fetuses were enrolled, with crown-rump length (CRL) between 45-84 mm. Seven cases of different types of CLP were detected by the 2 combined sections, including 4 cases with unilateral CLP, 1 case with median CLP, and 2 cases with bilateral CLP, which were confirmed by follow-up. In addition, 2 cases of isolated cleft lip (CL) were missed.Conclusions:Combination of fetal facial mid-sagittal section and RNT section is useful for the early diagnosis of fetal cleft lip and palate during first-trimester scanning.
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Although the contributions of sitagliptin to endothelial dysfunction in diabetes mellitus were previously reported, the mechanisms still undefined. Autophagy plays an important role in the development of diabetes mellitus, but its role in diabetic macrovascular complications is unclear. This study aims to observe the effect of sitagliptin on macrovascular endothelium in diabetes and explore the role of autophagy in this process. Diabetic rats were induced through administration of high-fat diet and intraperitoneal injection of streptozotocin. Then diabetic rats were treated with or without sitagliptin for 12 weeks. Endothelial damage and autophagy were measured. Human umbilical vein endothelial cells were cultured either in normal glucose or in high glucose medium and intervened with different concentrations of sitagliptin. Rapamycin was used to induce autophagy. Cell viability, apoptosis and autophagy were detected. The expressions of proteins in c-Jun N-terminal kinase (JNK)-Bcl-2-Beclin-1 pathway were measured. Sitagliptin attenuated injuries of endothelium in vivo and in vitro. The expression of microtubuleassociated protein 1 light chain 3 II (LC3II) and beclin-1 were increased in aortas of diabetic rats and cells cultured with high-glucose, while sitagliptin inhibited the over-expression of LC3II and beclin-1. In vitro pre-treatment with sitagliptin decreased rapamycin-induced autophagy. However, after pretreatment with rapamycin, the protective effect of sitagliptin on endothelial cells was abolished. Further studies revealed sitagliptin increased the expression of Bcl-2, while inhibited the expression of JNK in vivo . Sitagliptin attenuates injuries of vascular endothelial cells caused by high glucose through inhibiting over-activated autophagy. JNK-Bcl-2-Beclin-1 pathway may be involved in this process.
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Although the contributions of sitagliptin to endothelial dysfunction in diabetes mellitus were previously reported, the mechanisms still undefined. Autophagy plays an important role in the development of diabetes mellitus, but its role in diabetic macrovascular complications is unclear. This study aims to observe the effect of sitagliptin on macrovascular endothelium in diabetes and explore the role of autophagy in this process. Diabetic rats were induced through administration of high-fat diet and intraperitoneal injection of streptozotocin. Then diabetic rats were treated with or without sitagliptin for 12 weeks. Endothelial damage and autophagy were measured. Human umbilical vein endothelial cells were cultured either in normal glucose or in high glucose medium and intervened with different concentrations of sitagliptin. Rapamycin was used to induce autophagy. Cell viability, apoptosis and autophagy were detected. The expressions of proteins in c-Jun N-terminal kinase (JNK)-Bcl-2-Beclin-1 pathway were measured. Sitagliptin attenuated injuries of endothelium in vivo and in vitro. The expression of microtubuleassociated protein 1 light chain 3 II (LC3II) and beclin-1 were increased in aortas of diabetic rats and cells cultured with high-glucose, while sitagliptin inhibited the over-expression of LC3II and beclin-1. In vitro pre-treatment with sitagliptin decreased rapamycin-induced autophagy. However, after pretreatment with rapamycin, the protective effect of sitagliptin on endothelial cells was abolished. Further studies revealed sitagliptin increased the expression of Bcl-2, while inhibited the expression of JNK in vivo . Sitagliptin attenuates injuries of vascular endothelial cells caused by high glucose through inhibiting over-activated autophagy. JNK-Bcl-2-Beclin-1 pathway may be involved in this process.
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BACKGROUND@#The association of lipids and cancer has varied greatly among different cancer types, lipid components and study populations. This study is aimed to investigate the association of serum lipids and the risk of malignant lesions in esophageal squamous epithelium.@*METHODS@#In the "Endoscopic Screening for Esophageal Cancer in China" (ESECC) trial, serum samples were collected and tested for total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol at the time of subject enrollment. Cases were defined as malignant esophageal lesions identified by baseline endoscopic examination or by follow-up to May 31, 2018. Controls were randomly selected using incidence density sampling in the same cohort. Conditional logistic models were applied to identify the association of serum lipids and the risk of malignant esophageal lesions. Effect modification was evaluated by testing interaction terms of the factor under assessment and these serum lipid indicators.@*RESULTS@#No consistent association between serum lipid levels and esophageal malignant lesions were found in a pooled analysis of 211 cases and 2101 controls. For individuals with a family history of esophageal cancer (EC), high TC, and LDL-C were associated with a significantly increased risk of having malignant lesions (odds ratio [OR]High vs. Low TC = 2.22, 95% confidence interval [CI]: 1.14-4.35; ORHigh vs. Low LDL-C = 1.93, 95% CI: 1.01-3.65). However, a negative association was observed in participants without an EC family history (ORHigh vs. Low TC = 0.69, 95% CI: 0.48-0.98, Pinteraction = 0.002; ORHigh vs. Low LDL-C = 0.50, 95% CI: 0.34-0.76, Pinteraction < 0.001).@*CONCLUSIONS@#In this study, we found that the association of serum lipids and malignant esophageal lesions might be modified by EC family history. The stratified analysis would be crucial for population-based studies investigating the association of serum lipids and cancer. The mechanism by which a family history of EC modifies this association warrants further investigation.
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Humans , Case-Control Studies , China , Cholesterol, HDL , Early Detection of Cancer , Esophageal Neoplasms/genetics , Lipids , TriglyceridesABSTRACT
BACKGROUND@#The chaperonin containing t-complex (CCT) proteins play an important role in cell cycle-related protein degradation in yeast and mammals. The role of the chaperonin containing t-complex 4 (CCT4), one subtype of CCT proteins, in the progress of hepatocellular carcinoma (HCC) was not fully elucidated. Here, we aimed to explore the mechanisms of CCT4 in HCC.@*METHODS@#In this study, we used the UALCAN platform to analyze the relationship between CCT4 and HCC, and the association of CCT4 with the overall survival (OS) of HCC patients was also analyzed. CCT4 expression in HCC tumor tissues and normal tissues was also determined by western blot (WB) assay. Lentivirus vector was used to knock down the CCT4 expression, and quantitative polymerase chain reaction and WB were used to determine the level of CCT4 in HCC cell lines. Cell counting kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to detect the cell proliferation, and flow cytometry (FCM) was performed to evaluate the effect of CCT4 on the apoptosis of HCC cells. Co-immunoprecipitation (co-IP) assay and WB were used to explore the mechanisms of CCT4 regulating the growth of HCC. Data were calculated from at least three replicate experiments and expressed as mean ± standard deviation. Student's t test, paired t test, and Kaplan-Meier analysis were used to compare across different groups.@*RESULTS@#We found CCT4 was upregulated in HCC tissues compared with normal tissues, and its high expression was associated with poor prognosis (P < 0.001). CCT4 was significantly increased in HCC tumor tissues compared with normal tissues (0.98 ± 0.12 vs. 0.23 ± 0.05, t = 7.73, P < 0.001). After being transfected with CCT4 short-hairpin RNA (shRNA), CCT4 was decreased in mRNA level and protein level in both Huh7 (mRNA level: 0.41 ± 0.07 vs. 1.01 ± 0.11, t = 8.09, P = 0.001; protein level: 0.61 ± 0.03 vs. 0.93 ± 0.07, t = 7.19, P = 0.002) and Hep3b cells (mRNA level: 0.55 ± 0.11 vs. 1.04 ± 0.15, t = 4.51, P = 0.011; protein level: 0.64 ± 0.10 vs. 0.95 ± 0.08, t = 4.32, P = 0.012). CCK8 assay indicated that CCT4 knockdown inhibited cell proliferation in both Huh7 (OD value of 3 days: 0.60 ± 0.14 vs. 0.97 ± 0.16, t = 3.13, P = 0.036; OD value of 4 days: 1.03 ± 0.07 vs. 1.50 ± 0.12, t = 5.97, P = 0.004) and Hep3b (OD value of 3 days: 0.69 ± 0.14 vs. 1.10 ± 0.11, t = 3.91, P = 0.017; OD value of 4 days: 1.12 ± 0.12 vs. 1.48 ± 0.13, t = 3.55, P = 0.024) cells. EdU assay showed that CCT4 knockdown inhibited the cell proliferation in both Huh7 (EdU positive rate: [31.25 ± 3.41]% vs. [58.72 ± 3.78]%, t = 9.34, P = 0.001) and Hep3b cells (EdU positive rate: [44.13 ± 7.02]% vs. [61.79 ± 3.96]%, t = 3.79, P = 0.019). FCM assay suggested that CCT4 knockdown induced apoptosis in HCC cells (apoptosis rate of Huh7: [9.10 ± 0.80]% vs. [3.66 ± 0.64]%, t = -9.18, P = 0.001; apoptosis rate of Hep3b: [6.69 ± 0.72]% vs. [4.20 ± 0.86]%, t = -3.84, P = 0.018). We also found that CCT4 could regulate anaphase-promoting complex (APC)Cdc20 activity via interacting with Cdc20. Furthermore, CCT4 knockdown induced securin (0.65 ± 0.06 vs. 0.44 ± 0.05, t = -4.69, P = 0.009) and B-cell lymphoma-2 (Bcl-2) interacting mediator of cell death (Bim; 0.96 ± 0.06 vs. 0.61 ± 0.09, t = -5.65, P = 0.005) accumulation. The upregulation of securin inhibited cell growth by downregulating cyclin D1 (0.65 ± 0.05 vs. 1.04 ± 0.07, t = 8.12, P = 0.001), and the accumulation of Bim inhibited Bcl-2 (0.77 ± 0.04 vs. 0.87 ± 0.04, t = 3.00, P = 0.040) and activated caspase 9 (caspase 9: 0.77 ± 0.04 vs. 0.84 ± 0.05, t = 1.81, P = 0.145; cleaved caspase 9: 0.64 ± 0.06 vs. 0.16 ± 0.07, t = 1.81, P = 0.001), which led to elevated apoptosis.@*CONCLUSIONS@#Overall, these results showed that CCT4 played an important role in HCC pathogenesis through, at least partly, interacting with Cdc20.
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Animals , Humans , Apoptosis , Carcinoma, Hepatocellular/genetics , Cdc20 Proteins , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Liver Neoplasms/geneticsABSTRACT
Objective To analyze the difference and influential factors of clinical prognosis between liver transplantation with autoimmune liver disease (AILD) and viral hepatitis cirrhosis. Methods Clinical data of 75 recipients undergoing liver transplantation from January 2002 to January 2017 were retrospectively analyzed. All recipients were divided into the AILD group (n=25) and viral hepatitis cirrhosis group (n=50). The intraoperative conditions of the recipients were observed including warm ischemia time, cold ischemia time, operation time, anhepatic phase and blood transfusion volume. Postoperative complications were observed including severe acute kidney injury (AKI), infection, acute rejection, biliary tract-related complications, vascular-related complications and post transplantation diabetes mellitus (PTDM). The follow-up status were monitored after discharge. The prognostic factors of liver transplant recipients were analyzed. Results The warm ischemia time, cold ischemia time, operation time and anhepatic phase did not significantly differ between two groups (all P > 0.05). In the AILD group, the incidence of postoperative acute rejection was remarkably higher, whereas the incidence of postoperative severe AKI was significantly lower than those in the viral hepatitis cirrhosis group (both P < 0.05). The postoperative 1-, 3- and 5-year survival rates in the AILD group was 92%, 87%, and 87%, which did not significantly differ from 88%, 88% and 88% in the viral hepatitis cirrhosis group (all P > 0.05). Univariate analysis showed that age, model for end-stage liver disease (MELD) score, severe AKI, infection and biliary tract-related complications were the influencing factors of clinical prognosis of the recipients (all P < 0.05). Conclusions The overall survival prognosis does not significantly differ between the AILD and viral hepatitis cirrhosis groups. Age, MELD score, severe AKI, infection and biliary tract-related complications are the risk factors affecting the clinical prognosis of liver transplantation recipients.