The relationship between abnormal Core binding factor-ß expression in human cartilage and osteoarthritis.

BACKGROUND: This study aimed to investigate the effect of abnormal Core binding factor-ß expression on proliferation, differentiation and apoptosis of chondrocytes, and elucidate the relationship between Core binding factor-ß and osteoarthritis-related markers and degenerative joint disease. METHODS: Cartilage tissues, from healthy subjects and patients with osteoarthritis, were collected for histology and expression of Core binding factor-ß, MMP-13, IL-1ß, COMP, and YKL-40. Human articular chondrocytes were cultured in vitro, and a viral vector was constructed to regulate cellular Core binding factor-ß expression. Cellular proliferation and apoptosis were observed, and osteoarthritis-related inflammatory factor expression and cartilage metabolite synthesis assayed. RESULTS: Human osteoarthritis lesions had disordered cartilage structure and cellular arrangement, and increased emptying of cartilage lacunae. Normal cell counts were significantly reduced, cartilage extracellular matrix was obviously damaged, and type II collagen expression was significantly decreased. Core binding factor-ß was highly expressed in the osteoarthritis cartilage (p < 0.001), and MMP-13, IL-1ß, COMP and YKL-40 expression were greater than found in normal cartilage (p < 0.001). Cellular proliferation in the Core binding factor-ß high-expression group was reduced and the total apoptosis rate was increased (p < 0.05), while the opposite was found in the Core binding factor-ß inhibition group (p < 0.01). Compared with normal chondrocytes, high Core binding factor-ß expression (Osteoarthritis and CBFB/pCDH groups) was associated with significantly increased MMP13, IL-1ß, COMP and YKL-40 protein expression (p < 0.01), while Core binding factor-ß inhibition (CBFB/pLKO.1 group) was associated with significantly decreased COMP, MMP13, IL-1ß and YKL-40 expression in osteoarthritis cells (p < 0.001). CONCLUSIONS: Abnormal Core binding factor-ß expression might play an upstream regulatory role in mediating abnormal chondrocyte apoptosis and the inflammatory response. On inhibiting Core binding factor-ß expression, a delay in cartilage degeneration was expected. TRIAL REGISTRATION: The study was registered for clinical trials in ChiCTR: ChiCTR1800017066 (Reg. Date-2018/7/10).

Mortality and Associated Risk Factors in Dialysis Patients with Cardiovascular Disease.

BACKGROUND/AIMS: Although dialysis patients have a higher risk of morbidity and mortality related to cardiovascular disease (CVD) than the general population, the mortality and associated risk factors in Asian dialysis patients with CVD have not been well examined. METHODS: In this prospective cohort study, mortality and risk factors were investigated in 591 dialysis patients who were recruited from two dialysis centers from May 1, 2009 to May 1, 2014. The Cox proportional hazards regression assessed adjusted differences in mortality risk. A multivariate analysis was also performed, comparing the CVD and non-CVD groups. RESULTS: A total of 591 patients were enrolled in this study (mean age, 52.05 ± 16.46 years [SD]; 61.8% men; 20.8% with CVD), with a median follow-up of 21.9 (maximum, 72) months. The cumulative hazard of mortality was significantly higher in CVD patients (hazard ratio [HR], 1.835; 95% confidence interval [CI], 1.023-3.293; P=0.042) than in their non-CVD counterparts after adjusting for various confounders. On multivariate Cox analysis, stroke (HR, 4.574; 95% CI, 2.149-9.736; P<0.001) was an independent predictor of all-cause mortality in the CVD group. In the non-CVD group, diabetes mellitus (HR, 2.974; 95% CI, 1.560-5.668; P=0.001) and elevated high-sensitivity C-reactive lipoprotein (hs-CRP) (HR, 1.017; 95% CI, 1.005-1.030; P=0.005) were independent predictors of all-cause mortality. CONCLUSION: All-cause mortality was significantly higher in the CVD group than in the non-CVD group. Stroke is an independent risk factor for all-cause mortality in dialysis patients with CVD. These findings warrant further studies into preventive and interventional strategies.

Cementless bilateral synchronous total hip arthroplasty in ankylosing spondylitis with hip ankylosis.

PURPOSE: This study was a retrospective analysis of early and mid-term clinical effects and perioperative management of cementless bilateral synchronous total hip arthroplasty (THA) in patients with ankylosing spondylitis (AS) with bilateral hip ankylosis. METHODS: Fifteen AS patients (30 hips) with bilateral hip ankylosis were managed with cementless bilateral synchronous THA. Surgical outcome was evaluated using the visual analogue scale (VAS), the range of motion and the Harris score. RESULTS: The mean follow-up period was 29.3 months. At the last follow-up visit, the VAS score decreased from 7.53 ± 0.99 before the operation to 2.40 ± 0.91. The Harris score increased from 24.8 ± 7.42 before the operation to 83.8 ± 4.61. The total range of motion increased from 78.73 ± 14.53 before the operation to 209.73 ± 16.19 after the operation. After the operation, there was one case of early hip dislocation, one case of femoral nerve stretch injury and one case of superficial incision infection. There were no cases of deep venous thrombosis. X-ray examinations did not show prosthetic loosening or displacement. CONCLUSION: AS patients with bilateral hip ankylosis can be treated with cementless bilateral synchronous THA, which could greatly improve hip joint function without significant complications. The clinical effects proved to be satisfactory.

Doxorubicin suppresses chondrocyte differentiation by stimulating ROS production.

BACKGROUND: Doxorubicin (DOX) is widely used as an effective chemotherapy agent in human cancer. Our study aimed to explore the specific mechanism of DOX in osteoarthritis (OA). METHODS: A mouse OA model was established by destabilizing the medial meniscus (DMM), and the role of DOX was determined by intraperitoneally injecting 5 or 10 mg/kg DOX. The expression of collagen type-II (Col-2) was detected by immunohistochemistry staining, and the expression of plasma interleukin (IL)-6 (IL-6), IL-1beta (IL-1ß), and tumor necrosis factor (TNF)-alpha (TNF-α) was evaluated by specific ELISA kits, and the expression of Sry-related HMG box 9 (SOX-9) was detected by western blot. Bone marrow mesenchymal stem cells (BMMSCs) were used to explore the mechanism of DOX in vitro. Reactive oxygen species (ROS) production was determined by flow cytometry. Cell viability was measured by Cell Counting Kit-8 (CCK-8) assay. Chondrocyte differentiation was evaluated by Alcian blue staining assay. The expression of chondrocyte differentiation-related markers was detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: DOX exposure exacerbated OA progression and inhibited chondrocyte differentiation of BMMSCs. DOX also increased ROS production in BMMSCs. Meanwhile, DOX further increased the elevation of plasma IL-6, IL-1ß and TNF-α induced by DMM and obviously reduced the expression of chondrocyte differentiation-related markers, including collagen type II a1 (Col2A1), collagen type X alpha 1 (Col10A1), and aggrecan. Moreover, ROS scavengers NAC and MitoQ efficiently alleviated DOX toxicity, including ROS production and chondrocyte differentiation in BMMSCs. CONCLUSION: Our study revealed that DOX suppressed chondrocyte differentiation by stimulating ROS production, providing a novel theoretical strategy for the clinical treatment of OA caused by DOX.

Multilineage differentiation of muscle-derived stem cells from GFP transgenic mice.

It is unclear whether green fluorescent protein (GFP) expression is maintained during the course of multilineage differentiation of muscle-derived stem cells (MDSCs). We isolated MDSCs from GFP-transgenic mice and transferred them to chondrogenic, neurogenic or myogenic media. Multilineage differentiation was examined by morphological observation, histological staining, immunocytochemical staining, real-time RT-PCR and Western blot. Both differentiated cells and non-differentiated cells maintained stable GFP expression until the cells exhibited a senescent phenotype. Thus, MDSCs from GFP-transgenic mice have multilineage potential in vitro and that GFP expression does not influence the multilineage potential of MDSCs (or vice versa).

Clinical features and risk factors for ICU admission in COVID-19 patients with cardiovascular diseases.

Previous studies on coronavirus disease 2019 (COVID-19) have focused on the general population. However, cardiovascular disease (CVD) is a common comorbidity that has rarely been investigated in detail. This study aims to describe clinical characteristics and determine risk factors for intensive care unit (ICU) admission of COVID-19 patients with CVD. In this retrospective cohort study, we included 288 adult patients with COVID-19 in Guangzhou Eighth People's Hospital from January 15, 2020 to March 10, 2020. Demographic characteristics, laboratory results, radiographic findings, complications, and treatments were recorded and compared between CVD and non-CVD groups. A binary logistic regression model was used to identify risk factors associated with ICU admission for infected patients with underlying CVD. COVID-19 patients in the CVD group were older and had higher levels of troponin I (TnI), C-reactive protein (CRP), and creatinine. They were also more prone to develop into severe or critically severe cases, receive ICU admission, and require respiratory support treatment. Multivariate regression analysis showed that the following were risk factors for ICU admission in COVID-19 patients with CVD: each 1-year increase in age (odds ratio (OR), 1.08; 95% confidence interval (CI), 1.02-1.17; p = 0.018); respiratory rate over 24 times per min (OR, 25.52; 95% CI, 5.48-118.87; p < 0.0001); CRP higher than 10 mg/L (OR, 8.12; 95% CI, 1.63-40.49; p = 0.011); and TnI higher than 0.03 µg/L (OR, 9.14; 95% CI, 2.66-31.43; p < 0.0001). Older age, CRP greater than 10 mg/L, TnI higher than 0.03 µg/L, and respiratory rate over 24 times per minute were associated with increasing odds of ICU admission in COVID-19 patients with CVD. Investigating and monitoring these factors could assist in the risk stratification of COVID-19 patients with CVD at an early stage.

Clinical Features and Risk Factors of ICU Admission for COVID-19 Patients with Diabetes.

INTRODUCTION: Previous studies of coronavirus disease 2019 (COVID-19) have focused on the general population. However, diabetes (DM) as one of the most common comorbidities is rarely studied in detail. This study is aimed at describing clinical characteristics and determining risk factors of ICU admission for COVID-19 patients with DM. METHODS: Data were extracted from 288 adult patients with laboratory-confirmed COVID-19 from Guangzhou Eighth People's Hospital. Demographic characteristics, laboratory results, radiographic findings, complications, and treatments were collected and compared between DM and non-DM groups. Binary logistic regression was used to identify the risk factors associated with ICU admission for COVID-19 patients with DM or non-DM. RESULTS: COVID-19 patients with DM showed as older ages, higher levels of C-reactive protein (CRP), myoglobin, alanine transaminase (ALT), and aspartate transaminase (AST). They were also more prone to transfer to the intensive care unit (ICU) for treatment. Multiple regression analysis showed that the following were the independent risk factors for COVID-19 patients with DM that received ICU admission: each 1-year increase in age (odds ratio (OR), 1.07; 95% CI, 1.02-1.13; P = 0.007), respiratory rate over 24 times per minute (OR, 5.22; 95% CI, 2.26-16.58; P = 0.016), HbA1c greater than 7% (OR, 4.58; 95% CI, 1.82-10.55; P = 0.012), and AST higher than 40 U/L (OR, 2.96; 95% CI, 1.58-8.85; P = 0.022). In addition, each 1-year increase in age (OR, 1.05; 95% CI, 1.01-1.10; P = 0.006), diarrhea (OR, 4.62; 95% CI, 2.01-9.36; P = 0.022), respiratory rate over 24 times per minute (OR, 5.13; 95% CI, 1.18-16.82; P = 0.035), CRP greater than 10 mg/L (OR, 5.19; 95% CI, 1.37-13.25, P = 0.009), and TnI higher than 0.03 µg/L (OR, 6.48; 95% CI, 1.17-21.38; P = 0.036) were risk factors for ICU admission of COVID-19 patients with non-DM. CONCLUSIONS: The older age, respiratory rate over 24 times per minute, HbA1c greater than 7%, and AST higher than 40 U/L were risk factors of ICU admission for COVID-19 patients with diabetes. Investigating and monitoring these factors could assist in the risk stratification of COVID-19 patients with DM at an early stage.

The effects of PDTC on interleukin-1beta-induced nitric oxide production in chondrocytes.

In order to find new drugs to inhibit nitric oxide (NO) production, the effects of pyrrolidine dithiocarbamate (PDTC), a nuclear factor-kappa B (NF-kappaB) inhibitor, on recombinant human interleukin-1beta (rhIL-1beta)-induced NO production in chondrocytes were investigated. Rat chondrocytes were isolated and cultured, divided into control, P0, P1, P2, P3 and P4 groups. The chondrocytes in the P0, P1, P2, P3 and P4 groups were treated with different concentrations of PDTC (0, 3, 10, 30, and 50 micromol/L respectively) for 1 h and then incubated with 5 U/mL rhIL-1beta for 24 h. NO assay kit and RT-PCR were used to detect the NO content and the iNOS mRNA expression in the chondrocytes. The expression level of iNOS mRNA in control, P0, P1, P2, P3 and P4 groups was 0.02+/-0.01, 1.24+/-0.13, 1.21+/-0.14, 0.61+/-0.11, 0.40+/-0.09, 0.21+/-0.06, and the relative content of NO was 15.8+/-2.7, 100+/-14.8, 92.6+/-9.3, 68.3+/-14.2, 27.5+/-9.8, 19.8+/-3.6, respectively. In the P0, P1, P2, P3 and P4 groups, the expression of iNOS mRNA and NO production were significantly increased as compared with those in the control group. As compared with the P0 group, the expression of iNOS mRNA and NO content in control group were lower. In the P2, P3 and P4 groups, PDTC could significantly inhibit the expression of iNOS and NO production induced by rhIL-1beta in a concentration-dependent manner. It is suggested that PDTC can inhibit NO production and iNOS mRNA expression induced by IL-1beta, which may provide an alternative method for the treatment of osteoarthritis.

[Corrigendum] Correlation between the expression of IL­18 and deep venous thrombosis.

In the above paper, the authors realize that an error inadvertently appeared in the funding section on p. 895. Where "This study was supported by the National Natural Science Foundation of China Science Fund Project (grant no. 30960389 and 8176010097)" was written, the application number 8176010097 was featured incorrectly: This should have been written as grant no. 81760030. Therefore, this sentence in the funding section should have read as follows: "This study was supported by the National Natural Science Foundation of China Science Fund Project (grant nos. 30960389 and 81760030)". The authors regret this error was not noticed prior to the publication, and apologize to their funding body and to the readership of the Journal for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 42:883-896, 2018; DOI: 10.3892/ijmm.2018.3682].

Correlation between the expression of IL­18 and deep venous thrombosis.

The present study aimed to investigate the effect of the expression of interleukin (IL)­18 and related markers on deep venous thrombosis (DVT) to examine their correlation. Sprague­Dawley rats of different models were established and were randomly assigned into three groups. The expression of IL­18, nuclear factor (NF)­κB and von Willebrand factor (vWF) were detected in blood samples. The inferior vena cava (IVC) was ligated to establish the DVT model. Rat IL­18 overexpression and inhibition vectors were constructed. The expression levels of IL­18 and related markers in the venous wall were compared between the model group and the control group using reverse transcription­quantitative polymerase chain reaction and western blot analyses. Following the culture of human umbilical vein endothelial cells (HUVECs), IL­18 was added to the cells, following which the growth of the HUVECs, and changes in vWF and other endothelial functional markers were analyzed. The IVC model demonstrated complete thrombosis at 8 h and stable thrombosis at 24 h. At 24 h following model establishment, the expression levels of IL­18, NF­κB and vWF were high in the blood samples with the occurrence and development of thrombosis (P<0.05). The weight, length and weight/length ratio of thrombi in each model group showed significant differences from those in the control group (P<0.05) with the overexpression of IL­18, and the expression levels of NF­κB and vWF in venous tissues were altered with abnormal expression levels of IL­18. IL­18 damaged HUVECs and significantly increased viability in early­stage apoptosis, promoted the upregulation of vWF and P­selectin, and reduced tissue plasminogen activator. IL­18 and the related markers were closely associated with the occurrence and development of DVT.

Assessment of creatinine and cystatin C-based eGFR equations in Chinese older adults with chronic kidney disease.

INTRODUCTION: Glomerular filtration rate (GFR) estimation equations using creatinine and Cystatin-C appear to be superior to those based on creatinine or Cystatin-C in older adults. We sought to compare the performances of those based on creatinine and Cystatin-C in Chinese older adults with chronic kidney disease (CKD). METHODS: A total of 368 Chinese elderly with CKD underwent the dynamic imaging with technetium-99m diethylene-triamine-pentaacetic acid (99mTc-DTPA), and serum creatinine and Cystatin-C were measured on the same day. The comparison of GFR equations which were creatinine and Cystatin-C-based including chronic kidney disease epidemiology collaboration (CKD-EPI) equation (CKD-EPI-Cr-Cys), Berlin Initiative Study (BIS) equation (BIS-Cr-Cys, also known as BIS-2), MA equation (MA-Cr-Cys), and FENG equation (FENG-Cr-Cys) was conducted. RESULTS: Four equations overestimated GFR except for BIS-2 equation in mGFR ≥ 60 ml/min/1.73 m2 (bias: - 1.40, p = 0.7) and CKD-EPI-Cr-Cys equation in mGFR < 30 ml/min/1.73 m2 (bias: - 1.82, p = 0.2) were unbiased. BIS-2 equation had the smallest interquartile range (IQR, ml/min/1.73 m2) from 12.73 in age < 75 years group to 16.05 in age ≥ 75 years group. BIS-2 equation achieved highest values of 79.1% in overall participants, and 80.77% in age ≥ 75 years group, respectively, and CKD-EPI-Cr-Cys equation 82.26% in age < 75 years group. Lowest values of root-mean-square error (RMSE, ml/min/1.73 m2) were seen in BIS-2 equation from 13.22 in age < 75 years group to 16.18 in age ≥ 75 years group. BIS-2 equation had the lowest misclassification rates of 41.76% in age ≥ 75 years group and 34.41% in age < 75 years group. CONCLUSIONS: BIS-2 equation may be optimal for Chinese older adults with CKD especially in older adults ≥ 75 years and with mGFR ≥ 30 ml/min/1.73 m2, while CKD-EPI-Cr-Cys equation could yield a better performance than BIS-2 equation, especially in those < 75 years and mGFR < 30 ml/min/1.73 m2.

Prevalence and Impact on Stroke in Patients Receiving Maintenance Hemodialysis versus Peritoneal Dialysis: A Prospective Observational Study.

BACKGROUND: Patients undergoing maintenance dialysis are at increased risk of stroke, however, less is known about the prevalence and impact on stroke in the patients. METHODS: In this prospective cohort study, 590 patients undergoing hemodialysis (HD; n = 285) or peritoneal dialysis (PD; n = 305) from January 1, 2008 to December 31, 2012 were recruited. Baseline demographic, clinical, and laboratory data were collected. Timeline incidence data were analyzed using a Poisson model. The Cox proportional hazards regression assessed adjusted differences in stroke risk, a multivariate analysis was also performed. RESULTS: 62 strokes occurred during 1258 total patient-years of follow-up. Stroke occurred at a rate of 49.2/1,000 patient-years with a predominance in HD patients compared with PD patients (74.0 vs. 31.8/1,000 patient-years). The cumulative hazard of developing stroke was significantly higher in HD patients (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.15-3.62; p = 0.046) after adjusting for potential confounders. HD patients had an increased risk of ischemic stroke (HR, 2.62; 95% CI, 1.56-4.58; p = 0.002). The risk of hemorrhagic stroke was not significantly different between PD and HD patients. On multivariate Cox analysis, risk factors of stroke in both HD and PD patients were older age, diabetes, and cardiovascular disease. Other independent risk factors of stroke were lower albumin-corrected calcium in HD patients and higher triglycerides in PD patients. CONCLUSIONS: Patients undergoing PD were less likely to develop ischemic stroke than those undergoing HD. Comprehensive control of diabetes, cardiovascular disease, calcium-phosphorus metabolism, and triglyceride levels may be useful preventive strategies for stroke in dialysis patients.

PHB/PHBHHx scaffolds and human adipose-derived stem cells for cartilage tissue engineering.

The goal of this study was to investigate the potential of polyhydroxybutyrate (PHB)/poly(hydroxybutyrate-co-hydroxyhexanoate) (PHBHHx) (PHB/PHBHHx) to produce neocartilage upon seeding with differentiated human adipose-derived stem cells (hASCs). hASCs were grown on a three-dimensional PHB/PHBHHx scaffold in vitro with or without chondrogenic media for 14 days. Scanning electron microscopy showed that differentiated cells produced abundant extracellular matrices with increasing culture time. No cytotoxicity was observed by the live/dead cell viability assay. GAG and total collagen content in the differentiated cells increased significantly with in vitro culture time. After 14 days of in vitro culture, the differentiated cells grown on the (PHB/PHBHHx) scaffold (differentiated cells/(PHB/PHBHHx)) were implanted into the subcutaneous layer nude mice for 12 or 24 weeks, non-differentiated cells/(PHB/PHBHHx) were implanted as the control group. The differentiated cells/(PHB/PHBHHx) implants formed cartilage-like tissue after 24 weeks of implantation, and stained positive for collagen type II, safranin O, and toluidine blue. In addition, typical cartilage lacuna was observed, and there were no remnants of PHB/PHBHHx. Collagen type II was detected by Western blot at 12 and 24 weeks of implantation. In the control group, no cartilage formation was observed. This study demonstrated that PHB/PHBHHx is a suitable material for cartilage tissue engineering.

The Effects of PDTC on Interleukin-1β-induced Nitric Oxide Production in Chondrocytes / 华中科技大学学报（医学）（英德文版）

S and NO production induced by rhIL-1β in a concentration-dependent manner. It is suggested that PDTC can inhibit NO production and iNOS mRNA expression induced by IL-1β, which may provide an alternative method for the treatment of osteoarthritis.