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Introduction The clinical characteristics and outcomes of small fiber neuropathy (SFN) in Chinese patients with type 2 diabetes mellitus (T2DM) have not been thoroughly described. In this study, we investigated the metabolic and neurological indexes and the prognosis of patients with T2DM based on skin biopsy. Methods A total of 34 healthy Chinese volunteers were recruited for skin biopsy to establish the reference range of intra-epidermal nerve fiber density (IENFD), and 89 patients with T2DM attending the Nanjing Drum Tower Hospital were evaluated at baseline. Of these 89 patients, 17 with pure SFN and nine with mixed diabetic polyneuropathy (DPN) were reassessed at the end of the follow-up. Results Glycated hemoglobin and postprandial blood glucose levels were lower (P = 0.005 and P = 0.041, respectively) and postprandial C-peptide and insulin levels were higher (P = 0.001 and P = 0.019, respectively) in the pure SFN group than in the mixed DPN group. A partial correlation study showed that there was a negative correlation between IENFD of the distal leg and cardiovascular autonomic reflex test (CART) scores (r = − 0.513, P = 0.001) after adjusting for age and duration of diabetes. Only vitamin B12 level (P = 0.028) and motor nerve conduction velocity (MCV) of the common peroneal nerve (P = 0.045) were increased in the patients with pure SFN at the final visit while MCVs of the common peroneal nerve (P = 0.025) and tibial nerve (P = 0.047) were decreased in the mixed DPN group at the final visit. Conclusion Better islet function and cardiovascular autonomic function were observed in patients with pure SFN compared with mixed DPN. The metabolic and neurological indexes remained relatively stable in the patients with pure SFN during the follow-up. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-021-01111-0.

Background: Short-term continuous subcutaneous insulin infusion treatment (CSII) in patients with newly diagnosed type 2 diabetes (T2DM) can improve β-cell function and insulin sensitivity, which results in long-term remission. However, the effect of CSII on peripheral neuropathy is rarely studied. Methods: 63 T2DM patients (HbA1c>9%) were hospitalized and treated with CSII for 2 weeks. Peripheral autonomic neuropathy was measured by SUDOSCAN, which provides an age adjusted electrochemical skin conductance (ESC) composite score incorporating hands/feet ESC measurements, with a score ≤60 indicating sudomotor dysfunction. Blood glucose, HbA1c, C-peptide and SUDOSCAN were measured before and after CSII. HOMA-B was used for assessment of β-cell function. Results: The average HbA1c of included patients was 10.5% with median duration of T2DM was 3.5 years. There were 27 (42.9%) patients who had sudomotor dysfunction at baseline. After 2 weeks of CSII, the proportion of sudomotor dysfunction (42.9% vs. 31.7%, P=0.020) was significantly deceased along with significantly improved HbA1c (10.0±1.9 vs. 8.1±1.0, P Conclusion: Peripheral autonomic neuropathy could be improved by CSII in T2DM. The improvement of β-cell function could be responsible for the amelioration of peripheral nerve function. Keywords: Short-term continuous subcutaneous insulin infusion treatment; peripheral autonomic neuropathy; type 2 diabetes; β-cell function Disclosure J.Jin:None. Funding National Key R&D Program of China (2018YFC1314100) ; the Key-Area Research and Development Program ofGuangdong Province (2019B020230001) ; the China Postdoctoral ScienceFoundation (2018M640871)

The effects of different vibration frequencies on the microstructure, laves phases and microvoids of Inconel 718 weld joints were investigated in this research by using the laser welding combined with mechanical vibration. The results demonstrated that the application of vibration significantly suppressed the growth of columnar crystals, reduced the formation of carbides, and refined the microstructure. With the increase of the vibration frequency, the mechanical vibration stayed prominent. The molten pool was subjected to the pressure and vibration of the metal liquid, which expanded the depth and the width of the weld. Applying vibration could reduce the amount of Laves phase, and it is found that with the increase of vibration frequency, the morphology of Laves phase could change from granular to strips, as found during the experiment. The welds with 522 Hz vibration frequency had the smallest Laves phase size and the largest average microhardness value of 331 HV. At the vibration frequency of 1331 Hz, the amount of Laves phases was the least, and it was distributed in a miscellaneous manner in the form of granules and stripes. However, increasing the vibration frequency could not effectively reduce the number of microvoids in the weld.

Background Early integration of palliative care (PC) for patients with advanced cancer has been recommended to improve quality of care. This study aims to describe prevalence, temporal trend and predictors of PC use in metastatic breast cancer (mBCa) patients receiving critical care therapies (CCT; included invasive mechanic ventilation, percutaneous endoscopic gastrostomy tube, total parenteral nutrition, tracheostomy and dialysis). Methods The National Inpatient Sample was queried for mBCa patients receiving CCT between 2005 and 2014. Annual percent changes (APC) were calculated for PC prevalence in the overall cohort and subgroups. Multivariable logistic analysis was used to explore predictors of PC use. Results Of 5833 mBCa patients receiving CCT, 880 (15.09%) received PC. Rate of PC use increased significantly from 2.53% in 2005 to 25.96% in 2014 (APC: 35.75%; p, Highlights • Overall, 15.09% of mBCa patients with CCT receive inpatient PC. • Rate of inpatient PC use in mBCa patients receiving CCT increases significantly from 2005 to 2014. • This study highlights the underutilized PC in mBCa patients receiving CCT. • Future efforts to illustrate disparities in PC use are needed to improve quality of care.

Aim. To investigate the different effects on osteolysis between commercial pure Ti particles and TiAl6V4 particles obtained from prosthesis of patients with aseptic loosening. Method. Scanning electron microscope, energy dispersive X-ray spectrometry, and X-ray diffraction were used for the size test, chemical composition test, and phase analysis of two kinds of Ti particles. Microcomputed tomography (micro-CT) and 3-dimensional reconstruction analysis were applied to analyze the bone loss quantitatively and radiologically. Hematoxylin-eosin (HE) staining and tartrate-resistant acid phosphatase (TRAP) staining were used to assess the histologic difference. Result. TiAl6V4 particles were constituted by FeO, Al45V7, and Al3Ti while pure Ti particles were constituted by Ti, Ti3O, and C4H7NO3. Similar particle size of nanoscale was detected of two Ti particles. A TiAl6V4 osteolysis model had more severe bone loss when scanned with micro-CT and assessed by quantitative analysis. TiAl6V4 also presented deeper and wider calvarial bone loss in HE staining and more activated osteoclasts in TRAP staining. Conclusion. A mouse calvarial model is the most effective animal model for the primary in vivo research of aseptic loosening. Compared with commercial Ti particles, TiAl6V4 particles derived from prosthesis of an aseptic loosening patient had more severe bone loss and more activated osteoclast, which was more consistent with pathogenesis of aseptic loosening in vivo, had high success rate of establishment of a model, and was more desired in animal modeling.

Vibration-assisted laser welding experiment of 5052 aluminum alloys was carried out to focus on the influences of vibration parameters on microstructure and fatigue fracture. The experiment found that the vibration process homogenized the microstructure and promoted the formation of fine equiaxed grains significantly. In addition, vibration made the hardness uniform by reducing the area of the fusion zone. Experimental results of double welds showed that residual stress reduced by 58 to 77% under the action of micro-vibration. Vibration frequency and vibration acceleration had significant effects on the longitudinal and transverse residual stress, respectively. Under the same fatigue load condition, the average fatigue limits of the base metal (BM) and the welded joints were 160 and 120 MPa, respectively. Under the conditions of 107 cycles, the maximum fatigue strength of the welded joints has reached 74.95% fatigue strength of the BM. Vibration-assisted laser welding could obviously improve the fatigue performance and increase the fatigue life of the welded joints, which was a potential way to improve the quality of welded joints.

BackgroundBoth diabetes and obesity are risk factors for perioperative major adverse events. This study aims to evaluate the association between prior bariatric surgery (prior-BS) and perioperative cardiovascular outcomes following noncardiac surgery in patients with type 2 diabetes mellitus (T2DM).MethodsWe used the National Inpatient Sample Database to identify T2DM patients undergoing major noncardiac surgery from 2006 to 2014. The primary outcome was major perioperative adverse cardiovascular and cerebrovascular events (MACCEs), which include death, acute myocardial infarction and acute ischaemic stroke. In-hospital outcomes between patients with prior BS and morbid obesity were compared using unadjusted logistic, multivariable logistic and propensity score matching analyses.ResultsA weighted of 1,526,820 patients diagnosed with T2DM who underwent noncardiac surgery were included. The rates of both prior BS and morbid obesity significantly increased during the study period (P ConclusionsPrior bariatric surgery in T2DM patients undergoing noncardiac surgery is associated with a lower risk of MACCEs. Prospective studies are needed to verify the benefits of bariatric surgery in patients undergoing noncardiac surgery.

To investigate the association between serum bilirubin and distal symmetrical polyneuropathy (DSPN) in Chinese patients with type 2 diabetes (T2D).A total of 1800 inpatients with T2D (including 68 with 1-year follow-ups) were consecutively enrolled between June 2014 and March 2017. DSPN was diagnosed according to criteria recommended by the Toronto Diabetic Neuropathy Expert Group in 2010. Clinical data were retrospectively collected.Patients with vs. without DSPN had low levels of serum total bilirubin (9.9±3.1μmol/L vs. 10.7±2.8μmol/L; P0.01) and unconjugated bilirubin (6.7±2.2μmol/L vs. 7.3±2.1μmol/L; P0.01), respectively. Patients in the lowest tertiles of bilirubin had the highest rates of DSPN and slowest nerve conduction velocities (NCVs). After multivariate adjustment, low levels of unconjugated bilirubin were a risk factor (OR: 0.696, 95% CI: 0.494-0.981; P=0.038, highest vs. lowest) for the presence of DSPN. Furthermore, in the 68 patients who had 1-year follow-ups, those with the lowest tertiles of serum bilirubin showed maximum deterioration in NCVs. These changes remained significant even after multivariate adjustment.Low levels of serum bilirubin, especially unconjugated bilirubin, contributed to the presence and progression of DSPN in Chinese patients with T2D. Thus, serum unconjugated bilirubin may be used as an additional indicator of risk and progression of DSPN.

BackgroundThe clinical characteristics and outcomes of small fibre neuropathy (SFN) in Chinese patients with type 2 diabetes have not been thoroughly described, and we investigated metabolic and neurological indexes and the prognosis of type 2 diabetic patients based on skin biopsy. MethodsThirty-four healthy Chinese volunteers were recruited for skin biopsy to establish the reference range of intraepidermal nerve fibre density (IENFD). Eighty-nine patients with type 2 diabetes from the Department of Endocrinology at Nanjing Drum Tower Hospital between December 2015 and April 2020 were included in the final study. Metabolic and neurological indexes were evaluated at baseline. Diabetic cardiovascular autonomic function was tested through cardiovascular autonomic reflex tests (CARTs). Seventeen pure SFN subjects and 9 mixed diabetic polyneuropathy (DPN) subjects were reassessed after the follow-up. ResultsLevels of HbA1c and postprandial blood glucose were lower (P=0.005 and P=0.041, respectively), while postprandial C-peptide and insulin were higher (P=0.001 and P=0.019, respectively) in the pure SFN group than in the mixed DPN group. Regarding the CARTs, the mixed DPN group obtained the highest score, indicating the worst cardiovascular autonomic neuropathy (CAN). Among the four CART items, postural BP change was lower while deep breathing max-min was higher in the pure SFN group than in the mixed DPN group (P=0.023 and P=0.040, respectively). A partial correlation showed that there was a negative correlation between IENFD of the distal leg and CART scores (r=-0.513, P=0.001) after adjusting for age and duration of diabetes. Only vitamin B12 (p=0.028) and motor nerve conduction velocity (MCV) of the common peroneal nerve (p=0.045) were increased in the 17 patients with pure SFN after the follow-up. However, MCVs of the common peroneal nerve (p=0.025) and tibial nerve (p=0.047) were decreased at the final visit in the mixed DPN group. ConclusionsBetter islet function and cardiovascular autonomic function were observed in patients with pure SFN compared with mixed DPN. CART scores were negatively correlated with IENFD in the distal leg even after adjusting for age and duration of diabetes. The metabolic and neurological indexes remained relatively stable in the follow-up of pure SFN subjects.

Background: Aseptic loosening is the main reason for surgical revision after arthroplasty. Although a series of mechanisms have been explored, a specific therapeutic target is still desired. In the present study, we explored the role of the signal transducer and activator of the transcription (STAT)/interleukin-6 (IL-6) pathway in the induction of the inflammatory response in osteoblast and osteoclast formation during aseptic prosthesis loosening. Methods: The expression of activated STAT3 was examined in osteoblasts treated with TiAl6V4 nanoparticles (TiPs) from materials used in prosthetics and specimens from particle-induced osteolysis (PIO) animal models. Inflammatory responses associated with the IL-6 family in osteoblasts were identified by Quantitative Real-time PCR. A mimicking coculture system was used to directly determine the number of activated osteoclasts in vitro, and immunohistochemical staining with tartrate-resistant acid phosphatase (TRAP) was used in vivo. CP690,550, an inhibitor of STAT3, was administered to examine the effect of STAT3 on the inflammatory response and osteoclast formation. Results: STAT3 was activated in both nanoparticle-treated osteoblasts and PIO model animals. On the one hand, the activation of STAT3 mediated nanoparticle-induced IL-6-dependent inflammatory responses in osteoblasts. On the other hand, the activation of STAT3 induced receptor activator of nuclear factor kappa B ligand (RANKL) production and stimulated osteoclast formation. The application of the STAT3 inhibitor CP690,550 reduced the production of the IL-6 family and the formation of osteoclasts both in vitro and in vivo. Conclusion: STAT3 mediated inflammation-related signalling and osteoclast activation in nanoscale wear particle-induced aseptic loosening. Inhibition of STAT3 by tofacitinib may be a potential treatment for aseptic loosening.

Background: Diabetes mellitus is a risk factor for perioperative major adverse events. This study aims to evaluate the association between prior bariatric surgery (prior-BS) and perioperative cardiovascular outcomes following noncardiac surgery in patients with type 2 diabetes mellitus (T2DM). Methods: We used the National Inpatient Database to identify major noncardiac surgery in T2DM patients from 2006 to 2014. The primary outcome is major perioperative adverse cardiovascular and cerebrovascular events (MACCE), which included death, acute myocardial infarction and acute ischemic stroke. In-hospital outcomes between patients with prior-BS and morbid obesity were compared using unadjusted logistic, multivariable logistic and propensity score matching analyses. Results: A weighted of 152,6820 patients diagnosed with T2DM who underwent noncardiac surgery were included. Both rates of prior-BS and morbid obesity significantly increased during the study period (P Conclusions: Prior bariatric surgery in diabetes mellitus patients who underwent noncardiac surgery is associated with lower risk of MACCE. Prospective studies are need to verify the benefits of bariatric surgery in noncardiac surgery. Disclosure J. Jin: None. H. Li: None. P. Zhang: None. Y. Li: None. Funding China Postdoctoral Science Foundation (2018M640871)

Bone metabolic disorders include osteolysis, osteoporosis, osteoarthritis and rheumatoid arthritis. Osteoblasts and osteoclasts are two major types of cells in bone constituting homeostasis. The imbalance between bone formation by osteoblasts and bone resorption by osteoclasts has been shown to have a direct contribution to the onset of these diseases. Recent evidence indicates that autophagy and mitophagy, the selective autophagy of mitochondria, may play a vital role in regulating the proliferation, differentiation and function of osteoblasts and osteoclasts. Several signaling pathways, including PINK1/Parkin, SIRT1, MAPK8/FOXO3, Beclin-1/BECN1, p62/SQSTM1, and mTOR pathways, have been implied in the regulation of autophagy and mitophagy in these cells. Here we review the current progress about the regulation of autophagy and mitophagy in osteoblasts and osteoclasts in these bone metabolic disorders, as well as the molecular signaling activated or deactivated during this process. Together, we hope to draw attention to the role of autophagy and mitophagy in bone metabolic disorders, and their potential as a new target for the treatment of bone metabolic diseases and the requirements of further mechanism studies.

Additional file 1: Table S1. ICD-9-CM codes used in the study. Table S2. Changes in BMI categories from 2006 to 2014 in the prior-BS group. Table S3. Comparison of outcomes after additionally adjusted for diabetes-related complications. Table S4. Comparison of outcomes after adjusted for diabetes-related complications and BMI. Table S5. Comparison of outcomes stratified by BMI in the prior-BS group. Table S6. Comparison of outcomes between prior bariatric surgery and morbid obesity after excluding patients receiving BS interventions during the current hospitalization. Table S7. Baseline characteristics and standardized mean differences between prior bariatric surgery and morbid obesity in diabetes mellitus patients undergoing major noncardiac surgery before and after propensity score matching analysis. Table S8. Sensitivity analysis for comparison of MACCEs between prior bariatric surgery and morbid obesity in diabetes mellitus patients undergoing major noncardiac surgery in propensity score matched sample.

Alcohol withdrawal (AW) syndrome is an independent risk factor for postoperative complications. This study aims to evaluate the influence of AW on perioperative outcomes in patients who underwent primary total knee (TKA) or total hip arthroplasty (THA).We used the National Inpatient Sample database to identify patients undergoing TKA/THA from 2003 to 2014. The primary exposure of interest was AW. Multivariable adjusted models were used to evaluate the association of AW with in-hospital medical complications, surgical complications, mortality, cost, and length of stay (LOS) in patients undergoing TKA/THA.There were 2,971,539 adult hospitalizations for THAs and 6,367,713 hospitalizations for TKAs included in the present study, among which 0.14% of AW for THA patients and 0.10% of AW for TKA patients. Multivariable adjustment analysis suggested that AW was associated with an increased risk of medical complications (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.79-2.42, P.0001), surgical complications (OR 1.75, 95% CI 1.51-2.03, P.0001), and had 4.79 times increase of in-hospital mortality, 26% increase of total cost, and 53% increase of LOS in THA procedures. For TKA procedures, AW was also associated with increased risk of medical complications (OR 3.14, 95% CI 2.78-3.56, P.0001), surgical complications (OR 2.07, 95% CI 1.82-2.34, P.0001) and 4.24 times increase of in-hospital mortality, 29% increase of total cost, and 58% increase of LOS after multivariable adjustment.AW is associated with increased risk of in-hospital mortality, medical and surgical complications. Proactive surveillance and management of AW may be important in improving outcomes in patients who underwent THA and TKA procedure.

Background To enhance our understanding of the feasibility, effectiveness, safety and quality of life (QoL) of radiofrequency ablation (RFA) for inoperable patients with pulmonary tumors. Methods The data of 88 patients with pulmonary tumors undergoing RFA were collected. Proof of malignancy was obtained by biopsy in all patients. Diagnoses included non-small cell lung cancer (NSCLC) in 74 patients and pulmonary metastases in 14 patients. Patients underwent computed tomography (CT)-guided RFA according to standard protocol and had a 2-year follow-up. Results assessment included feasibility (correct placement of the ablation probe into all targeted tumors), effectiveness (overall survival rate and local control rate), safety (treatment-related complication and changes in pulmonary function) and QoL. Results One hundred and thirty-four RFAs were successfully conducted in 88 patients with 96 nodules. Correct placement of ablation probe into targeted tumors with completion of the planned treatment protocol was feasible in all 88 (100%) patients and no procedure-related deaths occurred. Major complication rate was 4.5% (4/88), which consisted of symptomatic pneumothorax (2/88) and high fever (2/88). No significant worsening of pulmonary function was observed. Tumors shrank obviously at 6 months after RFA with a statistically significance (P

Purpose Diabetic peripheral neuropathies are the common chronic complications of diabetes, but the diagnosis is insensitive by physical examination in busy outpatients. Here we evaluated the performance of SUDOSCAN in screening diabetic peripheral neuropathies in Chinese type 2 diabetic patients. Methods The study enrolled 180 patients for annually screening. All patients underwent neurological symptoms assessment, clinical examination, nerve conduction studies and cardiovascular autonomic reflex tests. SUDOSCAN was tested and evaluated with electrochemical skin conductance in hands and feet, asymmetry ratio in hands and feet and predicted cardiac neuropathy. Results Patients enrolled had an average age of 56.1 years, 9.8 years of diabetic duration. Patients with diabetic sensorimotor polyneuropathy showed significantly lower electrochemical skin conductance in feet and higher asymmetry ratio in feet compared with those without. Sensitivity and specificity of asymmetry ratio in feet for diagnosing diabetic sensorimotor polyneuropathy were 88.2% and 46.9% and area under ROC curve was 0.713. Patients with cardiovascular autonomic neuropathy showed significantly lower electrochemical skin conductance in hands and feet, and higher asymmetry ratio in feet and predicted cardiac neuropathy compared with those without. Sensitivity and specificity of electrochemical skin conductance in feet in diagnosing cardiovascular autonomic neuropathy were 85.6% and 76.1% with an area under ROC curve of 0.859. Conclusions SUDOSCAN is a sensitive test to detect diabetic peripheral neuropathy in China and could be an effective screening tool in in busy outpatients and primary health care.

Background: To compare the risk of type 2 diabetes (T2DM) between patients with and without chronic osteomyelitis (COM), both in humans and in mice, and to explore risk factors in COM patients who developed T2DM. Methods: One hundred seven patients with COM and 114 patients without COM were consecutively enrolled and retrospectively analysed. Clinical data concerning the time to develop diabetes, glucose metabolism, lipid metabolism, inflammatory factors, mental health and frequency of specialist visits were collected. A mouse model of osteomyelitis was used to verify the presence of impaired glucose metabolism and depression. All data were processed by SPSS. Results: The incidence of T2DM was 2.37-fold higher in patients with COM than in those without. In COM patients, subjects with T2DM (DDM) had higher BMI, less exercise and more frequent visits to specialists than those without (Con). Glucose and lipid metabolism were worse in patients with DDM. Patients with DDM had higher levels of white blood cells (12.9±2.1×109/L vs. 11.7±2.2×109/L, p=0.027), CRP (28.4±4.5 mg/L vs. 22.0±4.8 mg/L, p

Zhantao Deng,1–3,* Jiewen Jin,2,3,* Zhenheng Wang,1 Yong Wang,2,3 Qian Gao,2,3 Jianning Zhao1 1Department of Orthopedics, Jinling Hospital, School of Medicine, Nanjing University, 2Center for Translational Medicine, Nanjing University Medical School, 3Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing, Jiangsu, People’s Republic of China *These authors contributed equally to this work Abstract: Aseptic loosening is the most common cause of total hip arthroplasty (THA) failure, and osteolysis induced by wear particles plays a major role in aseptic loosening. Various pathways in multiple cell types contribute to the pathogenesis of osteolysis, but the role of Sirtuin 1 (SIRT1), which can regulate inflammatory responses through its deacetylation, has never been investigated. We hypothesized that the downregulation of SIRT1 in macrophages induced by metal nanoparticles was one of the reasons for osteolysis in THA failure. In this study, the expression of SIRT1 was examined in macrophages stimulated with metal nanoparticles from materials used in prosthetics and in specimens from patients suffering from aseptic loosening. To address whether SIRT1 downregulation triggers these inflammatory responses, the effects of the SIRT1 activator resveratrol on the expression of inflammatory cytokines in metal nanoparticle-stimulated macrophages were tested. The results demonstrated that SIRT1 expression was significantly downregulated in metal nanoparticle-stimulated macrophages and clinical specimens of prosthesis loosening. Pharmacological activation of SIRT1 dramatically reduced the particle-induced expression of inflammatory cytokines in vitro and osteolysis in vivo. Furthermore, SIRT1 regulated particle-induced inflammatory responses through nuclear factor kappa B (NF-κB) acetylation. Thus, the results of this study suggest that SIRT1 plays a key role in metal nanoparticle-induced inflammatory responses and that targeting the SIRT1 pathway may lead to novel therapeutic approaches for the treatment of aseptic prosthesis loosening. Keywords: metal nanoparticle, inflammatory response, SIRT1, NF-κB, aseptic loosening

We hypothesized that SIRT1 downregulation in osteoblasts induced by wear particles was one of the reasons for particle-induced osteolysis (PIO) in total joint arthroplasty failure. In the present study, the expression of SIRT1 was examined in osteoblasts treated with TiAl6V4 particles (TiPs) and CoCrMo particles (CoPs) from materials used in prosthetics and specimens from PIO animal models. To address whether SIRT1 downregulation triggers inflammatory responses and apoptosis in osteoblasts, the effect of a SIRT1 activator, resveratrol on the expression of inflammatory cytokines and apoptosis in particle-treated osteoblasts was tested. The results demonstrated that SIRT1 expression was significantly downregulated in particle-treated osteoblasts and PIO animal models. Both pharmacological activation and overexpression of SIRT1 dramatically reduced the particle-induced expression of inflammatory cytokines and osteoblast apoptosis through NF-κB and p53 signaling, respectively. Furthermore, in PIO animal models, resveratrol significantly reduced the severity of osteolysis. Collectively, the results of the present study indicated that SIRT1 plays a vital role in the pathogenesis of aseptic loosening, and further treatment targeted at SIRT1 possibly lead to novel approaches for prevention of aseptic prosthesis loosening. Statement of Significance Aseptic loosening is the most common cause of total hip arthroplasty (THA) and total knee arthroplasty (TKA) failure and revision surgery. However, there is still no effective therapeutic target in the clinical treatment. Besides, the underlying mechanism of aseptic loosening is largely unknown. The result of our study indicated that SIRT1 has the ability to effectively regulate the wear particle-induced inflammatory responses, apoptosis, osteolysis in particle-stimulated osteoblasts and particle-induced osteolysis animal models. Our study provides a potential target for the prevention and treatment of aseptic loosening and further investigated the underlying mechanism of aseptic loosening, which may make contribution to decrease the incidence of THA and TKA failure in the clinical practice.

Purpose: The purpose of this study was to investigate the profile of histone deacetylase (HDAC) activity and expression in osteosarcoma cells and tissues from osteosarcoma patients and to examine the mechanism by which a histone deacetylase (HDAC) inhibitor, Trichostatin A (TSA), promotes the apoptosis of osteosarcoma cells. Methods: HDAC activity and histone acetyltransferase (HAT) activity were determined in nuclear extracts of MG63 cells, hFOB 1.19 cells and tissues from 6 patients with primary osteosarcoma. The protein expression of Class I HDACs (1, 2, 3 and 8) and the activation of the p53 signaling pathway were examined by Western blot. Cell growth and apoptosis were determined by 3-(4, 5-dimethyl-2-thiazolyl)-2H-tetrazolium bromide (MTT) assay and flow cytometry, respectively. Results: Nuclear HDAC activity and class I HDAC expression were significantly higher in MG63 cells than in hFOB 1.19 cells, and a similar trend was observed in the human osteosarcoma tissues compared with the paired adjacent non-cancerous tissues. TSA significantly inhibited the growth of MG63 cells and promoted apoptosis in a dose-dependent manner through p53 signaling pathway activation. Conclusion: Class I HDACs play a central role in the pathogenesis of osteosarcoma, and HDAC inhibitors may thus have promise as new therapeutic agents against osteosarcoma.

BACKGROUND Cardiovascular autonomic neuropathy (CAN) is a risk factor for arrhythmias and adverse cardiovascular events, but the relationship between CAN severity and nocturnal arrhythmias needs to be clarified. This study evaluated the association between nocturnal arrhythmias and CAN severity in patients with type 2 diabetes (T2D). METHODS In all, 219 T2D patients were recruited from January 2017 to May 2018. Subjects were classified into no CAN (NCAN), early CAN (ECAN), definite CAN (DCAN), or advanced CAN (ACAN) based on cardiovascular autonomic reflex tests (CARTs). A 24-hour electrocardiogram was recorded and daytime (0700-2300 hours) and night-time (2300-0700 hours) heartbeats were analyzed separately. RESULTS After adjusting for age, the incidence of ventricular arrhythmias increased with CAN severity at night-time (18.6%, 29.9%, 36.2%, and 60.0% in the NCAN, ECAN, DCAN, and ACAN groups, respectively; Ptrend = 0.034). Patients with nocturnal ventricular arrhythmias (NVAs) had higher CART scores (2.0 ± 1.0 vs 1.5 ± 0.9; P

The name of coauthor Peilei Zhang was misspelled as “Peilie Zhang” in this article as originally published.

Stem cell-based therapy is a promising treatment for cartilage defects due to the pluripotency, abundant sources and low immunogenicity of stem cells. Hydrogels are a promising class of biomaterials for cartilage engineering and are characterized by bioactivity, degradability and elasticity as well as provide water content and mechanical support. The combination of stem cells and hydrogels opens new possibilities for cartilage tissue engineering. However, the selection of suitable types of stem cells and hydrogels is difficult. Currently, various types of stem cells, such as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and peripheral blood mononuclear cells (PBMSCs), and various types of hydrogels, including natural polymers, chemically modified natural polymers and synthetic polymers, have been explored based on their potential for cartilage tissue engineering. These materials are used independently or in combination; however, there is no clear understanding of their merits and disadvantages with regard to their suitability for cartilage repair. In this article, we aim to review recent progress in the use of stem cell-hydrogel hybrid constructs for cartilage tissue engineering. We focus on the effects of stem cell types and hydrogel types on efficient chondrogenesis from cellular, preclinical and clinical perspectives. We compare and analyze the advantages and disadvantages of these cells and hydrogels with the hope of increasing discussion of their suitability for cartilage repair and present our perspective on their use for the improvement of physical and biological properties for cartilage tissue engineering.

The differential steroid production in the theca and granulosa cells in ovary are resulted from unique enzyme expression profiles. Among them, c-fos, a downstream target of mitogen and extracellular signal-regulated kinases (MEK/ERK) signaling, takes part in this compartment. In this study, we investigated the effect of c-fos on the steady-state levels of CYP17 and CYP19 in human ovarian granulosa-like tumor cell line (KGN) by inhibiting MEK/ERK pathway with PD98059. As a result, our finding demonstrated the distinct distribution patterns of CYP17 and CYP19 in KGN. Moreover, the MEK/ERK pathway functions to inhibit the production of CYP17, while enhance the production of CYP19 in granulosa cells, probably involving a c-fos-dependent mechanism. In conclusion, factors such as c-fos may play a crucial role in the down-regulation of CYP17 and up-regulation of CYP19 in granulosa cells, thereby suppressing androstenedione synthesis.

Wear particle-induced osteolysis is a major cause of aseptic loosening in arthroplasty failure, but the underlying mechanism remains unclear. Due to long follow-ups necessary for detection and sporadic occurrence, it is challenging to assess the pathogenesis ofparticle-induced osteolysis in clinical cases. Hence, optimal animal models are required for further studies. The murine model of calvarial osteolysis established by exposure to CoCrMo particles is an effective and valid tool for assessing the interactions between particles and various cells in aseptic loosening. In this model, CoCrMo particles were first obtained by high-vacuum three-electrode direct current and resuspended in phosphate-buffered saline at a concentration of 50 mg/mL. Then, 50 µL of the resulting suspension was applied to the middle of the murine calvaria after separation of the cranial periosteum by sharp dissection. After two weeks, the mice were sacrificed, and calvaria specimens were harvested; qualitative and quantitative evaluations were performed by hematoxylin and eosin staining and micro computed tomography. The strengths of this model include procedure simplicity, quantitative evaluation of bone loss, rapidity of osteolysis development, potential use transgenic or knockout models, and a relatively low cost. However, this model cannot to be used to assess the mechanical force and chronic effects of particles in aseptic loosening. Murine calvarial osteolysis model generated by exposure to CoCrMo particles is an ideal tool for assessing the interactions between wear particles and various cells, e.g., macrophages, fibroblasts, osteoblasts and osteoclasts, in aseptic loosening.

Spinal metastasis is the most common tumor in the spine and can easily expand to the epidural space. A series of approaches have been developed to deal with this problem including radiation, surgery, and medicine. The further goal of the treatment is to relieve pain, stabilize spinal structure, maintain neurologic function and improve the quality of life. Different frameworks have been proposed to optimize the best therapy for different patients. This review briefly summarizes different treatments for spinal metastases and some popular decision-making frameworks.

Aim. This study aimed to evaluate the association between cardiovascular autonomic neuropathy (CAN) and left ventricular diastolic dysfunction (LVDD) in type 2 diabetes patients. Methods. 315 type 2 diabetes patients from inpatients of Drum Tower Hospital were included and classified into no CAN (NCAN), possible CAN (PCAN), and definite CAN (DCAN) based on cardiovascular autonomic reflex tests. The left ventricular diastolic function was assessed by tissue Doppler imaging echocardiography. Results. The distribution of NCAN, PCAN, and DCAN was 11.4%, 51.1%, and 37.5%, respectively. The proportion of LVDD increased among the groups of NCAN, PCAN, and DCAN (39.4%, 45.3%, and 68.0%, P=0.001). Patients with DCAN had higher filling pressure (E/e′ ratio) (10.9±2.7 versus 9.4±2.8, P=0.013) and impaired diastolic performance (e′) (6.8±1.7 versus 8.6±2.4, P=0.004) compared with NCAN. CAN was found to be an independent risk factor for LVDD from the multivariate regression analysis (OR = 1.628, P=0.009, 95% CI 1.131–2.344). Conclusions. Our results indicated that CAN was an independent risk marker for the presence of LVDD in patients with diabetes. Early diagnosis and treatment of CAN are advocated for preventing LVDD in type 2 diabetes.

Background. To compare the salvage rate and complication between internal fixation and external fixation in patients with small bone defects caused by chronic infectious osteomyelitis debridement. Methods. 125 patients with chronic infectious osteomyelitis of tibia fracture who underwent multiple irrigation, debridement procedure, and local/systemic antibiotics were enrolled. Bone defects, which were less than 4 cm, were treated with bone grafting using either internal fixation or monolateral external fixation. 12-month follow-up was conducted with an interval of 3 months to evaluate union of bone defect. Results. Patients who underwent monolateral external fixation had higher body mass index and fasting blood glucose, longer time since injury, and larger bone defect compared with internal fixation. No significant difference was observed in incidence of complications (23.5% versus 19.3%), surgery time (156±23 minutes versus 162±21 minutes), and time to union (11.1±3.0 months versus 10.9±3.1 months) between external fixation and internal fixation. Internal fixation had no significant influence on the occurrence of postoperation complications after multivariate adjustment when compared with external fixation. Furthermore, patients who underwent internal fixation experienced higher level of daily living scales and lower level of anxiety. Conclusions. It was relatively safe to use internal fixation for stabilization in osteomyelitis patients whose bone defects were less than 4 cm and infection was well controlled.

Articular cartilage defects have been addressed by using multiple strategies. In the last two decades, promising new strategies by using assorted scaffolds and cell sources to induce tissue regeneration have emerged, such as autologous chondrocyte implantation (ACI) and mesenchymal stem cell implantation (MSCI). However, it is still controversial in the clinical strategies when to choose these treatments. Thus, we conducted a systematic review and meta-analyses to compare the efficacy and safety of different cartilage treatments. In our study, 17 studies were selected to compare different treatments for cartilage defects. The results of meta-analyses indicated that cell-based cartilage treatments showed significant better efficacy than cell-free treatments did (OR: 4.27, 95% CI: 2.19–8.34; WMD: 10.11, 95% CI: 2.69–16.53). Another result indicated that MACT had significant better efficacy than traditional ACI did (OR: 0.49, 95% CI: 0.30–0.82). Besides, the incidence of graft hypertrophy of MACT was slightly lower than that of traditional ACI (OR: 2.43, 95% CI: 1.00–5.94). Current data showed that the cell-based treatments and MACT are better options for cartilage treatments, but more well-designed comparative studies are still needed to enhance our understanding of different treatments for cartilage defects.

Obesity and osteoporosis are two of the most common chronic disorders with high prevalence rates, and the literature reports contradictory results when considering the relationship between body mass index (BMI)/obesity and bone metabolism. Although several arguments support a key role played by the adipose tissue in this process, the exact mechanism remains poorly understood. First, the pattern of regional fat deposition into the subcutaneous and visceral compartments is suggested as a stronger predictor of osteoporosis risk than overall fat mass. Second, fat deposited in the bone marrow influences osteoblast differentiation and function, increases osteoclastic activity that in turn affects mineralization. Third, adipose tissue is a highly dynamic organ, secreting various adipokines with endocrine and metabolic roles, regulating bone homeostasis. Altogether these arguments support that abnormal local fat deposition and adipose tissue secretions are key factors in the interaction between obesity and impaired bone metabolism. In this review, we examine the interaction between fat and bone health from two perspectives: (I) the different deposition of adipose tissue [subcutaneous, visceral and marrow adipose tissue (MAT)] and (II) the influence of adipokines in bone metabolism.

The ovary is the main regulator of female fertility. Granulosa cell dysfunction may be involved in various reproductive endocrine disorders. Here we investigated the effect of insulin resistance on the metabolism and function of ovarian granulosa cells, and dissected the functional status of the mitogen-activated protein kinase signaling pathway in these cells. Our data showed that dexamethasone-induced insulin resistance in mouse granulosa cells reduced insulin sensitivity, accompanied with an increase in phosphorylation of p44/42 mitogen-activated protein kinase. Furthermore, up-regulation of cytochrome P450 subfamily 17 and testosterone and down-regulation of progesterone were observed in insulin-resistant mouse granulosa cells. Inhibition of p44/42 mitogen-activated protein kinase after induction of insulin resistance in mouse granulosa cells decreased phosphorylation of p44/42 mitogen-activated protein kinase, downregulated cytochrome P450 subfamily 17 and lowered progesterone production. This insulin resistance cell model can successfully demonstrate certain mechanisms such as hyperandrogenism, which may inspire a new strategy for treating reproductive endocrine disorders by regulating cell signaling pathways.

Since 2015, the Chinese health-care system reforms have been emphasizing the importance of constructing hierarchical medical system. Hierarchical medical system policy was aimed to enhance the development of primary medical care and redistribute medical resources more rationally. At present, most of patients prefer to go to tertiary hospitals, which increases the working load on doctors there.

Diabetes is one of most common chronic disease in modern society and the affected population is excepted to be 592 million by 2035. Inflammation was an established mechanism in the in the pathogenesis of diabetes and associated complications. Diabetes can increase the occurrence and deteriorate various diseases in orthopedics, such as osteoarthritis (OA) and osteomyelitis, which had been thoroughly investigated. On the other hand, inflammatory diseases are also common in orthopedics, such as inflammatory arthritis, OA and osteomyelitis. But whether patients with inflammation related diseases in orthopedics have higher risk for diabetes is seldom investigated. Here we reviewed studies concerning the risk of diabetes in various inflammation related diseases in orthopedics and intended to rise the attention of higher risk of diabetes in various arthritis and osteomyelitis.