Beijing Jishuitan Hospital

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is thatthere is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the completeprocess including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increasedautophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in manycases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as forreviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multipleassays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagyrelated protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

BACKGROUND: Higher levels of sodium intake are reported to be associated with higher blood pressure. Whether this relationship varies according to levels of sodium or potassium intake and in different populations is unknown. METHODS: We studied 102,216 adults from 18 countries. Estimates of 24-hour sodium and potassium excretion were made from a single fasting morning urine specimen and were used as surrogates for intake. We assessed the relationship between electrolyte excretion and blood pressure, as measured with an automated device. RESULTS: Regression analyses showed increments of 2.11 mm Hg in systolic blood pressure and 0.78 mm Hg in diastolic blood pressure for each 1-g increment in estimated sodium excretion. The slope of this association was steeper with higher sodium intake (an increment of 2.58 mm Hg in systolic blood pressure per gram for sodium excretion >5 g per day, 1.74 mm Hg per gram for 3 to 5 g per day, and 0.74 mm Hg per gram for <3 g per day; P<0.001 for interaction). The slope of association was steeper for persons with hypertension (2.49 mm Hg per gram) than for those without hypertension (1.30 mm Hg per gram, P<0.001 for interaction) and was steeper with increased age (2.97 mm Hg per gram at >55 years of age, 2.43 mm Hg per gram at 45 to 55 years of age, and 1.96 mm Hg per gram at <45 years of age; P<0.001 for interaction). Potassium excretion was inversely associated with systolic blood pressure, with a steeper slope of association for persons with hypertension than for those without it (P<0.001) and a steeper slope with increased age (P<0.001). CONCLUSIONS: In this study, the association of estimated intake of sodium and potassium, as determined from measurements of excretion of these cations, with blood pressure was nonlinear and was most pronounced in persons consuming high-sodium diets, persons with hypertension, and older persons. (Funded by the Heart and Stroke Foundation of Ontario and others.).

Abstract Until now there has been no fundamental theory applicable for biodegradable metals (BMs). First, this paper optimizes the definition of BMs given in 2014. Second, the dual criteria of biodegradability and biocompatibility are proposed for BMs, and all metallic elements in the periodic table with accessible data are screened on the basis of these criteria. Regarding biodegradability, electrode potential, reactivity series, galvanic series, Pilling–Bedworth ratio, and Pourbaix diagrams are all adopted as parameters to classify the degradable and nondegradable nature of a material, especially in a physiological environment. Considering the biocompatibility at different levels, cellular biocompatibility, tissue biocompatibility, and human/clinical related biocompatibility parameters are put forward to comprehensively evaluate the biosafety of BMs. Third, for the material design of BMs, mechanical properties, chemical properties, physical properties and biological properties should be considered and balanced to guarantee that the degradation behavior of BMs match well with a tissue regeneration/repair procedure as the function of time and spatial location. Besides the selected metallic elements, some nonmetallic elements are selected as suitable alloying elements for BMs. Finally, five classification/research directions for future BMs are proposed: biodegradable pure metals, crystalline alloys, bulk metallic glasses, high entropy alloys, and metal matrix composites.

The ability of articular cartilage to repair itself is limited because it lacks blood vessels, nerves, and lymph tissue. Once damaged, it can lead to joint swelling and pain, accelerating the progression of osteoarthritis. To date, complete regeneration of hyaline cartilage exhibiting mechanical properties remains an elusive goal, despite the many available technologies. The inflammatory milieu created by cartilage damage is critical for chondrocyte death and hypertrophy, extracellular matrix breakdown, ectopic bone formation, and progression of cartilage injury to osteoarthritis. In the inflammatory microenvironment, mesenchymal stem cells (MSCs) undergo aberrant differentiation, and chondrocytes begin to convert or dedifferentiate into cells with a fibroblast phenotype, thereby resulting in fibrocartilage with poor mechanical qualities. All these factors suggest that inflammatory problems may be a major stumbling block to cartilage repair. To produce a milieu conducive to cartilage repair, multi-dimensional management of the joint inflammatory microenvironment in place and time is required. Therefore, this calls for elucidation of the immune microenvironment of cartilage repair after injury. This review provides a brief overview of: (1) the pathogenesis of cartilage injury; (2) immune cells in cartilage injury and repair; (3) effects of inflammatory cytokines on cartilage repair; (4) clinical strategies for treating cartilage defects; and (5) strategies for targeted immunoregulation in cartilage repair. STATEMENT OF SIGNIFICANCE: Immune response is increasingly considered the key factor affecting cartilage repair. It has both negative and positive regulatory effects on the process of regeneration and repair. Proinflammatory factors are secreted in large numbers, and necrotic cartilage is removed. During the repair period, immune cells can secrete anti-inflammatory factors and chondrogenic cytokines, which can inhibit inflammation and promote cartilage repair. However, inflammatory factors persist, which accelerate the degradation of the cartilage matrix. Furthermore, in an inflammatory microenvironment, MSCs undergo abnormal differentiation, and chondrocytes begin to transform or dedifferentiate into fibroblast-like cells, forming fibrocartilage with poor mechanical properties. Consequently, cartilage regeneration requires multi-dimensional regulation of the joint inflammatory microenvironment in space and time to make it conducive to cartilage regeneration.

Electroconductive hydrogels are very attractive candidates for accelerated spinal cord injury (SCI) repair because they match the electrical and mechanical properties of neural tissue. However, electroconductive hydrogel implantation can potentially aggravate inflammation, and hinder its repair efficacy. Bone marrow stem cell-derived exosomes (BMSC-exosomes) have shown immunomodulatory and tissue regeneration effects, therefore, neural tissue-like electroconductive hydrogels loaded with BMSC-exosomes are developed for the synergistic treatment of SCI. These exosomes-loaded electroconductive hydrogels modulate microglial M2 polarization via the NF-κB pathway, and synergistically enhance neuronal and oligodendrocyte differentiation of neural stem cells (NSCs) while inhibiting astrocyte differentiation, and also increase axon outgrowth via the PTEN/PI3K/AKT/mTOR pathway. Furthermore, exosomes combined electroconductive hydrogels significantly decrease the number of CD68-positive microglia, enhance local NSCs recruitment, and promote neuronal and axonal regeneration, resulting in significant functional recovery at the early stage in an SCI mouse model. Hence, the findings of this study demonstrate that the combination of electroconductive hydrogels and BMSC-exosomes is a promising therapeutic strategy for SCI repair.

Mesoporous silica nanoparticles (MSNs) are recognized as a prime example of nanotechnology applied in the biomedical field, due to their easily tunable structure and composition, diverse surface functionalization properties, and excellent biocompatibility. Over the past two decades, researchers have developed a wide variety of MSNs-based nanoplatforms through careful design and controlled preparation techniques, demonstrating their adaptability to various biomedical application scenarios. With the continuous breakthroughs of MSNs in the fields of biosensing, disease diagnosis and treatment, tissue engineering, etc., MSNs are gradually moving from basic research to clinical trials. In this review, we provide a detailed summary of MSNs in the biomedical field, beginning with a comprehensive overview of their development history. We then discuss the types of MSNs-based nanostructured architectures, as well as the classification of MSNs-based nanocomposites according to the elements existed in various inorganic functional components. Subsequently, we summarize the primary purposes of surface-functionalized modifications of MSNs. In the following, we discuss the biomedical applications of MSNs, and highlight the MSNs-based targeted therapeutic modalities currently developed. Given the importance of clinical translation, we also summarize the progress of MSNs in clinical trials. Finally, we take a perspective on the future direction and remaining challenges of MSNs in the biomedical field.

Mimicking soft tissue mechanical properties and the high conductivity required for electrical transmission in the native spinal cord is critical in nerve tissue regeneration scaffold designs. However, fabricating scaffolds of high conductivity, tissue-like mechanical properties, and excellent biocompatibility simultaneously remains a great challenge. Here, a soft, highly conductive, biocompatible conducting polymer hydrogel (CPH) based on a plant-derived polyphenol, tannic acid (TA), cross-linking and doping conducting polypyrrole (PPy) chains is developed to explore its therapeutic efficacy after a spinal cord injury (SCI). The developed hydrogels exhibit an excellent electronic conductivity (0.05-0.18 S/cm) and appropriate mechanical properties (0.3-2.2 kPa), which can be achieved by controlling TA concentration. In vitro, a CPH with a higher conductivity accelerated the differentiation of neural stem cells (NSCs) into neurons while suppressing the development of astrocytes. In vivo, with relatively high conductivity, the CPH can activate endogenous NSC neurogenesis in the lesion area, resulting in significant recovery of locomotor function. Overall, our findings evidence that the CPHs without being combined with any other therapeutic agents have stimulated tissue repair following an SCI and thus have important implications for future biomaterial designs for SCI therapy.

ABSTRACT A number of studies investigated the distribution of BMD values and the prevalence of osteoporosis in China, but their findings varied. Until now, a BMD reference database based on uniform measurements in a large-scale Chinese population has been lacking. A total of 75,321 Chinese adults aged 20 years and older were recruited from seven centers between 2008 and 2018. BMD values at the lumbar spine (L1–L4), femoral neck, and total femur were measured by GE Lunar dual-energy X-ray absorptiometry systems. BMD values measured in each center were cross-calibrated by regression equations that were generated by scanning the same European spine phantom 10 times at every center. Cubic and multivariate linear regression were performed to assess associations between BMD values and demographic variables. Sex-specific prevalence of osteoporosis was age-standardized based on the year 2010 national census data for the Chinese population. The sex-specific BMD values at each site were negatively associated with age, positively associated with body mass index levels, and lower in the participants from southwest China than in those from other geographic regions after multivariate adjustment. Furthermore, BMD values at the femoral neck and total femur decreased with the year of BMD measurement. The peak BMD values at the lumbar spine, femoral neck, and total femur were 1.088 g/cm2, 0.966 g/cm2, and 0.973 g/cm2, respectively, for men, and 1.114 g/cm2, 0.843 g/cm2, and 0.884 g/cm2, respectively, for women. The age-standardized prevalence of osteoporosis at the spine or hip was 6.46% and 29.13% for men and women aged 50 years and older, respectively. Currently a total of 10.9 million men and 49.3 million women in China are estimated to have osteoporosis. In our national examination of BMD, we found that BMD values differed by demographic characteristics. We estimated the age-standardize prevalence of osteoporosis in China to be 6.46% and 29.13% respectively, for men and women aged 50 years and older.

Abstract Purpose: The prognosis for patients with refractory soft-tissue sarcoma (STS) is dismal. Anlotinib has previously shown antitumor activity on STS in preclinical and phase I studies. Patients and Methods: Patients 18 years and older, progressing after anthracycline-based chemotherapy, naïve from angiogenesis inhibitors, with at least one measurable lesion according to RECIST 1.1, were enrolled. The main subtypes eligible were undifferentiated pleomorphic sarcoma (UPS), liposarcoma (LPS), leiomyosarcoma (LMS), synovial sarcoma (SS), fibrosarcoma (FS), alveolar soft-part sarcoma (ASPS), and clear cell sarcoma (CCS). Participants were treated with anlotinib. The primary endpoint was progression-free rate at 12 weeks (PFR12 weeks). Results: A total of 166 patients were included in the final analysis. Overall, the PFR12 weeks was 68%, and objective response rate was 13% (95% confidence interval, 7.6%–18%). The median progression-free survival (PFS) and overall survival (OS) were 5.6 and 12 months, respectively. The PFR12 weeks, median PFS and OS were: 58%, 4.1 and 11 months for UPS (n = 19); 63%, 5.6 and 13 months for LPS (n = 13); 75%, 11 and 15 months for LMS (n = 26); 75%, 7.7 and 12 months for SS (n = 47); 81%, 5.6 and 12 months for FS (n = 18); 77%, 21 and not reached for ASPS (n = 13); 54%, 11 and 16 months for CCS (n = 7); and 44%, 2.8 and 8.8 months for other sarcoma (n = 23), respectively. The most common clinically significant grade 3 or higher adverse events were hypertension (4.8%), triglyceride elevation (3.6%), and pneumothorax (2.4%). No treatment-related death occurred. Conclusions: Anlotinib showed antitumor activity in several STS entities. The toxicity was manageable. Clin Cancer Res; 24(21); 5233–8. ©2018 AACR.

Objective. To compare the osteoporosis detection rates in postmenopausal women when measuring bone mineral density (BMD) with quantitative computed tomography (QCT) in the spine versus dual X-ray absorptiometry (DXA) in the spine and hip and to investigate the reasons for the discrepancy between the two techniques. Methods. Spinal volumetric BMD was measured with QCT, and areal spinal and hip BMDs were measured with DXA in 140 postmenopausal women. We calculated the osteoporosis detection rate for the two methods. Lumbar CT images of patients who had a discrepancy between QCT and DXA findings were reviewed to evaluate vertebral fractures, spinal degeneration, and abdominal aortic calcification. Results. For the entire 140 patients, the detection rate was 17.1% for DXA and 46.4% for QCT, a significant difference (P < 0.01). Of the 41 patients with conflicting diagnoses, 7 whose diagnosis by QCT was osteoporosis had vertebral fractures even though their DXA findings did not indicate osteoporosis. Varying degrees of spinal degeneration were seen in all of the 41 patients. Conclusion. QCT may avoid the overestimation of BMD by DXA associated with spinal degeneration, abdominal aortic calcification, and other sclerotic lesions. It may be more sensitive than DXA for detecting osteoporosis in postmenopausal women.

PURPOSE OF REVIEW: Abdominal obesity, especially the increase of visceral adipose tissue (VAT), is closely associated with increased mortality related to cardiovascular disease, diabetes, and fatty liver disease. This review provides an overview of the recent advances for abdominal obesity measurement. RECENT FINDINGS: Compared to simple waist circumference, emerging three-dimensional (3D) body-scanning techniques also measure abdominal volume and shape. Abdominal dimension measures have been implemented in bioelectrical impedance analysis to improve accuracy when estimating VAT. Geometrical models have been applied in ultrasound to convert depth measurement into VAT area. Only computed tomography (CT) and MRI can provide direct measures of VAT. Recent advances in imaging allow for evaluating functional aspects of abdominal fat such as brown adipose tissue and fatty acid composition. SUMMARY: Waist circumference is a simple, inexpensive method to measure abdominal obesity. CT and MRI are reference methods for measuring VAT. Further studies are needed to establish the accuracy for dual-energy X-ray absorptiometry in estimating longitudinal changes of VAT. Further studies are needed to establish whether bioelectrical impedance analysis, ultrasound, or 3D body scanning is consistently superior to waist circumference in estimating VAT in different populations.

OBJECTIVE: Uncertainty exists over the size of potential beneficial effects of medical treatments targeting hematoma growth in intracerebral hemorrhage (ICH). We report associations of hematoma growth parameters on clinical outcomes in the pilot phase, Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT1) (ClinicalTrials.gov NCT00226096). METHODS: In randomized patients with both baseline and 24-hour brain CT (n = 335), associations between measures of absolute and relative hematoma growth and 90-day poor outcomes of death and dependency (modified Rankin Scale score 3-5) were assessed in logistic regression models, with data reported as odds ratios (OR) and 95% confidence intervals (CI). RESULTS: A total of 10.7 mL (1 SD) increase in hematoma volume over 24 hours was strongly associated with poor outcome (adjusted OR 1.72, 95% CI 1.19-2.49; p = 0.004). An association was also evident for relative growth (adjusted OR 1.67, 95% 1.22-2.27; p = 0.001 for 1 SD increase). The analyses were adjusted for age, sex, achieved systolic blood pressure, elevated NIH Stroke Scale score (≥ 14), hematoma location, baseline hematoma volume, intraventricular extension, antithrombotic therapy, baseline glucose, time from ICH to baseline CT scan, and time from baseline to repeat CT scan. A 1 mL increase in hematoma growth was associated with a 5% (95% CI 2%-9%) higher risk of death or dependency. CONCLUSION: Medical treatments, such as rapid intensive blood pressure lowering, could achieve ∼2-4 mL absolute attenuation of hematoma growth. There is hope that this could translate into modest but still clinically worthwhile (∼10%-20% better chance) outcome from ICH.

BACKGROUND: A special type of repairable meniscal lesion involving the peripheral attachment of the posterior horn of the medial meniscus is commonly associated with anterior cruciate ligament deficiency and is termed a "ramp lesion." However, there are no previously published articles reporting the epidemiologic characteristics of ramp lesions. HYPOTHESIS: The ramp lesion is a special type of medial meniscal tear with high prevalence associated with anterior cruciate ligament rupture; the prevalence increases with time from anterior cruciate ligament injury. Age and gender are risk factors affecting the prevalence of the ramp lesion. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: From April 2002 to October 2007, 868 consecutive knees were diagnosed as having an anterior cruciate ligament injury and received arthroscopic surgery for anterior cruciate ligament reconstruction. All the patients had verified tears of the ramp area under arthroscopy. The prevalence of the ramp lesion was evaluated retrospectively. Then, all cases were divided into different groups depending on the time interval from anterior cruciate ligament injury to anterior cruciate ligament reconstruction and other relevant risk factors such as age and gender. The effects of age, gender, and time from injury on the prevalence of ramp lesions were analyzed. RESULTS: Among 868 knees that underwent surgery for anterior cruciate ligament reconstruction, 144 knees were diagnosed as having a ramp lesion. The mean age was 24.7 years; there were 113 male and 31 female patients. The mean time from injury to anterior cruciate ligament reconstruction was 27.2 months. The prevalence of ramp lesions was 16.6%, which was analyzed as a logarithmic correlation with time from injury. Patients younger than 30 years of age and male patients had a significantly higher prevalence of ramp lesions. CONCLUSION: The ramp lesion is a common meniscal injury that can occur at the time of anterior cruciate ligament rupture or as a result of knee laxity associated with anterior cruciate ligament insufficiency. The prevalence of ramp lesion in this patient group was 16.6%, which increased with time until 24 months after initial injury. Patients younger than 30 years of age and male patients had a higher prevalence of ramp lesions.

Hydrogels, because of their water-rich nature and soft mechanical characteristics that resemble those of skin tissues, are promising materials for artificial skin. Existing piezoresistive hydrogels combine unique tissue-like and sensory properties, but these materials are often plagued by problems such as poor mechanical properties and the requirement of an external power supply or batteries. Here, a tough and self-powered hydrogel based on a tough polyacrylonitrile hydrogel incorporating ferroelectric poly(vinylidene fluoride) (PAN-PVDF) is reported. The dipolar interactions between the PVDF and PAN chains cause an increase in the best electroactive β-phase PVDF percentage in the composites from 0 to 91.3%; thus, a maximum piezoelectric coefficient d33, 30 pC N–1, was achieved for the hydrogels. Skin-like Young’s modulus values (1.33–4.24 MPa), stretchability (90–175%), and high toughness (1.23 MJ/m2) were achieved simultaneously for the hydrogels. This tough gel is capable of generating an electrical signal output (≈30 mV and ≈2.8 μA) with a rapid response (≈31 ms) due to the stress-induced poling effect. Moreover, the gel can also precisely detect physiological signals (e.g., gesture, pulse, and words). This study provides a simple and efficient method for artificial skin with high toughness, self-power generation capability, fast response, low cost, and tissue-like properties.

OBJECTIVE: The purpose of this study was to determine the efficacy and feasibility of 5th generation wireless systems (5G) telerobotic spinal surgery in our first 12 cases. METHODS: A total of 12 patients (5 males, 7 females; age, 23-71 years) with spinal disorders (4 thoracolumbar fractures, 6 lumbar spondylolisthesis, 2 lumbar stenosis) were treated with 5G telerobotic spinal surgery. Sixty-two pedicle screws were implanted. RESULTS: All patients had substantial relief from their symptoms. Screw placements were classified using Gertzbein-Robbins criteria. There were 59 grade A, 3 grade B. Mean operation time was 142.5 ± 46.7 minutes. Mean guiding wire insertion time was 41.3 ± 9.8 minutes. The deviation between the planned and actual positions was 0.76 ± 0.49 mm. No intraoperative adverse event was found. CONCLUSION: 5G remote robot-assisted spinal surgery is accurate and reliable. We conclude that 5G telerobotic spinal surgery is both efficacious and feasible for the management of spinal diseases with safety.

OBJECTIVE: The object of this study was to compare the safety and accuracy of pedicle screw placement using the TiRobot system versus conventional fluoroscopy in thoracolumbar spinal surgery. METHODS: Patients with degenerative or traumatic thoracolumbar spinal disorders requiring spinal instrumentation were randomly assigned to either the TiRobot-assisted group (RG) or the freehand fluoroscopy-assisted group (FG) at a 1:1 ratio. The primary outcome measure was the accuracy of screw placement according to the Gertzbein-Robbins scale; grades A and B (pedicle breach < 2 mm) were considered clinically acceptable. In the RG, discrepancies between the planned and actual screw placements were measured by merging postoperative CT images with the trajectory planning images. Secondary outcome parameters included proximal facet joint violation, duration of surgery, intraoperative blood loss, conversion to freehand approach in the RG, postoperative hospital stay, and radiation exposure. RESULTS: A total of 1116 pedicle screws were implanted in 234 patients (119 in the FG, and 115 in the RG). In the RG, 95.3% of the screws were perfectly positioned (grade A); the remaining screws were graded B (3.4%), C (0.9%), and D (0.4%). In the FG, 86.1% screws were perfectly positioned (grade A); the remaining screws were graded B (7.4%), C (4.6%), D (1.4%), and E (0.5%). The proportion of clinically acceptable screws was significantly greater in the RG than in the FG (p < 0.01). In the RG, the mean deviation was 1.5 ± 0.8 mm for each screw. The most common direction of screw deviation was lateral in the RG and medial in the FG. Two misplaced screws in the FG required revision surgery, whereas no revision was required in the RG. None of the screws in the RG violated the proximal facet joint, whereas 12 screws (2.1%) in the FG violated the proximal facet joint (p < 0.01). The RG had significantly less blood loss (186.0 ± 255.3 ml) than the FG (217.0 ± 174.3 ml; p < 0.05). There were no significant differences between the two groups in terms of surgical time and postoperative hospital stay. The mean cumulative radiation time was 81.5 ± 38.6 seconds in the RG and 71.5 ± 44.2 seconds in the FG (p = 0.07). Surgeon radiation exposure was significantly less in the RG (21.7 ± 11.5 μSv) than in the FG (70.5 ± 42.0 μSv; p < 0.01). CONCLUSIONS: TiRobot-guided pedicle screw placement is safe and useful in thoracolumbar spinal surgery.Clinical trial registration no.: NCT02890043 (clinicaltrials.gov).

OBJECTIVE: To identify an optimal lifestyle profile to protect against memory loss in older individuals. DESIGN: Population based, prospective cohort study. SETTING: Participants from areas representative of the north, south, and west of China. PARTICIPANTS: Individuals aged 60 years or older who had normal cognition and underwent apolipoprotein E (APOE) genotyping at baseline in 2009. MAIN OUTCOME MEASURES: Participants were followed up until death, discontinuation, or 26 December 2019. Six healthy lifestyle factors were assessed: a healthy diet (adherence to the recommended intake of at least 7 of 12 eligible food items), regular physical exercise (≥150 min of moderate intensity or ≥75 min of vigorous intensity, per week), active social contact (≥twice per week), active cognitive activity (≥twice per week), never or previously smoked, and never drinking alcohol. Participants were categorised into the favourable group if they had four to six healthy lifestyle factors, into the average group for two to three factors, and into the unfavourable group for zero to one factor. Memory function was assessed using the World Health Organization/University of California-Los Angeles Auditory Verbal Learning Test, and global cognition was assessed via the Mini-Mental State Examination. Linear mixed models were used to explore the impact of lifestyle factors on memory in the study sample. RESULTS: 29 072 participants were included (mean age of 72.23 years; 48.54% (n=14 113) were women; and 20.43% (n=5939) were APOE ε4 carriers). Over the 10 year follow-up period (2009-19), participants in the favourable group had slower memory decline than those in the unfavourable group (by 0.028 points/year, 95% confidence interval 0.023 to 0.032, P<0.001). APOE ε4 carriers with favourable (0.027, 95% confidence interval 0.023 to 0.031) and average (0.014, 0.010 to 0.019) lifestyles exhibited a slower memory decline than those with unfavourable lifestyles. Among people who were not carriers of APOE ε4, similar results were observed among participants in the favourable (0.029 points/year, 95% confidence interval 0.019 to 0.039) and average (0.019, 0.011 to 0.027) groups compared with those in the unfavourable group. APOE ε4 status and lifestyle profiles did not show a significant interaction effect on memory decline (P=0.52). CONCLUSION: A healthy lifestyle is associated with slower memory decline, even in the presence of the APOE ε4 allele. This study might offer important information to protect older adults against memory decline. TRIAL REGISTRATION: ClinicalTrials.gov NCT03653156.

The radiological assessment of muscle properties-size, mass, density (also termed radiodensity), composition, and adipose tissue infiltration-is fundamental in muscle diseases. More recently, it also became obvious that muscle atrophy, also termed muscle wasting, is caused by or associated with many other diseases or conditions, such as inactivity, malnutrition, chronic obstructive pulmonary disorder, cancer-associated cachexia, diabetes, renal and cardiac failure, and sarcopenia and even potentially with osteoporotic hip fracture. Several techniques have been developed to quantify muscle morphology and function. This review is dedicated to quantitative computed tomography (CT) of skeletal muscle and only includes a brief comparison with magnetic resonance imaging. Strengths and limitations of CT techniques are discussed in detail, including CT scanner calibration, acquisition and reconstruction protocols, and the various quantitative parameters that can be measured with CT, starting from simple volume measures to advanced parameters describing the adipose tissue distribution within muscle. Finally, the use of CT in sarcopenia and cachexia and the relevance of muscle parameters for the assessment of osteoporotic fracture illustrate the application of CT in two emerging areas of medical interest.

ABSTRACT Opportunistic screening for osteoporosis can be performed using low-dose computed tomography (LDCT) imaging obtained for other clinical indications. In this study we explored the CT-derived bone mineral density (BMD) and prevalence of osteoporosis from thoracic LDCT in a large population cohort of Chinese men and women. A total of 69,095 adults (40,733 men and 28,362 women) received a thoracic LDCT scan for the purpose of lung cancer screening between 2018 and 2019, and data were obtained for analysis from the China Biobank Project, a prospective nationwide multicenter population study. Lumbar spine (L1–L2) trabecular volumetric bone mineral density (vBMD) was derived from these scans using quantitative computed tomography (QCT) software and the American College of Radiology QCT diagnostic criteria for osteoporosis were applied. Geographic regional differences in the prevalence of osteoporosis were assessed and the age-standardized, population prevalence of osteoporosis in Chinese men and women was estimated from the 2010 China census. The prevalence of osteoporosis by QCT for the Chinese population aged &amp;gt;50 years was 29.0% for women and 13.5% for men, equating to 49.0 million and 22.8 million, respectively. In women, this rate is comparable to estimates from dual-energy X-ray absorptiometry (DXA), but in men, the prevalence is double. Prevalence varied geographically across China, with higher rates in the southwest and lower rates in the northeast. Trabecular vBMD decreased with age in both men and women. Women had higher peak trabecular vBMD (185.4 mg/cm3) than men (176.6 mg/cm3) at age 30 to 34 years, but older women had lower trabecular vBMD (62.4 mg/cm3) than men (92.1 mg/cm3) at age 80 years. We show that LDCT-based opportunistic screening could identify large numbers of patients with low lumbar vBMD, and that future cohort studies are now required to evaluate the clinical utility of such screening in terms of fracture prevention and supporting national health economic analyses. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..

Hydrogel scaffolds are attractive for tissue defect repair and reorganization because of their human tissue-like characteristics. However, most hydrogels offer limited cell growth and tissue formation ability due to their submicron- or nano-sized gel networks, which restrict the supply of oxygen, nutrients and inhibit the proliferation and differentiation of encapsulated cells. In recent years, 3D printed hydrogels have shown great potential to overcome this problem by introducing macro-pores within scaffolds. In this study, we fabricated a macroporous hydrogel scaffold through horseradish peroxidase (HRP)-mediated crosslinking of silk fibroin (SF) and tyramine-substituted gelatin (GT) by extrusion-based low-temperature 3D printing. Through physicochemical characterization, we found that this hydrogel has excellent structural stability, suitable mechanical properties, and an adjustable degradation rate, thus satisfying the requirements for cartilage reconstruction. Cell suspension and aggregate seeding methods were developed to assess the inoculation efficiency of the hydrogel. Moreover, the chondrogenic differentiation of stem cells was explored. Stem cells in the hydrogel differentiated into hyaline cartilage when the cell aggregate seeding method was used and into fibrocartilage when the cell suspension was used. Finally, the effect of the hydrogel and stem cells were investigated in a rabbit cartilage defect model. After implantation for 12 and 16 weeks, histological evaluation of the sections was performed. We found that the enzymatic cross-linked and methanol treatment SF5GT15 hydrogel combined with cell aggregates promoted articular cartilage regeneration. In summary, this 3D printed macroporous SF-GT hydrogel combined with stem cell aggregates possesses excellent potential for application in cartilage tissue repair and regeneration.