Identification of a cinnamoyl-CoA reductase from Cinnamomum cassia involved in trans-cinnamaldehyde biosynthesis.

MAIN CONCLUSION: The identification of a functional cinnamoyl-CoA reductase enzyme from Cinnamomum cassia involved in trans-cinnamaldehyde biosynthesis offers the potential for enhancing trans-cinnamaldehyde production through genetic engineering. A significant accumulation of trans-cinnamaldehyde has been found in the bark tissues of C. cassia, used in traditional Chinese medicine. trans-Cinnamaldehyde exhibits various pharmacological properties such as anti-inflammatory, analgesic, and protection of the stomach and the digestive tract. However, further elucidation and characterization of the biosynthetic pathway for trans-cinnamaldehyde is required. In this study, we conducted an integrated analysis of trans-cinnamaldehyde accumulation profiles and transcriptomic data from five different C. cassia tissues to identify the genes involved in its biosynthesis. The transcriptome data we obtained included nearly all genes associated with the trans-cinnamaldehyde pathway, with the majority demonstrating high abundance in branch barks and trunk barks. We successfully cloned four C. cassia cinnamoyl-CoA reductases (CcCCRs), a key gene in trans-cinnamaldehyde biosynthesis. We found that the recombinant CcCCR1 protein was the only one that more efficiently converted cinnamoyl-CoA into trans-cinnamaldehyde. CcCCR1 exhibited approximately 14.7-fold higher catalytic efficiency (kcat/Km) compared to the Arabidopsis thaliana cinnamoyl-CoA reductase 1 (AtCCR1); therefore, it can be utilized for engineering higher trans-cinnamaldehyde production as previously reported. Molecular docking studies and mutagenesis experiments also validated the superior catalytic activity of CcCCR1 compared to AtCCR1. These findings provide valuable insights for the functional characterization of enzyme-coding genes and hold potential for future engineering of trans-cinnamaldehyde biosynthetic pathways.

Multidimensional characteristics of musculoskeletal pain and risk of hip fractures among elderly adults: the first longitudinal evidence from CHARLS.

BACKGROUND: Hip fractures are a major public health concern among middle-aged and older adults. It is important to understand the associated risk factors to inform health policies and develop better prevention strategies. Musculoskeletal pain is a possible implicating factor, being associated with physical inactivity and risk of falls. However, the association between musculoskeletal pain and hip fractures has not been clearly investigated. METHODS: A nationally representative sample of the Chinese population was obtained from the China Health and Retirement Longitudinal Study (CHARLS). The study collected patient information on their demographic characteristics, socioeconomic status, other health-related behavior, and history of musculoskeletal pain and hip fractures. Univariate and multivariate analyses were conducted to investigate the factors influencing the risk of hip fracture, including factors related to the individual and to musculoskeletal pain. P for trend test was performed to assess the trend of each continuous variable. The robustness and bias were assessed using the bootstrap method. Restricted cubic spline regression was utilized to identify linear or non-linear relationships. RESULTS: Among the 18,813 respondents, a total of 215 individuals reported that they have experienced a hip fracture. An increased risk of hip fracture was associated with the presence of waist pain and leg pain (P < 0.05), as well as with an increased number of musculoskeletal pain sites (P < 0.05). For individuals aged 65 and above, a significant association was found between age and the risk of hip fracture (P < 0.05). Furthermore, respondents with lower education level had a higher risk of hip fracture compared to those with higher education levels (P < 0.05). CONCLUSION: In the Chinese population, the risk of hip fracture was found to be associated with both the location and extent of musculoskeletal pain, as well as with other factors such as age and demographic characteristics. The findings of this study may be useful for informing policy development and treatment strategies, and provide evidence for comparison with data from other demographic populations.

Steric Hindrance Engineering to Modulate the Closed Pores Formation of Polymer-Derived Hard Carbon for High-Performance Sodium-Ion Batteries.

The closed pores play a critical role in improving the sodium storage capacity of hard carbon (HC) anode, however, their formation mechanism as well as the efficient modulation strategy at molecular level in the polymer-derived HCs is still lacking. In this work, the steric hindrance effect has been proposed to create closed pores in the polymer-derived HCs for the first time through grafting the aromatic rings within and between the main chains in the precursor. The experimental data and theoretical calculation demonstrate that steric-hindrance effect from the aromatic ring side group can increase backbone rigidity and the internal free volumes in the polymer precursor, which can prevent the over graphitization and facilitate the formation of closed pores during the carbonization process. As a result, the as-prepared HC anode exhibits a remarkably enhanced discharge capacity of 340.3 mAh/g at 0.1 C, improved rate performance (210.7 mAh/g at 5 C) as well as boosted cycling stability (86.4% over 1000 cycles at 2C). This work provides a new insight into the formation mechanisms of closed pores via steric hindrance engineering, which can shed light on the development of high-performance polymer-derived HC anode for sodium-ion batteries.

Preference of musculoskeletal pain treatment in middle-aged and elderly chinese people: a machine learning analysis of the China health and retirement longitudinal study.

BACKGROUND: Musculoskeletal pain is a major cause of physical disability, associated with huge socioeconomic burden. Patient preference for treatment is an important factor contributing to the choice of treatment strategies. However, effective measurements for evaluating the ongoing management of musculoskeletal pain are lacking. To help improve clinical decision making, it's important to estimate the current state of musculoskeletal pain management and analyze the contribution of patient treatment preference. METHODS: A nationally representative sample for the Chinese population was derived from the China Health and Retirement Longitudinal Study (CHARLS). Information on the patients' demographic characteristics, socioeconomic status, other health-related behavior, as well as history on musculoskeletal pain and treatment data were obtained. The data was used to estimate the status of musculoskeletal pain treatment in China in the year 2018. Univariate analysis and multivariate analysis were used to find the effect factors of treatment preference. XGBoost model and Shapley Additive exPlanations (SHAP) method were performed to analyze the contribution of each variable to different treatment preferences. RESULTS: Among 18,814 respondents, 10,346 respondents suffered from musculoskeletal pain. Approximately 50% of musculoskeletal pain patients preferred modern medicine, while about 20% chose traditional Chinese medicine and another 15% chose acupuncture or massage therapy. Differing preferences for musculoskeletal pain treatment was related to the respondents' gender, age, place of residence, education level, insurance status, and health-related behavior such as smoking and drinking. Compared with upper or lower limb pain, neck pain and lower back pain were more likely to make respondents choose massage therapy (P < 0.05). A greater number of pain sites was associated with an increasing preference for respondents to seek medical care for musculoskeletal pain (P < 0.05), while different pain sites did not affect treatment preference. CONCLUSION: Factors including gender, age, socioeconomic status, and health-related behavior may have potential effects on people' s choice of treatment for musculoskeletal pain. The information derived from this study may be useful for helping to inform clinical decisions for orthopedic surgeons when devising treatment strategies for musculoskeletal pain.

Identification of the joint line in revision total knee arthroplasty using a multiple linear regression model: a cadaveric study.

INTRODUCTION: The results of revision total knee arthroplasty (rTKA) may be compromised by excessive joint line (JL) elevation. It is critical but challenging in reestablishing the JL in rTKA. Previous studies have confirmed that, biomechanically and clinically, JL elevation should not exceed 4 mm. Image-based studies described several approaches to locate the JL intraoperatively, however magnification errors could occur. In this cadaveric study, we aim to define an accurate and reliable method to determine the JL. MATERIALS AND METHODS: Thirteen male and eleven female cadavers were used, with an average age of death being 48.3 years. The transepicondylar width (TEW), the distance from the medial (MEJL) and lateral (LEJL) epicondyle, adductor tubercle (ATJL), fibular head (FHJL) and tibial tubercle (TTJL) to the JL were measured in 48 knees. Intra- and interobserver reliability and validity were tested prior to any additional analysis. Pearson correlation and linear regression analysis were used to examine the correlations between landmark-JL distances (LEJL, MEJL, ATJL, FHJL and TTJL) and the TEW, and to further derive models for intraoperative JL determination. The accuracy of different models, quantified by errors between estimated and measured landmark-JL distances, was compared using the Friedman and post hoc Dunn tests. RESULTS: The intra- and inter-observer measurements for TEW, MEJL, LEJL, ATJL, TTJL and FHJL did not differ significantly (p > 0.05). Between genders, significant differences were found on TEW, MEJL, LEJL, ATJL, FHJL and TTJL (p < 0.05). There was no association between TEW and either FHJL or TTJL (p > 0.05), while ATJL, MEJL, and LEJL were found to be correlated with TEW (p < 0.05). Six models were derived: (1) MEJL = 0.37*TEW (r = 0.384), (2) LEJL = 0.28*TEW (r = 0.380), (3) ATJL = 0.47*TEW (r = 0.608), (4) MEJL = 0.413*TEW - 4.197 (R2 = 0.473), (5) LEJL = 0.236*TEW + 3.373 (R2 = 0.326), (6) ATJL = 0.455*TEW + 1.440 (R2 = 0.556). Errors were defined as deviations between estimated and actual landmark-JL distances. The mean absolute value of the errors, created by Model 1-6 was 3.18 ± 2.25, 2.53 ± 2.15, 2.64 ± 2.2, 1.85 ± 1.61, 1.60 ± 1.59 and 1.71 ± 1.5, respectively. The error could be limited to 4 mm in 72.9%, 83.3%, 72.9%, 87.5%, 87.5%, and 93.8% of the cases by referencing Model 1-6, respectively. CONCLUSION: Compared to previous image-based measurements, the current cadaveric study most closely resembles a realistic view of intraoperative settings and could circumvents magnification errors. We recommend using Model 6, the JL can be best estimated by referencing the AT and the ATJL can be calculated as ATJL (mm) = 0.455*TEW (mm) + 1.440 (mm).

[Analysis of diet structure of Kashin-beck disease area in Chamdo-Lhorong of Tibet in 2021].

OBJECTIVE: To investigate and compare the dietary structure between healthy people and patients in KBD area of Chamdo-Lhorong of Tibet. METHODS: A case-control study design was used, retrospectively select patients who had completed screening and registered in the national Kashin-Beck Disease surveillance system in 2021 in Luolong County, Qamdo, Tibet as the source population of the case group, and randomly selected people who had not been screened for Kashin-Beck disease in the same county as the control group. The self-made diet questionnaire was used to record the types of food consumption, frequency of food intake, basic information of the respondents, family size and other basic information in the past year by one-on-one interview. RESULTS: The staple food with the highest response among the patients(97.33%) was rice(rice/rice noodle), and the highest response among the healthy people(90%) was non-wheat products, non-fried pasta(bread/steamed bun/noodles/dumplings), except instant noodles.78.7% of patients chose not to eat local wheat(Tibetan noodles), and the number of non-patients who chose to eat non-local wheat(Tibetan noodles) 3-4 times a week was significantly higher than that of patients. The meat and meat products with the highest response in both patients(93.33%) and healthy people(90%) was yak meat(local). The control group also chose to consume beef(non-local/lamb/mutton/other non-processed meat), poultry and livestock offal, fish(all seawater and freshwater fish), shrimp and crabs or other seafood, and their consumption rate and intake frequency were significantly higher than those of the case group. The consumption rate and frequency of tomato, onion and garlic(garlic shoots/leek/onion/onion) and fresh eggs(egg/duck egg/quail egg/goose egg) in control group were significantly higher than those in case group. There was no significant difference in consumption rate and frequency of fruits, milk and dairy products between the two groups. CONCLUSION: In addition to the local highland barley(zanba), most people also chose to purchase rice and flour, which changed the situation of single staple food in the past. However, compared with the healthy population in the disease area, the consumption rate and intake frequency of fish, shrimp and crabs, poultry and livestock viscera, eggs(fresh eggs) and vegetables(tomatoes, scallions, ginger and garlic) in KBD patients were significantly lower, the selection of meat varieties is single, mainly local yak meat, and the overall dietary structure still presents the risk of single type and unbalanced diet.

Influencing factors of weak grip strength and fall: a study based on the China Health and Retirement Longitudinal Study (CHARLS).

BACKGROUND: Fall is a major cause of mortality and cause a significant burden on the healthcare system and economic system. Weak grip strength signifies impaired function. Older people with weak grip strength are at a higher risk of death. China has the largest ageing population in the world today. This study aims to analyze the factors contributing to weak grip strength and fall among Chinese. METHODS: This study analyzed data from the 2011 baseline and 2015 follow-up survey of the China Health and Retirement Longitudinal Study (CHARLS). To identify the risk factors of fall and weak grip strength, we used a stepwise multivariable logistic regression model and a least absolute shrinkage and selection operator (LASSO) regression model. RESULTS: In the LASSO regression model, all the risk factors were not shrunken. In the stepwise logistic regression model, adjusted for gender, age, grip strength, depression, and chronic disease, we found that female (aOR = 1.376, 95% CI = 1.243-1.523; P < 0.001), history of ischemic stroke (aOR = 1.786, 95% CI = 1.263-2.524; P = 0.001), depression (aOR = 1.559, 95% CI = 1.396-1.742; P < 0.001), weak grip strength (aOR = 1.285, 95% CI = 1.105-1.494; P = 0.001), older age (aOR = 1.227, 95% CI = 1.163-1.294; P < 0.001), rheumatoid arthritis (aOR = 1.410, 95% CI = 1.270-1.560; P < 0.001), history of kidney disease (aOR = 1.383, 95% CI = 1.136-1.682; P = 0.001) were factors associated with fall significantly. After further adjusting, we found the risk factors of weak grip strength included symptomatic knee osteoarthritis (aOR = 1.755, 95% CI 1.158-2.661; P = 0.008), living in rural area (aOR = 2.056, 95% CI 1.290-3.277; P = 0.002), depression (aOR = 1.523, 95% CI 1.116-2.078; P = 0.008), older age (aOR = 2.116, 95% CI 1.801-2.486; P < 0.001). CONCLUSION: From the study, we found that older age and depression were risk factors of weak grip strength and fall. Weak grip strength was a risk factor of fall. Female, ischemic stroke, kidney disease, rheumatoid arthritis were risk factors of fall; living in rural area and symptomatic knee osteoarthritis were risk factors of weak grip strength.

Influencing factors for the decline of limb muscle strength and the association with all-cause mortality: evidence from a nationwide population-based cohort study.

BACKGROUND: The decline of muscle strength, a typical characteristic of sarcopenia, greatly affects aging-related health outcomes; however, prospective data on influencing factors and mortality in the Chinese population are relatively sparse. AIMS: We investigated the influencing factors for the declined limb muscle strength and the association with all-cause mortality among the elderly Chinese individuals aged ≥ 65 years in a large long-term prospective cohort study. METHODS: We used data from the China Health and Retirement Longitudinal Study (CHARLS). Logistic regression analyses were performed to investigate the influencing factors of declined limb muscle strength. Cox proportional hazard models were used to analyze the impact on all-cause mortality, whose performance was evaluated by train-test cross-validation. RESULTS: The prevalences of declined upper and lower limb strength, which were defined by low hand grip strength (HS) and gait speed (GS), respectively, were 34.4% and 59.7%. The declined HS was significantly associated with older age (p < 0.001), female (p < 0.001), lower educational level (p < 0.001), lower BMI (p < 0.001), and combined with chronic diseases (p = 0.001). Moreover, the declined limb muscle strength was correlated with all-cause mortality (HR: 1.13, 95% CI 1.03-1.21 for HS; HR: 1.09, 95% CI 1.04-1.15 for GS), according to a multi-adjusted model with moderate predictive ability (C-index: 0.714, AUC of 7 year follow-up: 0.716). CONCLUSIONS: The decline of limb muscle strength was prevalent among elderly Chinese individuals and had a strong impact on all-cause mortality. Identification of key populations and tailored interventions on their influencing factors should be implemented in further research.

Hyaluronic Acid Oligosaccharide Derivatives Alleviate Lipopolysaccharide-Induced Inflammation in ATDC5 Cells by Multiple Mechanisms.

High molecular weight hyaluronic acids (HMW-HAs) have been used for the palliative treatment of osteoarthritis (OA) for decades, but the pharmacological activity of HA fragments has not been fully explored due to the limited availability of structurally defined HA fragments. In this study, we synthesized a series glycosides of oligosaccharides of HA (o-HAs), hereinafter collectively referred to as o-HA derivatives. Their effects on OA progression were examined in a chondrocyte inflammatory model established by the lipopolysaccharide (LPS)-challenged ATDC5 cells. Cell Counting Kit-8 (CCK-8) assays and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) showed that o-HA derivatives (≤100 µg/mL) exhibited no cytotoxicity and pro-inflammatory effects. We found that the o-HA and o-HA derivatives alleviated LPS-induced inflammation, apoptosis, autophagy and proliferation-inhibition of ATDC5 cells, similar to the activities of HMW-HAs. Moreover, Western blot analysis showed that different HA derivatives selectively reversed the effects of LPS on the expression of extracellular matrix (ECM)-related proteins (MMP13, COL2A1 and Aggrecan) in ATDC5 cells. Our study suggested that o-HA derivatives may alleviate LPS-induced chondrocyte injury by reducing the inflammatory response, maintaining cell proliferation, inhibiting apoptosis and autophagy, and decreasing ECM degradation, supporting a potential oligosaccharides-mediated therapy for OA.

Global research trends in hyperuricemia: a bibliometric and visualized study.

OBJECTIVES: The global trend of research on hyperuricaemia (HUA) has not been well studied. Therefore, this study aimed to investigate the trend of research on HUA and compare the findings in publications from different countries, institutions, journals, and authors, to predict the research hotspots. METHODS: Publications related to HUA were searched using the Science Citation Index-Expanded Web of Science. The data were analysed by using the bibliometric methodology. Additionally, a graphical mapping was generated by using the VOS viewer software to carry out a co-occurrence analysis and to investigate the trend of publications in this field. RESULTS: A total of 6313 articles were included. The number of publications was increasing globally yearly. USA was the leading country in global research in this field, with the largest number of publications and citations as well as the highest H-index (H-index reflects both the number of publications and the number of citations per publication). PLOS One published the largest number of publications related to HUA. JOHNSON RJ T has published the largest number of papers in this field. Published studies could be classified into six clusters: 'Pathophysiology', 'HUA and metabolic syndrome', 'HUA and cardiovascular disease', 'HUA and gout', 'HUA and nephropathy', and 'Genome-wide research'. 'Pathophysiology', 'HUA and cardiovascular disease', 'HUA and gout', and 'Genome-wide research' were predicted as the next hot topics in HUA research. CONCLUSIONS: USA was the leading country in global research in this field. It is expected that an increasing research output will continue to be observed in the near future. 'Pathophysiology', 'HUA and cardiovascular disease', 'HUA and gout', and 'Genome-wide research' may be the next hotspots and hence need more attention in the future.

Knee osteoarthritis and time-to all-cause mortality in six community-based cohorts: an international meta-analysis of individual participant-level data.

BACKGROUND: Osteoarthritis (OA) is a chronic joint disease, with increasing global burden of disability and healthcare utilisation. Recent meta-analyses have shown a range of effects of OA on mortality, reflecting different OA definitions and study methods. We seek to overcome limitations introduced when using aggregate results by gathering individual participant-level data (IPD) from international observational studies and standardising methods to determine the association of knee OA with mortality in the general population. METHODS: Seven community-based cohorts were identified containing knee OA-related pain, radiographs, and time-to-mortality, six of which were available for analysis. A two-stage IPD meta-analysis framework was applied: (1) Cox proportional hazard models assessed time-to-mortality of participants with radiographic OA (ROA), OA-related pain (POA), and a combination of pain and ROA (PROA) against pain and ROA-free participants; (2) hazard ratios (HR) were then pooled using the Hartung-Knapp modification for random-effects meta-analysis. FINDINGS: 10,723 participants in six cohorts from four countries were included in the analyses. Multivariable models (adjusting for age, sex, race, BMI, smoking, alcohol consumption, cardiovascular disease, and diabetes) showed a pooled HR, compared to pain and ROA-free participants, of 1.03 (0.83, 1.28) for ROA, 1.35 (1.12, 1.63) for POA, and 1.37 (1.22, 1.54) for PROA. DISCUSSION: Participants with POA or PROA had a 35-37% increased association with reduced time-to-mortality, independent of confounders. ROA showed no association with mortality, suggesting that OA-related knee pain may be driving the association with time-to-mortality. FUNDING: Versus Arthritis Centre for Sport, Exercise and Osteoarthritis and Osteoarthritis Research Society International.

The accelerometer-based navigation system demonstrated superior radiological outcomes in restoring mechanical alignment and component sagittal positioning in total knee arthroplasty.

BACKGROUND: This study aimed to determine whether the accelerometer-based navigation (ABN) could improve the accuracy of restoring mechanical axis (MA), component positioning, and clinical outcomes compared to conventional (CON) total knee arthroplasty (TKA). METHODS: A total of 301 consecutive patients (ABN: 27, CON: 274) were included. A 1:4 propensity score matching (PSM) was performed between the two groups according to preoperative demographic and clinical parameters. The postoperative MA, femoral coronal angle (FCA), femoral sagittal angle (FSA), tibial coronal angle (TCA) and tibial sagittal angle (TSA) were compared. Absolute deviations of aforementioned angles were calculated as the absolute value of difference between the exact and ideal value and defined as norms if within 3°, otherwise regarded as outliers. Additional clinical parameters, including the Knee Society knee and function scores (KSKS and KSFS) and range of motion (ROM), were assessed at final follow-up (FU) (mean FU was 21.88 and 21.56 months respectively for ABN and CON group). A secondary subgroup analysis and comparison on clinical outcomes were conducted between norms and outliers in different radiological parameters. RESULTS: A total of 98 patients/102 knees were analyzed after the PSM (ABN: 21 patients/24 knees, CON: 77 patients/78 knees). In the ABN group, the mean MA, FCA and TSA were significantly improved (p = 0.019, 0.006, < 0.001, respectively). Proportions of TKAs within a ± 3°deviation were significantly improved in all the postoperative radiological variables except for TCA (p = 0.003, 0.021, 0.042, 0.013, respectively for MA, FCA, FSA, and TSA). The absolute deviations of FSA and TSA were also significantly lower in the ABN group (p = 0.020, 0.048, respectively). No significant differences were found in either mean value, absolute deviation or outlier ratio of TCA between two groups. On clinical outcomes, there were no significant differences between two groups, although KSKS, KSFS and ROM (p < 0.01, respectively) dramatically improved compared to baseline. The subgroup analysis also demonstrated no statistical difference on clinical outcomes between the outliers and norms in varied radiological parameters. CONCLUSIONS: The ABN could improve the accuracy and precision of mechanical alignment and component positioning without significant improvement of clinical outcomes. Further high quality studies with long term FU are warranted to comprehensively evaluate the value of the ABN.

The usage of drainage after primary total hip or knee arthroplasty: best evidence selection and risk of bias considerations.

BACKGROUND: Numerous systematic reviews investigating the benefit of the usage of drainage after primary total hip or knee arthroplasty have been published with divergent conclusions. We aim to determine the best available evidence and consider risk of bias of these articles and to provide recommendations. METHODS: A systematic search of systematic reviews published through to May 2020 was performed in MEDLINE, EMBASE and Cochrane library. Methodological quality, risk of bias and best evidence choice of included articles were evaluated by AMSTAR instrument, ROBIS tool and Jadad decision algorithm, respectively. We selected systematic reviews with high methodological quality and low risk of bias ultimately as best evidence. RESULTS: Twelve meta-analyses were included lastly. According to the ROBIS tool, seven of the included systematic reviews were with low risk of bias and five with high risk of bias. The Jadad decision algorithm suggested that two reviews conducted by Zan et al. for hip and Si et al. et al. for knee were selected as the best evidence, with highest AMSTAR score and low risk of bias. CONCLUSIONS: Ten systematic reviews were included as low-quality with only two high-quality studies. Based on the current available evidence, we have insufficient confidence to draw conclusion that whether to use closed suction drainage for both total knee and hip arthroplasty. To verify the necessity and benefit of using closed suction drainage after primary total knee and hip arthroplasty, and develop exact recommendations, further studies are still required.

Quality of life and treatment satisfaction with pharmacological interventions in Chinese adults with chronic pain due to osteoarthritis.

BACKGROUND: Aim of this multicenter, observational, cross-sectional study was to evaluate health-related quality of life (HRQoL) and treatment satisfaction of current medications in Chinese knee OA patients. METHODS: Brief Pain Inventory (BPI), Treatment Satisfaction Questionnaire (TSQM-1.4), and HRQoL (EQ-5D-5L) were assessed in total of 601 OA of knee patients. Impact on QoL (EQ-5D-5L) and treatment satisfaction (TSQM-1.4) by BPI-Severity score (< 4 and ≥ 4) were presented using mean standard deviations (SDs) and were compared using a t-test. For each of self-assessed health EQ-5D-5L and TSQM, a linear regression model was used to estimate the regression coefficient along with corresponding 95% confidence interval (CI) for BPI-Severity. RESULTS: Mean score of EQ-5D-5L of patients with BPI-Severity ≥4 was significantly lower than those with BPI-Severity < 4. All the scores of TSQM in 4 dimensions were lower in patients with BPI-Severity ≥4 than in those with BPI-Severity < 4. Both HRQoL scores and TSQM scores showed a statistically significant decreasing trend with increasing BPI-Severity pain score. CONCLUSION: Chronic knee OA pain has a significant impact on patients' HRQoL. More severe patients with OA were less satisfied with current treatments.

Efficacy and safety of a single intra-articular injection of 6 ml Hylan G-F 20 compared to placebo in Chinese patients with symptomatic knee osteoarthritis : C-SOUND study, a 26-week multicenter double-blind randomized placebo-controlled trial in China.

BACKGROUND: Single 6 ml Hylan G-F 20 injection, is indicated for knee osteoarthritis patients who have failed to respond to non-pharmacologic therapy and/or simple analgesics. To obtain more thorough understanding of the clinical efficacy and safety, a randomized clinical trial was conducted comparing intra-articular (IA) administration of single 6 ml Hylan G-F 20 injection versus placebo in knee OA patients of Chinese ethnicity. METHODS: This was a randomized, multi-center, double-blind, placebo-controlled clinical trial conducted in 21 centers across China. Four hundred forty adults with knee OA received a single 6 ml Hylan G-F 20 or placebo injection and were evaluated for clinical efficacy and safety outcomes over 26 weeks. Western Ontario and McMaster Universities OA (WOMAC) A1 index, treatment-emergent adverse events (TEAEs) and standard safety parameters were measured at pre-injection, and at weeks 1, 4, 8, 12, 16, 20 and 26 post-injection. RESULTS: Four hundred forty patients (male: 98 [22.3%]; female: 342 [77.7%]) were randomized. The mean age [standard deviation (SD)] was 61.5 (7.9) years. All patients were of East Asian ethnicity. Mean WOMAC A1 score at baseline was 5.3 (1.2) and 5.2 (1.3) in single 6 ml Hylan G-F 20 injection and placebo groups, respectively. Significant reductions of WOMAC A1 score were observed in both treatment groups when compared to baseline at 26 weeks post-injection, with the mean reduction of [standard error (SE)/percentage] -2.146 (0.108)/- 40.5% and - 2.271 (0.110) /- 43.7% in the single 6 ml Hylan G-F 20 injection and the placebo groups, respectively. Additionally, clinically important reductions in pain at 26 weeks was reported in 67.0 and 68.2% in single 6 ml Hylan G-F 20 injection and placebo groups (p = 0.36). Regarding safety, TEAEs were similar between the two treatment groups (hylan G-F 20 single: 61.5%; placebo: 64.5%). CONCLUSIONS: While the magnitude of the effect of a single 6 ml Hylan G-F 20 injection in this study is consistent with previously published literature with respect to the efficacy and safety of the drug, the current study shows a strong IA placebo effect and did not established superiority of single 6 ml Hylan G-F 20 injection over IA placebo in Chinese knee OA patients. TRIAL REGISTRATION: Prospectively registered Jun 16, 2017 at www.clinicaltrials.gov ( NCT03190369 ).

A Keyhole Approach Centered by Anterior Squamous Suture to Hypertensive Basal Ganglia Hemorrhage.

OBJECTIVE: This study aimed to improve the accuracy and efficacy of the keyhole transsylvian approach to remove hypertensive basal ganglia hemorrhage. The authors presented a stable keyhole craniotomy based on anterior squamous suture to expose insular cortex and basal ganglia. METHODS: Twenty-nine patients with hypertensive basal ganglia hemorrhage were treated with keyhole surgery and studied in Guangdong sanjiu brain hospital. RESULTS: By using a bone suture marked keyhole transsylvian approach, near-complete (90%) hematoma evacuation was achieved in 21 cases (72.4), 70% to 90% in 8 cases (24.1), and less than 70% in 1 case (3.4%). In our cohort, 55.1% (16/29) with good function (GOS score 4-5), 41.3% (12/29) with disability (GOS score 3), and 3.4% (1/29) in a vegetative state (GOS score 2). No patients died within 6 months of operation. CONCLUSIONS: Our method can greatly minimize the bone exposure and precisely located the distal Sylvian fissure. A stable keyhole craniotomy based on bone suture can be identically safe and effective in comparison with classic surgery, and it consumes less time and less intra-operative bleeding.

Dual Delivery of TGF-ß3 and Ghrelin in Microsphere/Hydrogel Systems for Cartilage Regeneration.

Articular cartilage (AC) damage is quite common, but due to AC's poor self-healing ability, the damage can easily develop into osteoarthritis (OA). To solve this problem, we developed a microsphere/hydrogel system that provides two growth factors that promote cartilage repair: transforming growth factor-ß3 (TGF-ß3) to enhance cartilage tissue formation and ghrelin synergy TGF-ß to significantly enhance the chondrogenic differentiation. The hydrogel and microspheres were characterized in vitro, and the biocompatibility of the system was verified. Double emulsion solvent extraction technology (w/o/w) is used to encapsulate TGF-ß3 and ghrelin into microspheres, and these microspheres are encapsulated in a hydrogel to continuously release TGF-ß3 and ghrelin. According to the chondrogenic differentiation ability of mesenchymal stem cells (MSCs) in vitro, the concentrations of the two growth factors were optimized to promote cartilage regeneration.

The Role of Extracellular Vesicles in the Pathogenesis, Diagnosis, and Treatment of Osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease that affects the entire joint and has been a tremendous burden on the health care system worldwide. Although cell therapy has made significant progress in the treatment of OA and cartilage regeneration, there are still a series of problems. Recently, more and more evidence shows that extracellular vesicles (EVs) play an important role in the progression and treatment of OA. Here, we discuss that EVs from different cell sources not only participate in OA progression, but can also be used as effective tools for the diagnosis and treatment of OA. In addition, cell pretreatment strategies and EV tissue engineering play an increasingly prominent role in the field of OA treatment. This article will systematically review the latest developments in these areas. As stated above, it may provide new insights for improving OA and cartilage regeneration.

Clinical-Grade Human Embryonic Stem Cell-Derived Mesenchymal Stromal Cells Ameliorate the Progression of Osteoarthritis in a Rat Model.

Mesenchymalstem cell (MSC)-based therapy is being increasingly explored in preclinical and clinical studies as a regenerative method for treating osteoarthritis (OA). However, the use of primary MSCs is hampered by a number of limitations, including donor heterogeneity and inconsistent cell quality. Here, we tested the therapeutic potential of embryonic stem cell-derived MSCs (ES-MSCs) in anOA rat model. ES-MSCs were generated and identified by morphology, trilineage differentiation and flow cytometry. Sprague Dawley rats were treated with either a single dose (106 cells/rat) of ES-MSCs or with three doses spaced one week apart for each dose, starting at four weeks after anterior cruciate ligament transectionto induce OA. Cartilage quality was evaluated at 6 and 10 weeks after treatment with behavioral analysis, macroscopic examination, and histology. At sixweeks after treatment, the groups treated with both single and repeated doses of ES-MSCs had significantly better modified Mankin scores and International Cartilage Repair Society (ICRS) macroscopic scores in the femoral condyle compared to the control group. At 10 weeks after treatment, the repeated doses group had a significantly better ICRS macroscopic scores in the femoral condyle compared to the single dose and control groups. Histological analysis also showed more proteoglycan and less cartilage loss, along with lower Mankin scores in the repeated doses group. In conclusion, treatment with multiple injections of ES-MSCs can ameliorate OA in a rat model. TheES-MSCs have potential to be considered as a regenerative therapy for OA, and can provide an infinite cellular source.

Level of physical activity among middle-aged and older Chinese people: evidence from the China health and retirement longitudinal study.

BACKGROUND: With data from different regions accumulated, physical inactivity (PI) was found to be pandemic worldwide. Using China Health and Retirement Longitudinal Study (CHARLS), a nationwide longitudinal survey data, we aimed to delineate the prevalence, incidence and risk factors of physical inactivity (PI) among Chinese people aged 45 years and older. METHODS: The CHARLS covered nearly all provinces, autonomous regions, municipalities of mainland China. With data from CHARLS, three cross-sectional analyses and a cohort analysis were conducted. In cross-sectional studies, we used surveys at 2011, 2013 and 2015 to examine the prevalence and its trend of PI. Multivariate generalized linear model was conducted in survey at 2011 to examine the risk factors for prevalent PI. Multiple imputation of missing values was used and results before and after imputation were compared. In cohort analysis, we identified people free of PI at 2011 and followed them up until 2015 to estimate the incidence of PI. Generalized estimating equation was used to examine the risk factors associated with incidence PI. In all analyses, PI was defined as insufficient physical activity according to the International Physical Activity Questionnaire (IPAQ) criterion. RESULTS: 6650, 5946 and 9389 participants were eligible for cross-sectional analyses, and 4525 participants were included for cohort analysis. The weighted prevalence of PI was 22.25% (95% CI: 20.63-23.95%) in 2011, 20.64% (95% CI: 19.22-22.14%) in 2013 and 19.31% (95% CI: 18.28-20.38%) in 2015. In multivariate analysis, PI was associated with older age, higher education, overweight, obesity and difficulties in daily living, and was negatively associated with working and higher level of expenditure. No material change was detected in results after multiple imputation. In cohort analysis, older age, abundant public facilities, difficulties in daily living were identified as risk factors of incidence PI, while urban areas, college and above education, and working were protective factors. CONCLUSIONS: PI is pandemic in 45 years and older people in China. People with older age, difficulties in daily living and people who are not working are at higher risk. More efforts should be paid in estimating and promoting leisure-time physical activities.