Young human plasma-derived extracellular vesicles rescue and reactivate IL-1ß and TNF-α treated chondrocytes.

Osteoarthritis (OA) is a degenerative disease that affects millions of individuals worldwide. Despite its prevalence, the exact causes and mechanisms behind OA are still not fully understood, resulting in a lack of effective treatments to slow down or halt disease progression. Recent research has discovered that extracellular vesicles (EVs) present in the circulation of young mice have a remarkable ability to activate musculoskeletal stem cells in elderly mice. Conversely, EVs derived from elderly mice do not exhibit the same potential, indicating that EVs obtained from young individuals may hold promise to activate aging cells in degenerative tissue. However, it remains unknown whether EVs derived from young individuals can also address cartilage degeneration caused by aging. In this study, we first evaluated EVs derived from young human plasma (YEVs) and EVs derived from old human plasma (OEVs) in an in vitro experiment using chondrocytes. The results revealed that YEVs effectively stimulated chondrocyte proliferation and migration, while OEVs from old plasma did not exhibit a similar effect. Given that OA represents a more complex inflammatory microenvironment, we further determine whether the benefits of YEVs on chondrocytes can be maintained in this context. Our findings indicate that YEVs have the ability to positively regulate chondrocyte function and protect them against apoptosis induced by IL-1ß and TNF-α in an in vitro OA model. Furthermore, we discovered that lyophilized EVs could be stored under mild conditions without any alterations in their physical characteristics. Considering the exceptional therapeutic effects and the wide availability of EVs from young plasma, they hold significant promise as a potential approach to activate chondrocytes and promote cartilage regeneration in early-stage OA.

Metabolic Syndrome Components and Its Impact on Acute Kidney Injury after Total Joint Arthroplasty.

BACKGROUND: Metabolic syndrome (MetS) is an independent risk factor for postoperative complications. This study aimed to evaluate the associated risk of MetS for perioperative complications, especially urinary complications, in patients who underwent primary total knee (TKA) or total hip arthroplasty (THA). METHODS: We used a publicly available all-payer administrative database to identify patients undergoing TKA and THA from 2016 to 2020. The primary exposure of interest was MetS. Multivariable adjusted models based on propensity score matching were used to evaluate the association of MetS components with acute kidney injury (AKI), urinary tract infection (UTI), and acute posthemorrhagic anemia (APHA) in patients who underwent TKA and THA. A Counterfactual-Based Mediation Analysis was conducted to investigate the mediating effect of APHA on the relationship between MetS and AKI. RESULTS: The analysis included 2,097,940 (16.4% with MetS) THA and 3,073,310 (24.0% with MetS) TKA adult hospitalizations. Multivariable adjustment analysis indicated MetS was associated with an increased risk of AKI (OR [odds ratio] 1.78, 95% CI [confidence interval]1.69 to 1.89 for THA; OR 1.88, 95% CI 1.79 to 1.96 for TKA), UTI (OR 1.13, 95% CI 1.03 to 1.23 for THA; OR 1.26, 95% CI 1.17 to 1.35 for TKA), and APHA (OR 1.17, 95% CI 1.14 to 1.20 for THA; OR 1.7, 95% CI 1.15 to 1.19 for TKA). The risk of AKI increased with the number of MetS components, with odds ratios ranging from 2.58 to 9.46 in TKA patients and from 2.22 to 5.75 in THA patients. This increase was particularly associated with diabetes and hypertension, which were the most significant associated risk factors. Furthermore, APHA mediated the association between MetS and AKI. CONCLUSION: The prevalence of MetS is increasing in TKA and THA patients. Metabolic syndrome was associated with increased risk of AKI, UTI, and APHA. The risk of AKI increased with each additional MetS component, with diabetes and hypertension contributing most. In addition, APHA may play a partial mediating role in MetS-induced AKI.

Transcription and proteome changes involved in re-innervation muscle following nerve crush in rats.

Severe peripheral nerve injury leads to the irreparable disruption of nerve fibers. This leads to disruption of synapses with the designated muscle, which consequently go through progressive atrophy and damage of muscle function. The molecular mechanism that underlies the re-innervation process has yet to be evaluated using proteomics or transcriptomics. In the present study, multi-dimensional data were therefore integrated with transcriptome and proteome profiles in order to investigate the mechanism of re-innervation in muscles. Two simulated nerve injury muscle models in the rat tibial nerve were compared: the nerve was either cut (denervated, DN group) or crushed but with the nerve sheath intact (re-innervated, RN group). The control group had a preserved and intact tibial nerve. At 4 weeks, the RN group showed better tibial nerve function and recovery of muscle atrophy compared to the DN group. As the high expression of Myh3, Postn, Col6a1 and Cfi, the RN group demonstrated superior re-innervation as well. Both differentially expressed genes (DEGs) and proteins (DEPs) were enriched in the peroxisome proliferator-activated receptors (PPARs) signaling pathway, as well as the energy metabolism. This study provides basic information regarding DEGs and DEPs during re-innervation-induced muscle atrophy. Furthermore, the crucial genes and proteins can be detected as possible treatment targets in the future.

Hydrogen sulfide protects against particle-induced inflammatory response and osteolysis via SIRT1 pathway in prosthesis loosening.

Wear debris-induced osteolysis and ensuing aseptic loosening is the main cause of implant failure and revision surgery. Wear debris-induced inflammatory response plays key roles in peri-implant osteolysis. Recently, substantial of evidence suggests that hydrogen sulfide (H2 S), the third gasotransmitter, is a critical player regulating inflammation. However, the role and therapeutic potential of H2 S in wear debris-induced inflammation and osteolysis remains to be defined. In the present study, we investigated the effect of H2 S on wear debris-induced pro-inflammatory cytokines expression and osteolysis in vitro and in vivo. With a slow-releasing H2 S donor GYY4137, our study demonstrated that H2 S attenuated wear debris-induced osteolysis and osteoclastogenesis in murine calvaria resorption models. The expression of tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) that stimulated by wear particles were significantly reduced by GYY4137. Further, the level of sirtuin 1 (SIRT1), which possesses anti-inflammation property, was examined in vivo and in macrophages. And we found that wear debris decreased the expression of SIRT1. Cotreated macrophages with GYY4137 in part reversed the decline of SIRT1. More importantly, with the SIRT1 recombinant lentivirus and small interfering RNAs (siRNA) against SIRT1, our data indicated that SIRT1 mediated the inhibitory effects of GYY4137 on wear debris-induced inflammation. Collectively, these results suggested that exogenous H2 S production (via H2 S donors) may represent a potential approach for the treatment of wear particle-induced osteolysis.

The Upregulation of COX2 in Human Degenerated Nucleus Pulposus: The Association of Inflammation with Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is an important risk factor of low back pain. We previously found upregulated markers of fibrosis, the late stage of chronic inflammation, in degenerated IVD with a small number of clinical specimens. Here, we aimed to study on a larger scale the association of cyclooxygenase 2 (COX2), an inflammation and/or pain marker, with IVDD. This study involved 107 LBP participants. The IVD degeneration level was graded on a 1-5 scale according to the Pfirrmann classification system. Discs at grades 1-3 were further grouped as white discs with grades 4-5 as black discs. We recorded baseline information about age, gender, body mass index (BMI), diabetes history, smoking history, and magnetic resonance imaging (MRI). Their association with IVDD was statistically analyzed. The expression level of COX2 was investigated by immunohistochemistry. The total integrated COX2 optical density (IOD), number of COX2-positive cells, and total cell number of each image were counted and analyzed by Image-Pro Plus software. The IOD and number of COX2-positive cells were divided by the total cell number to obtain COX2 expression density (IOD/cell) and COX2 positivity (cell+/cell). As a result, among the baseline information investigated, only age was found to have a significant association with IVDD. The IOD/cell was found to be significantly increased from grade 2 to grade 5, as well as in black discs compared to white discs. The cell+/cell displayed the same trend that it increased in highly degenerative discs compared to their counterparts. In conclusion, the expression of COX2 is associated with IVDD, which highlights COX2 as a biomarker for IVD degeneration and indicates the involvement of inflammation and pain signaling in IVDD.

Alcohol Withdrawal Is Associated With Worse Outcomes in Patients Undergoing Primary Total Knee or Total Hip Arthroplasty.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Prior bariatric surgery and perioperative cardiovascular outcomes following noncardiac surgery in patients with type 2 diabetes mellitus: hint from National Inpatient Sample Database.

BACKGROUND: Both 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). METHODS: We 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. RESULTS: A 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 < 0.0001). Patients with prior BS were younger, were more likely to be female, and had lower rates of cardiovascular risk factors but had higher rates of smoking, alcohol abuse, anaemia, prior venous thromboembolism and prior percutaneous coronary intervention. The incidence of MACCEs was 1.01% and 3.25% in patients with prior BS and morbid obesity, respectively. After multivariable adjustment, we found that prior BS was associated with a reduced risk of MACCEs (odds ratio [OR] = 0.71; 95% confidence interval [CI] 0.62-0.81), death (OR = 0.64, 95% CI 0.52-0.78), acute kidney injury (OR = 0.66, 95% CI 0.62-0.70) and acute respiratory failure (OR: 0.46; 95% CI 0.42-0.50). CONCLUSIONS: Prior 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.

How to predict early clinical outcomes and evaluate the quality of primary total knee arthroplasty: a new scoring system based on lower-extremity angles of alignment.

BACKGROUND: A method that can accurately predict the outcome of surgery can give patients timely feedback. In addition, to some extent, an objective evaluation method can help the surgeon quickly summarize the patient's surgical experience and lessen dependence on the long wait for follow-up results. However, there was still no precise tool to predict clinical outcomes of total knee arthroplasty (TKA). This study aimed to develop a scoring system to predict clinical results of TKA and then grade the quality of TKA. METHODS: We retrospectively reviewed 98 primary TKAs performed between April 2013 and March 2017 to determine predictors of clinical outcomes among lower-extremity angles of alignment. Applying multivariable linear-regression analysis, we built Models (i) and (ii) to predict detailed clinical outcomes which were evaluated using the Knee Society Score (KSS). Multivariable logistic-regression analysis was used to establish Model (iii) to predict probability of getting a good clinical outcome (PGGCO) which was evaluated by Knee Injury and Osteoarthritis Outcome Score (KOOS) score. Finally, we designed a new scoring system consisting of 3 prediction models and presented a method of grading TKA quality. Thirty primary TKAs between April and December 2017 were enrolled for external validation. RESULTS: We set up a scoring system consisting of 3 models. The interpretations of Model (i) and (ii) were good (R2 = 0.756 and 0.764, respectively). Model (iii) displayed good discrimination, with an area under the curve (AUC) of 0.936, and good calibration according to the calibration curve. Quality of surgery was stratified as follows: "A" = PGGCO ≥0.8, "B" = PGGCO ≤0.6 but < 0.8, and "C" = PGGCO < 0.6. The scoring system performed well in external validation. CONCLUSIONS: This study first developed a validated, evidence-based scoring system based on lower-extremity angles of alignment to predict early clinical outcomes and to objectively evaluate the quality of TKA.

Impact of Bariatric Surgery on Inpatient Complication, Cost, and Length of Stay Following Total Hip or Knee Arthroplasty.

BACKGROUND: Morbid obesity is an important risk factor for arthroplasty and also closely associated with worse postoperative outcomes. Bariatric surgery is effective in losing weight and decreasing comorbidities associated with obesity. However, no study had demonstrated the influence of bariatric surgery on the outcome of arthroplasty in a large population. METHODS: We used 2006-2014 discharge records from the Nationwide Inpatient Sample, and identified study population and inpatient complications by International Classification of Diseases, 9th Revision, Clinical Modification diagnosis/procedure codes. Propensity score analysis was used to match total hip arthroplasty (THA) or total knee arthroplasty (TKA) patients with morbid obesity and THA or TKA patients with bariatric surgery. RESULTS: Proportion of morbid obesity in both TKA and THA patients demonstrated a rising trend, while proportion of bariatric surgery in morbidly obese TKA and THA patients remains steady after 2007. For THA patients, there was fewer pulmonary embolism, more blood transfusion and anemia, and shorter length of stay in bariatric surgery group. For TKA patients, bariatric surgery group had a lower risk of pulmonary embolism, respiratory complications, death, and shorter length of stay, but bariatric surgery group had a higher risk of blood transfusion and anemia. CONCLUSION: There is evidence that bariatric surgery prior to arthroplasty, especially THA, appears to reduce rates of pulmonary complications and length of stay. But anemia and blood transfusion seem to be more common in patients with prior bariatric surgery.

Epigenetic pattern changes in prenatal female Sprague-Dawley rats following exposure to androgen.

Androgen excess is generally considered to be one of the major characteristics of polycystic ovary syndrome (PCOS). Evidence from both clinical research and animal studies has revealed that this syndrome may have fetal origins, with epigenetics being proposed as the underlying mechanism. Our PCOS rat model induced by prenatal administration of 3mg testosterone from Embryonic Day (E) 16 to E19 showed polycystic ovaries, irregular oestrous cycles and endocrine disorders in adulthood. The methylation status of 16, 8 and 4 cytosine-phosphate-guanine (CpG) sites in the promoter regions of the androgen receptor (Ar), cytochrome P450 family 11, subfamily A, polypeptide 1 (Cyp11a1) and cytochrome P450, family 17, subfamily A, polypeptide 1 (Cyp17a1) genes, respectively, were measured by pyrosequencing. We identified three hypomethylated sites (CpG +58, +65 and +150) in Ar and one hypomethylated site (CpG +1016) in Cyp11a1 in peripheral blood cells of prenatally androgenised (PNA) rats. In ovarian tissue, five CpG sites of Ar (CpG +87, +91, +93, +98, +150) and one single CpG site in Cyp11a1 (CpG +953) were significantly hypomethylated in PNA rats, but the modified methylation of these two genes may not be sufficient to significantly alter levels of gene expression. Furthermore, tissue-specific methylation analysis revealed that both Ar and Cyp11a1 exhibited significant hypomethylation in testis in contrast with ovary and blood. PNA may lead to methylation pattern changes and the development of PCOS, but further studies are required to reveal causal relationships.

Can statins reduce risk of lung cancer, especially among elderly people? A meta-analysis.

OBJECTIVE: As the most common cause of cancer mortality throughout the world, lung cancer has drawn people's attention on how to reduce the risk with chemopreventive ways. Many epidemiological studies have shown inconsistent effects of statins on lung cancer, but some observational studies have showed that statins had protective effect on lung cancer among elderly people. So we preformed this meta-analysis to find whether statins were chemopreventive. METHODS: We searched MEDLINE, EMBASE and Web of Science databases from inception to September, 2013. A total of 23 studies were selected, including 15 observational studies and 8 randomized controlled trials (RCTs). Both fixed and random-effects models were used to calculate pooled estimates in primary and sensitivity analyses. We used Q and I(2) statistics to assess statistical heterogeneity, and evaluated publication bias by Begg's test and Egger's test. RESULTS: No association between statins and lung cancer risk was identified either in the meta-analysis among RCTs [relative risk (RR): 0.95, 95% confidence interval (95% CI): 0.85-1.06] or observational studies (RR: 0.89, 95% CI: 0.77-1.04). We also selected 6 observational studies that all researched on elderly people. The result of meta-analysis showed that there was still no protective effect between statins and lung cancer among elderly people (RR: 1.03, 95% CI: 0.96-1.11). CONCLUSIONS: Our results did not support a protective effect of statins on the overall lung cancer risk and the lung cancer risk among elderly people. More well-designed RCTs are needed to enhance our understanding of the chemopreventive effect of statins on lung cancer.

In situ fabrication of an anisotropic double-layer hydrogel as a bio-scaffold for repairing articular cartilage and subchondral bone injuries.

Articular cartilage is a smooth and elastic connective tissue playing load-bearing and lubricating roles in the human body. Normal articular cartilage comprises no blood vessels, lymphatic vessels, nerves, or undifferentiated cells, so damage self-repair is very unlikely. The injuries of articular cartilage are often accompanied by damage to the subchondral bone. The subchondral bone mainly provides mechanical support for the joint, and the successful repair of articular cartilage depends on the ability of the subchondral bone to provide a suitable environment. Currently, conventional repair treatments for articular cartilage and subchondral bone defects can hardly achieve good results due to the poor self-repairing ability of the cartilage Here, we propose a bioactive injectable double-layer hydrogel to repair articular cartilage and subchondral bone. The hydrogel scaffold mimics the multilayer structure of articular cartilage and subchondral bone. Agarose was used as a common base material for the double-layer hydrogel scaffold, in which a sodium alginate (SA)/agarose layer was used for the repair of artificially produced subchondral bone defects, while a decellularized extracellular matrix (dECM)/agarose layer was used for the repair of articular cartilage defects. The double-layer hydrogel scaffold is injectable, easy to use, and can fill in the damaged area. The hydrogel scaffold is also anisotropic both chemically and structurally. Animal experiments showed that the surface of the new cartilage tissue in the double-layer hydrogel scaffold group was closest to normal articular cartilage, with a structure similar to that of hyaline cartilage and a preliminary calcified layer. Moreover, the new subchondral bone in this group exhibited many regular bone trabeculae, and the new cartilage and subchondral bone were mechanically bound without mutual intrusion and tightly integrated with the surrounding tissue. The continuous double-layer hydrogel scaffold prepared in this study mimics the multilayer structure of articular cartilage and subchondral bone and promotes the functional repair of articular cartilage and subchondral bone, favoring close integration between the newborn tissue and the original tissue.

Baseline Knee Pain Predicts Long-Term Response of Intra-Articular Steroid Injection in Symptomatic Knee Osteoarthritis: Data from OAI.

OBJECTIVE: The current study aims to investigate the factors that could predict response to intra-articular corticosteroid injection (IACI) in patients with knee osteoarthritis (KOA). METHODS: Data of participants were retrieved from the Osteoarthritis Initiative database. Participants with at least one IACI treatment on single or bilateral knees within the first 5 years of follow-up were retrospectively included. Demographic data, clinical and radiographic variables were collected at both baseline and the first follow-up after IACI treatment. Positive response to IACI treatment was defined as >20% reduction of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score from V0 to V1. All the variables with P < 0.2 after the comparison between the response and non-response groups were included in a multivariable logistic regression model to identify independent response predictive patient-specific valuables. Receiver operating characteristic curves were performed to establish the cutoff values of independent predictors. RESULTS: The current study included a total of 385 participants (473 knees), with 155 and 318 knees classified into the response group and non-response group, respectively. Those with satisfied responses to IACI treatment had significantly higher WOMAC pain score (P < 0.001), disability score (P = 0.002), and stiffness score (P = 0.015) at the baseline. Baseline WOMAC pain score showed significant association with positive response to IACI treatment in multivariate logistic analysis and the best cutoff value was 5 points. The rate of analgesics utilization was lower (P = 0.014) in the response group than the non-response group after the IACI treatment. CONCLUSION: KOA patients with a baseline WOMAC pain score ≥5 are more likely to benefit from IACI treatment.

Protein-energy malnutrition and worse outcomes after major cancer surgery: A nationwide analysis.

Background: Protein-energy malnutrition (PEM) has been recognized as a poor prognostic factor in many clinical issues. However, nationwide population studies concerning the impact of PEM on outcomes after major cancer surgery (MCS) are lacking. We aimed to evaluate the postoperative outcomes associated with PEM following MCS. Methods: By using the Nationwide Inpatient Sample database, data of patients undergoing MCS including colectomy, cystectomy, esophagectomy, gastrectomy, hysterectomy, lung resection, pancreatectomy, or prostatectomy were analyzed retrospectively from 2009 to 2015, resulting in a weighted estimate of 1,335,681 patients. The prevalence trend of PEM, as well as mortality and major complications after MCS were calculated. Multivariable regression analysis was applied to estimate the impact of PEM on postoperative outcomes after MCS. Results: PEM showed an estimated annual percentage increase of 7.17% (95% confidence interval (CI): 4-10.44%) from 2009 to 2015, which contrasts with a 4.52% (95% CI: -6.58-2.41%) and 1.21% (95% CI: -1.85-0.56%) annual decrease in mortality and major complications in patients with PEM after MCS. PEM was associated with increased risk of mortality (odds ratio (OR)=2.26; 95% CI: 2.08-2.44; P < 0.0001), major complications (OR=2.46; 95% CI: 2.36-2.56; P < 0.0001), higher total cost ($35814 [$22292, $59579] vs. $16825 [$11393, $24164], P < 0.0001), and longer length of stay (14 [9-21] days vs. 4 [2-7] days, P < 0.0001), especially in patients underwent prostatectomy, hysterectomy and lung resection. Conclusions: PEM was associated with increased worse outcomes after major cancer surgery. Early identification and timely medical treatment of PEM for patients with cancer are crucial for improving postoperative outcomes.

Bone turnover biomarkers predict one-year all-cause mortality and walking ability in geriatric hip fracture patients.

PURPOSE: To investigate the utility of serum C-terminal cross-linking telopeptides (ß-CTX) and procollagen type I N propeptide (PINP) for predicting one-year mortality and walking ability in Chinese geriatric hip fracture patients who underwent surgical interventions. METHOD: Elderly patients (≥ 60 years) who underwent surgical interventions for unilateral low-energy hip fracture from 2015 to 2020 in our center were included. Demographic data was retrospectively retrieved from the electronic medical database. The PINP and ß-CTX concentrations were measured before the surgery. The patients were divided into two groups according to the outcome of mortality and walking ability after hip surgery, respectively. ß-CTX and PINP were divided into four grades based on quartiles [Quartile(Q)1-4] for further analysis. All the variables with p < 0.1 in univariable analysis were included in a multivariable model. RESULTS: In univariable analysis, the levels of serum ß-CTX (p = 0.007) and PINP (p = 0.025) was associated with one-year mortality, while the association between levels of serum ß-CTX (p = 0.072) or PINP (p = 0.055) with one-year disability was marginally significant. After adjustment for confounders, the relative risk [OR (95 % CI), Q4 v sQ1, p-value] of one-year mortality and one-year disability were 7.28 (2.08-29.78, p = 0.003) and 3.97 (1.44-11.69, p = 0.009) for ß-CTX and 5.87 (1.70-23.80, p = 0.008) and 3.48 (1.30-9.93, p = 0.016) for PINP, respectively. The coefficient of determination, AUC and bias-corrected C-index of predictive models based on previously reported predictors were significantly improved after integrating ß-CTX or PINP. CONCLUSION: Higher serum ß-CTX and PINP are independently associated with an increased risk of one-year mortality and disability in patients with hip fractures. The application of BTMs improves the performance of currently available predictive models.

Nano wear particles and the periprosthetic microenvironment in aseptic loosening induced osteolysis following joint arthroplasty.

Joint arthroplasty is an option for end-stage septic arthritis due to joint infection after effective control of infection. However, complications such as osteolysis and aseptic loosening can arise afterwards due to wear and tear caused by high joint activity after surgery, necessitating joint revision. Some studies on tissue pathology after prosthesis implantation have identified various cell populations involved in the process. However, these studies have often overlooked the complexity of the altered periprosthetic microenvironment, especially the role of nano wear particles in the etiology of osteolysis and aseptic loosening. To address this gap, we propose the concept of the "prosthetic microenvironment". In this perspective, we first summarize the histological changes in the periprosthetic tissue from prosthetic implantation to aseptic loosening, then analyze the cellular components in the periprosthetic microenvironment post prosthetic implantation. We further elucidate the interactions among cells within periprosthetic tissues, and display the impact of wear particles on the disturbed periprosthetic microenvironments. Moreover, we explore the origins of disease states arising from imbalances in the homeostasis of the periprosthetic microenvironment. The aim of this review is to summarize the role of relevant factors in the microenvironment of the periprosthetic tissues, in an attempt to contribute to the development of innovative treatments to manage this common complication of joint replacement surgery.

Contralateral advanced radiographic knee osteoarthritis predicts radiographic progression and future arthroplasty in ipsilateral knee with early-stage osteoarthritis.

PURPOSE: To explore whether the severity of contralateral knee osteoarthritis (OA) is associated with OA progression in ipsilateral knee with early OA. METHODS: Knees in early OA (Kellgren-Lawrence grade (KLG):1-2) with intact baseline demographic and clinical data were retrieved from OAI database and defined as target knees. The target knees were divided into the exposure group (contralateral knees KLG 3 to 4) and the control group (contralateral knees KLG 0 to 2). Both groups underwent propensity score matching (PSM) concerning demographic data, as well as radiographic and clinical outcomes at the baseline. The primary outcome was the upgrade of KLG in the target knee in the first 12 and 24 months. The secondary outcome was the incidence of knee arthroplasty in ipsilateral knee during the first 108 months. RESULTS: One thousand seven hundred fifty-two knees were included, with 449 in the exposure cohort and 1276 in the control cohort. Four hundred thirty-four knees in each group were matched after PSM. Target knees in the exposure cohort showed a significantly higher rate of radiographic progression in the first 12 months (12.9% vs. 5.1%, P < 0.001) and 24 months (19.6% vs. 8.1%, P < 0.001). As for the risk of future arthroplasty, a significant difference was also found between the two groups (7.8% vs. 4.0%, P = 0.02). Kaplan-Meier analysis showed that the 108-month accumulated knee survival rate was significantly lower in the exposure group (P = 0.01). CONCLUSION: The ipsilateral knee with early-stage OA is prone to have worse early to mid-, and long-term prognosis in the circumstance of contralateral radiographic advanced knee OA. Key Points •Identifying early knee osteoarthritis (OA) with a high risk of radiographic progression and future arthroplasty enables early personalized intervention. •This is a novel study to investigate the relationship between the risk of future arthroplasty and contralateral knee status. •Propensity score matching holds promise to minimize selection bias in observational studies. •Knees with early OA are prone to have a high risk of radiographic progression and future arthroplasty in the circumstance of contralateral advanced knee OA.

Anisotropic hydrogel fabricated by controlled diffusion as a bio-scaffold for the regeneration of cartilage injury.

Controlled fabrication of anisotropic materials has become a hotspot in materials science, particularly biomaterials, since the next generation of tissue engineering is based on the application of heterogeneous structures that can simulate the original biological complexity of the body. The current fabrication method of producing anisotropic materials involves expensive and highly specialized equipment, and not every conventional method can be applied to preparing anisotropic materials for corresponding tissue engineering. Anisotropic materials can be easily applied to a problem in tissue engineering: cartilage injury repairing. The articular cartilage consists of four spatially distinct regions: superficial, transitional, deep, and calcified. Each region has a specific extracellular matrix composition, mechanical properties, and cellular organization; this calls for the application of an anisotropic hydrogel. Controlled diffusion, under the assistance of buoyancy, has been considered a generalized method to prepare materials using a gradient. The diffusion of two solutions can be controlled through the difference in their densities. In addition to providing anisotropy, this method realizes the in situ formation of an anisotropic hydrogel, and simplifies the preparation process, freeing it from the need for expensive equipment such as 3D printing and microfluidics. Herein, an anisotropic hydrogel based on a decellularized extracellular matrix is fabricated and characterized. The as-prepared scaffold possessed specific chemical composition, physical properties, and physiological factor gradient. In vitro experiments ensured its biocompatibility and biological effectiveness; further in vivo experiments confirmed its application in the effective regeneration of cartilage injury.

Brain morphology changes after spinal cord injury: A voxel-based meta-analysis.

Objectives: Spinal cord injury (SCI) remodels the brain structure and alters brain function. To identify specific changes in brain gray matter volume (GMV) and white matter volume (WMV) following SCI, we conducted a voxel-based meta-analysis of whole-brain voxel-based morphometry (VBM) studies. Methods: We performed a comprehensive literature search on VBM studies that compared SCI patients and healthy controls in PubMed, Web of Science and the China National Knowledge Infrastructure from 1980 to April 2022. Then, we conducted a voxel-based meta-analysis using seed-based d mapping with permutation of subject images (SDM-PSI). Meta-regression analysis was performed to identify the effects of clinical characteristics. Results: Our study collected 20 studies with 22 GMV datasets and 15 WMV datasets, including 410 patients and 406 healthy controls. Compared with healthy controls, SCI patients showed significant GMV loss in the left insula and bilateral thalamus and significant WMV loss in the bilateral corticospinal tract (CST). Additionally, a higher motor score and pinprick score were positively related to greater GMV in the right postcentral gyrus, whereas a positive relationship was observed between the light touch score and the bilateral postcentral gyrus. Conclusion: Atrophy in the thalamus and bilateral CST suggest that SCI may trigger neurodegeneration changes in the sensory and motor pathways. Furthermore, atrophy of the left insula may indicate depression and neuropathic pain in SCI patients. These indicators of structural abnormalities could serve as neuroimaging biomarkers for evaluating the prognosis and treatment effect, as well as for monitoring disease progression. The application of neuroimaging biomarkers in the brain for SCI may also lead to personalized treatment strategies. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021279716, identifier: CRD42021279716.

Nanosecond pulsed electric fields prime mesenchymal stem cells to peptide ghrelin and enhance chondrogenesis and osteochondral defect repair in vivo.

Mesenchymal stem cells (MSCs) are important cell sources in cartilage tissue development and homeostasis, and multiple strategies have been developed to improve MSCs chondrogenic differentiation with an aim of promoting cartilage regeneration. Here we report the effects of combining nanosecond pulsed electric fields (nsPEFs) followed by treatment with ghrelin (a hormone that stimulates release of growth hormone) to regulate chondrogenesis of MSCs. nsPEFs and ghrelin were observed to separately enhance the chondrogenesis of MSCs, and the effects were significantly enhanced when the bioelectric stimulation and hormone were combined, which in turn improved osteochondral tissue repair of these cells within Sprague Dawley rats. We further found that nsPEFs can prime MSCs to be more receptive to subsequent stimuli of differentiation by upregulated Oct4/Nanog and activated JNK signaling pathway. Ghrelin initiated chondrogenic differentiation by activation of ERK1/2 signaling pathway, and RNA-seq results indicated 243 genes were regulated, and JAK-STAT signaling pathway was involved. Interestingly, the sequential order of applying these two stimuli is critical, with nsPEFs pretreatment followed by ghrelin enhanced chondrogenesis of MSCs in vitro and subsequent cartilage regeneration in vivo, but not vice versa. This synergistic prochondrogenic effects provide us new insights and strategies for future cell-based therapies.