A young woman with atypical McCune-Albright syndrome and the difficult road to recovery: a case report.

Background: Fiber dysplasia is a complex condition that presents with various clinical manifestations, such as deformity, dysfunction, pathological fractures, and endocrine disorders. McCune-Albright syndrome (MAS) is a rare subtype of fiber dysplasia. This article reports a case of atypical McCune-Albright syndrome in a patient with a femoral neck fracture. Case presentation: A patient with atypical McCune-Albright syndrome sustained a right femoral neck fracture and underwent multiple treatments, including total hip replacement, intravenous infusion of zoledronic acid, oral calcium supplementation, right supracondylar osteotomy, orthopedic surgery, plate and screw internal fixation for a left femoral shaft fracture, and removal of the right femoral plate. The patient also developed a submaxillary infection complicated by mandibular osteonecrosis. Conclusion: Patients with MAS may experience rare complications as a result of their unique condition, regardless of whether they receive drug or surgical treatment. Therefore, personalized drug regimens and feasible surgical options are necessary.

Engineering extracellular vesicles mimetics for targeted chemotherapy of drug-resistant ovary cancer.

Aim: To develop nanocarriers for targeting the delivery of chemotherapeutics to overcome multidrug-resistant ovarian cancer. Materials & methods: Doxorubicin-loaded nanovesicles were obtained through serial extrusion, followed by loading of P-glycoprotein siRNA and folic acid. The targeting ability and anticancer efficacy of the nanovesicles were evaluated. Results: The doxorubicin-loaded nanovesicles showed a high production yield. The presence of P-glycoprotein siRNA and folic acid resulted in reversed drug resistance and tumor targeting. This nanoplatform tremendously inhibited the viability of multidrug-resistant ovarian cancer cells, which was able to target tumor tissue and suppress tumor growth without adverse effects. Conclusion: These bioengineered nanovesicles could serve as novel extracellular vesicles mimetics for chemotherapeutics delivery to overcome multidrug resistance.

When treating cancer affecting the ovaries, which is an organ in the female reproductive system, two challenges that arise are the inefficient delivery of chemotherapeutic drugs and the development of drug resistance inside the tumor. In this study, very small nano-scale particles called nanovesicles, which contain a chemotherapeutic drug called doxorubicin, were developed in an attempt to overcome both of these concerns. These nanovesicles were secreted by a healthy cell from an ovary, isolated and loaded with doxorubicin. These nanovesicles were also loaded with siRNA, which, in this case, prevents the synthesis of a protein in ovarian tumor cells called P-glycoprotein. This protein is responsible for pumping chemotherapy drugs back out of tumor cells, so preventing its synthesis was intended to counter chemotherapeutic resistance. The targeting ability of the nanovesicle was also enhanced with folic acid, as folic acid receptors are present on the surface of these tumor cells in higher numbers. These nanovesicles were readily and specifically taken up by ovarian tumor cells in mice with induced ovarian cancer. This reversed drug resistance and enhanced the toxic effects of doxorubicin on the tumor cells, which, in turn, increased tumor cell death and prevented tumor cell migration. No obvious adverse effect was found in mice treated with the nanovesicle system compared with the free chemotherapy drug with critical systematic toxicity. This research provides new avenues for ovarian cancer treatment, with combined therapies of siRNAs and chemotherapeutic drugs, targeted to tumor cells specifically, within nanovesicles.

A Femoral Neck Osteotomy for the Patients with Ankylosing Spondylitis and Thoracolumbar Kyphosis Combined with Hip Flexion Contracture.

OBJECTIVE: The surgical treatment of patients with ankylosing spondylitis and severe thoracolumbar kyphosis combined with hip flexion contracture is very difficult for all the surgeons. The femoral neck osteotomy (FNO) is the first step to break the ice. The evaluation of a new modified FNO method is very important to improve the curative effect. METHODS: Five male patients with nine bone-fused hips who underwent the new femoral neck osteotomy were included from October 2021 to March 2022. The FNO was designed that the saw blade was manipulated from the lateral femoral neck base to the inferior part of the femoral head, keeping Pauwels' angle less than 30° on the coronal plane. On the transverse plane, the angle between the saw blade and the coronal plane was more than 15°. On the sagittal plane, the saw blade cut through the femoral neck. They accepted pedicle subtraction osteotomy (PSO) after FNO according to the patient' recovery. Then, 2 weeks later, the patients underwent total hip arthroplasty (THA). The visual analogue scale (VAS), Harris hip score (HHS) and passive hip flexion-extension range of motion (ROM) were used to evaluate hip function. The data were analyzed by paired t-test. RESULTS: The average operation time and blood loss of FNO, the average interval between FNO and THA were collected. The average angle of the trunk and lower limb (ATL) was 36.33° ± 16.36° pre-FNO, 82.89° ± 13.51° post-FNO and 175.22° ± 3.42° post-THA. The average VAS scores were 0 pre-FNO, 5 ± 1.58 post-FNO and 2.6 ± 0.55 post-THA. The average HHS was 43.56 ± 1.59 preoperatively and 83.89 ± 2.21 postoperatively. The average hip extension ROM was 23.89° ± 12.69° pre-FNO, -22.67° ± 14.18° post-FNO and - 3.33° ± 2.50 post-THA°. The average hip flexion ROM was 23.89° ± 12.69° pre-FNO, 35.56° ± 12.11° post-FNO and 104.44° ± 5.27° post-THA. The differences among them were significant (p < 0.05). Only one hip (11.11%) displaced completely after FNO. CONCLUSION: A new modified FNO was developed, which can provide osteotomy with a certain degree of stability and greater ease for performing PSO and THA.

Clinical Approach to Inconclusive Subscapularis Tear Diagnosis: a Meta-analysis.

To identify factors associated with subscapularis (SSC) tears and provide a theoretical basis for clinical diagnosis, we included studies related to subscapularis tears published before February 1, 2023. We screened for six predictors across previous studies for the meta-analysis. The predictors included age, sex, coracoid overlap (CO), coracohumeral distance (CHD), impairment of the long head of the biceps tendon (LHB), and dominant arm. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the studies. The risk ratios (RRs) and the weighted mean differences (WMDs) were used to evaluate the effect size of categorical variables and continuous variables, respectively. The Egger test was used to assess the publication bias of the studies. Ten studies were included from seven countries. A total of 2 126 patients were enrolled, of whom 1 041 had subscapularis tears and 1 085 did not. The study showed that age (WMD, 4.23 [95% CI, 2.32-6.15]; P<.00001), coracoid overlap (WMD, 1.98 [95% CI, 1.55-2.41]; P<.00001), coracohumeral distance(WMD, -1.03 [95% CI, -1.17- -0.88]; P<.00001), and an injury of the long head of the biceps tendon (RR, 4.98 [95% CI, 3.75-6.61]; P<.00001) were risk factors for subscapularis tears. These risk factors can help clinicians identify subscapularis tears early and select appropriate interventions. The level of evidence is 3.

Reduction quality in lateral view of X-ray and hypoalbuminemia are associated with postoperative mortality in elderly pertrochanteric fracture patients.

Background: Pertrochanteric fracture is one of the most prevalent public health issues across the world for the elderly population. The purpose of this study was to investigate the association between surgical factors and postoperative mortality in patients with intramedullary nail-treated pertrochanteric fractures. Methods: A retrospective cohort study was designed to evaluate the pertrochanteric fracture patients treated with intramedullary nail between January 2016 to February 2021. The surgical factors included the Dorr morphology, Arbeitsgemeinschaft für Osteosynthesefragen/Orthopedic Trauma Association (AO/OTA) classification of fractures, the tip-apex distance (TAD), location of the cephalic screw, reduction quality in anterior-posterior (AP) and lateral views, the integrity of the lateral wall, and the design of cephalic screws. Using univariate and multivariate Cox proportional hazard models, the association between these risk factors and postoperative mortality in patients with this type of fractures was evaluated. Results: A total of 169 pertrochanteric fracture patients treated with intramedullary nails were included in our study, with the average age of 82.68±5.93 years. The mortality rates at 3 months, 1 year, and the end of follow-up were 4.14%, 11.24%, and 26.04%, respectively. According to the univariate Cox analysis, age, gender, preoperative levels of hemoglobin (Hb) and albumin (Alb) were associated with a poor overall survival (OS) (P<0.05). After multivariate adjustment, the pre-operative level of Alb (P<0.001) and the reduction in lateral view (P<0.001) were shown to be independent risk factors for poor OS. Conclusions: The preoperative hypoalbuminemia and reduction quality in lateral view were associated with postoperative mortality in our study. Therefore, optimizing both parameters could improve the prognosis in elderly pertrochanteric fracture patients.

A Higher Postoperative Barthel Index at Discharge is Associated with a Lower One-Year Mortality After Hip Fracture Surgery for Geriatric Patients: A Retrospective Case‒Control Study.

Purpose: To evaluate the relationship between the postoperative Barthel index assessing activities of daily living at discharge and the one-year mortality after hip fracture surgery. Methods: Patients with hip fracture admitted to Peking University First Hospital from January 2015 to January 2020 were enrolled retrospectively according to the inclusion and exclusion criteria. The Barthel index and other related confounding variables were collected. Logistic regression and Kaplan‒Meier survival curves were constructed to explore the relationship between the postoperative Barthel index at discharge and the one-year mortality of geriatric patients after hip fracture surgery. Results: A total of 444 patients with a mean age of 81.61±6.14 years were included. A significant difference was not observed in the preoperative Barthel index at admission between the deceased group and the surviving group (38.90±15.83 vs 36.96±10.74, p=0.446). However, the difference in the postoperative Barthel index at discharge between these two groups was statistically significant (43.08±14.40 vs 53.18±13.43, P<0.001). The multivariable logistic regression analysis revealed that the postoperative Barthel index at discharge was an independent risk factor for one-year mortality after adjustment for confounding variables (adjusted OR 0.73, 95% CI 0.55-0.98, p˂0.05). The Kaplan‒Meier survival curve showed that patients who had a high Barthel index (≥50) at discharge had a significantly lower mortality in the long term than patients with a low Barthel index (<50) at discharge (P< 0.001). Conclusion: The postoperative Barthel index at discharge was independently associated with the one-year mortality of geriatric patients after hip fracture surgery. A higher postoperative Barthel index at discharge indicated a lower mortality after hip fracture surgery. The Barthel index at discharge has the potential to provide essential prognostic information for early risk stratification and directing future care.

Incidence and predictors of postoperative acute kidney injury in older adults with hip fractures.

OBJECTIVES: Main Purpose: To clarify the incidence and predictors of acute kidney injury (AKI) after hip fracture surgery; Secondary Purpose: To investigate the impact of AKI on the length of stay (LOS) and mortality of patients. METHODS: We retrospectively evaluated data from 644 hip fracture patients at Peking University First Hospital from 2015 to 2021, and divided the patients into AKI and Non-AKI groups according to whether AKI occurred after surgery. Logistic regression was used to clarify the risk factors for AKI, draw ROC curves, and analyze the odds ratio (OR) for LOS and death at 30 days, 3 months, and 1 year for patients with AKI. RESULTS: The prevalence of AKI after hip fracture was 12.1%. Age, BMI, and postoperative brain natriuretic peptide (BNP) levels were risk factors for AKI after hip fracture surgery. The risk of AKI in underweight patients, overweight patients and obese patients was 2.24, 1.89, and 2.58 times. Compared to patients with BNP levels <800 pg/ml, the risk of AKI was 22.34-fold for postoperative BNP levels>1500 pg/ml. The risk of a one-grade increase in LOS was 2.84 times higher in the AKI group and the mortality of patients with AKI were higher. CONCLUSION: The incidence of AKI after hip fracture surgery was 12.1%. Advanced age, low BMI, and postoperative high level BNP were risk factors for AKI. Surgeons need to pay more attention to patients with older age, low BMI and high postoperative BNP levels in order to proactively prevent the development of postoperative AKI.

Construction and Validation of a Nomogram for Predicting Acute Kidney Injury After Hip Fracture Surgery.

Background: Acute kidney injury (AKI), characterized by sudden impairment of kidney function, is an uncommon complication following hip fracture surgery that is associated with increased morbidity and mortality. We constructed a nomogram to stratify patients according to risk of AKI after hip fracture surgery to guide clinicians in the implementation of timely interventions. Methods: Patients who received hip fracture surgery from January 2015 to December 2021 were retrospectively identified and divided into a training set (n=448, surgery from January 2015 to December 2019) and a validation set (n=200, surgery from January 2020 to December 2021). Univariate and multivariate logistic regression were used to identify risk factors for AKI after surgery in the training set. A nomogram was constructed based the risk factors for AKI, and was evaluated by receiver operating characteristic (ROC) analysis, calibration curves, and decision curve analysis (DCA). Results: The mean age was 82.0±6.22 years-old and the prevalence of post-surgical AKI was 13.3%. Age, American Society of Anesthesiologists (ASA) score, the preexistence of chronic kidney disease (CKD), cemented surgery and the decrease of hemoglobin on the first day after surgery were identified as independent risk factors of AKI after hip fracture surgery, and a predictive nomogram was established based on the multivariable model. The predictive nomogram had good discrimination ability (training set: AUC: 0.784, 95% CI: 0.720-0.848; validation set: AUC: 0.804, 95% CI: 0.704-0.903), and showed good validation ability and clinical usefulness based on a calibration plot and decision curve analysis. Conclusion: A nomogram that incorporated five risk factors including age, ASA score, preexisting CKD, cemented surgery and the decrease of hemoglobin on the first day after surgery had good predictive performance and discrimination. Use of our results for early stratification and intervention has the potential to improve the outcomes of patients receiving hip fracture surgery. Future large, multicenter cohorts are needed to verify the model's performance.

Obese elderly patients with hip fractures may have better survival outcomes after surgery.

BACKGROUND: In recent years, there has been an increasing amount of research on the "obesity paradox". So our primary objective was to explore whether this phenomenon exists in our study, and secondary objective was to determine the effect of body mass index (BMI) on major complications, and the incidence of acute kidney injury (AKI) after hip fracture surgery after controlling for confounding factors. METHODS: We included patients over 70 years old with hip fracture who were admitted to the Department of Orthopedics, Peking University First Hospital between 2015 and 2021. Patients were classified as underweight (UW, < 18.5 kg/m2), normal weight (NW, 18.5-24.9 kg/m2), overweight (OW, 25.0-29.9 kg/m2) and obese (OB, ≥ 30.0 kg/m2). We analyzed demographic characteristics, operation information and postoperative outcomes. Using multivariate regression with normal-weight patients as the reference, we determined the odds of 1-year mortality, major complications, and AKI by BMI category. RESULTS: A total of 644 patients were included. Nine percent of patients died after 1 year, 18% had major postoperative complications, and 12% had AKI. There was a U-shaped relationship between BMI and the rates of major complications or AKI. However, there was a linear decreasing relationship between 1-year mortality and BMI. After controlling for confounding factors, multivariate regression analysis showed that the risk of 1-year mortality after surgery was 2.24 times higher in underweight patients than in normal-weight patients (P < 0.05, OR: 2.24, 95% CI 1.14-4.42). Compared with normal-weight patients, underweight patients had a 2.07 times increased risk of major complications (P < 0.05, OR 2.07, 95% CI 1.21-3.55), and the risk of major complications in obese patients was 2.57 times higher than that in normal-weight patients (P < 0.05, OR 2.57, 95% CI 1.09-6.09). Compared with normal-weight, underweight patients had a 2.18 times increased risk of AKI (P < 0.05, OR 2.18, 95% CI 1.17-4.05). CONCLUSIONS: The 1-year mortality risk of patients with higher BMI was significantly reduced. Besides, compared with normal-weight patients, underweight patients and obese patients have a higher risk of major complications; low-weight and obese patients are at higher risk for AKI.

C-reactive protein (CRP)/albumin-to-globulin ratio (AGR) is a valuable test for diagnosing periprosthetic joint infection: a single-center retrospective study.

BACKGROUND: The diagnosis of periprosthetic joint infection (PJI) is challenging for clinicians, and the commonly used methods are too complicated and expensive for many clinical practices. The neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the platelet-to-mean-platelet-volume ratio (PVR), globulin (GLB), the albumin-to-globulin ratio (AGR), and the C-reactive protein (CRP)/AGR ratio are simple biomarkers for infection and can be easily determined from routine blood tests. Due to their low cost and ready availability in clinical practice, many clinicians have considered the diagnostic value of these biomarkers for PJI. The aim of our study is to determine the value of NLR, PLR, PVR, GLB, AGR, and CRP/AGR for the diagnosis of PJI. MATERIALS AND METHODS: One hundred sixty-four patients who received revision surgery after total knee or total hip replacements were enrolled, 47 in a PJI group and 117 in an aseptic failure group. Receiver operating characteristic (ROC) analysis was used to evaluate the performance of NLR, PLR, PVR, GLB, AGR, and CRP/AGR for the diagnosis of PJI, and their performance levels were then compared with those of CRP and the erythrocyte sedimentation rate (ESR). RESULTS: The levels of all tested biomarkers were significantly higher in patients with PJI (all P < 0.05). ROC analysis showed that CRP/AGR performed best in diagnosing PJI, with an area under curve (AUC) value of 0.902, and the AUCs of NLR (0.740), PLR (0.721), PVR (0.668), GLB (0.719), and AGR (0.767) were all lower than those for CRP (0.896) and ESR (0.829). CONCLUSION: CRP/AGR was a valuable test for diagnosing PJI, but other novel biomarkers had only limited diagnostic value. LEVEL OF EVIDENCE: Level III.

Endoplasmic reticulum stress triggered autophagy and regulated the phenotype transformation of rheumatoid arthritis synovial fibroblasts via the IRE1/JNK pathway.

Background: Previous studies have indicated that endoplasmic reticulum (ER) stress may actively promote the pathogenesis of rheumatoid arthritis (RA) by evoking autophagy. However, the underlying mechanism remains largely unknown. This study aimed to explore the mechanism of the ER stress-autophagy pathway in regulating the phenotype transformation of rheumatoid arthritis synovial fibroblasts (RASFs). Methods: Synovial tissue was obtained from RA and osteoarthritis (OA) patients during joint replacement surgery. ER stress/autophagy signature markers were examined in synovial tissue by real-time quantitative polymerase chain reaction (RT-PCR), western blot, and immunohistochemistry. Phenotype transformation of RASFs, including increased cell proliferation and invasion capability, was measured by CCK-8 assay and transwell invasion assay. Signaling pathways were further investigated and inositol requiring enzyme 1 (IRE1) was down-regulated in RASFs by transfecting specific short hairpin RNA-ERN1 (shRNA-ERN1) carried by lentiviral vectors. Results: The expression of ER stress/autophagy pathway-associated proteins, including GRP78, IRE1, protein kinase R-like endoplasmic reticulum kinase (PERK), and LC3, was significantly increased in RA synovium compared with OA synovium. After stimulation with tumor necrosis factor alpha (TNF-α) in vitro, the proliferation and invasion ability of RASFs were upregulated, while this phenomenon could be inhibited by 4-PBA (ER stress inhibitor) or 3-MA (autophagy inhibitor). The expression of IRE1 and p-JNK in particular, occurred in an obviously time-dependent manner after stimulation with TNF-α. Moreover, the proliferation and invasion of RASFs were inhibited after transfection with sh-RNA-ERN1 to downregulate IRE1 expression. Conclusions: ER stress triggered autophagy via the IRE1/JNK pathway to regulate the phenotype transformation of RASFs, indicating an important role of the ER stress-autophagy pathway in the pathological process of synovitis in RA.

Prognostic nomogram for risk of mortality after hip fracture surgery in geriatrics.

PURPOSE: Hip fracture is a significant public health problem, with associated high morbidity and mortality. Orthopedic surgeons are concerned to improve prognosis and stratify mortality risk after hip fracture surgery. This study established a nomogram that combines the Charlson Comorbidity Index (CCI) with specific laboratory parameters to predict mortality risk after hip fracture surgery in geriatrics. METHODS: The records of consecutive patients who underwent hip fracture surgery from January 2015 through May 2020 at one medical center were reviewed for perioperative factors and mortality. Patients with age ≥ 70 years who were diagnosed with intertrochanteric or femoral neck fractures were included. Patients who were diagnosed with pathological fracture, received only conservative treatment or lost to follow-up were excluded. A multivariate Cox proportional hazards regression model was used to identify risk factors. A nomogram was established with R software and evaluated using concordance (C)-index, area under receiver operating characteristic (AUC), calibration curves, and decision curve analysis (DCA). RESULTS: In total, 454 patients were included with a mean age of 81.6 years. The mean follow-up and one-year mortality rate were 37.2 months and 10.4%, respectively. Five identified risk variables for mortality after hip fracture surgery in geriatrics comprised age (HR 1.05, 95% CI 1.01-1.08; P = 0.003), CCI (HR 1.38, 95% CI 1.24-1.54; P = 0.000), albumin (HR 1.78, 95% CI 1.31-2.43; P = 0.000), sodium (HR 1.59, 95% CI 1.18-2.15; P = 0.002) and hemoglobin (HR 1.46, 95% CI 1.07-2.00; P = 0.02). A nomogram was proposed and evaluated, showing a C-index of 0.76 ± 0.02. The AUCs for 6-month, 1-year, and 3-year mortality predictions were 0.83, 0.79, and 0.77, respectively. The calibration curve and DCA showed good discrimination and clinical usefulness. CONCLUSION: This novel nomogram for stratifying the mortality risk after hip fracture surgery in geriatrics incorporated age, CCI, serum albumin, sodium, and hemoglobin. Internal validation indicated that the model has good accuracy and usefulness. This nomogram had improved convenience and precision compared with other models. External validation is warranted to confirm its performance.

2021 revised algorithm for the management of knee osteoarthritis-the Chinese viewpoint.

AIM: The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) algorithm for the management of knee osteoarthritis (OA) is available worldwide from 2014, but in 2019 an update was published. Based on this algorithm, a Working Group (WG), including ESCEO members and Chinese experts, wished to see how the new ESCEO algorithm was perceived by Chinese experts in knee OA and how it was integrated into their clinical practice. METHODS: A WG was held between members of the international ESCEO task force and a group of Chinese experts. RESULTS: Non-pharmacological approach should be combined with pharmacological interventions. In step 1, symptomatic slow-acting drugs for osteoarthritis (SYSADOA) are the most important background drugs. Evidence, supported by high-quality research, is available only for crystalline glucosamine sulfate (pCGS) and chondroitin sulfate. Topical NSAIDs could be used as an additional option. In step 2, oral NSAIDs could be useful, but cardiovascular/renal/gastrointestinal profiles of the patients should be considered. Intra-articular hyaluronic acid and corticosteroids are alternative to oral NSAIDs, but the evidence is still limited. If steps 1 and 2 are not sufficient, weak opioids could be used. Overall, the conclusions of the ESCEO algorithm are accepted in China for products available in this country. The WG suggests the importance of economic studies, specifically made in China. CONCLUSION: This work provides evidence-based advice to establish a treatment algorithm in knee OA, for practical implementation in clinical practice in China.

Fibrinogen performs better than D-dimer for the diagnosis of periprosthetic joint infection: a meta-analysis of diagnostic trials.

PURPOSE: D-dimer and fibrinogen, both belonging to coagulation parameters, are controversial for the diagnosis of periprosthetic joint infection (PJI). This meta-analysis was conducted to compare their diagnostic accuracies for PJI by synthesizing currently available evidence. METHODS: Cochrane Library, MEDLINE, Web of Science, and Embase up to March 1, 2020, and other relevant articles were searched. Five hundred and eighty-one articles were identified after initial research, and 11 studies were included finally. No threshold effects were found between studies. The pooled sensitivity, specificity, and positive and negative likelihood ratio were reported to evaluate the diagnostic performance with heterogeneity analysis. Z test statistics was used to analyze the difference of diagnostic performance between D-dimer and fibrinogen. RESULTS: The pooled sensitivity, specificity, and positive and negative likelihood ratio of D-dimer for PJI were 0.79 (95% [CI], 0.72-0.85), 0.77 (0.67-0.84), 3.38 (2.21-5.18), and 0.27 (0.18-0.41), respectively. As for fibrinogen, the pooled sensitivity, specificity, and positive and negative likelihood ratio for PJI were 0.75 (0.68-0.80), 0.85 (0.82-0.88), 5.12 (4.22-6.22), and 0.30 (0.23-0.37), respectively. Great heterogeneity was found in studies for D-dimer, and univariate meta-regression analysis revealed that number of involved joints, disease spectrum, comorbidities influencing D-dimer, and sample sources were the source of heterogeneity. Z test found that the pooled specificity of fibrinogen was significantly higher than D-dimer (0.85 ± 0.01 versus 0.77 ± 0.04, p = 0.03). The pooled positive likelihood ratio of fibrinogen was significantly higher than D-dimer (5.12 ± 0.51 versus 3.38 ± 0.74, p = 0.03). CONCLUSION: Based on currently available evidence, the meta-analysis suggests that fibrinogen performs better than D-dimer as a rule-in diagnostic tool for its higher specificity. However, more prospective trials with larger size are still needed to provide further confirmation. TRIAL REGISTRATION: This meta-analysis was prospectively registered on PROSPERO (International prospective register of systematic reviews), and the registering number was CRD42020177176 .

Efficacy and Safety of Lower Limb Progressive Resistance Exercise for Patients With Total Knee Arthroplasty: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To evaluate the efficacy and safety of progressive resistance exercise (PRE) for patients with total knee arthroplasty (TKA) in a meta-analysis. DATA SOURCES: PubMed, MEDLINE, Cochrane's Library, and EMBASE databases. STUDY SELECTION: Randomized controlled trials evaluating the effect of PRE on mobility and function in patients with TKA. DATA EXTRACTION: A random-effects model was applied if significant heterogeneity was detected; otherwise, a fixed-effects model was applied. DATA SYNTHESIS: Seven randomized controlled trials. Compared with a rehabilitation program without PRE, physiotherapy including PRE was associated with improvements in the 6-minute walking test (weighed mean difference [WMD], 19.22m; P=.04) with a wide confidence interval (CI, 0.48∼37.95). However, sensitivity analysis by omitting 1 study with preoperative rehabilitation revealed nonsignificant results (WMD, 15.15m; P=.16). Moreover, PRE did not significantly improve the maximal walking speed (WMD, 0.05m/s, 95% CI, 0.00∼0.11; P=.05). However, PRE was associated with improved knee strength of extension (standardized mean difference [SMD], 0.72; 95% CI, 0.47∼0.96; P<.001) and flexion (SMD, 0.47; 95% CI, 0.19∼0.74; P<.001) but not self-reported physical function (SMD, -0.17; 95% CI, -0.37∼0.03; P=.10) or changes in pain score (SMD, 0.11; 95% CI, -0.15∼0.37; P=.40). PRE did not increase the risk of adverse events (risk ratio, 1.19; 95% CI, 0.52∼2.71; P=.68). CONCLUSIONS: PRE may lead to improvements in physical function among patients receiving a TKA. PRE leads to higher ultimate strength in the surgical knee and is safe to perform.

Dexmedetomidine as an adjunct to local anesthetics in nerve block relieved pain more effectively after TKA: a meta-analysis of randomized controlled trials.

BACKGROUND: Dexmedetomidine has shown potential in pain control in patients undergoing total knee arthroplasty (TKA). However, the combination of nerve block and dexmedetomidine may be a preferred alternative for postoperative analgesia after TKA. The aim of this study was to perform a meta-analysis on existing randomized controlled trials (RCTs) to determine the efficacy and safety of dexmedetomidine as an adjunct to local anesthetics in nerve block after TKA. METHODS: A literature survey was conducted in the databases of PubMed, Embase, Cochrane Library, Web of science, and ScienceDirect for the RCTs completed before February 1st, 2020 that met pre-specified inclusion criteria. The primary outcomes included the pain scores, duration of analgesia, opioid consumption within 24 h postoperatively, and the level of patient satisfaction. The secondary outcomes included the motor strength, degree of sedation, postoperative nausea and vomiting, and other related complications. The methodological quality was assessed by the Cochrane risk of bias tool. RESULTS: The initial literature search yielded 143 studies, out of which seven studies met the inclusion criteria. The pooled data indicated that dexmedetomidine combined with local anesthetics in nerve block in TKA decreased the postoperative pain scores at rest as well as at motion (SMD = - 1.01 [95% CI - 1.29 to - 0.72], p < 0.01; SMD = - 1.01 [- 1.25 to - 0.77], p < 0.01) respectively, decreased the total opioid consumption within 24 h (SMD = - 0.63 [- 0.86 to - 0.40], p < 0.01), prolonged the duration of analgesia (SMD = 0.90 [0.64 to 1.17], p < 0.01), improved motor strength (SMD = 0.23 [0.01 to 0.45], p = 0.04), improved the degree of sedation (SMD = 0.94 [0.70 to 1.18], p < 0.01), and increased the level of patient satisfaction (SMD = 0.88 [0.60 to 1.17], p < 0.01) without increasing nausea and vomiting (RD = - 0.05 [- 0.11 to 0.01], p = 0.14), as well as other complications (RD = - 0.01 [- 0.08 to 0.07], p = 0.89), compared with local anesthetics alone. CONCLUSIONS: It is effective and safe for dexmedetomidine as an adjunct to local anesthetics in nerve block in TKA to relieve postoperative pain, decrease total opioid consumption, prolong analgesic duration, and increase patient satisfaction without increasing related complications. Based on the quality of evidence, this meta-analysis recommends that dexmedetomidine can be used in a regular treatment regimen and as an adjunct addition to local anesthetics in nerve block for patients undergoing TKA. REGISTRATION: This meta-analysis was prospectively registered on PROSPERO (International prospective register of systematic reviews) and the registering number was CRD42020169171.

Triggering of Apoptosis in Osteosarcoma 143B Cell Line by Carbon Quantum Dots via the Mitochondrial Apoptotic Signal Pathway.

OBJECTIVES: Carbon-based nanomaterials have gained attention in the field of biomedicine in recent years, especially for the treatment of complicated diseases such as cancer. Here, we report a novel carbon-based nanomaterial, named carbon quantum dots (CQDs), which has potential for cancer therapy. We performed a systematic study on the effects of CQDs on the osteosarcoma 143B cell line in vitro and in vivo. METHODS: Cell counting assay, the neutral red assay, lactic dehydrogenase assay, and fluorescein isothiocyanate (FITC) Annexin V/Propidium iodide (PI) were used to detect the cytotoxicity and apoptosis of CQDs on the 143B cell line. Intracellular reactive oxygen species (ROS) were detected by the oxidation-sensitive fluorescent probe 2',7'-dichlorofluorescein diacetate. The JC-10 assay was used to detect the mitochondrial membrane potential (MMP) of 143B cells incubated with CQDs. The effects of CQDs on the 143B cell line were evaluated by Western blot and immunofluorescence analysis of apoptosis-related proteins Bax, Bcl-2, cytochrome-C, caspase-3, cleaved-caspase-3, PARP1, and cleaved-PARP1. Male tumor-bearing BALB/c nude mice were used to investigate the antitumor effects of CQDs, and the biosafety of CQDs in vivo was tested in male BALB/c mice by measuring weight changes, hematology tests, and histological analyses of major organs. RESULTS: CQDs exhibited a high cytotoxicity and induced apoptosis toward the 143B cell line. CQDs can also significantly increase the intracellular level of ROS and lower the mitochondrial membrane potential levels of 143B cells. CQDs increase apoptotic protein expression to induce apoptosis of 143B cells by triggering the mitochondrial apoptotic signaling pathway. The tumor volume in the CQD-treated mice was smaller than that in the control group, the tumor volume inhibition rate was 38.9%, and the inhibitory rate by tumor weight was 30.1%. All biosafety test indexes were within reference ranges, and neither necrosis nor inflammation was observed in major organs. CONCLUSIONS: CQDs induced cytotoxicity in the 143B cell line through the mitochondrial apoptotic signaling pathway. CQDs not only showed an antitumor effect but also high biocompatibility in vivo. As a new carbon-based nanomaterial, CQDs usage is a promising method for novel cancer treatments.

Mitochondrial transfer from bone-marrow-derived mesenchymal stromal cells to chondrocytes protects against cartilage degenerative mitochondrial dysfunction in rats chondrocytes.

BACKGROUND: Previous studies have reported that mitochondrial dysfunction participates in the pathological process of osteoarthritis (OA). However, studies that improve mitochondrial function are rare in OA. Mitochondrial transfer from mesenchymal stem cells (MSCs) to OA chondrocytes might be a cell-based therapy for the improvement of mitochondrial function to prevent cartilage degeneration. This study aimed to determine whether MSCs can donate mitochondria and protect the mitochondrial function and therefore reduce cartilage degeneration. METHODS: Bone-marrow-derived mesenchymal stromal cells (BM-MSCs) were harvested from the marrow cavities of femurs and tibia in young rats. OA chondrocytes were gathered from the femoral and tibial plateau in old OA model rats. BM-MSCs and OA chondrocytes were co-cultured and mitochondrial transfer from BM-MSCs to chondrocytes was identified. Chondrocytes with mitochondria transferred from BM-MSCs were selected by fluorescence-activated cell sorting. Mitochondrial function of these cells, including mitochondrial membrane potential (Δψm), the activity of mitochondrial respiratory chain (MRC) enzymes, and adenosine triphosphate (ATP) content were quantified and compared to OA chondrocytes without mitochondrial transfer. Chondrocytes proliferation, apoptosis, and secretion ability were also analyzed between the two groups. RESULTS: Mitochondrial transfer was found from BM-MSCs to OA chondrocytes. Chondrocytes with mitochondrial from MSCs (MSCs + OA group) showed increased mitochondrial membrane potential compared with OA chondrocytes without mitochondria transfer (OA group) (1.79 ±â€Š0.19 vs. 0.71 ±â€Š0.12, t = 10.42, P < 0.0001). The activity of MRC enzymes, including MRC complex I, II, III, and citrate synthase was also improved (P < 0.05). The content of ATP in MSCs + OA group was significantly higher than that in OA group (161.90 ±â€Š13.49 vs. 87.62 ±â€Š11.07 nmol/mg, t = 8.515, P < 0.0001). Meanwhile, we observed decreased cell apoptosis (7.09% ±â€Š0.68% vs.15.89% ±â€Š1.30%, t = 13.39, P < 0.0001) and increased relative secretion of type II collagen (2.01 ±â€Š0.14 vs.1.06 ±â€Š0.11, t = 9.141, P = 0.0008) and proteoglycan protein (2.08 ±â€Š0.20 vs. 0.97 ±â€Š0.12, t = 8.227, P = 0.0012) in MSCs + OA group, contrasted with OA group. CONCLUSIONS: Mitochondrial transfer from BM-MSCs provided protection for OA chondrocytes against mitochondrial dysfunction and degeneration through improving mitochondrial function, cell proliferation, and inhibiting apoptosis in chondrocytes. This finding may offer a new therapeutic direction for OA.