Malignancy progression and treatment efficacy estimation of osteosarcoma patients based on in vitro cell culture model and analysis.

BACKGROUND: Osteosarcoma (OS) usually happens in patients under 20 years old and is notorious for its low survivorship and limb loss. Personalized medicine is a viable approach to increase the efficiency of chemotherapy which is the main prognostic factor for survivorship after surgical treatment. METHODS: In this five-year prospective observational study, we collected primary cells of osteosarcoma from 15 patients, and examined the correlation between clinical characters of patients and cell properties characterized using various in vitro assays. The properties including genes expression, pro-angiogenic capability and anti-cancer drug response are characterized respectively by using RT-PCR, tube formation assay, osteogenesis assay and drug testing on 3D tumor spheroid model. RESULT: The results suggest that OS patients with higher MMP9 expression levels have higher probability to develop skip metastasis (p = 0.041). The 3D tumor spheroid test based on the median lethal dose from 2D culture provides some prognostic value. Patients do not response well to methotrexate (MTX) show higher percentage of high pathology grade (p = 0.009) and lung metastasis (p = 0.044). Also, patients respond well to ifosfamide (IFO) have higher probability to achieve high tumor necrosis rate (p = 0.007). CONCLUSION: The association between cell properties and clinical characters of patients provided by our data can act as potential prognostic factors to help physicians to develop effective personalized chemotherapy for osteosarcoma treatments.

Age-adjusted Charlson Comorbidity Index as an effective tool for the choice between simultaneous or staged bilateral total knee arthroplasty.

INTRODUCTION: The choice between simultaneous and staged bilateral total knee arthroplasty (BTKA) remains controversial. Age-adjusted Charlson Comorbidity Index(CCI) is a promising tool for risk-stratification. We aimed to compare the outcomes between patients who underwent simultaneous and staged BTKA, stratified by age-adjusted CCI scores. MATERIALS AND METHODS: We conducted this retrospective, single-surgeon case series from 2010 to 2020. This study consisted of 1558 simultaneous BTKA and 786 staged BTKA procedures. The outcome domains included 30-day and 90-day readmission and 1-year reoperation events. We performed multivariate regression analysis to compare the risk of readmission and reoperation following simultaneous and staged BTKA. Other factors included age, sex, body mass index, diabetes mellitus, rheumatoid arthritis, smoking, receiving thromboprophylaxis and blood transfusion. RESULTS: The rates of 30-day, 90-day readmission and 1-year reoperation following simultaneous BTKA was 1.99%, 2.70% and 0.71%, respectively. The rates of 30-day, 90-day readmission and 1-year reoperation following staged BTKA was 0.89%, 1.78% and 0.89%, respectively. For patients with age-adjusted CCI ≥ 4 points, simultaneous BTKA was associated with a higher risk of 30-day (aOR:3.369, 95% CI:0.990-11.466) and 90-day readmission (aOR:2.310, 95% CI:0.942-5.668). In patients with age-adjusted CCI ≤ 3 points, the risk of readmission and reoperation was not different between simultaneous or staged BTKA. CONCLUSION: Simultaneous BTKA was associated with an increased risk of short-term readmissions in patients with age-adjusted CCI ≥ 4 points but not in those with age-adjusted CCI ≤ 3 points. Age-adjusted CCI can be an effective index for the choice between simultaneous and staged BTKA procedures.

Enhancing COVID-19 booster vaccination among the elderly through text message reminders.

The BOOST (Booster promotion for older outpatients using SMS text reminders) program at Taipei Veterans General Hospital assessed the effectiveness of text message reminders in enhancing COVID-19 booster vaccination rates among the elderly, guided by the Health Belief Model (HBM). Targeting patients aged 65 and above, eligible yet unvaccinated for a COVID-19 booster, this cohort study sent personalized reminders a week prior to their scheduled appointments between April 18, 2022, and May 12, 2022, acting as cues to action to enhance vaccination uptake by overcoming perceived barriers and raising awareness of benefits. Over 5 weeks, the study observed a 38% increase in vaccination rate among 3,500 eligible patients, markedly surpassing the concurrent national rate increase of 4% for the same demographic. The majority of vaccinations occurred within two weeks after the reminder, illustrating the effectiveness of the strategy. Cox regression analysis identified age and time since last vaccination as significant predictors of responsiveness, with those aged 65-74 and 75-84 showing higher uptake, particularly when reminders were sent within 4 months after the last dose. A single reminder proved to be effective. The findings of this study demonstrate the potential of SMS reminders to promote COVID-19 vaccination among the elderly through the strategic use of HBM principles, suggesting a feasible and effective approach to public health communication.

The cementless taper wedge vs. fit-and-fill stem in primary total hip arthroplasty: risk of stem-related complication differs across Dorr types.

INTRODUCTION: The choice between a cementless taper wedge stem and a fit-and-fill stem in total Hip arthroplasty (THA) for various proximal femoral morphological types has not been thoroughly evaluated. This study aimed to compare the risk of stem-related complications between these two stem types in Dorr type A, B, and C femurs. MATERIALS AND METHODS: From January 2015 through April 2021, we retrospectively reviewed 1995 cementless THA procedures. We stratified all procedures into three groups: Dorr type A (N = 360, 18.0%), B (N = 1489, 74.7%) and C (N = 146, 7.3%). The primary outcome domain was stem-related complications, including stem subsidence ≥ 3 mm, intraoperative fracture, periprosthetic fracture and aseptic stem loosening. We performed multivariate regression analysis to compare the risk of stem-related complication between the two stem types. Other factors included age, sex, body mass index, diagnosis, age-adjusted Charlson comorbidity index, stem alignment and canal fill ratio. RESULTS: The incidence of stem-related complications in the taper wedge and fit-and-fill stem groups was 4.4% (N = 15) and 6.5% (N = 107), respectively. Fit-and-fill stems showed an increased risk of stem-related complications (aOR: 9.903, 95% CI: 1.567-62.597) only in Dorr type C femurs. No significant difference in risk was observed in Dorr type A and B femurs. Furthermore, the canal fill ratio at the lesser trochanter, 2 cm and 7 cm below the lesser trochanter, did not exhibit an association with stem-related complications in any Dorr type. CONCLUSIONS: Concerning the risk of stem-related complications, the taper wedge stem was a better choice in Dorr type C femurs. However, there was no difference in risk between the taper wedge stem and fit-and-fill stem in Dorr type A and B femurs.

Development and evaluation of a usable blastocyst predictive model using the biomechanical properties of human oocytes.

PURPOSE: The purposes of this study were to determine whether biomechanical properties of mature oocytes could predict usable blastocyst formation better than morphological information or maternal factors, and to demonstrate the safety of the aspiration measurement procedure used to determine the biomechanical properties of oocytes. METHODS: A prospective split cohort study was conducted with patients from two IVF clinics who underwent in vitro fertilization. Each patient's oocytes were randomly divided into a measurement group and a control group. The aspiration depth into a micropipette was measured, and the biomechanical properties were derived. Oocyte fertilization, day 3 morphology, and blastocyst development were observed and compared between measured and unmeasured cohorts. A predictive classifier was trained to predict usable blastocyst formation and compared to the predictions of four experienced embryologists. RESULTS: 68 patients and their corresponding 1252 oocytes were included in the study. In the safety analyses, there was no significant difference between the cohorts for fertilization, while the day 3 and 5 embryo development were not negatively affected. Four embryologists predicted usable blastocyst development based on oocyte morphology with an average accuracy of 44% while the predictive classifier achieved an accuracy of 71%. Retaining the variables necessary for normal fertilization, only data from successfully fertilized oocytes were used, resulting in a classifier an accuracy of 81%. CONCLUSIONS: To date, there is no standard guideline or technique to aid in the selection of oocytes that have a higher likelihood of developing into usable blastocysts, which are chosen for transfer or vitrification. This study provides a comprehensive workflow of extracting biomechanical properties and building a predictive classifier using these properties to predict mature oocytes' developmental potential. The classifier has greater accuracy in predicting the formation of usable blastocysts than the predictions provided by morphological information or maternal factors. The measurement procedure did not negatively affect embryo culture outcomes. While further analysis is necessary, this study shows the potential of using biomechanical properties of oocytes to predict embryo developmental outcomes.

Risk factors for venous thromboembolism after primary total joint arthroplasty: An analysis of 7511 Taiwanese patients.

BACKGROUND: The need for thromboprophylaxis in Asian patients after primary total joint arthroplasty (TJA) remains inconclusive. We aimed to identify the risk factors for venous thromboembolism (VTE) events following primary TJA in a Taiwanese population. METHODS: From January 2010 to December 2019, we studied 7511 patients receiving primary TJA from a single surgeon. We validated the incidence and risk factors for 30- and 90-day symptomatic VTE events, including age, sex, body mass index (BMI), smoking, medical comorbidities, VTE history, presence of varicose veins, total knee arthroplasty (TKA) vs total hip arthroplasty (THA), unilateral vs bilateral procedure and receipt of VTE prophylaxis, transfusion, and length of stay. RESULTS: The incidence of 30- and 90-day symptomatic VTE events was 0.33% and 0.44%, respectively. Multivariate regression analysis showed that BMI ≥30 (adjusted odds ratio (aOR): 4.862, 95% CI, 1.776-13.313), bilateral TJA procedure (aOR: 2.665, 95% CI, 1.000-7.104), and presence of varicose veins (aOR: 9.946, 95% CI, 1.099-90.024) were associated with increased odds of 30-day symptomatic VTE events. Age ≥77 years (aOR, 2.358, 95% CI, 1.034-5.381) and BMI ≥30 (aOR: 2.832, 95% CI, 1.039-7.721) were associated with increased odds of 90-day symptomatic VTE events. CONCLUSION: Age ≥77 years, BMI ≥30, bilateral TJA procedure, or presence of varicose veins may require pharmacological thromboprophylaxis because such patients have a higher risk of VTE after primary TJA.

Development of a Novel Endometrial Signature Based on Endometrial microRNA for Determining the Optimal Timing for Embryo Transfer.

Though tremendous advances have been made in the field of in vitro fertilization (IVF), a portion of patients are still affected by embryo implantation failure issues. One of the most significant factors contributing to implantation failure is a uterine condition called displaced window of implantation (WOI), which refers to an unsynchronized endometrium and embryo transfer time for IVF patients. Previous studies have shown that microRNAs (miRNAs) can be important biomarkers in the reproductive process. In this study, we aim to develop a miRNA-based classifier to identify the WOI for optimal time for embryo transfer. A reproductive-related PanelChip® was used to obtain the miRNA expression profiles from the 200 patients who underwent IVF treatment. In total, 143 out of the 167 miRNAs with amplification signals across 90% of the expression profiles were utilized to build a miRNA-based classifier. The microRNA-based classifier identified the optimal timing for embryo transfer with an accuracy of 93.9%, a sensitivity of 85.3%, and a specificity of 92.4% in the training set, and an accuracy of 88.5% in the testing set, showing high promise in accurately identifying the WOI for the optimal timing for embryo transfer.

Advanced TiO2/Al2O3 Bilayer ALD Coatings for Improved Lithium-Rich Layered Oxide Electrodes.

Surface modification is a highly effective strategy for addressing issues in lithium-rich layered oxide (LLO) cathodes, including phase transformation, particle cracking, oxygen gas release, and transition-metal ion dissolution. Existing single-/double-layer coating strategies face drawbacks such as poor component contact and complexity. Herein, we present the results of a low-temperature atomic layer deposition (ALD) process for creating a TiO2/Al2O3 bilayer on composite cathodes made of AS200 (Li1.08Ni0.34Co0.08Mn0.5O2). Electrochemical analysis demonstrates that TiO2/Al2O3-coated LLO electrodes exhibit improved discharge capacities and enhanced capacity retention compared with uncoated samples. The TAA-5/AS200 bilayer-coated electrode, in particular, demonstrates exceptional capacity retention (∼90.4%) and a specific discharge capacity of 146 mAh g-1 after 100 cycles at 1C within the voltage range of 2.2 to 4.6 V. The coated electrodes also show reduced voltage decay, lower surface film resistance, and improved interfacial charge transfer resistances, contributing to enhanced stability. The ALD-deposited TiO2/Al2O3 bilayer coatings exhibit promising potential for advancing the electrochemical performance of lithium-rich layered oxide cathodes in lithium-ion batteries.

Safety and Tolerability of Intra-Articular Injection of Adipose-Derived Mesenchymal Stem Cells GXCPC1 in 11 Subjects With Knee Osteoarthritis: A Nonrandomized Pilot Study Without a Control Arm.

The current study aimed to determine the safety profile of intra-articular-injected allogeneic adipose-derived mesenchymal stem cells (ADSCs) GXCPC1 in subjects with knee osteoarthritis (OA) and its preliminary efficacy outcome. The 3 + 3 phase I study was designed with two dose-escalation cohorts: low dose (6.7 × 106 GXCPC1, N = 5) and high dose (4 × 107 GXCPC1, N = 6). The primary endpoint was safety, which was evaluated by recording adverse events throughout the trial; the secondary endpoints included total, pain, stiffness, and function subscales of the Western Ontario and McMaster Universities Arthritis Index (WOMAC), Visual Analogue Scale (VAS) for pain, and 12-Item Short Form (SF-12) health survey questionnaire. The GXCPC1 treatment was found to be safe after 1 year of follow-up with no treatment-related severe adverse events observed. When compared to baseline, subjects in both the low- and high-dose cohorts demonstrated improving trends in pain and knee function after receiving GXCPC1 treatment. Generally, the net change in pain (95% confidence interval (CI) = -7.773 to -2.561t at 12 weeks compared to baseline) and knee function (95% CI = -24.297 to -10.036t at 12 weeks compared to baseline) was better in subjects receiving high-dose GXCPC1. Although this study included a limited number of subjects without a placebo arm, it showed that the intra-articular injection of ADSCs was safe and well-tolerated in subjects with therapeutic alternatives to treat knee OA. However, a larger scale study with an appropriate control would be necessary for clinical efficacy in the following study.

Weight Gain and Increased Body Mass Index in Patients with Hepatitis C after Eradication Using Direct-Acting Antiviral Therapy in Taiwan.

Few studies have reported weight gain in patients with hepatitis C virus (HCV) infection treated with direct-acting antiviral agents (DAAs). This retrospective cohort study identified factors associated with substantial weight gain after DAA treatment in Taiwan. This study involved patients treated using DAAs at the Chiayi and Yunlin branches of Chang Gung Memorial Hospital from 1 January 2017 to 31 October 2020. Body weight data were collected at the start of DAA therapy and 2 years after the confirmation of a sustained virologic response. We performed multiple logistic regression to evaluate the clinical and laboratory parameters associated with a large body mass index (BMI) increase (≥5%). The mean BMI was 25.56 ± 4.07 kg/m2 at baseline and 25.77 ± 4.29 kg/m2 at the endpoint (p = 0.005). A considerable reduction in fibrosis-4 (FIB-4) score was a significant predictor of a large BMI increase (OR: 1.168; 95% CI: 1.047-1.304, p = 0.006). By contrast, older age (OR: 0.979; 95% CI: 0.963-0.996, p = 0.013) and a higher baseline BMI (OR: 0.907; 95% CI: 0.863-0.954, p < 0.001) were associated with a reduced risk of a large increase in BMI at the endpoint. In summary, a larger BMI increase was closely associated with a younger age, lower baseline BMI, and higher FIB-4 score reduction. Notably, differences in DAA regimens did not affect outcomes. Future studies are needed to elucidate the long-term effects and metabolic outcomes associated with this body weight change and investigate the exact underlying mechanisms.

A therapeutic dose and its pharmacokinetics of ropeginterferon Alfa-2b for hepatitis C treatment.

AIM: Ropeginterferon alfa-2b is a novel mono-pegylated proline-interferon. Its biweekly dosing schema has demonstrated tolerability and clinical efficacy for treating chronic hepatitis in previous clinical studies. This trial evaluates the pharmacokinetics of 400 µg ropeginterferon alfa-2b in patients with chronic hepatitis C virus (HCV) and provides the data to support the clinical utility of ropeginterferon alfa-2b at 400 µg. METHODS: Seventeen patients with chronic HCV genotype 2 were enrolled to receive a single injection of 400 µg ropeginterferon alfa-2b plus 14-day treatment of ribavirin. Pharmacokinetics, safety, and HCV RNA reduction/clearance were assessed. RESULTS: Tmax was 154.003 h and T1/2 was 114.273 h. The Cmax was 29.823 ng mL-1. AUClast was 9364.292 h∗ng mL-1 and AUCinf was 11084.317 h∗ng mL-1. All adverse events were mild or moderate, and there were no serious adverse events. A 1000-fold reduction in the geometric mean of HCV RNA was observed 14 d after the single injection of ropeginterferon alfa-2b. Two patients achieved clearance of HCV RNA, and the other five patients had HCV RNA levels lower than 200 IU mL-1. CONCLUSION: Ropeginterferon alfa-2b at 400 µg led to PK exposures associated with safety and notable clinical activity in patients with chronic HCV. This study suggests that ropeginterferon alfa-2b at 400 µg is an acceptable dosing regimen for treating chronic HCV and also provides supporting data for the clinical use of ropeginterferon alfa-2b at a higher starting dose for other indications.

Perioperative complications of using freezing nitrogen ethanol composite to treat bone tumors: Clinical experience from a single center.

BACKGROUND: The cryoablation efficacy of semisolid freezing nitrogen ethanol composite (FNEC) has been demonstrated. We aimed to investigate the feasibility of adjuvant FNEC-assisted cryoablation in different bone cavity types by assessing the perioperative complication rates. METHODS: The medical charts of patients who received intraoperative adjuvant cryoablation using semisolid FNEC for bone tumors from December 2013 to January 2018 were reviewed. The bone cavities were categorized into three types according to liquid spill potential (type 1, able to hold liquid without limb manipulation; type 2, required extensive limb manipulation to retain liquid; type 3, unable to retain liquid). The overall complication rate and the complication rates stratified by bone cavity type were determined. RESULTS: Among the 76 patients, 30.3%, 57.9%, and 11.8% had type 1, 2, and 3 bone cavities, respectively. The mean follow-up time for perioperative complications was 43.5 ± 24.1 days. Five patients experienced complications, including two cases of skin damage, two cases of skin infection, and one case of fracture, yielding an overall perioperative complication rate of 6.4%. All cases of skin damage and skin infection were superficial and manageable by oral antibiotics. The patient with a pathologic fracture recovered well after being treated with open reduction and plate fixation. No neuropraxia was noted within the first few days postsurgery in any patient. The complication rates in type 1, 2, and 3 bone cavities were 13%, 4.6%, and 0%, respectively. CONCLUSION: All bone cavity types had a low incidence of perioperative complications after treatment with adjuvant FNEC-assisted cryoablation. Semisolid FNEC-assisted cryoablation is a feasible alternative to overcome the liquid spill potential in bone cavities resulting from tumor resection and intralesional curettage.

High-fat diet induces C-reactive protein secretion, promoting lung adenocarcinoma via immune microenvironment modulation.

To understand the effects of a high-fat diet (HFD) on lung cancer progression and biomarkers, we here used an inducible mutant epidermal growth factor receptor (EGFR)-driven lung cancer transgenic mouse model fed a regular diet (RD) or HFD. The HFD lung cancer (LC-HFD) group exhibited significant tumor formation and deterioration, such as higher EGFR activity and proliferation marker expression, compared with the RD lung cancer (LC-RD) group. Transcriptomic analysis of the lung tissues revealed that the significantly changed genes in the LC-HFD group were highly enriched in immune-related signaling pathways, suggesting that an HFD alters the immune microenvironment to promote tumor growth. Cytokine and adipokine arrays combined with a comprehensive analysis using meta-database software indicated upregulation of C-reactive protein (CRP) in the LC-HFD group, which presented with increased lung cancer proliferation and metastasis; this was confirmed experimentally. Our results imply that an HFD can turn the tumor growth environment into an immune-related pro-tumorigenic microenvironment and demonstrate that CRP has a role in promoting lung cancer development in this microenvironment.

Combination of enoxaparin and low-dose aspirin for thromboprophylaxis in selective patients after primary total joint arthroplasty in a Taiwanese population.

BACKGROUND: The incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) after total joint arthroplasty (TJA) procedures are lower in Asian populations than in Caucasian populations. Therefore, the need for thromboprophylaxis in Asian patients undergoing TJA remains inconclusive. The aim of this study was to validate the clinical outcomes of thromboprophylaxis in selective TJA patients in a Taiwanese population. METHODS: We retrospectively reviewed records of patients who underwent TJA procedures performed by a single-surgeon between January 2010 through December 2019. Patients received thromboprophylaxis with a combination of enoxaparin and low-dose aspirin if they fulfilled any of the following criteria: 1) body mass index >30 (kg/m 2 ), 2) presence of varicose veins, 3) history of DVT or PE, or 4) simultaneous bilateral TJA procedure. We assessed the incidence of DVT and PE, 90-day postoperative complications, length of stay, in-hospital mortality, 30-day and 90-day readmission, and 1-year reoperation. RESULTS: Of the 7511 patients included in this study, 2295 (30.6%) patients received thromboprophylaxis. For patients who received thromboprophylaxis(N = 2295), the incidence of DVT and PE were 0.44% and 0%, respectively. For patients who did not receive thromboprophylaxis (N = 5216), the incidence of DVT and PE was 0.46% and 0.04%, respectively. The overall rates of 90-day postoperative complications (2.3%), 30-day (1.8%) and 90-day readmission (2.3%), and 1-year reoperation (1.1%) were low. CONCLUSION: Providing thromboprophylaxis for selective TJA patients within the Taiwanese population was effective, as indicated by the low incidence of DVT and PE. Complications, such as surgical site infection, should be carefully weighed and managed.

Effect of Ultrasonic Treatment on Structure, Antibacterial Activity of Sugarcane Leaf Polysaccharides.

This study investigated the impact of ultrasonic extraction (UE) on the structure and in vitro antibacterial activity of polysaccharides from sugarcane leaves (SLW). Native sugarcane leaf polysaccharides were treated with ultrasound (480 W) for 3 h to yield sugarcane leaf polysaccharides (SLU). Compared to SLW (33.59 kDa), the molecular weight of SLU (13.08 kDa) was significantly decreased, while the monosaccharide composition of SLU was unchanged. The results of SEM and XRD indicated that UE significantly changed the surface morphology of SLW and destroyed its inner crystalline structure. In vitro experiments showed that SLU had stronger antibacterial activity. These findings revealed that UE treatment could alter the tertiary structure of SLW but had no impact on its primary structure. Furthermore, the antibacterial activity of SLW could be greatly enhanced after UE treatment. As a bioactive additive, SLU has great application potential in functional foods, cosmetics, and pharmaceuticals.

A novel nomogram for predicting post-recurrence survival in recurrent neuroblastoma patients.

Patients with recurrent neuroblastoma (NB) have a broad range of prognoses. This research aimed to develop a nomogram to assess post-recurrence survival (PRS) in patients with recurrent neuroblastoma. The TARGET database was utilized to enroll 825 individuals diagnosed with neuroblastoma between 1986 and 2012, 250 of whom were diagnosed with recurrent NB. These patients were randomly divided into a training group (n = 175) and a validation group (n = 75) at a ratio of 7:3. The Kaplan-Meier method was used for survival analysis. A prognosis nomogram was constructed based on post-recurrence survival indicators identified through Cox regression and LASSO analysis. The nomogram's capability for classification and calibration was assessed using the calibration curve, the area under the time-dependent receiver operating characteristic curve (AUC), and the consistency index (C-index). The nomogram was verified in the validation cohort, and its clinical applicabilities were assessed using the decision curve analysis (DCA). Four PRS predictors, COG risk group, INSS stage, MYCN status, and age, were identified to construct the nomogram, which showed good discrimination and calibration in the training and validation sets. The C-index of the training and validation sets was 0.681 [95% confidence interval (CI), 0.632-0.730] and 0.666 [95% CI, 0.593-0.739], respectively. The nomogram's AUC values for the training and validation sets at 1, 3, and 5 years were 0.747, 0.775, and 0.782 vs. 0.721, 0.757, and 0.776. The nomogram's AUC values were consistently higher than those of the COG risk groups and INSS stage, indicating that the nomogram had superior differentiation compared to the INSS stage and COG risk group. The DCA curve also demonstrated that the nomogram we developed outperformed conventional COG risk groups and INSS stage regarding clinical advantage. In the present study, we developed and validated a novel nomogram that should facilitate more accurate and personalized assessment of the survival probability of children with relapsed neuroblastoma. This model should assist physicians in their clinical decision-making process.

GuiLu-ErXian Glue extract promotes mesenchymal stem cells (MSC)-Induced chondrogenesis via exosomes release and delays aging in the MSC senescence process.

ETHNOPHARMACOLOGICAL RELEVANCE: The treatment of osteoarthritis (OA) patients is a challenging problem. Mesenchymal stem cells (MSCs) are multipotent cells and play key roles in regenerative medicine for cartilage degeneration. GuiLu-ErXian Glue (GLEXG) is an herbal remedy widely used in traditional Chinese medicine to treat joint pain and disability in elderly OA patients. However, the mechanisms of how GLEXG affects MSCs-induced chondrogensis remains to be elucidated. AIM OF THE STUDY: The aim of this study was to investigate the effects of GLEXG on MSC-derived chondrogenesis, both in vitro and in vivo and its potential mechanisms. METHODS: Using human MSC (hMSCs) as in vitro model, the effects of HPLC-profiled GLEXG water extract on chondrogenic differentiation were investigated by 3D spheroid cultures under chondrogenesis-inducing medium (CIM) condition. The chondrogenesis process was evaluated by measuring the sphere sizes, chondrogenesis-related genes expression by reverse transcription real-time PCR that targeted type II/X collagens, SOX9, aggrecan, and protein expression by immunostaining. Anti-TGF-ß1 neutralization antibody was used for mechanistic study. Mono-iodoacetate (MIA) induced OA joint was used to evaluate the effects of GLEXG on in vivo model. MSCs-derived exosomes were purified for proteomics study and senescence process was evaluated by cumulative population doublings and senescence-associated ß-Galactosidase staining. RESULTS: The results showed that GLEXG enhanced hMSCs chondrogenesis and upregulated RNA expression of type II/X collagen, SOX9 and aggrecan at 0.1 µg/mL, 0.3 µg/mL in vitro. In vivo, GLEXG at the dose of 0.3 µg intraarticular (i.a.) injection rescued the MIA-induced cartilage defect. Proteomics and ingenuity pathway analysis obtained from MSCs-released exosomes suggested that senescence pathway was less activated in GLEXG group than in vehicle group. Besides, GLEXG was able to increase cumulative population doubling and delayed hMSCs senescence process after four passages in cultures. CONCLUSION: we conclude that GLEXG promotes in vitro MSC-induced chondrogenesis possibly via exosomes release and delays aging in the MSC senescence process and that treatment with GLEXG (0.3 µg, i.a.) rescued cartilage defects in rat OA knee model.

The Impact of Human Platelet Antigen Allele on Antiplatelet Antibodies and Cryoglobulins in Patients with Primary Immune Thrombocytopenia and Hepatitis C Virus-Associated Immune Thrombocytopenia.

Background And Objectives: Human platelet antigens (HPAs) are alloantigens associated with antiplatelet alloantibodies and the risk of immune thrombocytopenia (ITP). However, few studies have investigated associations among HPAs, antiplatelet autoantibodies, and cryoglobulins. Methods: We enrolled 43 patients with primary ITP, 47 with hepatitis C virus-associated ITP (HCV-ITP), 21 with hepatitis B virus-associated ITP (HBV-ITP), 25 controls with HCV, and 1013 normal controls. We analyzed HPA allele frequencies, including HPA1-6 and 15, antiplatelet antibodies binding to platelet glycoprotein (GP) IIb/IIIa, Ia/IIa, Ib/IX, IV, human leukocyte antigen class I, cryoglobulin IgG/A/M, and their associations with thrombocytopenia. Results: In the ITP cohort, HPA2ab, rather than HPA2aa, predicted a low platelet count. HPA2b was associated with the risk of developing ITP. HPA15b was correlated with multiple antiplatelet antibodies. In HCV-ITP patients, HPA3b was correlated with anti-GPIIb/IIIa antibodies. HCV-ITP patients with anti-GPIIb/IIIa antibodies had a higher positive rate of cryoglobulin IgG and IgA compared with those without anti-GPIIb/IIIa antibodies. Overlapping detection was also found among other antiplatelet antibodies and cryoglobulins. Like the antiplatelet antibodies, cryoglobulins were associated with clinical thrombocytopenia, implying their close relationship. Finally, we extracted cryoglobulins to confirm the exhibition of cryoglobulin-like antiplatelet antibodies. In contrast, in primary ITP patients, HPA3b was correlated with cryoglobulin IgG/A/M rather than anti-GPIIb/IIIa antibodies. Conclusion: HPA alleles were associated with antiplatelet autoantibodies and had different impacts in primary ITP and HCV-ITP patients. HCV-ITP was considered to be a symptom of mixed cryoglobulinemia in HCV patients. The pathophysiology may differ between these two groups.

The impact of Charlson Comorbidity Index on surgical complications and reoperations following simultaneous bilateral total knee arthroplasty.

Simultaneous bilateral total knee arthroplasty (TKA) might be associated with higher postoperative morbidity and mortality rates compared with staged bilateral TKA. However, risk factors for surgical complications and reoperations following simultaneous bilateral TKA remain elusive. We conducted this retrospective, single-surgeon case series from 2010 through 2019. A total of 1561 patients who underwent simultaneous bilateral TKA procedures were included. The outcome domains included 30-day and 90-day readmission events for medical or surgical complications and 1-year reoperation events. We performed logistic regression analysis and backward stepwise selection to identify possible risk factors, including age, sex, body mass index, diabetes mellitus (DM), rheumatoid arthritis, American Society of Anesthesiologist (ASA) classification, Charlson Comorbidity Index (CCI), receiving venous thromboembolism (VTE) prophylaxis, or blood transfusion. The overall 30-day, 90-day readmission, and 1-year reoperation rates were 2.11%, 2.88%, and 1.41%, respectively. Higher CCI score (CCI = 4+) was a risk factor for 90-day readmission (aOR: 2.783; 95% CI 0.621-12.465), 90 day readmission for surgical complications (aOR: 10.779; 95% CI 1.444-80.458), and 1 year reoperation (aOR: 4.890; 95% CI 0.846-28.260). Other risk factors included older age, higher ASA level, DM, and receiving VTE prophylaxis. In conclusion, high CCI scores were associated with increased risks of surgical complications and reoperations following simultaneous bilateral TKA procedures.

Effect of co-medications and potential risk factors of high-dose methotrexate-mediated acute hepatotoxicity in patients with osteosarcoma.

BACKGROUND: Taiwanese patients frequently experience severe hepatotoxicity associated with high-dose methotrexate (HD-MTX) treatment, which interferes with subsequent treatment. Drug-drug interactions occur when MTX is used in combination with proton pump inhibitors (PPIs), trimethoprim-sulfamethoxazole (TMP-SMX), or non-steroidal anti-inflammatory drugs (NSAIDs). In East Asia, real-world analyses on the effects of co-medication and other potential risk factors on the clinical course of HD-MTX-mediated acute hepatotoxicity in patients with osteogenic sarcoma (OGS) are limited. METHODS: This cohort study included patients with newly diagnosed OGS who were treated with HD-MTX between 2009 and 2017 at Taipei Veterans General Hospital. We collected data on the clinical course of HD-MTX-mediated acute hepatotoxicity, co-medications, and other potential risk factors, and analyzed the effects of these factors on the clinical course of HD-MTX-mediated acute hepatotoxicity. RESULTS: Almost all patients with OGS treated with HD-MTX developed acute hepatotoxicity with elevated alanine aminotransferase (ALT) levels. Most patients with Grade 3-4 ALT elevation failed to recover to Grade 2 within 7 days. Women and children are high-risk subgroups for HD-MTX-mediated elevation of ALT levels. Age is a factor that contributes to the pharmacokinetic differences of HD-MTX. However, the concurrent use of PPIs, TMP-SMX, or NSAIDs did not affect the elimination of MTX when administered with adequate supportive therapy. CONCLUSIONS: Co-administration of PPIs, TMP-SMX, or NSAIDs may have limited effects on acute hepatotoxicity in well-monitored and adequately pre-medicated patients with OGS undergoing chemotherapy with HD-MTX. Clinicians should pay particular attention to ALT levels when prescribing HD-MTX to children and women.