Exploring flatfeet morphology in children aged 6-12 years: relationships with body mass and body height through footprints and three-dimensional measurements.

The aim of the study was to determine the relationship between flatfoot morphology and body mass and height in children aged 6-12 years. A total of 6471 Chinese children (mean age 9.0 ± 1.9 years, 41% female) were assessed for foot morphometry, body height, and body mass index. Foot morphology, including foot length, width, girth, arch height, hallux valgus angle, and rearfoot valgus angle, was measured using a 3D laser scanner. Flatfoot evaluations were conducted using the Sztriter-Godunov index (KY) from footprints. All measurements were analyzed by age and sex using the mean values of the left and right sides. Comparisons were performed between flatfoot groups, between body mass index (BMI) groups, and between body height groups. The study revealed a significant decrease in the incidence of bipedal flatfoot with age (p < 0.001), whereas the prevalence of obesity remained consistent (p > 0.05). Bipedal flatfoot was associated with distinct morphological changes, including lower arches, reduced instep height, diminished ankle heights and a greater rearfoot valgus angle (p < 0.05). When comparing the BMI groups, overweight children had larger and thicker feet (p < 0.05), but no differences were found in arch height and ankle height (p > 0.05). When comparing the body height groups, short-statured children had a shorter feet girth, shorter arches, and shorter ankle height (p < 0.05), but no differences were found in the rearfoot valgus angle (p > 0.05). CONCLUSION: The main characteristics of flat feet include lower arches and instep heights and ankle heights but higher rearfoot valgus angles. In general, overweight children's feet do not have the common features of flat feet. In contrast, short children had similar features of flatfoot except for rearfoot valgus. Assessment of posture, such as rearfoot valgus, can be critical in identifying children with flat feet. WHAT IS KNOWN: • The morphology of children's feet is associated with body growth, but the relationship between flatfeet and body mass and height remains controversial. WHAT IS NEW: • Three-dimensional foot measurement shows that body mass is generally not associated with flatfeet, while short children have lower arches but no rearfoot valgus.

Mitochondrial homeostasis regulation: A promising therapeutic target for Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) and the presence of Lewy bodies (LBs) or Lewy neurites (LNs) which consist of α-synuclein (α-syn) and a complex mix of other biomolecules. Mitochondrial dysfunction is widely believed to play an essential role in the pathogenesis of PD and other related neurodegenerative diseases. But mitochondrial dysfunction is subject to complex genetic regulation. There is increasing evidence that PD-related genes directly or indirectly affect mitochondrial integrity. Therefore, targeted regulation of mitochondrial function has great clinical application prospects in the treatment of PD. However, lots of PD drugs targeting mitochondria have been developed but their clinical therapeutic effects are not ideal. This review aims to reveal the role of mitochondrial dysfunction in the pathogenesis of neurodegenerative diseases based on the mitochondrial structure and function, which may highlight potential interventions and therapeutic targets for the development of PD drugs to recover mitochondrial dysfunction in neurodegenerative diseases.

Micro-223 Promotes Diabetic Osteoarthritis Progression by Regulating Cartilage Degeneration and Subchondral Bone Remodeling.

OBJECTIVE: Our study was performed to investigate whether micro-223 promotes diabetic Osteoarthritis (OA) progression by regulating cartilage degeneration and subchondral bone remodeling. METHODS: The expression of miR-223 in human normal cartilage, OA cartilage, and subchondral bone tissue with or without DM was detected by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). miR-223 mimic or inhibitor was transfected into chondrocytes. Cell viability and apoptosis were assessed by 3-(4,5)-dimethylthiahiazo(-2)-3,5-diphenyltetrazolium bromide (MTT) and Terminal Deoxynucleotidyl Transferase(TdT)-mediated dUTP nick end labeling (TUNEL) assay, respectively. RESULTS: miR-223 was significantly higher in human diabetic OA cartilage and subchondral bone compared with normal OA and healthy control. Overexpression of miR-223 accelerated cartilage degeneration and subchondral bone sclerosis in diabetic OA mice, whereas miR-223 inhibition had the opposite effect. In vitro upregulation of miR-223 decreased proliferation and enhanced apoptosis of chondrocytes. Meanwhile, downregulation of miR-223 promoted glycosaminoglycan (GAG) production in chondrocytes. CONCLUSION: miR-223 promotes diabetic OA progression by regulating cartilage degeneration and subchondral bone remodeling both in vitro and in vivo.

Utilization of lipidic food waste as low-cost nutrients for enhancing the potentiality of biofuel production from engineered diatom under temperature variations.

The scarcity of natural fossil fuels presents a promising opportunity for the development of renewable microalgae-based biofuels. However, the current microalgae cultivation is unable to effectively address the high costs of the production of biofuels. To tackle this challenge, this study focused on recruiting engineered Phaeodactylum tricornutum (FabG-OE) to enhance biomass accumulation and lipid production by employing food waste hydrolysate under temperature variations. The biomass and lipid accumulations of FabG-OE were improved effectively in mixed culture medium and food waste hydrolysate at a volume ratio (v/v) of 80:20 at 30 °C. It was found that oxidative stress might contribute to the overexpression of lipogenic genes, thereby leading to lipogenesis at 30 °C. Upscaling cultivation of FabG-OE at 30 °C using a semi-continuous strategy and batch strategy was conducted to achieve 0.73 and 0.77 g/L/d of biomass containing 0.35 and 0.38 g/L/d of lipid, respectively. In summary, these findings provide valuable insights for advancing microalgae-based biofuel production.

Occult colon cancer with sepsis as the primary manifestation identified by bone marrow puncture: A case report.

BACKGROUND: Bone marrow metastasis is common in liver and lung cancer, but there are few reports on bone marrow metastasis in colon cancer. To date, there are no such reports from mainland China, and reports of bone marrow metastasis with septic shock as the main manifestation are even rarer. CASE SUMMARY: A 71-year-old woman with sepsis as the first symptom presented with high fever, low blood pressure and high inflammation indicators. Computed tomography (CT) examination revealed mild inflammation of the lungs and no obvious abnormalities in the abdomen. Blood culture suggested Escherichia coli, Aeromonas hydrophila and Aeromonas caviae infection. Antibiotic treatment significantly improved the patient's sepsis symptoms; however, her thrombocytopenia (TCP) could not be corrected despite repeated platelet transfusions. Many malignant cells were ultimately found following a bone marrow puncture smear, and further positron emission tomography/CT (PET/CT) examination confirmed that the malignant tumor in the ascending colon was accompanied by multiple metastases, including the liver and bones. Colon adenocarcinoma was confirmed by autopsy. CONCLUSION: Patients with advanced colon cancer may not have typical clinical symptoms, and sepsis may be the first symptom. When patients have severe TCP that cannot be explained by sepsis of intestinal origin, it is necessary to be aware of the possibility of bone marrow metastasis of intestinal tumors. As such patients often cannot tolerate endoscopy, bone marrow biopsy smears or biopsy tests for specialized cells can help obtain a diagnosis, especially in less developed countries where PET/CT is scarce.

Effect of Diabetes Mellitus on Implant Osseointegration of Titanium Screws: An Animal Experimental Study.

OBJECTIVE: To explore the effect of diabetes mellitus (DM) on implant osseointegration of titanium screws. METHODS: Sixty rats were randomly divided into a DM group and a control group (each group, n = 30). DM group rats were injected with 1% Streptozotocin solution at 65 mg/kg to establish a DM model. Titanium screws were implanted into the rats' distal femurs in both groups. The rats were sacrificed for micro-CT scanning, micro-indentation, biomechanical detection, confocal Raman microspectroscopy, and histological and histomorphometric analysis at 4, 8, and 12 weeks post-implantation, respectively. Messenger RNA (mRNA) expression and protein expression of the related growth factors around the implant were analyzed using real-time polymerase chain reaction and Western blots. RESULTS: At 4, 8 and 12 weeks, micro-CT scanning, hematoxylin-eosin (HE) staining, Gieson's acid-magenta staining, and fluorescent labeled staining showed disorder in the bone tissue arrangement, a lack of new bone tissue, poor maturity and continuity, and poor trabecular bone parameters around the implant in the DM group. At 4, 8, and 12 weeks, the interfacial bone binding rate in the DM group was significantly lower (16.2% ± 4.8%, 25.7% ± 5.7%, 42.5% ± 5.8%, respectively) than that in the control group (23.6% ± 5.2%, 40.8% ± 6.3%, 64.2% ± 7.3%, respectively; P < 0.05). At 8 and 12 weeks, the elastic modulus (17.0 ± 1.8 and 15.1 ± 1.5 GPa, respectively) and trabecular bone hardness (571 ± 39 and 401 ± 37 MPa, respectively) in the DM group were significantly lower than the elastic modulus (23.4 ± 2.3 and 23.8 ± 1.8 GPa, respectively) and trabecular bone hardness (711 ± 45 and 719 ± 46 MPa, respectively) in the control group (P < 0.05). The maximum load required for the prosthesis pull-out experiment in the DM group at 4, 8, and 12 weeks (55.14 ± 6.74 N, 73.34 ± 8.43 N, and 83.45 ± 8.32 N, respectively) was significantly lower than that in the control group (77.45 ± 7.48 N, 93.28 ± 8.29 N, and 123.62 ± 9.43 N, respectively, P < 0.05). At 8 and 12 weeks, the mineral-to-collagen ratio in the DM group (6.56 % ± 1.35% and 4.45%± 1.25%, respectively) was significantly higher than that in the control group (5.31% ± 1.42% and 3.62% ± 1.33%, respectively, P < 0.05). At 12 weeks, mRNA and protein expression levels of bone morphogenetic protein 2, transforming growth factor-ß1, vascular endothelial growth factor, osteopontin, osteocalcin, and runt-related transcription factor 2 in the DM group were significantly lower than that in the control group. CONCLUSIONS: DM can negatively affect bone osseointegration, manifesting as disorder in bone tissue arrangement around the implant, a lack of new bone tissue, poor maturity and continuity, poor trabecular bone parameters and lower expression of the related growth factors.

The efficacy of ankle arthroplasty on motor function recovery in patients with orthopedic ankle injury: a systematic review and meta-analysis.

BACKGROUND: This study analyzed the effects of ankle arthroplasty on the recovery of motor function in patients with orthopedic ankle injury. METHODS: English databases including PubMed, Web of Science, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) examining the effects of ankle arthroplasty, ankle replacement, and joint prosthesis on motor function recovery in patients with orthopedic ankle injury. The outcome indicators included the American Orthopedic Foot and Ankle Society (AOFAS) score, the 36-item short form survey (SF-36) score, the Foot and Ankle Ability Measures (FAAM) score, and the visual analog scale (VAS) score. The quality of the included literature was evaluated using the Jadad tool, and meta-analysis of the experimental data was performed using the Review Manager 5.3 software. RESULTS: A total of 7 articles, including 443 patients, were analyzed. The meta-analysis showed significant improvement in AOFAS scores among patients in the experiment group (who underwent ankle replacement) compared with those in the control group (who did not undergo ankle replacement) [mean difference (MD) =-41.89, 95% confidence interval (CI): -51.29 to 32.49, Z=8.73, P<0.00001], VAS scores (MD =5.59, 95% CI: 4.84 to 6.34, Z=14.56, P<0.00001), SF-36 scores (MD =-13.89, 95% CI: -26.74 to 1.04, Z=2.12, P=0.03), and FAAM scores (MD =-25.78, 95% CI: -31.27 to 20.29, Z=9.20, P<0.00001) compared to patients in the control group. DISCUSSION: Ankle arthroplasty had a positive effect on the quality of life, daily activities, and motor function recovery of patients with orthopedic ankle injuries. While ankle arthroplasty has potential for clinical application, future high-quality, long-term studies with larger samples and more outcome indicators are warranted to verify these results.

Long noncoding RNA H19 accelerates tenogenic differentiation by modulating miR-140-5p/VEGFA signaling.

Rotator cuff tear (RCT) is a common tendon injury, but the mechanisms of tendon healing remain incompletely understood. Elucidating the molecular mechanisms of tenogenic differentiation is essential to develop novel therapeutic strategies in clinical treatment of RCT. The long noncoding RNA H19 plays a regulatory role in tenogenic differentiation and tendon healing, but its detailed mechanism of action remains unknown. To elucidate the role of H19 in tenogenic differentiation and tendon healing, tendon-derived stem cells were harvested from the Achilles tendons of Sprague Dawley rats and a rat model of cuff tear was established for the exploration of the function of H19 in promoting tenogenic differentiation. The results showed that H19 overexpression promoted, while H19 silencing suppressed, tenogenic differentiation of tendon-derived stem cells (TDSCs). Furthermore, bioinformatic analyses and a luciferase reporter gene assay showed that H19 directly targeted and inhibited miR-140-5p to promote tenogenic differentiation. Further, inhibiting miR-140-5p directly increased VEGFA expression, revealing a novel regulatory axis between H19, miR-140-5p, and VEGFA in modulating tenogenic differentiation. In rats with RTC, implantation of H19-overexpressing TDSCs at the lesion promoted tendon healing and functional recovery. In general, the data suggest that H19 promotes tenogenic differentiation and tendon-bone healing by targeting miR-140-5p and increasing VEGFA levels. Modulation of the H19/miR-140-5p/VEGFA axis in TDSCs is a new potential strategy for clinical treatment of tendon injury.

Arthroscopic Hip Surgery versus Conservative Therapy on Femoroacetabular Impingement Syndrome: A Meta-Analysis of RCTs.

To determine the outcome and differences between arthroscopic hip surgery and conservative therapy in patients suffering from femoroacetabular impingement syndrome, we searched articles from PubMed, Embase, Cochrane, Web of Science and Clinicaltrials.gov using a Boolean search algorithm. Only randomized controlled trials comparing arthroscopic hip surgery and conservative therapy were included in this meta-analysis of femoroacetabular impingement syndrome management. Two authors determined eligibility, extracted the needed data and assessed the risk of bias of eligible studies independently. Then we meta-analyzed three articles to assess pooled estimate size (ES) and 95% confidence interval for Hip Outcome Score of activities of daily living (HOS ADL subscale), Hip Outcome Score sport (HOS sports subscale) and International Hip Outcome Tool (iHOT-33) analyses were performed by using STATA version 14.0 MP (STATA, College Station, TX, USA) with the principal summary measures are mean between group difference, sample size, and standard deviation. We collected 52 articles in total after removing duplicates and screened by titles and abstracts. A total of three RCTs were included finally. There was definite evidence of additional benefit of arthroscopic hip surgery against conservative therapy in the field of improving quality of life (three trials, 575 participants, ES = 2.109, 95% CI: 1.373 to 2.845, I2  = 42.8%, P = 0.000) and activity of daily living (two trials, 262 participants, ES = 9.220, 95% CI: 5.931 to 12.508, I2  = 16.5%, P = 0.000). However, no significant difference could be seen in sports function improvement (two trials, ES = 7.562, 95% CI: -2.957 to 18.082, I2  = 60.1%, P = 0.159). In conclusion, this meta-analysis suggests that arthroscopic hip surgery provided essential benefit compared with conservative therapy in improving activity of daily living and quality of life.

Diabetes mellitus accelerates the progression of osteoarthritis in streptozotocin-induced diabetic mice by deteriorating bone microarchitecture, bone mineral composition, and bone strength of subchondral bone.

BACKGROUND: The purpose of this study was to develop an optimal diabetes-osteoarthritis (DM-OA) mouse model to validate that diabetes aggravates osteoarthritis (OA) and to evaluate the microarchitecture, chemical composition, and biomechanical properties of subchondral bone (SB) as a consequence of the DM-OA-induced damage induced. METHODS: Mice were randomly divided into three groups: DM-OA group, OA group, and sham group. Blood glucose levels, body weight, and food intake of all animals were recorded. Serum calcium (Ca) and osteocalcin (OCN) levels were compared in the three groups. The messenger ribonucleic acid (mRNA) and protein expression of key regulators for bone metabolism were detected. A semi-quantitative grading system [Osteoarthritis Research Society International (OARSI)] was used to evaluate cartilage and SB degeneration. Microspectroscopy, microindentations, micro-computed tomography (CT) imaging, and fracture load of compression testing were also used to evaluate trabecular SB properties. RESULTS: Glycemic monitoring and pancreas pathological results indicated stable high blood glucose and massive destruction of pancreas and islet cells in the DM-OA group. Serum levels of bone specific alkaline phosphatase (ALP-B) and tartrate-resistant acid phosphatase 5b (TRACP-5b) in the DM-group were higher than those of the other two groups while levels of serum Ca and OCN were lower. Meanwhile, the protein and mRNA expression of osteoblast-specific biomarkers [osteoprotegerin/receptor activator of nuclear factor kappa-B ligand (OPG/RANKL) ratio, collagen type I (COL-I), Runt-related transcription factor 2 (RUNX-2), OCN] were suppressed, and osteoclast-specific biomarkers [sclerostin (SOST)] was elevated in the DM-OA group. The mineral-to-collagen ratio, microindentation elastic modulus, hardness, micro-architectural parameters, bone mineral density, and fracture load of SB trabecular bone of the DM-OA group joint were lower than those of the other two groups. On the other hand, The OARSI score, trabecular spacing, and structural model index of the DM-OA group joint were higher than those of the other two groups. CONCLUSIONS: The glycemic and pancreatic pathological results indicated that the DM-OA model was a simple and reliable model induced by streptozotocin (STZ) and surgery. The results revealed the mechanisms through which diabetes accelerates OA; that is, by damaging and deteriorating the functions of SB, including its microarchitecture, chemical composition, and biomechanical properties.

LncPVT1 promotes cartilage degradation in diabetic OA mice by downregulating miR-146a and activating TGF-ß/SMAD4 signaling.

INTRODUCTION: To investigate the role of LncRNA PVT1 (plasmacytoma variant translocation 1) in hyperglycemia-triggered cartilage damage using the diabetic osteoarthritis (OA) mice model. MATERIALS AND METHODS: Streptozotocin (STZ) was used to induce mouse diabetes. Knee OA model was induced through transection of anterior cruciate ligament (ACLT). Severity of arthritis was assessed histologically by Safranin O-Fast Green Staining using Mankin Scores. LncRNA PVT1 and miR-146a were detected by real-time polymerase chain reaction (PCR) in cartilage tissue. Moreover, the interaction among PVT1, miR-146a, and SMAD4 was examined by luciferase reporter assays. Mice were injected intra-articularly with ad-siRNA-PVT1 and ad-siRNA scramble control. Articular concentrations of TNF-α, IL-1, IL-6 and TGF-ß1 were determined using enzyme-linked immunosorbent assay. Levels of type II Collagen (COL2A1), TGF-ß1, p-SMAD2, SMAD2, p-SMAD3, SMAD3, SMAD4 and nuclear SMAD4 were detected by western blot analysis. RESULTS: PVT1 expression was significantly increased, whereas miR-146a was markedly decreased in diabetic OA mice than in non-diabetic OA and control. Increased PVT1 expression in diabetic OA mice was significantly associated with Mankin score and reduced miR-146a as well as Collagen alpha-1(II) (COL2A1) expressions. In vivo, intra-articular injection of ad-siRNA-PVT1 efficiently increased miR-146a and COL2A1 expressions, alleviated joint inflammation, decreased the expression of pro-inflammatory mediators, and suppressed TGF-ß/SMAD4 pathway in diabetic OA mice. CONCLUSIONS: Our results demonstrate LncRNA PVT1 is involved in cartilage degradation in diabetic OA and correlated with disease severity. Efficiency of ad-siRNA-PVT1 in controlling joint inflammation in diabetic OA mice is associated with the suppression of the expression of miR-146a, pro-inflammatory cytokines and activation of TGF-ß/SMAD4 pathway.

Long Non-Coding KCNQ1OT1 Promotes Oxygen-Glucose-Deprivation/Reoxygenation-Induced Neurons Injury Through Regulating MIR-153-3p/FOXO3 Axis.

BACKGROUND: Long non-coding RNAs (LncRNAs) have been reported to play important roles in the pathogenesis and development of many diseases, including cerebral ischemia and reperfusion (I/R) injury. In this study, we aimed to investigate the role of LncRNA-Potassium Voltage-Gated Channel Subfamily Q Member 1 opposite strand/antisense transcript 1 (KCNQ1OT1) in cerebral I/R induced neuronal injury, and its underlying mechanisms. METHODS: Primary mouse cerebral cortical neurons treated with oxygen-glucose deprivation and reoxygenation (OGD/R) in vitro and mice subjected to middle cerebral artery occlusion (MCAO) and reperfusion were used to mimic cerebral I/R injury. Small inference RNA (siRNA) was used to knockdown KCNQ1OT1 or microRNA-153-3p (miR-153-3p). Dual-luciferase assay was performed to detect the interaction between KCNQ1OT1 and miR-153-3p and interaction between miR-153-3p and Fork head box O3a (Foxo3). Flow cytometry analysis was performed to detect neuronal apoptosis. qRT-PCR and Western blotting were performed to detect RNA and protein expressions. RESULTS: KCNQ1OT1 and Foxo3 expressions were significantly increased in neurons subjected to I/R injury in vitro and in vivo, and miR-153-3p expression were significantly decreased. Knockdown of KCNQ1OT1 or overexpression of miR-153-3p weakened OGD/R-induced neuronal injury and regulated Foxo3 expressions. Dual-luciferase analysis showed that KCNQ1OT1 directly interacted with miR-153-3p and Foxo3 is a direct target of miR-153-3p. CONCLUSIONS: Our results indicate that LncRNA-KCNQ1OT1 promotes OGD/R-induced neuronal injury at least partially through acting as a competing endogenous RNA (ceRNA) for miR-153-3p to regulate Foxo3a expression, suggesting LncRNA-KCNQ1OT1 as a potential therapeutic target for cerebral I/R injury.

[Research progress on mechanism of acupuncture and moxibustion promoting fracture healing].

Acupuncture has a significant effect on promoting fracture healing. It can dredge meridians and collaterals, regulate qi and blood, eliminate swelling and remove stasis. However, its mechanism is still not fully elucidated. With the development of research, it has been found in recent years that the mechanism of acupuncture and moxibustion promoting fracture healing involves regulating the expression level of cell growth factor, activating Wnt/ß-Catenin and other signal pathways, improving local blood circulation, affecting the content of mineral elements in bone, regulating the endocrine system, promoting the differentiation and proliferation of bone cells, promoting the proliferation and activation of osteoblasts and influencing the apoptosis of bone cells And so on. The mechanism of acupuncture and moxibustion promoting fracture healing is very complex, which is still at the level of animal experiments and cells.

[Effect of electroacupuncture on rehabilitation of knee joint movement after anterior cruciate ligament reconstruction].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the rehabilitation of knee joint function after anterior cruciate ligament (ACL) reconstruction. METHODS: A total of 140 patients with ACL reconstruction were randomly divided into an observation group (58 cases recruited, 12 cases dropped out) and a control group (65 cases recruited, 5 cases dropped out). The patients in the control group were treated with routine rehabilitation treatment. The patients in the observation group, on the basis of the treatment in the control group, were treated with EA at Fengshi (GB 31), Futu (ST 32), Zusanli (ST 36), Shangjuxu (ST 37), Fenglong (ST 40), Xuanzhong (GB 39), Diji (SP 8) and Sanyinjiao (SP 6) on the affected side (2 Hz/100 Hz of dilatational wave, 2-5 mA). Each EA treatment lasted 20-30 min, twice a day for 7 days. The swelling degree (d), pain visual analogue scale (VAS), knee joint range of motion (ROM), scores of International Knee Documentation Committee (IKDC) subjective short form and scores of Lysholm were observed in the two groups 1 day, 1 month, 3 months, 6 months and 1 year after operation. RESULTS: One month and 3 months after operation, the swelling degree (d) and VAS scores in the observation group were lower than those in the control group (P<0.05); 6 months and 1 year after operation, there was no significant difference between the two groups on the swelling degree (d) and VAS scores (P>0.05). One month, 3 months, 6 months and 1 year after operation, the ROM of the knee joint in the observation group was higher than that in the control group (P<0.05), the IKDC score and Lysholm score were higher than those in the control group (P<0.05). Within one year, there were no relaxations, fractures and other related complications in the two groups. The pivot shift test, anterior drawer test and the Lachman test were all negative. CONCLUSION: EA combined with routine rehabilitation training could obviously reduce the pain of knee joint, improve the swelling degree, increase the ROM of knee joint, promote the functional recovery in patients with ACL reconstruction, which are superior to rehabilitation training alone.

Relationship between serum and synovial fluid CCL20 concentrations with disease severity in primary knee osteoarthritis.

OBJECTIVES: The current study was performed to examine serum and synovial fluid (SF) CCL20 levels and their correlations with disease severity in primary knee osteoarthritis patients. METHODS: A total of 99 patients diagnosed with primary knee OA were enrolled in the study, and 95 healthy individuals receiving regular medical examination were recruited as controls. Serum and SF CCL20 concentrations were determined using an enzyme-linked immunosorbent assay. The radiographic severity of OA was assessed by the Kellgren-Lawrence (K-L) classification system. The Lequesne algofunctional index and a visual analogue scale (VAS) were used to evaluate the clinical severity of knee OA in patients. RESULTS: The serum CCL20 levels were not significantly different between patients with knee OA and controls. Patients with a K-L grade of 4 had significantly higher SF CCL20 levels than those with K-L grades of 2 and 3. Knee OA patients with a K-L grade of 3 showed significantly higher levels of CCL20 in SF than those with a K-L grade of 2. In addition, SF CCL20 levels were significantly related to the Lequesne algofunctional index and VAS score. CONCLUSIONS: These findings suggest that local CCL20 levels may reflect the disease severity of knee OA.

YY1/LncRNA GAS5 complex aggravates cerebral ischemia/reperfusion injury through enhancing neuronal glycolysis.

Yin-Yang 1 (YY1) has been identified as playing critical roles in multiple diseases. However, little is known regarding its roles and mechanisms in cerebral ischemia/reperfusion (I/R) injury. This study is aimed to explore the roles of YY1 in regulating neuronal apoptosis in cerebral I/R injury and its underlying mechanisms. Primary mouse cerebral cortical neurons were isolated and subjected to OGD/R to mimic cerebral I/R injury in vitro. The roles of YY1 on OGD/R-induced neuronal injury were investigated by performing western blotting, quantitative real-time polymerase chain reaction, TUNEL, RNA-binding protein immunoprecipitation, chromatin immunoprecipitation, chromatin isolation by RNA purification assay, glucose uptake assay, lactate production assay, and extracellular acidification rate assay. YY1-binding long non-coding RNAs (LncRNAs) in neurons subjected to OGD/R were identified by RIP and RNA sequencing. The roles of YY1 on cerebral I/R in vivo were detected by assessing neuronbehaviour, infarct size, and neuronal apoptosis. We found that YY1 expression is downregulated, and LncRNA GAS5 is upregulated in neurons subjected to OGD/R. OGD/R treatment promotes YY1 interacting with GAS5 in neurons, and YY1 negatively regulates GAS5 expression by binding to GAS5 promoter to repress its transcription. Besides, YY1 and GAS5 bind to the same region of PFKFB3 promoter to promote PFKFB3 expression and strengthen neuronal glycolysis, resulting in aggravating OGD/R-induced neuronal apoptosis. Knockdown of YY1 or GAS5 protects against I/R-induced ischemic brain damage and improves overall neurological functions in vivo. Overall, YY1 interacts with LncRNA GAS5 to promote PFKFB3 transcription to enhance neuronal glycolysis, resulting in aggravating cerebral I/R injury.

Synovial fluid alpha-melanocyte-stimulating hormone may act as a protective biomarker for primary knee osteoarthritis.

OBJECTIVE: The current study was carried out to investigate the serum and synovial fluid (SF) alpha-melanocyte-stimulating hormone (α-MSH) levels in correlation with disease severity in primary knee osteoarthritis (OA). METHODS: This study comprised of 105 primary knee OA patients and 98 healthy controls. The radiographic severity was verified according to the Kellgren-Lawrence radiographic grading criteria. The symptomatic severity of knee OA was assessed by the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index. Serum α-MSH concentrations were measured by ELISA. The inflammation markers IL-6 and TNF-α, as well as cartilage damage markers MMP-3 (matrix metalloproteinase 3) and COMP (cartilage oligomeric matrix protein), were also measured. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value between α-MSH and other four markers with regard to the radiographic progression. RESULTS: SF α-MSH concentrations were negatively related to Kellgren-Lawrence grades and WOMAC index. SF α-MSH levels in knee OA patients were negatively associated with inflammation markers IL-6, TNF-α, and cartilage damage factors COMP and MMP-3. In addition, ROC analysis implied that attenuated α-MSH levels may serve as a favorable diagnostic marker for the radiographic progression. The difference of serum α-MSH concentration was not significant between knee OA patients and healthy controls. CONCLUSIONS: Reduced SF α-MSH expression may be a characteristic of OA patients. Attenuated α-MSH level in SF may serve as a potential biomarker for disease severity of knee OA, and further studies are needed to identify its potential application for monitoring the course of the disease and the efficacy of therapies in OA patients.

Development of a Rat Model of Sick Sinus Syndrome Using Pinpoint Press Permeation.

OBJECTIVE: Sick sinus syndrome (SSS) is one of the most common causes of cardiac impairment necessitating pacemaker implantation. However, studies of SSS pathogenesis are neither comprehensive nor conclusive due to limited success in achieving a stable rat SSS model. Here, we modified pinpoint press permeation to establish a stable rat SSS model. METHODS: We randomly assigned 138 male Sprague-Dawley rats into three groups: normal control (n = 8), sham (n = 10), and SSS (n = 120). Postoperatively, the SSS group was further divided into SSSA (n = 40), SSSB (n = 40), and SSSC (n = 40), based on reduction in heart rates by 20-30%, 31-40%, and 41-50%, respectively. We also assessed histomorphological characteristics and hyperpolarization-activated cyclic nucleotide-gated cation channel 4 (HCN4) expression in the sinoatrial node (SAN) at 1, 2, 3, and 4 weeks after surgery. RESULTS: Mortality was statistically higher in SSSC compared to SSSA and SSSB (7.5% versus 90.0% and 87.5%; P < 0.05). Heart rate in SSSA was gradually restored to preoperative levels by week 4 after surgery. In contrast, heart rate in SSSB was stable at 2-3 weeks after surgery. However, we observed that the tissues and cells in SAN were severely injured and also found a time-dependent increase in collagen content and atrium myocardium in SSSB. HCN4 expression was significantly reduced at all 4 time points in SSSB, with statistically significant differences among the groups (P < 0.01). CONCLUSION: We successfully developed a rat SSS model that was sustainable for up to 4 weeks.