MiR-146b-5p enriched bioinspired exosomes derived from fucoidan-directed induction mesenchymal stem cells protect chondrocytes in osteoarthritis by targeting TRAF6.

Osteoarthritis (OA) is a common degenerative joint disease characterized by progressive cartilage degradation and inflammation. In recent years, mesenchymal stem cells (MSCs) derived exosomes (MSCs-Exo) have attracted widespread attention for their potential role in modulating OA pathology. However, the unpredictable therapeutic effects of exosomes have been a significant barrier to their extensive clinical application. In this study, we investigated whether fucoidan-pretreated MSC-derived exosomes (F-MSCs-Exo) could better protect chondrocytes in osteoarthritic joints and elucidate its underlying mechanisms. In order to evaluate the role of F-MSCs-Exo in osteoarthritis, both in vitro and in vivo studies were conducted. MiRNA sequencing was employed to analyze MSCs-Exo and F-MSCs-Exo, enabling the identification of differentially expressed genes and the exploration of the underlying mechanisms behind the protective effects of F-MSCs-Exo in osteoarthritis. Compared to MSCs-Exo, F-MSCs-Exo demonstrated superior effectiveness in inhibiting inflammatory responses and extracellular matrix degradation in rat chondrocytes. Moreover, F-MSCs-Exo exhibited enhanced activation of autophagy in chondrocytes. MiRNA sequencing of both MSCs-Exo and F-MSCs-Exo revealed that miR-146b-5p emerged as a promising candidate mediator for the chondroprotective function of F-MSCs-Exo, with TRAF6 identified as its downstream target. In conclusion, our research results demonstrate that miR-146b-5p encapsulated in F-MSCs-Exo effectively inhibits TRAF6 activation, thereby suppressing inflammatory responses and extracellular matrix degradation, while promoting chondrocyte autophagy for the protection of osteoarthritic cartilage cells. Consequently, the development of a therapeutic approach combining fucoidan with MSC-derived exosomes provides a promising strategy for the clinical treatment of osteoarthritis.

Bone-targeting delivery of platelet lysate exosomes ameliorates glucocorticoid-induced osteoporosis by enhancing bone-vessel coupling.

BACKGROUND: Glucocorticoids (GCs) overuse is associated with decreased bone mass and osseous vasculature destruction, leading to severe osteoporosis. Platelet lysates (PL) as a pool of growth factors (GFs) were widely used in local bone repair by its potent pro-regeneration and pro-angiogenesis. However, it is still seldom applied for treating systemic osteopathia due to the lack of a suitable delivery strategy. The non-targeted distribution of GFs might cause tumorigenesis in other organs. RESULTS: In this study, PL-derived exosomes (PL-exo) were isolated to enrich the platelet-derived GFs, followed by conjugating with alendronate (ALN) grafted PEGylated phospholipid (DSPE-PEG-ALN) to establish a bone-targeting PL-exo (PL-exo-ALN). The in vitro hydroxyapatite binding affinity and in vivo bone targeting aggregation of PL-exo were significantly enhanced after ALN modification. Besides directly modulating the osteogenic and angiogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs), respectively, PL-exo-ALN also facilitate their coupling under GCs' stimulation. Additionally, intravenous injection of PL-exo-ALN could successfully rescue GCs induced osteoporosis (GIOP) in vivo. CONCLUSIONS: PL-exo-ALN may be utilized as a novel nanoplatform for precise infusion of GFs to bone sites and exerts promising therapeutic potential for GIOP.

Modified double-pulley suture-bridge techniques with or without medial knot tying show comparable clinical and radiological outcomes in arthroscopic rotator cuff repair.

PURPOSE: The optimal technique for arthroscopic rotator cuff repair is still controversial. The aim of this study was to compare modified arthroscopic double-pulley suture-bridge (DPSB) technique with medial knot tying to those without tying, considering clinical and radiological outcomes. METHODS: This study included 292 patients with large full-thickness rotator cuff tears treated with modified DPSB technique. The patients were divided into 158 cases with medial knot tying (knot-tying group) and 134 without tying (knotless group). At follow-up, clinical outcome was assessed by the Constant score, American Shoulder and Elbow Surgeons (ASES) score, and Shoulder Rating Scale of the University of California at Los Angeles (UCLA) score. The assessment of tendon healing was performed with magnetic resonance imaging (MRI) at a minimum of 12 months postoperatively. RESULTS: The Constant score, ASES score and UCLA score in the knot-tying and knotless groups all improved significantly from before surgery to 12 months postoperatively (P < 0.05, respectively). No significant differences were observed between groups for each phase evaluated (n.s.). Tendon healing was categorised according to Sugaya's classification. The retearing rate was 27/158 (17.0%) in the knot-tying group and 20/134 (14.9%) in the knotless group, with no statistically significant difference between groups (n.s.). Additionally, the retear was classified using the Cho's classification. When comparing the retear rates of different types independently, no statistically significant differences were found between groups (n.s.). CONCLUSIONS: The knotless modified DPSB technique showed comparable short-term functional outcomes to those of the knot tying method in large full-thickness rotator cuff tears. Additionally, no significant differences in repair integrity were observed between the two methods. Both techniques can be considered effective treatments for patients with large-sized full-thickness rotator cuff tears. LEVEL OF EVIDENCE: III.

The use of 2-octyl cyanoacrylate as an adjuvant to wound closure in total knee arthroplasty.

PURPOSE: The efficacy of the use of 2-octyl cyanoacrylate (OCA) as an adjuvant to wound closure in preventing wound complications after total knee arthroplasty (TKA) is rarely reported. This study was aimed to determine whether the use of OCA as a supplement to conventional wound closure reduces the incidence of wound complications following TKA. PATIENTS AND METHODS: This retrospective study reviewed 1106 consecutive patients who underwent TKA for symptomatic end-stage osteoarthritis (OA) between 2012 and 2017. The first 562 patients who did not receive OCA were grouped into the Control group, and the subsequent 544 patients who received OCA as an adjuvant to wound closure were grouped into the OCA group. All patients were followed up for at least 2 years. The main outcome was the development of operative site complications, including aseptic and infectious complications. Aseptic wound complications were wound leakage, hematoma, wound dehiscence and delayed wound healing, and infectious complication was mainly referred to the superficial infection. RESULTS: No significant difference with regard to hematoma was observed between groups (3.0% vs. 3.7%, P = 0.617, φ = - 0.02). The incidences were significantly higher in the Control group versus the OCA group in regard to wound leakage (9.4% vs. 2.0%, P = 0.000, φ = 0.16), wound dehiscence (5.7% vs. 1.3%, P = 0.000, φ = 0.12), delayed wound healing (4.4% vs. 1.5%, P = 0.004, φ = 0.09) and superficial infection (2.0% vs. 0.4%, P = 0.022, φ = 0.07). No serious adverse events (AEs) occurred. CONCLUSIONS: The present study showed that the addition of OCA reduced the incidence of wound leakage, wound dehiscence, delayed wound healing and superficial infection after TKA compared to conventional wound closure. Based on the outcomes above, we decide to use OCA routinely for wound closure after TKA. LEVEL OF EVIDENCE: III, retrospective, cohort study.

Procyanidin B3 alleviates intervertebral disc degeneration via interaction with the TLR4/MD-2 complex.

As a chronic musculoskeletal degeneration disease, intervertebral disc degeneration (IVDD) has been identified as a crucial cause for low back pain. This condition has a prevalence of 80% among adults without effective preventative therapy. Procyanidin B3 (Pro-B3) is a procyanidin dimer, which is widely present in the human diet and has multiple functions, such as preventing inflammation. But the inhibiting effect of Pro-B3 in IVDD development is still no known. Thus, our study aimed to demonstrate the therapeutical effect of Pro-B3 in IVDD and explain the underlying mechanism. In vitro studies, human nucleus pulposus (NP) cells were isolated and exposed in lipopolysaccharide (LPS) to simulate IVDD development. Pro-B3 pre-treatment inhibited LPS-induced production of inflammation correlated factors such as tumour necrosis factor α (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2) and Nitric oxide (NO). On the other hand, LPS-medicated extracellular matrix (ECM) breakdown was blocked in Pro-B3 treated NP cells. Additionally, Pro-B3 treatment blocked the activation of NF-κB/toll-like receptor 4 pathway in LPS-exposed NP cells. Mechanistically, Pro-B3 could occupy MD-2's hydrophobic pocket exhibiting high affinity for LPS to intervene LPS/TLR4/MD-2 complex formation. In vivo, Pro-B3 treatment prevented the loss of gelatin NP cells and structural damage of annulus fibrosus in rat IVDD model. In brief, Pro-B3 is considered to be a treatment agent for IVDD.

Arctigenin prevents the progression of osteoarthritis by targeting PI3K/Akt/NF-κB axis: In vitro and in vivo studies.

Osteoarthritis (OA), which is principally featured by progressive joint metabolic imbalance and subsequent degeneration of articular cartilage, is a common chronic joint disease. Arctigenin (ATG), a dietary phyto-oestrogen, has been described to have potent anti-inflammatory effects. Nevertheless, its protective effects on OA have not been clearly established. The target of our following study is to evaluate the protective effects of ATG on IL-1ß-induced human OA chondrocytes and mouse OA model. Our results revealed that the ATG pre-treatment effectively decreases the level of pro-inflammatory mediators, such as prostaglandin E2 (PGE2), nitrous oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), IL-6 and tumour necrosis factor alpha (TNF-α) in IL-1ß-induced human chondrocytes. In addition, ATG protects against the degradation of extracellular matrix (ECM) under the stimulation of IL-1ß and the possible mechanism might be connected with the inactivation of phosphatidylinositol-3-kinase (PI3K)/Akt/nuclear factor-kappa B (NF-κB) axis. Furthermore, a powerful binding capacity between ATG and PI3K was also uncovered in our molecular docking research. Meanwhile, ATG may act as a protector on the mouse OA model. Collectively, all these findings suggest that ATG could be utilized as a promising therapeutic agent for the treatment of OA.

The natural course of unruptured intracranial aneurysms in a Chinese cohort: protocol of a multi-center registration study in CIAP.

BACKGROUND: Subarachnoid hemorrhage (SAH) accounts for 4.4% of cerebral vascular disease, which is one of the leading causes of death in China. Rupture of intracranial aneurysms (IAs) is the most common cause of SAH. The natural history of unruptured IAs (UIAs) and the risk factors for rupture are among the key issues regarding the pathogenesis of IA and SAH that remain unclear in the Chinese population. METHODS: The China Intracranial Aneurysm Project (CIAP) is a prospective, observational, multicenter registry study of the natural courses, risk factors for the onset and rupture, treatment methods, comorbidity management and other aspects of intracranial aneurysms. To date, there are five studies in the CIAP. CIAP-1 is a prospective observational cohort study of UIAs. More than 5000 patients who will be followed for at least 1 year are expected to be enrolled in this cohort. These participants come from more than 20 centers that represent different regions in China. Enrollment began on May 1, 2017, and will take approximately 5 years. A nationwide online database of UIAs will be built. Participants' basic, lifestyle, clinical and follow-up information will be collected. The blood samples will be stored in the Central Biological Specimen Bank. Strict standards have been established and will be followed in this study to ensure efficient implementation. DISCUSSION: The natural course of UIAs in the Chinese population will be explored in this registry study. In addition, the risk factors for the rupture of the UIAs and the joint effect of those factors will be analyzed. The present study aims to create a nationwide database of UIAs and investigate the natural course of UIAs in China. Trial registration The Natural Course of Unruptured Intracranial Aneurysms in a Chinese Cohort (ClinicalTrials.gov Identifier: NCT03117803). Registered: July 5, 2017.

No effectiveness of anticoagulants for thromboprophylaxis after non-major knee arthroscopy: a systemic review and meta-analysis of randomized controlled trials.

Arthroscopic knee surgery is the most commonly performed orthopedic procedure worldwide and whether thromboprophylaxis should be undertaken after knee arthroscopy is still controversial. To evaluate the efficacy of thromboprophylaxis for deep venous thrombosis (DVT) and venous thromboembolism (VTE) after knee arthroscopic surgery. A meta-analysis was conducted using data from eight randomized trials (4148 patients) to compare thromboprophylaxis with placebo or no prophylactic treatment in patients undergoing knee arthroscopy. The benefits and harms of thromboprophylaxis were evaluated, including the incidence of asymptomatic DVT, symptomatic VTE, pulmonary embolism and anti-coagulation related adverse events. Thromboprophylaxis significantly decreased the incidence of DVT (95% CI 0.07-0.64, P = 0.006) and symptomatic VTE in patients undergoing knee arthroscopy (95% CI 0.23-0.76, P = 0.004), but not significantly decreased the incidence of pulmonary embolism (n.s.). Regarding to non-major knee arthroscopy surgery (simple surgical procedures without ligament reconstruction), no significant difference of the incidence of DVT or symptomatic VTE was noted between thromboprophylactic group and control group (n.s.). Thromboprophylactic treatment showed higher incidence rate of anti-coagulation related adverse events compared with the control group (95% CI 1.12-1.90, P = 0.005). There was no significant difference of the incidence of clinically relevant major bleeding between the two groups (n.s.). This meta-analysis indicates no effectiveness of thromboprophylaxis for preventing DVT or symptomatic VTE in patients undergoing non-major knee arthroscopy. Regarding to patient undergoing knee ligament construction, the thromboprophylactic strategy should mainly take into account the patient's risk factors.

Association of osteoarthritis and circulating adiponectin levels: a systematic review and meta-analysis.

BACKGROUND: The objective of this study was to perform a meta-analysis to investigate the specific relationship between the expression level of circulating adiponectin and osteoarthritis (OA). METHOD: Multiple databases were searched to estimate the high quality of studies relevant to adiponectin and OA. We extracted the data from the eligible studies and included them in the meta-analysis using a random effects model. Subgroup analysis and meta-regression were further performed to explore the potential sources of heterogeneity. RESULTS: Ten articles consisting of thirteen case-control studies that contained a combined total of 1255 subjects. Our results revealed that the OA patients displayed higher adiponectin levels than the healthy controls (SMD = 0.327, 95% CI: 0.11-0.55, P = 0.003). The ethnicity-stratified subgroup analysis indicated that the adiponectin was a sensitive biomarker in both Caucasians (P = 0.021) and Asians (P = 0.037). Moreover, the meta-regression analysis suggested that the sample size (P = 0.03) and nationality (p = 0.01) could account for a part of heterogeneity in our study. CONCLUSION: Taken together, the current study indicated that the adiponectin expression levels were higher in the OA patients than in the healthy controls and might be associated with OA prevalence.

Adiponectin attenuates NADPH oxidase-mediated oxidative stress and neuronal damage induced by cerebral ischemia-reperfusion injury.

Adiponectin (APN), which is a major adipokine that regulated glucose and lipid metabolism, plays an important role in the protection of the cerebral nervous system. It also has been suggested to have anti-inflammatory effects and ameliorate oxidative stress. Stroke is a universal cause of death and permanent disability. Ischemic stroke accounts for most cases of stroke, and is characterized by cerebral ischemia and neurological deficits. We aimed to investigate the effects of APN-peptide (APN-P) in neurons following ischemia reperfusion (I/R) in C57BL/6J mice, and to study the potential mechanisms underlying its effects. Mice were treated with vehicle, 2.5, 5, or 10mg/kg of APN-P and 2.5mg/kg of apocynin or vehicle before middle cerebral artery occlusion. Neurological deficits, infarct size, neuronal injury, and the ultrastructure of neurons were assessed. In addition, the levels of reactive oxygen species, superoxide dismutase, and malondialdehyde were measured. We assessed neuronal apoptosis using terminal deoxynucleotidyl transferase dUTP nick end labeling. The levels of oxidative stress- and apoptosis-related proteins were measured by western blot. Our results suggest that APN-P at 5mg/kg markedly improved neurological deficits, decreased infarct size, and attenuated neuronal injury after cerebral I/R injury. APN-P treatment also decreased neuronal apoptosis. Additionally, the increased levels of oxidative stress- and apoptosis-related proteins levels following I/R were alleviated by APN-P treatment. In conclusion, APN-P inhibits neuronal apoptosis and alleviates oxidative stress in neurons subjected to I/R, suggesting that it may be beneficial for the treatment of brain damage following ischemic stroke.

An ultrastructural study of chondroptosis: programmed cell death in degenerative intervertebral discs in vivo.

Apoptosis has been regarded to mediate intervertebral disc degeneration (IDD); however, the basic question of how the apoptotic bodies are cleared in the avascular intervertebral disc without phagocytes, which are essential to apoptosis, remains to be elucidated. Our goals were to investigate the ultrastructure of nucleus pulposus (NP) cells undergoing chondroptosis, a variant of apoptotic cell death, in a rabbit annular needle-puncture model of IDD. Experimental IDD was induced by puncturing discs with a 16-G needle in New Zealand rabbits. At 4 and 12 weeks after puncture, progressive degeneration was demonstrated by X-ray, magnetic resonance imaging and histological staining. TUNEL staining suggested a significant increase in the apoptosis index in the degenerated NP. However, the percentage of apoptotic cells with the classic ultrastructure morphology was much less than that with chondroptotic ultrastructure morphology under transmission electron microscopy (TEM). The chondroptotic cells from the early to late stage were visualized under TEM. In addition, the percentage of chondroptotic cells was significantly enhanced in the degenerated NP. Furthermore, 'paralyzed' cells were found in the herniated tissue. Western blotting revealed an increase in caspase3 expression in the degenerated NP. The expression of the Golgi protein (58K) was increased by the fourth week after puncture but decreased later. These findings indicate that chondroptosis is a major type of programmed cell death in the degenerated rabbit NP that may be related to the progressive development of IDD.

Melatonin attenuates sepsis-induced cardiac dysfunction via a PI3K/Akt-dependent mechanism.

Myocardial dysfunction is an important manifestation of sepsis. Previous studies suggest that melatonin is protective against sepsis. In addition, activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway has been reported to be beneficial in sepsis. However, the role of PI3K/Akt signaling in the protective effect of melatonin against sepsis-induced myocardial dysfunction remains unclear. Here, LY294002, a PI3K inhibitor, was used to investigate the role of PI3K/Akt signaling in mediating the effects of melatonin on sepsis-induced myocardial injury. Cecal ligation and puncture (CLP) surgery was used to establish a rat model of sepsis. Melatonin was administrated to rats intraperitoneally (30 mg/kg). The survival rate, measures of myocardial injury and cardiac performance, serum lactate dehydrogenase level, inflammatory cytokine levels, oxidative stress level, and the extent of myocardial apoptosis were assessed. The results suggest that melatonin administration after CLP surgery improved survival rates and cardiac function, attenuated myocardial injury and apoptosis, and decreased the serum lactate dehydrogenase level. Melatonin decreased the production of the inflammatory cytokines TNF-α, IL-1ß, and HMGB1, increased anti-oxidant enzyme activity, and decreased the expression of markers of oxidative damage. Levels of phosphorylated Akt (p-Akt), unphosphorylated Akt (Akt), Bcl-2, and Bax were measured by Western blot. Melatonin increased p-Akt levels, which suggests Akt pathway activation. Melatonin induced higher Bcl-2 expression and lower Bax expression, suggesting inhibition of apoptosis. All protective effects of melatonin were abolished by LY294002, the PI3K inhibitor. In conclusion, our results demonstrate that melatonin mitigates myocardial injury in sepsis via PI3K/Akt signaling activation.

Shorter survival rate in varus-aligned knees after total knee arthroplasty.

PURPOSE: One long-held tenet of total knee arthroplasty (TKA) is that post-operative neutral limb alignment promotes implant durability. Recently, the concept of generic safe zone (0° ± 3°) has been challenged. This meta-analysis aimed to evaluate whether neutral alignment was superior to malalignment in long-term survival of TKAs. METHODS: The MEDLINE, Embase, Cochrane Library, China National Knowledge Infrastructure, Wan Fang Chinese Periodical, Google and reference lists of all the included studies were searched. Of the 1512 studies initially identified, ten met the eligibility criteria, including eight case-control studies and two cohort trials. Relative risks of implant failure were compared between post-operative neutrally aligned and malaligned knees. RESULTS: Post-operative malalignment showed higher failure rate of knee implants compared with neutral alignment (95 % CI 1.00-1.88, P = 0.05). Failure rate in knees with varus alignment was significantly higher than with neutral alignment (95 % CI 1.07-2.55, P = 0.02). There was no significant difference in the likelihood of implant failure between knees with valgus and neutral alignment (95 % CI 0.78-2.41, n.s.). No significant difference of failure rate was noted between neutral alignment and malalignment for fixed-bearing prothesis (95 % CI 0.94-1.95, n.s.) or rotating-platform prothesis (95 % CI 0.75-2.73, n.s.). There was no significant difference of failure rate between knees with neutral alignment and malalignment for studies with a mean follow-up of more than 10 years (95 % CI 0.81-2.01, n.s.) or studies using long-leg weight-bearing radiographs (95 % CI 0.79-1.79, n.s.). CONCLUSIONS: Post-operative varus alignment results in shorter survival rate after TKA. Not only neutral limb alignment but also the valgus alignment promotes implant durability. Neutral or valgus alignment rather than varus alignment is essential to achieve long-term survival of TKAs and patient satisfaction. LEVEL OF EVIDENCE: III.

Real-Time Two-Dimensional Mapping of Relative Local Surface Temperatures with a Thin-Film Sensor Array.

Dynamic mapping of an object's local temperature distribution may offer valuable information for failure analysis, system control and improvement. In this letter we present a computerized measurement system which is equipped with a hybrid, low-noise mechanical-electrical multiplexer for real-time two-dimensional (2D) mapping of surface temperatures. We demonstrate the performance of the system on a device embedded with 32 pieces of built-in Cr-Pt thin-film thermocouples arranged in a 4 × 8 matrix. The system can display a continuous 2D mapping movie of relative temperatures with a time interval around 1 s. This technique may find applications in a variety of practical devices and systems.

A Novel Endoscopic Cerenkov Luminescence Imaging System for Intraoperative Surgical Navigation.

Cerenkov luminescence imaging is an emerging optical technique for imaging the distribution of radiopharmaceuticals in vivo. However, because of the light scattering effect, it cannot obtain optical information from deep internal organs. To overcome this challenge, we established a novel endoscopic Cerenkov luminescence imaging system that used a clinically approved laparoscope and an electron-multiplying charge-coupled device camera. We assessed the performance of the system through a series of in vitro and in vivo experiments. The results demonstrated superior superficial imaging resolution (0.1 mm), a large field of view (500 mm2 with 10 mm imaging distance), and superb imaging sensitivity (imaging 1 µCi) of our system. It captured the weak Cerenkov signal from internal organs successfully and was applied to intraoperative surgical navigation of tumor resection. It offered objective information of the tumor location and tumor residual during the surgical operation. This technique holds great potential for clinical translation.

Absence of the Adenosine A2A Receptor Confers Pulmonary Arterial Hypertension Through RhoA/ROCK Signaling Pathway in Mice.

Numerous evidence suggests that RhoA/Rho kinase (ROCK) signaling pathway plays an important role in the pathogenesis of pulmonary arterial hypertension (PAH), but little is known about its effects on the development of PAH in mice with absence of the adenosine A2A receptor (A2AR). Eight A2AR knockout (KO) and 8 wild-type mice were used. Morphometric analysis of pulmonary arterioles included right ventricle/left ventricle plus ventricular septum (Fulton index), vessel wall thickness/total vascular diameter (WT%), and vessel wall area/total vascular area (WA%). The expression of RhoA and ROCK1 mRNA was determined by real-time polymerase chain reaction. The expression of RhoA, ROCK1, and phosphorylation of myosin phosphatase target subunit 1 proteins in pulmonary tissue was tested by Western blot. The position of ROCK1 protein was evaluated by immunohistochemistry. Compared with wild-type mice, A2AR KO mice displayed (1) increased Fulton index, WT%, and WA% (P < 0.01); (2) increased mRNA expression of RhoA and ROCK1 (each P < 0.05); (3) increased protein expression of RhoA, ROCK1, and phosphorylation of myosin phosphatase target subunit 1 (each P < 0.01); (4) increased location of ROCK1 protein in endothelial and smooth muscle cells of pulmonary artery, bronchial, and alveolar epithelial cells. Activation of RhoA/ROCK signaling pathway may cause pulmonary vascular constriction, pulmonary artery remodeling, and PAH in adenosine A2A receptor KO mice.

Melatonin alleviates brain injury in mice subjected to cecal ligation and puncture via attenuating inflammation, apoptosis, and oxidative stress: the role of SIRT1 signaling.

Sepsis is a systemic inflammatory response to infection that causes severe neurological complications. Previous studies have suggested that melatonin is protective during sepsis. Additionally, silent information regulator 1 (SIRT1) was reported to be beneficial in sepsis. However, the role of SIRT1 signaling in the protective effect of melatonin against septic encephalopathy remains unclear. This study aimed to investigate the role of SIRT1 in the protective effect of melatonin. EX527, a SIRT1 inhibitor, was used to reveal the role of SIRT1 in melatonin's action. Cecal ligation and puncture or sham operation was performed in male C57BL/6J mice. Melatonin was administrated intraperitoneally (30 mg/kg). The survival rate of mice was recorded for the 7-day period following the sham or CLP operation. The blood-brain barrier (BBB) integrity, brain water content, levels of inflammatory cytokines (TNF-α, IL-1ß, and HMGB1), and the level of oxidative stress (superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA)) and apoptosis were assessed. The expression of SIRT1, Ac-FoxO1, Ac-p53, Ac-NF-κB, Bcl-2, and Bax was detected by Western blot. The results suggested that melatonin improved survival rate, attenuated brain edema and neuronal apoptosis, and preserved BBB integrity. Melatonin decreased the production of TNF-α, IL-1ß, and HMGB1. Melatonin increased the activity of SOD and CAT and decreased the MDA production. Additionally, melatonin upregulated the expression of SIRT1 and Bcl-2 and downregulated the expression of Ac-FoxO1, Ac-p53, Ac-NF-κB, and Bax. However, the protective effects of melatonin were abolished by EX527. In conclusion, our results demonstrate that melatonin attenuates sepsis-induced brain injury via SIRT1 signaling activation.

Quadriceps tendon pie-crusting release of stiff knees in total knee arthroplasty.

BACKGROUND: Traditional treatments for stiff knees, such as quadriceps snip and V-Y quadricepsplasty, require extensive soft tissue exposure and lead to recurrent poor arc of motion and a permanent extensor lag. In this study, we evaluated the effect of the quadriceps tendon pie-crusting release for treating limited knee flexion in total knee arthroplasty (TKA) and compared the outcomes of two surgical approaches. METHODS: Sixteen knees with severe osteoarthritis were treated with TKA using either a midvastus (eight knees) or parapatellar (eight knees) approach. Quadriceps tendon pie-crusting release was performed after fixation of the knee prosthesis. Maximum knee flexion, Knee Society Score (KSS), and quadriceps strength were recorded and compared between the two surgical approach groups at different time points. RESULTS: The average maximum flexion angle of the knee increased from 40.6 ± 11.8 preoperatively to 63.1 ± 8.4 after fixation of the knee prosthesis in the midvastus group and from 38.8 ± 10.3 to 65.6 ± 9.0 in the parapatellar group. TKA did not lead to adequate correction of extension contracture in these stiff knees. The quadriceps tendon pie-crusting release further improved knee flexion by 35.0 ± 4.6 and 25.6 ± 4.2 in the midvastus and parapatellar groups, respectively (p < 0.001). Patients in the midvastus group had higher mean KSS (88.2 ± 2.4) compared with the parapatellar group (84.1 ± 3.1) at the last follow-up (p = 0.048). CONCLUSIONS: The quadriceps tendon pie-crusting release technique was an effective procedure for improving knee flexion in cases of stiff knee. The midvastus approach maintained the integrity of the extensor mechanism and resulted in better outcomes than the parapatellar approach.

A nano-stripe based sensor for temperature measurement at the submicrometer and nano scales.

Submicrometer dual-stripe temperature sensors made from a single piece of metal thin film (e.g., Pd) are developed. With the narrowest sensor being 900 nm in width, they show sensitivity of 1-2 µV/K for the full range of 10-300 K. The results confirm the size effect in Seebeck coefficient previously observed in microstripe sensors of the same device configuration.

From PET/CT to PET/MRI: advances in instrumentation and clinical applications.

Multimodality imaging of positron emission tomography/computed tomography (PET/CT) provides both metabolic information and the anatomic structure, which is significantly superior to either PET or CT alone and has greatly improved its clinical applications. Because of the higher soft-tissue contrast of magnetic resonance imaging (MRI) and no extra ionizing radiation, PET/MRI imaging is the hottest topic currently. PET/MRI is swiftly making its way into clinical practice. However, it has many technical difficulties to overcome, such as photomultiplier tubes, which cannot work properly in a magnetic field, and the inability to provide density information on the object for attenuation correction. This paper introduces the technique process of PET/MRI and summarizes its clinical applications, including imaging in oncology, neurology, and cardiology.