A case of recurrent proximal femoral fracture after open reduction and internal fixation with bilateral locking plates for a Rorabeck type II periprosthetic fracture.

INTRODUCTION AND IMPORTANCE: Periprosthetic distal femur fractures (PDFFs) are rare complications that may occur during or after total knee arthroplasty (TKA). The incidence of PDFFs is increasing. Plate internal fixation has demonstrated positive results. However, there is limited research available on the recurrence of periimplant fractures following open reduction and internal fixation with bilateral locking plates. CASE PRESENTATION: A 70-year-old female patient was diagnosed with a Rorabeck type II fracture. Based on the patient's physical condition and available surgical options, minimally invasive open reduction, bilateral plate fixation, and allograft artificial bone grafting were chosen. The postoperative recovery was successful. However, the patient experienced a fall 2 months after the surgery, resulting in a proximal femoral fracture. After considering the patient's condition and family preferences, conservative treatment was ultimately decided upon. CLINICAL DISCUSSION: Minimally invasive bilateral Locking Compression Plate (LCP) as a surgical approach can effectively reduce surgical risks prior to the procedure. Careful selection of screws and the use of C-arm fluoroscopy during plate contouring and fixation are essential to prevent screw penetration through the contralateral cortex. Treatment outcomes were not impacted in patients with normal bone mass; however, in this particular case, the patient had severe osteoporosis, significantly increasing the risk of refracture. It is crucial to improve postoperative monitoring and raise awareness about safety among patients and their families. CONCLUSION: The management of periprosthetic distal femur fractures (PDFFs) is influenced by the type of fracture and bone quality. Mechanical stability and stress dispersion of internal fixation are key factors to consider. In the perioperative setting, involving experienced clinicians is essential to reduce the risk of secondary injuries that may impact treatment outcomes, especially when choosing screws for fixation in patients with low bone density.

Scapulothoracic separation: A severe injury to the upper extremity.

INTRODUCTION AND IMPORTANCE: Scapulothoracic separation is an infrequent ailment marked by the detachment of the upper limb bones from the chest wall, resulting in a range of symptoms. In this report, we present a collection of instances of Scapulothoracic separation. CASE PRESENTATION: A female patient, aged 35, was referred to our emergency department from a primary healthcare center for treatment following a high-energy motor vehicle accident that occurred two days prior. Upon examination, no vascular damage was detected. Following the critical period, the patient underwent surgery to repair a clavicle fracture. Despite the passage of three months since the surgery, the patient continues to experience functional limitations in the affected limb. CLINICAL DISCUSSION: The incidence of Scapulothoracic separation.is uncommon and stems from forceful injuries, predominantly resulting from vehicular mishaps. In managing this condition, it is imperative to prioritize the individual's safety and prioritize targeted treatment thereafter. CONCLUSIONS: The presence or absence of vascular injury determines the need for emergency surgical treatment, while the presence or absence of neurological injury affects the recovery of limb function.

Changes in gap junction proteins Connexin30. 2 and Connexin40 expression in the sinoatrial node of rats with dexmedetomidine-induced sinus bradycardia

Abstract Background Dexmedetomidine (Dex) is widely used, and its most common side effect is bradycardia. The complete mechanism through which Dex induces bradycardia has not been elucidated. This research investigates the expression of gap junction proteins Connexin30.2 (Cx30.2) and Connexin40 (Cx40) within the sinoatrial node of rats with Dex-induced sinus bradycardia. Methods Eighty rats were randomly assigned to five groups. Saline was administered to rats in Group C. In the other four groups, the rats were administered Dex to induce bradycardia. In groups D1and D2, the rats were administered Dex at a loading dose of 30 μg.kg−1 and 100 μg.kg−1 for 10 min, then at 15 μg.kg−1.h−1 and 50 μg.kg−1.h−1 for 120 min separately. The rats in group D1A and D2A were administered Dex in the same way as in group D1and D2; however, immediately after the administration of the loading dose, 0.5 mg atropine was administered intravenously, and then at 0.5 mg.kg−1.h−1 for 120 min. The sinoatrial node was acquired after intravenous infusion was completed. Quantitative real-time polymerase chain reaction and western blot analyses were performed to measure mRNA and protein expression of Cx30.2 and Cx40, respectively. Results The expression of Cx30.2 increased, whereas the expression of Cx40 decreased within the sinoatrial node of rats with Dex-induced sinus bradycardia. Atropine reversed the effects of Dex on the expression of gap junction proteins. Conclusion Dex possibly altered the expression of gap junction proteins to slow down cardiac conduction velocity in the sinoatrial node.

Cerebral cavernous malformation development in chronic mouse models driven by dual recombinases induced gene deletion in brain endothelial cells.

Cerebral cavernous malformation (CCM) is a brain vascular disease which can cause stroke, cerebral hemorrhage and neurological deficits in affected individuals. Loss-of-function mutations in three genes (CCM1, CCM2 and CCM3) cause CCM disease. Multiple mouse models for CCM disease have been developed although each of them are associated with various limitations. Here, we employed the Dre-Cre dual recombinase system to specifically delete Ccm genes in brain endothelial cells. In this new series of CCM mouse models, robust CCM lesions now develop in the cerebrum. The survival curve and lesion burden analysis revealed that Ccm2 deletion causes modest CCM lesions with a median life expectance of ∼10 months and Ccm3 gene deletion leads to the most severe CCM lesions with median life expectance of ∼2 months. The extended lifespan of these mutant mice enables their utility in behavioral analyses of neurologic deficits in adult mice, and allow the development of methods to quantify lesion burden in mice over time and also permit longitudinal drug testing in live animals.

Molecular pathways in sepsis-induced cardiomyocyte pyroptosis: Novel finding on long non-coding RNA ZFAS1/miR-138-5p/SESN2 axis.

OBJECTIVE: ZNFX1 antisense RNA1 (ZFAS1) has been emerged as a tumor oncogene or suppressor. However, understanding the biological role and underlying molecular mechanism of ZFAS1 in sepsis induced myocardial injury (SIMI) requires more evidence. This study was assigned to probe the effect of lncRNA ZFAS1 on sepsis-induced pyroptosis in cardiomyocytes and its underlying mechanism. METHODS: Serums of 22 patients with sepsis-induced myocardial injury (SIMI) and 24 healthy controls were collected to determine the expression levels of ZFAS1 and miR-138-5p. Cardiomyocytes (H9C2) or rats were treated by lipopolysaccharide (LPS) to establish in vivo and in vitro sepsis models. H&E staining was applied to observe myocardial injury of rats. The interactions between ZFAS1 and miR-138-5p as well as miR-138-5p and SESN2 were determined by dual-luciferase reporter gene assay and RNA pull-down assay. TUNEL staining was applied to inspect apoptosis level and CCK-8 to measure cell viability. The mRNA levels of ZFAS1, miR-138-5p and SESN2 were measured by qRT-PCR, while the protein expressions of SESN2 and pyroptosis-related proteins (Caspase-1, ASC and NLRP3) were assessed by Western blotting. Levels of inflammatory factors (TNF-α, IL-1ß, IL-6 and IL-18) were evaluated by ELISA. RESULTS: Patients with SIMI had suppressed ZFAS1 and increased miR-138-5p expression when compared with those in healthy controls. LPS treatment in rats triggered myocardial injury accompanied by interstitial edema and moderate inflammatory cell infiltration. Besides, LPS caused elevated cell apoptosis rate and enhanced cell pyroptosis and inflammation in sepsis cell models. However, ZFAS1 overexpression or SESN2 overexpression in LPS induced rats and in H9C2 cells had meliorated myocardial injury and inflammatory response, indicating that ZFAS1 and SESN2 can inhibit sepsis-induced pyroptosis of cardiomyocytes. MiR-138-5p is a target gene of ZFAS1, while miR-138-5p can negatively mediate SESN2. ZFAS1 alleviated sepsis induced cardiomyocyte pyroptosis by exerting competing endogenous RNA (ceRNA) function to indirectly regulate SESN2, which evidenced by loss and gain functions of ZFAS1 and SESN2. CONCLUSION: LncRNA ZFAS1 serves as a ceRNA of miR-138-5p to up-regulate the expression of SESN2, thereby ameliorating sepsis-induced cardiomyocyte pyroptosis.

Dexmedetomidine inhibits pyroptosis by down-regulating miR-29b in myocardial ischemia reperfusion injury in rats.

OBJECTIVE: Dexmedetomidine (DEX) was reported to protect heart against ischemic-reperfusion (IR) but the mechanism herein remains elusive. This study aims to explore the mechanism of DEX on pyroptosis induced by myocardial ischemic reperfusion (MIR). METHODS: MIR rat models were established and injected DEX or miR-29b agomir/antagomir separately. The possible effect of DEX or miR-29b on myocardial cells was assessed according to measurement on creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), interleukin-1ß (IL-1ß) and interleukin-18 (IL-18), myocardial infarction size, myocardial injury and apoptosis. Western blot determined the expression levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC) and cleaved-caspase-1. Hypoxia/reoxygenation (H/R) cell model was established. The lactate dehydrogenase (LDH) content released by myocardial cells was examined. The relation between miR-29b and FoxO3a was confirmed by dual luciferase reporter gene assay. FoxO3a or ARC level was elevated in H/R myocardial cells to detect its effect on pyroptosis. RESULTS: MIR rat models were successfully established, in which cell pyroptosis was triggered as evidenced by increased expression levels of NLRP3, ASC and cleaved-caspase-1. Rats with DEX precondition had attenuated cell pyroptosis and ameliorated inflammatory response. FoxO3a was a target of miR-29b. MiR-29b agomir or miR-29b antagomir could inhibit or promote the protective effect of DEX on MIR. Overexpression of FoxO3a/ARC axis could suppress myocardial pyroptosis induced by H/R. CONCLUSION: DEX could ameliorate MIR injury (MIRI) and H/R injury in rats and inhibit H/R induced pyroptosis in myocardial cells via down-regulating miR-29b to activate FoxO3a/ARC axis.

Blockade of adenosine A1 receptor in nucleus tractus solitarius attenuates baroreflex sensitivity response to dexmedetomidine in rats.

The α2-adrenergic receptor (α2-AR) agonist dexmedetomidine increases baroreflex sensitivity (BRS). In the current study, we examined the potential role of adenosine A1 receptor (A1R) within the nucleus tractus solitaries (NTS) in such a response. Briefly, adult male Sprague-Dawley rats were anesthetized and randomly received microinjection of selective A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 0.1 pmol/1 µl) or saline vehicle into the right NTS. Ten min after the microinjection, dexmedetomidine infusion started at a rate of 30 µg/kg over 15 min followed by infusion at 15 µg·kg-1·h-1 for 105 min, or 100 µg/kg over 15 min followed by infusion at 50 µg·kg-1·h-1 for 105 min. BRS was examined using a standard phenylephrine method prior to infusion (T0), 60 min (T1) and 120 min (T2) after dexmedetomidine infusion started. Adenosine concentration in plasma and brainstem was measured with high-performance liquid chromatography with vs. without α2-AR antagonist atipamezole pretreatment (0.5 mg/kg, i.p.). Dexmedetomidine increased BRS at both 30 (T0: 0.55 ± 0.25 vs. T1: 2.45 ± 0.37, T2: 2.26 ± 0.56 ms/mmHg, P < 0.05) and 100 µg/kg (T0: 0.63 ± 0.24 vs. T1: 6.21 ± 1.87, T2: 6.30 ± 2.12 ms/mmHg, P < 0.05). DPCPX pretreatment obliterated BRS response to 100-µg/kg dexmedetomidine. At 100 µg/kg, dexmedetomidine increased adenosine concentration in plasma (0.23 ± 0.11 to 0.45 ± 0.07 µg/ml, P < 0.05) and brainstem (1.46 ± 0.30 to 2.52 ± 0.22 µg/ml, P < 0.05); such effect was blocked by atipamezole pretreatment. Western blot analysis showed α2-AR up-regulation by 100-µg/kg dexmedetomidine, which can be prevented by DPCPX. Double-labeling with glial fibrillary acidic protein showed α2-AR up-regulation in astrocytes in the NTS. These results suggest that dexmedetomidine enhances baroreflex sensitivity, possibly by increasing adenosine in NTS and α2-AR expression in astrocytes.

Nur77 limits endothelial barrier disruption to LPS in the mouse lung.

Nur77 is an orphan nuclear receptor implicated in the regulation of a wide range of biological processes, including the maintenance of systemic blood vessel homeostasis. Although Nur77 is known to be expressed in the lung, its role in regulating pulmonary vascular functions remains entirely unknown. In this study, we found that Nur77 is expressed at high levels in the lung, and its expression is markedly upregulated in response to LPS administration. While the pulmonary vasculature of mice that lacked Nur77 appeared to function normally under homeostatic conditions, we observed a dramatic decrease in its barrier functions after exposure to LPS, as demonstrated by an increase in serum proteins in the bronchoalveolar lavage fluid and a reduction in the expression of endothelial junctional proteins, such as vascular endothelial cadherin (VE-cadherin) and ß-catenin. Similarly, we found that siRNA knockdown of Nur77 in lung microvascular endothelial cells also reduced VE-cadherin and ß-catenin expression and increased the quantity of fluorescein isothiocyanate-labeled dextran transporting across LPS-injured endothelial monolayers. Consistent with Nur77 playing a vascular protective role, we found that adenoviral-mediated overexpression of Nur77 both enhanced expression of VE-cadherin and ß-catenin and augmented endothelial barrier protection to LPS in cultured cells. Mechanistically, Nur77 appeared to mediate its protective effects, at least in part, by binding to ß-catenin and preventing its degradation. Our findings demonstrate a key role for Nur77 in the maintenance of lung endothelial barrier protection to LPS and suggest that therapeutic strategies aimed at augmenting Nur77 levels might be effective in treating a wide variety of inflammatory vascular diseases of the lung.

Dioscin inhibits intimal hyperplasia in rat carotid artery balloon injury model through inhibition of the MAPK-FoxM1 pathway.

Vascular smooth muscle cell (VSMC) proliferation and migration are crucial events in the pathological course of atherosclerosis and restenosis after percutaneous coronary intervention (PCI). Dioscin has been shown to exhibit powerful cardiovascular protective effects and potent therapeutic potential in cancer owing to the inhibition of cell proliferation and migration. However, its effects on arterial wall hypertrophy-related diseases caused by VSMC proliferation and migration remain unclear. In this study, we investigated the effects of dioscin on intimal hyperplasia after balloon injury in vivo, its effects on VSMC proliferation and migration in vitro, and the mechanisms underlying these effects. Results showed that dioscin treatment significantly inhibited VSMC proliferation and intimal thickening after balloon injury. In cultured VSMCs, treatment with dioscin significantly decreased fetal bovine serum or platelet-derived growth factor-induced cell proliferation and migration. Moreover, dioscin inhibited the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and expression of Forkhead box M1 (FoxM1) and its downstream target genes. FoxM1 knockdown with shRNA partially counteracted the inhibitory effects of dioscin on cell proliferation and migration. In conclusion, we demonstrated that dioscin attenuated neointima formation in response to balloon injury by suppressing VSMC proliferation and migration through MAPK-FoxM1 pathway. Our data suggested that dioscin might be a potential therapeutic agent for atherosclerosis and restenosis after PCI.

The Cardioprotective Effects of Remote Ischemic Conditioning in a Rat Model of Acute Myocardial Infarction.

BACKGROUND Cardiac remote ischemic conditioning (RIC) is a noninvasive cardioprotective method in ischemia-reperfusion injury and acute myocardial infarction (AMI). The aims of this study were to investigate the effects of RIC in a rat model of AMI. MATERIAL AND METHODS Adult male Sprague-Dawley rats included the AMI group that underwent ligation of the left anterior descending (LAD) coronary artery (n=24), the RIC group that consisted the AMI rat model treated with RIC once daily in the left hind limb until days 1, 7 and 14 (n=24), and the sham group (n=24). Myocardial infarct size was measured by routine histology with triphenyltetrazolium chloride (TTC) and Masson's trichrome histochemical staining for myocardial necrosis and fibrosis, respectively. Serum levels of Bcl-2, Bax, caspase-3, and inducible nitric oxide synthase (iNOS) were measured by enzyme-linked immunosorbent assay (ELISA). The apoptosis index was detected using the TUNEL assay. Spectrophotometry of the myocardium was used to identify mitochondrial complexes and myocardial ATP. RESULTS The RIC group showed improved cardiac hemodynamics, reduced the size of the myocardial infarction, upregulated expression of Bcl-2, and down-regulation of the levels of Bax, caspase-3, and iNOS, and reduced cardiac myocyte apoptosis and inhibited the opening of the mitochondrial permeability transition pore (MPTP). CONCLUSIONS In a rat model of AMI, RIC improved the hemodynamic index, reduce the levels of apoptosis and myocardial injury, and improved mitochondrial function.

Therapeutic effects of a taurine-magnesium coordination compound on experimental models of type 2 short QT syndrome.

Short QT syndrome (SQTS) is a genetic arrhythmogenic disease that can cause malignant arrhythmia and sudden cardiac death. The current therapies for SQTS have application restrictions. We previously found that Mg· (NH2CH2CH2SO3)2· H2O, a taurine-magnesium coordination compound (TMCC) exerted anti-arrhythmic effects with low toxicity. In this study we established 3 different models to assess the potential anti-arrhythmic effects of TMCC on type 2 short QT syndrome (SQT2). In Langendorff guinea pig-perfused hearts, perfusion of pinacidil (20 µmol/L) significantly shortened the QT interval and QTpeak and increased rTp-Te (P<0.05 vs control). Subsequently, perfusion of TMCC (1-4 mmol/L) dose-dependently increased the QT interval and QTpeak (P<0.01 vs pinacidil). TMCC perfusion also reversed the rTp-Te value to the normal range. In guinea pig ventricular myocytes, perfusion of trapidil (1 mmol/L) significantly shortened the action potential duration at 50% (APD50) and 90% repolarization (APD90), which was significantly reversed by TMCC (0.01-1 mmol/L, P<0.05 vs trapidil). In HEK293 cells that stably expressed the outward delayed rectifier potassium channels (IKs), perfusion of TMCC (0.01-1 mmol/L) dose-dependently inhibited the IKs current with an IC50 value of 201.1 µmol/L. The present study provides evidence that TMCC can extend the repolarization period and inhibit the repolarizing current, IKs, thereby representing a therapeutic candidate for ventricular arrhythmia in SQT2.

Effects of non-invasive remote ischemic conditioning on rehabilitation after myocardial infarction.

Recent studies have demonstrated that remote ischemic conditioning (RIC) creates cardioprotection against ischemia/reperfusion injury and myocardial infarction (MI); however, the effects of non-invasive remote ischemic conditioning (nRIC) on prognosis and rehabilitation after MI (post-MI) remain unknown. We successfully established MI models involving healthy adult male Sprague-Dawley rats. The nRIC group repeatedly underwent 5 min of ischemia and 5 min of reperfusion in the left hind limb for three cycles every other day until weeks 4, 6, and 8 after MI. nRIC improved cardiac hemodynamic function and mitochondrial respiratory function through increasing myocardial levels of mitochondrial respiratory chain complexes I, II, III, IV, and adenosine triphosphate (ATP) and decreasing the activity of nitric oxide synthase (NOS). nRIC could inhibit cardiomyocytes apoptosis and reduce myocardium injury through raising the expression of Bcl-2 and reduced the content of creatine kinase-MB, cardiac troponin I and Bax. The results indicated that long-term nRIC could accelerate recovery and improve prognosis and rehabilitation in post-MI rats.

Inhibition of sodium current by taurine magnesium coordination compound prevents cesium chloride-induced arrhythmias.

The mechanism(s) by which taurine magnesium coordination compound (TMCC) inhibits experimental arrhythmias remains poorly understood. The purpose of this study was to observe the effects of TMCC against cesium chloride-induced arrhythmia in the rabbit heart and find whether the antiarrhythmic activity is related to inhibition of sodium current. Early afterdepolarization was induced by 1.5 mM cesium chloride (1 ml kg(-1)) through intravenous injection. The monophasic action potentials (MAP) and electrocardiograms were simultaneously recorded. The effect of TMCC on functional refractory periods (FRPs) in the left atrium was also observed in vitro. Arrhythmias onset was significantly retarded by TMCC. The number of ventricular premature contractions and incidence of monophasic ventricular tachycardia and polyphasic ventricular tachycardia in 10 min were decreased by TMCC. These effects can be abolished by veratridine (10 µg kg(-1)). MAP duration at 90% repolarization was significantly prolonged by TMCC, which can be prolonged even longer by veratridine (10 µg kg(-1)). In vitro experiments showed that FRPs was prolonged by TMCC which can be cancelled by veratridine (10 µg kg(-1)). TMCC prevents cesium chloride-induced arrhythmias, and inhibition of sodium current, in part, contributes to the antiarrhythmic effect of TMCC.