Supplementary decompression and extended surgical time contribute to hidden blood loss In percutaneous endoscopic lumbar discectomy.

Background: It is widely believed that the Percutaneous endoscopic lumbar discectomy (PELD) is associated with minimal blood loss. However, significant perioperative hidden blood loss (HBL) is frequently unaccounted for. This study aimed to investigate HBL and peri-operative factors contributing to HBL in a series of individuals undergoing PELD. Method: ology: A total of 156 consecutive patients with a mean age of 43.6 years (ranging from 18 to 80 years) who underwent PELD at our department from May 2019 to November 2020, were included in the study. Factors including gender, age, body mass index, symptom duration, operation approach/technique, operation duration, the presence of associated chronic diseases, and improvements in the Visual Analog Scale (VAS) score, Japanese Orthopaedic Association (JOA) score and the Oswestry Disability Index (ODI) were analyzed, and Gross's formula was applied to calculate blood loss, which was used to determine HBL. Results: The average total blood loss (TBL) was 221.0 ± 126.2 mL, while the average HBL was 181.7 ± 119.0 mL (82.2 % of TBL). There was no statistically significant difference in HBL between the transverse surgical approach and the interlayer approach. Additionally, no significant differences were observed in improvements in VAS, JOA, and ODI scores between the two surgical approaches. However, the multivariate linear regression analysis revealed that longer surgical time and foraminal decompression were factors contributing to the increase in HBL, which subsequently led to the occurrence of post-operative anemia. Conclusion: HBL is significant in PELD cases with long surgical time and lumbar foraminal decompression.

Activation of transient receptor potential vanilloid 1 ameliorates tau accumulation-induced synaptic damage and cognitive dysfunction via autophagy enhancement.

AIMS: The autophagy-lysosomal pathway is important for maintaining cellular proteostasis, while dysfunction of this pathway has been suggested to drive the aberrant intraneuronal accumulation of tau protein, leading to synaptic damage and cognitive impairment. Previous studies have demonstrated that the activation of transient receptor potential vanilloid 1 (TRPV1) by capsaicin has a positive impact on cognition and AD-related biomarkers. However, the effect and mechanism of TPRV1 activation on neuronal tau homeostasis remain elusive. METHODS: A mouse model of tauopathy was established by overexpressing full-length human tau in the CA3 area. Mice were fed capsaicin diet (0.0125%) or normal diet for 9 weeks. The cognitive ability, synaptic function, tau phosphorylation levels, and autophagy markers were detected. In vitro, capsaicin-induced alterations in cellular autophagy and tau degradation were characterized using two cell models. Besides, various inhibitors were applied to validate the role of TRPV1-mediated autophagy enhancement in tau clearance. RESULTS: We observed that TRPV1 activation by capsaicin effectively mitigates hippocampal tau accumulation-induced synaptic damages, gliosis, and cognitive impairment in vivo. Capsaicin promotes the degradation of abnormally accumulated tau through enhancing autophagic function in neurons, which is dependent on TRPV1-mediated activation of AMP-activated protein kinase (AMPK) and subsequent inhibition of the mammalian target of rapamycin (mTOR). Blocking AMPK activation abolishes capsaicin-induced autophagy enhancement and tau degradation in neurons. CONCLUSION: Our findings reveal that capsaicin-induced TRPV1 activation confers neuroprotection by restoring neuronal tau homeostasis via modulating cellular autophagy and provides additional evidence to support the potential of TRPV1 as a therapeutic target for tauopathies.

Polysorbate 80 as a possible allergenic component in cross-allergy to docetaxel and fosaprepitant: A literature review.

OBJECTIVE: Patients had allergies to both fosaprepitant and docetaxel with similar signs and symptoms. To explore the possible causes of allergy and whether there is cross-allergy between fosaprepitant and docetaxel, we conducted a literature review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. METHODS: A systematic search of the following databases was performed: Pubmed, Embase, Cochrane Library, CINAHL, Scopus, Web of Science and Taylor & Francis. The final search was on 12 November 2022. Two investigators independently selected eligible studies and extracted data according to inclusion and exclusion criteria and assessed the methodological quality of included studies. Any disagreement was resolved by a third researcher. RESULTS: The main cause of fosaprepitant and docetaxel allergy is polysorbate 80. Fosaprepitant and docetaxel have similar allergic symptoms, mainly facial flushing (19.0%, 18.5%); erythema/dermatitis (17.2%, 1.9%); fluid retention (17.2%, 22.2%); and dyspnea, bronchospasm, shortness of breath and coughing (15.5%, 16.7%). Hypotension (1.7%, 7.4%) and decreased oxygen saturation (1.7%, 1.9%) are rare. The treatments for both allergies are similar: stop injection, oxygen, glucocorticoid, antihistamines and symptomatic treatments. CONCLUSION: Polysorbate 80 is the same allergenic component of docetaxel and fosaprepitant. The symptoms and treatments caused by the two drugs are similar. Most allergic reactions are not serious. Medications containing the same allergy ingredient need to be used with caution for patients with severe allergies to polysorbate 80.

Death-associated protein kinase 1 phosphorylates MDM2 and inhibits its protein stability and function.

Breast cancer is one of the major malignancies in women, and most related deaths are due to recurrence, drug resistance, and metastasis. The expression of the mouse double minute 2 (MDM2) oncogene is upregulated in breast cancer; however, its regulatory mechanism has yet to be fully elucidated. Herein, we identified the tumor suppressor death-associated protein kinase 1 (DAPK1) as a novel MDM2 regulator by unbiased peptide library screening. DAPK1 is directly bound to MDM2 and phosphorylates it at Thr419. DAPK1-mediated MDM2 phosphorylation promoted its protein degradation via the ubiquitin-proteasome pathway, resulting in upregulated p53 expression. DAPK1 overexpression, but not its kinase activity-deficient form, decreased colony formation and increased doxorubicin-induced cell death; however, DAPK1 knockdown produced the opposite effects in human breast cancer cells. In a xenograft tumorigenesis assay, DAPK1 overexpression significantly reduced tumor formation, whereas inhibition of DAPK1 kinase activity reduced its antitumorigenic effect. Finally, DAPK1 expression was negatively correlated with MDM2 levels in human breast cancer tissues. Thus, these results suggest that DAPK1-mediated MDM2 phosphorylation and its protein degradation may contribute to its antitumorigenic function in breast cancer.

Neurovascular protection of alisol A on cerebral ischemia mice through activating the AKT/GSK3ß pathway.

Alisol A, a triterpene isolated from Alisma Orientale, has been shown to exhibit anti-inflammatory effects and vascular protection. This study was designed to observe the effect of alisol A on cerebral ischemia (CI)-induced neurovascular dysfunction in the hippocampus and to further explore the potential mechanisms. The results showed that alisol A treatment improved the neurological deficits and cognitive impairment of CI mice. Alisol A reduced gliosis and improved neuronal/glial metabolism. Accordingly, alisol A inhibited inflammatory factors IL-6 and IL-1ß induced by overactivation of astrocytes and microglia, thus protecting the neurovasculature. Furthermore, alisol A promoted the survival of neurons by decreasing the ratio of Bax/Bcl-2, and protected brain microvascular endothelial cells (BMECs) by upregulating the expression of ZO-1, Occludin and CD31. The phosphorylation of protein kinase B (AKT) and glycogen synthase kinase 3ß (GSK3ß) increased after treatment with alisol A. To explore the underlying mechanism, AKT was inhibited. As expected, the neurovascular protection of alisol A above was eliminated by AKT inhibition. The present study primarily suggested that alisol A could exert neurovascular protection in the hippocampus of CI mice by activating the AKT/GSK3ß pathway and may potentially be used for the treatment of CI.

Biological Activities and Solubilization Methodologies of Naringin.

Naringin (NG), a natural flavanone glycoside, possesses a multitude of pharmacological properties, encompassing anti-inflammatory, sedative, antioxidant, anticancer, anti-osteoporosis, and lipid-lowering functions, and serves as a facilitator for the absorption of other drugs. Despite these powerful qualities, NG's limited solubility and bioavailability primarily undermine its therapeutic potential. Consequently, innovative solubilization methodologies have received considerable attention, propelling a surge of scholarly investigation in this arena. Among the most promising solutions is the enhancement of NG's solubility and physiological activity without compromising its inherent active structure, therefore enabling the formulation of non-toxic and benign human body preparations. This article delivers a comprehensive overview of NG and its physiological activities, particularly emphasizing the impacts of structural modification, solid dispersions (SDs), inclusion compound, polymeric micelle, liposomes, and nanoparticles on NG solubilization. By synthesizing current research, this research elucidates the bioavailability of NG, broadens its clinical applicability, and paves the way for further exploration and expansion of its application spectrum.

The combination of Alisma and Atractylodes ameliorates cerebral ischaemia/reperfusion injury by negatively regulating astrocyte-derived exosomal miR-200a-3p/141-3p by targeting SIRT1.

ETHNOPHARMACOLOGICAL RELEVANCE: The combination of Alisma and Atractylodes (AA), a classical traditional Chinese herbal decoction, may protect against cerebral ischaemia/reperfusion injury (CIRI). However, the underlying mechanism has not been characterized. Intriguingly, exosomal microRNAs (miRNAs) have been recognized as vital factors in the pharmacology of Chinese herbal decoctions. AIM OF THE STUDY: The aim of the present study was to assess whether the neuroprotective effect of AA was dependent on the efficient transfer of miRNAs via exosomes in the brain. MATERIALS AND METHODS: Bilateral common carotid artery ligation (BCAL) was used to induce transient global cerebral ischaemia/reperfusion (GCI/R) in C57BL/6 mice treated with/without AA. Neurological deficits were assessed with the modified neurological severity score (mNSS) and Morris water maze (MWM) test. Western blot (WB) analysis was used to detect the expression of sirtuin 1 (SIRT1) in the cerebral cortex. The inflammatory state was quantitatively evaluated by measuring the expression of phospho-Nuclear factor kappa B (p-NF-κB), Interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) using WB analysis and glial fibrillary acidic protein (GFAP) immunohistochemical staining. The protein expression of zonula occluden-1 (ZO-1), occludin, caudin-5 and CD31 was examined by immunohistochemical staining to determine blood‒brain barrier (BBB) permeability. Exosomes were extracted from the brain interstitial space by ultracentrifugation and identified by transmission electron microscopy (TEM), WB analysis and nanoparticle tracking analysis (NTA). The origin of exosomes was clarified by measuring the specific mRNAs within exosomes via Real Time Quantitative PCR (RT‒qPCR). Differential miRNAs in exosomes were identified using microarray screening and were validated by RT‒qPCR. Exosomes were labelled with fluorescent dye (PKH26) and incubated with bEnd.3 cells, the supernatant was collected, IL-1ß/TNF-α expression was measured using enzyme-linked immunosorbent assay (ELISA), total RNA was extracted, and miR-200a-3p/141-3p expression was examined by RT‒qPCR. In addition, the levels of miR-200a-3p/141-3p in oxygen glucose deprivation/reoxygenation (OGD/R)-induced bEnd.3 cells were quantified. The direct interaction between miR-200a-3p/141-3p and the SIRT1 3' untranslated region (3'UTR) was measured by determining SIRT1 expression in bEnd.3 cells transfected with the miR-200a-3p/141-3p mimic/inhibitor. RESULTS: Severe neurological deficits and memory loss caused by GCI/R in mice was markedly ameliorated by AA treatment, particularly in the AA medium-dose group. Moreover, AA-treated GCI/R-induced mice showed significant increases in SIRT1, ZO-1, occludin, caudin-5, and CD31 expression levels and decreases in p-NF-κB, IL-1ß, TNF-α, and GFAP expression levels compared with those in untreated GCI/R-induced mice. Furthermore, we found that miR-200a-3p/141-3p was enriched in astrocyte-derived exosomes from GCI/R-induced mice and could be inhibited by treatment with a medium dose of AA. The exosomes mediated the transfer of miR-200a-3p/141-3p into bEnd.3 cells, promoted IL-1ß and TNF-α release and downregulated the expression of SIRT1. No significant changes in the levels of miR-200a-3p/141-3p were observed in OGD/R-induced bEnd.3 cells. The miR-200a-3p/141-3p mimic/inhibitor decreased/increased SIRT1 expression in bEnd.3 cells, respectively. CONCLUSION: Our findings demonstrated that AA attenuated inflammation-mediated CIRI by inhibiting astrocyte-derived exosomal miR-200a-3p/141-3p by targeting the SIRT1 gene, which provided further evidence and identified a novel regulatory mechanism for the neuroprotective effects of AA.

Electrophysiological evidence of diabetes' impacts on central conduction recoveries in degenerative cervical myelopathy after surgery.

OBJECTIVES: To assess the impact of diabetes mellitus (DM) on the postoperative motor and somatosensory functional recoveries of degenerative cervical myelopathy (DCM) patients. METHODS: Motor and somatosensory evoked potentials (MEP and SSEPs) and modified Japanese Orthopedic Association (mJOA) scores were recorded in 27 diabetic (DCM-DM group) and 38 non-diabetic DCM patients (DCM group) before and 1 year after surgery. The central motor (CMCT) and somatosensory (CSCT) conduction time were recorded to evaluate the conductive functions of the spinal cord. RESULTS: The mJOA scores, CMCT and CSCT improved (t test, p < 0.05) in both of the DCM-DM and DCM groups 1 year after surgery. The mJOA recovery rate (RR) and CSCT recovery ratio were significantly worse (t test, p < 0.05) in the DCM-DM group compared to the DCM group. DM proved to be a significant independent risk factor for poor CSCT recovery (OR = 4.52, 95% CI 2.32-7.12) after adjusting for possible confounding factors. In DCM-DM group, CSCT recovery ratio was also correlated with preoperative HbA1 level (R = - 0.55, p = 0.003). Furthermore, DM duration longer than 10 years and insulin dependence were risk factors for lower mJOA, CMCT and CSCT recoveries among all DCM-DM patients (t test, p < 0.05). CONCLUSIONS: DM may directly hinders spinal cord conduction recovery in DCM patients after surgery. Corticospinal tract impairments are similar between DCM and DCM-DM patients, but significantly worsened in chronic or insulin-dependent DM patients. The dorsal column is more sensitively affected in all DCM-DM patients. Deeper investigation into the mechanisms and neural regeneration strategies is needed.

Mycobacterium bovis BCG Given at Birth Followed by Inactivated Respiratory Syncytial Virus Vaccine Prevents Vaccine-Enhanced Disease by Promoting Trained Macrophages and Resident Memory T Cells.

Respiratory syncytial virus (RSV) infects more than 60% of infants in their first year of life. Since an experimental formalin-inactivated (FI) RSV vaccine tested in the 1960s caused enhanced respiratory disease (ERD), few attempts have been made to vaccinate infants. ERD is characterized by Th2-biased responses, lung inflammation, and poor protective immune memory. Innate immune memory displays an increased nonspecific effector function upon restimulation, a process called trained immunity, or a repressed effector function upon restimulation, a process called tolerance, which participates in host defense and inflammatory disease. Mycobacterium bovis bacillus Calmette-Guérin (BCG) given at birth can induce trained immunity as well as heterologous Th1 responses. We speculate that BCG given at birth followed by FI-RSV may alleviate ERD and enhance protection through promoting trained immunity and balanced Th immune memory. Neonatal mice were given BCG at birth and then vaccinated with FI-RSV+Al(OH)3. BCG/FI-RSV+Al(OH)3 induced trained macrophages, tissue-resident memory T cells (TRM), and specific cytotoxic T lymphocytes (CTL) in lungs and inhibited Th2 and Th17 cell immune memory, all of which contributed to inhibition of ERD and increased protection. Notably, FI-RSV+Al(OH)3 induced tolerant macrophages, while BCG/FI-RSV+Al(OH)3 prevented the innate tolerance through promoting trained macrophages. Moreover, inhibition of ERD was attributed to trained macrophages or TRM in lungs but not memory T cells in spleens. Therefore, BCG given at birth to regulate trained immunity and TRM may be a new strategy for developing safe and effective RSV killed vaccines for young infants. IMPORTANCE RSV is the leading cause of severe lower respiratory tract infection of infants. ERD, characterized by Th2-biased responses, inflammation, and poor immune memory, has been an obstacle to the development of safe and effective killed RSV vaccines. Innate immune memory participates in host defense and inflammatory disease. BCG given at birth can induce trained immunity as well as heterologous Th1 responses. Our results showed that BCG/FI-RSV+Al(OH)3 induced trained macrophages, TRM, specific CTL, and balanced Th cell immune memory, which contributed to inhibition of ERD and increased protection. Notably, FI-RSV+Al(OH)3 induced tolerant macrophages, while BCG/FI-RSV+Al(OH)3 prevented tolerance through promoting trained macrophages. Moreover, inhibition of ERD was attributed to trained macrophages or TRM in lungs but not memory T cells in spleens. BCG at birth as an adjuvant to regulate trained immunity and TRM may be a new strategy for developing safe and effective RSV killed vaccines for young infants.

Quality of life in patients with breast cancer with neoadjuvant chemotherapy: a systematic review.

OBJECTIVES: The aims of this systematic review were to assess the impact of neoadjuvant chemotherapy (NAC) on breast cancer (BC) patients' quality of life (QOL), to compare the different regimens of NAC on BC patients' QOL, to compare NAC versus adjuvant chemotherapy on BC patients' QOL and to identify predictors of QOL on patients with BC receiving NAC. DESIGN: The design used Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES: Cinahl, Embase, Pubmed, Scopus, Web of Science, Cochrane library and PsycINFO were searched through 27 December 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: The inclusion criteria were included: patients with BC receiving NAC, outcome measures related to QOL and published in English. The exclusion criteria were included: duplicates or overlapping participants, not original research, data or full text not available and qualitative study. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers used standardised methods to search, screen and code included studies. The risk of bias in individual studies was evaluated with Cochrane collaboration's tool for assessing risk bias, Newcastle Ottawa Score or Joanna Briggs Institute Critical Appraisal tool. This systematic review performs narrative synthesis based on several different themes. RESULTS: The initial search resulted in 2994 studies; 12 of these studies fulfilled inclusion criteria. There was no significant difference in the QOL of BC before and after NAC, but patients experienced adverse reactions and depression during chemotherapy. Different regimens of NAC have different effects on patients' QOL. Patients with NAC had more severe physical discomfort than those with adjuvant chemotherapy. However, BC patients' QOL can be improved by intervening on social or family support, and these predictors, including chronotype, QOL before NAC and depression. CONCLUSIONS: More original research is needed in future to understand the profile and predictors of QOL in patients with BC on NAC, which will help clinicians and patients make decisions and deal with NAC-related issues.

Proline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to development of allergic asthma in childhood of mice.

Background: Infants with respiratory syncytial virus (RSV)-associated bronchiolitis are at increased risk of childhood asthma. Recent studies demonstrated that certain infections induce innate immune memory (also termed trained immunity), especially in macrophages, to respond more strongly to future stimuli with broad specificity, involving in human inflammatory diseases. Metabolic reprogramming increases the capacity of the innate immune cells to respond to a secondary stimulation, is a crucial step for the induction of trained immunity. We hypothesize that specific metabolic reprogramming of lung trained macrophages induced by neonatal respiratory infection is crucial for childhood allergic asthma. Objective: To address the role of metabolic reprogramming in lung trained macrophages induced by respiratory virus infection in allergic asthma. Methods: Neonatal mice were infected and sensitized by the natural rodent pathogen Pneumonia virus of mice (PVM), a mouse equivalent strain of human RSV, combined with ovalbumin (OVA). Lung CD11b+ macrophages in the memory phase were re-stimulated to investigate trained immunity and metabonomics. Adoptive transfer, metabolic inhibitor and restore experiments were used to explore the role of specific metabolic reprogramming in childhood allergic asthma. Results: PVM infection combined with OVA sensitization in neonatal mice resulted in non-Th2 (Th1/Th17) type allergic asthma following OVA challenge in childhood of mice. Lung CD11b+ macrophages in the memory phage increased, and showed enhanced inflammatory responses following re-stimulation, suggesting trained macrophages. Adoptive transfer of the trained macrophages mediated the allergic asthma in childhood. The trained macrophages showed metabolic reprogramming after re-stimulation. Notably, proline biosynthesis remarkably increased. Inhibition of proline biosynthesis suppressed the development of the trained macrophages as well as the Th1/Th17 type allergic asthma, while supplement of proline recovered the trained macrophages as well as the allergic asthma. Conclusion: Proline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to development of allergic asthma in childhood. Proline metabolism could be a well target for prevention of allergic asthma in childhood.

Comparison of blood loss between tranexamic acid-soaked absorbable Gelfoam and topical retrograde injection via drainage catheter plus clamping in cervical laminoplasty surgery.

BACKGROUND: To compare the safety and efficacy of tranexamic acid (TXA)-soaked absorbable Gelfoam and the retrograde injection of TXA through a drain with drain-clamping in degenerative cervical laminoplasty patients. METHODS: Patients were assigned into either TXA retrograde injection (TXA-RI), TXA-soaked absorbable Gelfoam (TXA-Gel), or control groups. The demographics, operative measurements, volume and length of drainage, length of hospital stay, complete blood cell count, coagulopathy, postoperative complications, and blood transfusion were recorded. RESULTS: We enrolled 133 patients, with 44, 44, and 45 in the TXA-RI, TXA-Gel, and control groups, respectively. The baseline characteristics did not differ significantly among the three groups. The TXA-RI group exhibited a lower volume and length of postoperative drainage compared to the TXA-Gel and control groups (126.60 ± 31.27 vs. 156.60 ± 38.63 and 275.45 ± 75.27 mL; 49.45 ± 9.70 vs 58.70 ± 10.46 and 89.31 ± 8.50 hours, all P < 0.01). The TXA-RI group also had significantly shorter hospital stays compared to the control group (5.31 ± 1.18 vs 7.50 ± 1.25 days, P < 0.05) and higher hemoglobin and hematocrit levels (12.58 ± 1.67 vs 11.28 ± 1.76 g/dL; 36.62 ± 3.66% vs 33.82 ± 3.57%, both P < 0.05) at hospital discharge. In the TXA-RI and TXA-Gel groups, the D-dimmer (DD) and fibrinogen (FIB) were significantly lower than those in the control group after surgery (P < 0.05). None of the patients required blood transfusion. No complications, including thromboembolic events, were reported. CONCLUSION: Topical retrograde injection of TXA through a drain with drain-clamping at the conclusion of unilateral posterior cervical expansive open-door laminoplasty may effectively reduce postoperative blood loss and the length of hospital stays without increasing postoperative complications.

Microencapsulation of algae oil by complex coacervation of chitosan and modified starch: Characterization and oxidative stability.

The formation of complex coacervation using chitosan and octenyl succinic anhydride modified starch (OSA starch) and microencapsulation of algae oil were investigated in this study. The zeta-potential, turbidity and coacervate yield were evaluated as a function of pH and the chitosan- OSA starch mass ratio. The highest coacervate yield was achieved at pH 6.0 with a chitosan to OSA starch ratio of 1:3 (w/w). Isothermal titration calorimetry (ITC) indicated favorable affinity (Ka = 1.51 × 105 M-1) between chitosan and OSA starch. The microcapsules yielded an encapsulation efficiency (EE) in the range of 42.8 ± 0.8%- 93.1 ± 1.2%, the loading capacity ranged between 30.4 ± 2.7% and 58.3 ± 1.3%. Fourier transform infrared spectroscopy (FT-IR) spectra and scanning electron microscopy (SEM) further confirmed the microencapsulation. In comparison with the bulk oil, the microencapsulated algae oil exhibited improved oxidative stability during storage.

Comparison of Bazaz scale, Dysphagia Short Questionnaire, and Hospital for Special Surgery-Dysphagia and Dysphonia Inventory for Assessing Dysphagia Symptoms After Anterior Cervical Spine Surgery in Chinese Population.

Dysphagia is one of the most common complaints after anterior cervical spine surgery. The Bazaz scale, the Dysphagia Short Questionnaire (DSQ), and the Hospital for Special Surgery-Dysphagia and Dysphonia Inventory (HSS-DDI) were patient-reported outcome measures assessing the patients' perceptions of their swallowing functions after surgery. This prospective diagnostic test study aimed to compare these surveys' psychometric properties in the Chinese population. We evaluated 150 consecutive patients after anterior cervical spine surgery with the Bazaz scale, DSQ, HSS-DDI, and M.D. Anderson Dysphagia Inventory (MDADI). The reliability and validity of the Bazaz scale, DSQ, and HSS-DDI were compared. Receiver operating characteristic (ROC) curves of the DSQ, Bazaz scale, and HSS-DDI were constructed using the MDADI as a reference criterion. Their areas under the curve (AUCs) were further analyzed. In total, 132 participants completed all of the surveys. The results showed that all surveys were significantly correlated with each other. The HSS-DDI and HSS-Dysphagia subscale showed near-perfect reliability (Cronbach α = 0.969 and 0.957, respectively). ROC curves showed both HSS-DDI and HSS-Dysphagia subscale had greater accuracy (AUCs > 0.9) in detecting mild dysphagia and moderate/severe dysphagia. The HSS-Dysphagia subscale achieved higher accuracy in assessing the dysphagia symptoms after anterior cervical spine surgery. The Bazaz scale was considered less accurate than other scales. Our results provided guidance for selecting the appropriate measuring tool during clinical and research practices.

The Role of Oxidative Stress in Epigenetic Changes Underlying Autoimmunity.

Significance: Epigenetic dysregulation plays an important role in the pathogenesis and development of autoimmune diseases. Oxidative stress is associated with autoimmunity and is also known to alter epigenetic mechanisms. Understanding the interplay between oxidative stress and epigenetics will provide insights into the role of environmental triggers in the development of autoimmunity in genetically susceptible individuals. Recent Advances: Abnormal DNA and histone methylation patterns in genes and pathways involved in interferon and tumor necrosis factor signaling, cellular survival, proliferation, metabolism, organ development, and autoantibody production have been described in autoimmunity. Inhibitors of DNA and histone methyltransferases showed potential therapeutic effects in animal models of autoimmune diseases. Oxidative stress can regulate epigenetic mechanisms via effects on DNA damage repair mechanisms, cellular metabolism and the local redox environment, and redox-sensitive transcription factors and pathways. Critical Issues: Studies looking into oxidative stress and epigenetics in autoimmunity are relatively limited. The number of available longitudinal studies to explore the role of DNA methylation in the development of autoimmune diseases is small. Future Directions: Exploring the relationship between oxidative stress and epigenetics in autoimmunity will provide clues for potential preventative measures and treatment strategies. Inception cohorts with longitudinal follow-up would help to evaluate epigenetic marks as potential biomarkers for disease development, progression, and treatment response in autoimmunity. Antioxid. Redox Signal. 36, 423-440.

Iron deficiency exacerbates cisplatin- or rhabdomyolysis-induced acute kidney injury through promoting iron-catalyzed oxidative damage.

Iron deficiency is the most common micronutrient deficiency worldwide. While iron deficiency is known to suppress embryonic organogenesis, its effect on the adult organ in the context of clinically relevant damage has not been considered. Here we report that iron deficiency is a risk factor for nephrotoxic intrinsic acute kidney injury of the nephron (iAKI). Iron deficiency exacerbated cisplatin-induced iAKI by markedly increasing non-heme catalytic iron and Nox4 protein which together catalyze production of hydroxyl radicals followed by protein and DNA oxidation, apoptosis and ferroptosis. Crosstalk between non-heme catalytic iron/Nox4 and downstream oxidative damage generated a mutual amplification cycle that facilitated rapid progression of cisplatin-induced iAKI. Iron deficiency also exacerbated a second model of iAKI, rhabdomyolysis, via increasing catalytic heme-iron. Heme-iron induced lipid peroxidation and DNA oxidation by interacting with Nox4-independent mechanisms, promoting p53/p21 activity and cellular senescence. Our data suggests that correcting iron deficiency and/or targeting specific catalytic iron species are strategies to mitigate iAKI in a wide range of patients with diverse forms of kidney injury.

A minimum 8-year follow-up comparative study of decompression and coflex stabilization with decompression and fusion.

The current study aimed to compare the outcomes of decompression and interlaminar stabilisation with those of decompression and fusion for the treatment of lumbar degenerative disease (LDD) at a minimum 8-year follow-up. The current study also aimed to analyse the risk factors of radiographic adjacent segment degeneration (ASD). A total of 82 consecutive patients with LDD who underwent surgery between June 2007 and February 2011 were retrospectively reviewed. Of these patients, 39 underwent decompression and Coflex interspinous stabilisation (Coflex group) and 43 underwent decompression and posterior lumbar interbody fusion (PLIF) (PLIF group). All patients had a minimum of 8-years of follow-up data. Radiographic and clinical outcomes were compared between the groups, and the risk factors of developing radiographic ASD were also evaluated. The Oswestry disability index and visual analogue scale leg and back pain scores of both groups significantly improved compared with the baseline (all P<0.05), and no difference were indicated between the two groups at each follow-up time point (P>0.05). The Coflex group exhibited preserved mobility (P<0.001), which was associated with a decreased amount of blood loss (P<0.001), shorter duration of surgery (P=0.001), shorter duration of hospital stay and a lower incidence of ASD (12.8 vs. 32.56%; P=0.040) compared with the fusion group. The current study indicated that coflex and fusion technologies are safe and effective for the treatment of LDD, based on long-term follow-up data. However, Coflex interspinous stabilisation was revealed to reduce ASD incidence. Under strict indications, Coflex interspinous stabilisation is an effective and safe treatment method.

Intravascular papillary endothelial hyperplasia as a rare cause of cervicothoracic spinal cord compression: A case report.

BACKGROUND: Intravascular papillary endothelial hyperplasia (IPEH) is a rare benign reactive vascular lesion that grows into an expansile compressing mass. It most commonly involves the skin and subcutaneous tissue. Spinal involvement is rare, with only 11 reported cases in the literature. We report, to our knowledge, the first case of IPEH in the cervicothoracic spinal canal and present a literature review. CASE SUMMARY: A 27-year-old man presented with acute-onset neck pain, numbness, and weakness in his extremities. Magnetic resonance imaging showed an epidural mass in the cervicothoracic (C6-T1) spinal canal and vertebral hemangioma (VH) involving the C7 vertebral body. C6-T1 Laminectomy and radical excision of the mass were performed. Histopathological examinations revealed papillary proliferation of vascular endothelial cells with thrombus formation, and an IPEH diagnosis was made. By his 6-mo follow-up appointment, his symptoms were relieved without recurrence. The possible pathogenesis, clinical and imaging features, differential diagnosis, and management of IPEH were reviewed. CONCLUSION: We report, to our knowledge, the first case of IPEH in the cervicothoracic spinal canal, treated via complete resection, and showing a favorable outcome. We found a causal relationship between spinal IPEH and VH; this partly explains the mechanism of IPEH.

Increased lateral femoral condyle ratio is associated with greater risk of ALC injury in non-contact anterior cruciate ligament injury.

PURPOSE: To examine whether increased lateral femoral condyle ratio (LFCR) correlates with increased risk of Anterior cruciate ligament (ACL) injury (1) and to evaluate the relationship between the LFCR and anterolateral complex (ALC) injury in non-contact ACL torn knees (2). METHODS: Six hundred and seventy-two patients who underwent ACL reconstruction surgery between 2013 and 2019 were retrospectively reviewed, and 120 patients were finally included in the study. Forty patients (ACL + ALC injury) were included in the study group, while forty patients with isolated ACL injury (isolated ACL injury group) and 40 patients who suffered from meniscal tear without ACL or ALC injury were matched in a 1:1 fashion by age, sex, and BMI to the study group (ACL + ALC injury). The LFCR was measured on standard lateral radiographs in a blinded fashion. The differences between the three groups were analyzed by ANOVA. A ROC (Receiver Operating Characteristic) curve was produced to determine risk of ACL injury and risk of concomitant ALC injury in non-contact ACL injury. RESULTS: The mean LFCR was 71.9% ± 3.1% in the ACL + ALC injury group, 68.4% ± 3.2% in the isolated ACL injury group, and 66.8% ± 2.6% in the control group (patients who suffered from meniscal tear without ACL or ALC injury). Significantly greater LFCR was found in the ACL + ALC injury group than that in the isolated ACL injury group (p < 0.017). Greater LFCR was additionally confirmed in the ACL injury group as compared to the control group (p < 0.05). ROC curve analysis demonstrated that LFCR > 68.3% was predictive for an increased risk of ACL injury in the entire cohort. LFCR > 69.4% was predictive for an increased risk of ALC injury in non-contact ACL ruptured patients. CONCLUSION: Increased LFCR was found to be associated with greater risk of ALC injury in non-contact ACL ruptured patients. Additionally, increased LFCR was further confirmed to be correlated with increased risk of ACL injury in an Asian population. The data from this study may help recognize patients undergoing ACL reconstruction that could benefit from additional extra-articular tenodesis. LEVEL OF EVIDENCE: III.

Evaluation on the application of transcranial Doppler (TCD) and electroencephalography (EEG) in patients with vertebrobasilar insufficiency.

BACKGROUND: To evaluate the diagnostic value of transcranial Doppler (TCD) and electroencephalography (EEG) in patients with vertebrobasilar insufficiency (VBI) during clinical diagnosis and treatment METHODS: Eighty patients diagnosed with VBI in our hospital from June 2018 to December 2019 were randomly selected as the observation group, and 80 healthy people who received physical examination in the same period were selected as the control group. The abnormal rate, main performance and results, and the peak velocity of blood flow and vertebrobasilar artery blood flow of the two groups were compared. RESULTS: The abnormal rate of EEG and TCD in VBI patients was 38.75% (31/80) and the 93.75% (75/80), respectively. In TCD examination, ACA, PCA, MCA, and VA of both sides of the observation group were higher than those of the control group, while BA was lower than that of the control group (P < 0.05). The Vs, Vd, and Vm on both sides of BA and VA in the observation group were lower than those in the control group, while PI and RI were higher than those in the control group (P < 0.05). CONCLUSIONS: TCD examination is highly sensitive to the degree and pattern of cerebral ischemia in VBI patients. EEG examination will define the changes of brain cell function after cerebral ischemia. Therefore, EEG and TCD have their own advantages. The application of TCD and EEG can be considered in the early diagnosis, curative effect, and prognosis evaluation of VBI patients, so as to improve the accuracy of diagnosis and prognosis.