Promotion of Raf-1/ASK1 complex formation by corylin inhibits cell apoptosis in myocardial ischemia/reperfusion injury.

Effective treatment of myocardial ischemia-reperfusion (MIR) injury remains an unmet clinical need. Cardiomyocyte apoptosis is common at this stage and poses a significant risk. Corylin, a flavonoid compound extracted from Psoralea corylifolia L., has been shown to have anti-inflammatory, anticancer, and antiatherosclerotic properties. However, whether and how corylin affects MIR injury remain unclear. In this study, we explored the mechanism of corylin as a potent therapeutic agent for MI/R injury, using a left anterior descending (LAD) coronary artery ligation and oxygen-glucose deprivation and reperfusion (OGD/R) model in vivo and in vitro. TUNEL, Annexin-V/PI double staining,Ki67 immunohistochemistry, western blot analysis, and immunofluorescence were used to validate cell apoptosis level and Raf-1/ASK1 complex activity. The interaction between corylin and Raf-1/ASK1 complex was detected using molecular docking, corylin-Raf-1 binding assays, and coimmunoprecipitation (Co-IP). Moreover, TTC staining, echocardiography, HE staining, Masson trichrome staining and serological testing were performed to assess the cardioprotective effects of corylin in vivo. These findings showed that corylin reduces MIR injury-induced cardiomyocyte apoptosis and improves cardiac function. Mechanistically, corylin can interact with Raf-1 and promote the formation of the Raf-1/ASK1 complex, thus inhibiting cardiomyocyte apoptosis. In conclusion, our results demonstrate that corylin ameliorated cardiac dysfunction after MIR injury by reducing myocardial apoptosis.

An ultra-sensitive and rapid immunosensor for the onsite detection of circulating tumor DNA in breast cancer.

Breast cancer currently stands as the most prevalent form of cancer worldwide and the primary cause of cancer-related deaths among women. However, the current diagnostic methods for breast cancer exhibit several limitations, including invasiveness, high costs, and limited sensitivity and specificity. The detection of the PIK3CA-H1047R variant is of paramount importance due to its close association with tumor growth and treatment resistance. Consequently, developing a straightforward, rapid, and highly sensitive approach for detecting PIK3CA-H1047R is of utmost importance. We have been working on the development of a rapid and ultrasensitive biosensor, leveraging the alternating current (AC) electrokinetic (ACEK) capacitive sensing method. This biosensor involves modifying the surface of interdigital electrodes with antibodies, facilitating the antibody-antigen-binding process through AC electrokinetic techniques. Our sensor strategy directly measures the interface capacitance, and the rate of change serves as a quantitative marker for event identification. Remarkably, our biosensor successfully detects the PIK3CA-H1047R antigen within a concentration range of 1 ng/mL to 1 µg/mL. In conclusion, this study proposes a fast and highly sensitive biosensor for the detection of a key breast cancer marker, the PIK3CA-H1047R variant. This technology is expected to improve breast cancer diagnosis, address the limitations of current methods, and provide patients with better treatment options. This detection method offers a promising avenue for on-site and real-time sensitive detection of the PIK3CA-H1047R antigen, potentially revolutionizing breast cancer diagnosis.

Radial extracorporeal shockwave promotes osteogenesis-angiogenesis coupling of bone marrow stromal cells from senile osteoporosis via activating the Piezo1/CaMKII/CREB axis.

Radial extracorporeal shockwave (r-ESW) and bone marrow stromal cells (BMSCs) have been reported to alleviate senile osteoporosis (SOP), but its regulatory mechanism remains unclear. In this study, we firstly isolated human BMSCs from bone marrow samples and treated with varying r-ESW doses. And we found that r-ESW could enhance the proliferation of SOP-BMSCs in a dose-dependent manner by EdU assay. Subsequently, the impact of r-ESW on the proliferation, apoptosis and multipotency of BMSCs was assessed. And the outcomes of flow cytometry, Alizarin red S (ARS), and tube formation test demonstrated that the optimal shockwave obviously boosted SOP-BMSCs osteogenesis and angiogenesis but exhibited no significant impact on cell apoptosis. Additionally, the signaling of Piezo1 and CaMKII/CREB was examined by Western blotting, qPCR and immunofluorescence. And the results showed that r-ESW promoted the expression of Piezo1, increased intracellular Ca2+ and activated the CaMKII/CREB signaling pathway. Then, the application of Piezo1 siRNA hindered the r-ESW-induced enhancement ability of osteogenesis coupling with angiogenesis of SOP-BMSCs. The use of the CaMKII/CREB signaling pathway inhibitor KN93 suppressed the Piezo1-induced increase in osteogenesis and angiogenesis in SOP-BMSCs. Finally, we also found that r-ESW might alleviate SOP in the senescence-accelerated mouse prone 6 (SAMP6) model by activating Piezo1. In conclusion, our research offers experimental evidence and an elucidated underlying molecular mechanism to support the use of r-ESW as a credible rehabilitative treatment for senile osteoporosis.

Comparison between solid pseudopapillary neoplasms of the pancreas and pancreatic ductal adenocarcinoma with cystic changes using computed tomography.

BACKGROUND: Solid pseudopapillary neoplasms of the pancreas (SPN) share similar imaging findings with pancreatic ductal adenocarcinoma with cystic changes (PDAC with cystic changes), which may result in unnecessary surgery. AIM: To investigate the value of computed tomography (CT) in differentiation of SPN from PDAC with cystic changes. METHODS: This study retrospectively analyzed the clinical and imaging findings of 32 patients diagnosed with SPN and 14 patients diagnosed with PDAC exhibiting cystic changes, confirmed through pathological diagnosis. Quantitative and qualitative analysis was performed, including assessment of age, sex, tumor size, shape, margin, density, enhancement pattern, CT values of tumors, CT contrast enhancement ratios, "floating cloud sign," calcification, main pancreatic duct dilatation, pancreatic atrophy, and peripancreatic invasion or distal metastasis. Multivariate logistic regression analysis was used to identify relevant features to differentiate between SPN and PDAC with cystic changes, and receiver operating characteristic curves were obtained to evaluate the diagnostic performance of each variable and their combination. RESULTS: When compared to PDAC with cystic changes, SPN had a lower age (32 years vs 64 years, P < 0.05) and a slightly larger size (5.41 cm vs 3.90 cm, P < 0.05). SPN had a higher frequency of "floating cloud sign" and peripancreatic invasion or distal metastasis than PDAC with cystic changes (both P < 0.05). No significant difference was found with respect to sex, tumor location, shape, margin, density, main pancreatic duct dilatation, calcification, pancreatic atrophy, enhancement pattern, CT values of tumors, or CT contrast enhancement ratios between the two groups (all P > 0.05). The area under the receiver operating characteristic curve of the combination was 0.833 (95% confidence interval: 0.708-0.957) with 78.6% sensitivity, 81.3% specificity, and 80.4% accuracy in differentiation of SPN from PDAC with cystic changes. CONCLUSION: A larger tumor size, "floating cloud sign," and peripancreatic invasion or distal metastasis are useful CT imaging features that are more common in SPN and may help discriminate SPN from PDAC with cystic changes.

Case report: Near-fatal hypermagnesemia resulting from the use of Epsom salts in a patient with normal renal function.

Hypermagnesemia commonly occurs in patients with renal dysfunction. Diagnosing hypermagnesemia represents a challenge due to its rarity and the absence of routine monitoring of magnesium levels. Furthermore, the lack of awareness among clinicians regarding this uncommon condition frequently leads to delayed diagnoses. Few patients survive with a serum magnesium level exceeding 7 mmol/L. This article presents a case study of near-fatal hypermagnesemia resulting from the oral administration of Epsom salts in a patient with normal renal function. A 60-year-old female presented to the gastroenterology department on Oct. 6, 2023, with a 3-day history of black stools. She underwent subtotal gastrectomy in 2005 and has a stable history of nephrotic syndrome. To investigate the cause of her bleeding, electronic gastroscopy and colonoscopy were scheduled for Oct. 11, 2023. She experienced a sudden loss of consciousness 30 min after the ingestion of Epsom salts. The attending physician suspected a severe magnesium poisoning. She was promptly administered calcium gluconate, underwent tracheal intubation with ambu bag ventilation, and received early continuous renal replacement therapy (CRRT). Swift diagnosis and CRRT contributed to a reduction in her serum magnesium levels from an initial 8.71 mmol/L to 1.35 mmol/L, leading to a remarkable improvement in the toxic symptoms associated with hypermagnesemia. Subsequently, she was managed in the gastroenterology department, with gastroscopy revealing bleeding from the gastrointestinal anastomotic ulcer. Following conservative treatments including acid suppression, stomach protection, and hemostasis, her symptoms improved, and she was successfully discharged. This study aims to alert clinicians to the possibility of hypermagnesemia in individuals with normal renal function. Physicians should exercise caution when prescribing Epsom salts to patients with underlying gastrointestinal conditions. If necessary, alternative drug therapies may be considered to mitigate the risk of hypermagnesemia. Timely intervention is pivotal in averting life-threatening complications linked to hypermagnesemia.

Loss of Smooth Muscle Tenascin-X Inhibits Vascular Remodeling Through Increased TGF-ß Signaling.

BACKGROUND: Vascular smooth muscle cells (VSMCs) are highly plastic. Vessel injury induces a phenotypic transformation from differentiated to dedifferentiated VSMCs, which involves reduced expression of contractile proteins and increased production of extracellular matrix and inflammatory cytokines. This transition plays an important role in several cardiovascular diseases such as atherosclerosis, hypertension, and aortic aneurysm. TGF-ß (transforming growth factor-ß) is critical for VSMC differentiation and to counterbalance the effect of dedifferentiating factors. However, the mechanisms controlling TGF-ß activity and VSMC phenotypic regulation under in vivo conditions are poorly understood. The extracellular matrix protein TN-X (tenascin-X) has recently been shown to bind TGF-ß and to prevent it from activating its receptor. METHODS: We studied the role of TN-X in VSMCs in various murine disease models using tamoxifen-inducible SMC-specific knockout and adeno-associated virus-mediated knockdown. RESULTS: In hypertensive and high-fat diet-fed mice, after carotid artery ligation as well as in human aneurysmal aortae, expression of Tnxb, the gene encoding TN-X, was increased in VSMCs. Mice with smooth muscle cell-specific loss of TN-X (SMC-Tnxb-KO) showed increased TGF-ß signaling in VSMCs, as well as upregulated expression of VSMC differentiation marker genes during vascular remodeling compared with controls. SMC-specific TN-X deficiency decreased neointima formation after carotid artery ligation and reduced vessel wall thickening during Ang II (angiotensin II)-induced hypertension. SMC-Tnxb-KO mice lacking ApoE showed reduced atherosclerosis and Ang II-induced aneurysm formation under high-fat diet. Adeno-associated virus-mediated SMC-specific expression of short hairpin RNA against Tnxb showed similar beneficial effects. Treatment with an anti-TGF-ß antibody or additional SMC-specific loss of the TGF-ß receptor reverted the effects of SMC-specific TN-X deficiency. CONCLUSIONS: In summary, TN-X critically regulates VSMC plasticity during vascular injury by inhibiting TGF-ß signaling. Our data indicate that inhibition of vascular smooth muscle TN-X may represent a strategy to prevent and treat pathological vascular remodeling.

Biological functions and therapeutic potential of SRY related high mobility group box 5 in human cancer.

Cancer is a heavy human burden worldwide, with high morbidity and mortality. Identification of novel cancer diagnostic and prognostic biomarkers is important for developing cancer treatment strategies and reducing mortality. Transcription factors, including SRY associated high mobility group box (SOX) proteins, are thought to be involved in the regulation of specific biological processes. There is growing evidence that SOX transcription factors play an important role in cancer progression, including tumorigenesis, changes in the tumor microenvironment, and metastasis. SOX5 is a member of SOX Group D of Sox family. SOX5 is expressed in various tissues of human body and participates in various physiological and pathological processes and various cellular processes. However, the abnormal expression of SOX5 is associated with cancer of various systems, and the abnormal expression of SOX5 acts as a tumor promoter to promote cancer cell viability, proliferation, invasion, migration and EMT through multiple mechanisms. In addition, the expression pattern of SOX5 is closely related to cancer type, stage and adverse clinical outcome. Therefore, SOX5 is considered as a potential biomarker for cancer diagnosis and prognosis. In this review, the expression of SOX5 in various human cancers, the mechanism of action and potential clinical significance of SOX5 in tumor, and the therapeutic significance of Sox5 targeting in cancer were reviewed. In order to provide a new theoretical basis for cancer clinical molecular diagnosis, molecular targeted therapy and scientific research.

Advancements in Chemical and Biosensors for Point-of-Care Detection of Acrylamide.

Acrylamide (AA), an odorless and colorless organic small-molecule compound found generally in thermally processed foods, possesses potential carcinogenic, neurotoxic, reproductive, and developmental toxicity. Compared with conventional methods for AA detection, bio/chemical sensors have attracted much interest in recent years owing to their reliability, sensitivity, selectivity, convenience, and low cost. This paper provides a comprehensive review of bio/chemical sensors utilized for the detection of AA over the past decade. Specifically, the content is concluded and systematically organized from the perspective of the sensing mechanism, state of selectivity, linear range, detection limits, and robustness. Subsequently, an analysis of the strengths and limitations of diverse analytical technologies ensues, contributing to a thorough discussion about the potential developments in point-of-care (POC) for AA detection in thermally processed foods at the conclusion of this review.

Identification of disease-specific genes related to immune infiltration in nonalcoholic steatohepatitis using machine learning algorithms.

To identify disease signature genes associated with immune infiltration in nonalcoholic steatohepatitis (NASH), we downloaded 2 publicly available gene expression profiles, GSE164760 and GSE37031, from the gene expression omnibus database. These profiles represent human NASH and control samples and were used for differential genes (DEGs) expression screening. Two machine learning methods, the Least Absolute Shrinkage and Selection Operator regression model and Support Vector Machine Recursive Feature Elimination, were used to identify candidate disease signature genes. The CIBERSORT deconvolution algorithm was employed to analyze the infiltration of 22 immune cell types in NASH. Additionally, we constructed a NASH cell model using HepG2 cells treated with oleic acid and free fatty acids. The construction of the cell model was verified using oil red O staining, and Western blotting was used to detect the protein expression of the disease signature genes in both control and model groups. As a result, a total of 262 DEGs were identified. These DEGs were primarily associated with metal ion transmembrane transporter activity, sodium ion transmembrane transporter protein activity, calcium ion, and neuroactive ligand-receptor interactions. FOS, IGFBP2, dual-specificity phosphatase 1 (DUSP1), and IKZF3 were identified as disease signature genes of NASH by the least absolute shrinkage and selection operator and Support Vector Machine Recursive Feature Elimination algorithms for DEGs analysis. The receiver operating characteristic curves showed that FOS, IGFBP2, DUSP1, and IKZF3 had good diagnostic value (area under receiver operating characteristic curve > 0.8). These findings were validated in the GSE89632 dataset and through cellular assays. Immunocyte infiltration analysis revealed that NASH was associated with CD8 T cells, CD4 T cells, follicular helper T cells, resting NK cells, eosinophils, regulatory T cells, and γδ T cells. The FOS, IGFBP2, DUSP1, and IKZF3 genes were specifically associated with follicular helper T cells. Lipid droplet aggregation significantly increased in HepG2 cells treated with oleic acid and free fatty acids, indicating successful construction of the cell model. In this model, the expression of FOS, IGFBP2, and DUSP1 was significantly decreased, while that of IKZF3 was significantly elevated (P < .01, P < .001) compared with the control group. Therefore, FOS, IGFBP2, DUSP1, and IKZF3 can be considered as disease signature genes associated with immune infiltration in NASH.

The Efficacy and Safety of Anlotinib Plus Etoposide with Cisplatin/Carboplatin in the First-Line Treatment of Lung Cancer: A Phase II Clinical Study.

Background: The primary aim of this phase II clinical study was to assess the safety and efficacy of combining anlotinib, etoposide, and platinum-based drugs as a first-line treatment for ES-SCLC. Methods: Patients underwent the standard chemotherapeutic regimen, consisting of four courses of etoposide plus cisplatin/carboplatin. Additionally, each patient received a 2-week intervention with anlotinib (12 mg/day, once daily). Anlotinib was continued until disease progression, occurrence of unbearable adverse events (AEs), or withdrawal from the research. Progression-free survival (PFS) served as the primary prognostic measure. Secondary measures included the disease control rate (DCR), objective response rate (ORR), overall survival time (OS), and the incidence of AEs. Results: The DCR and ORR were 97.6% and 91.0%, respectively. Estimated PFS and OS were 5.0 months (95% CI: 1.0-10.8 months) and 13.0 months (95% CI: 8.4-18.6 months), respectively. No unexpected adverse effects were reported during the trial. The most common adverse reactions included anemia (42.22%), hypertension (53.33%), alopecia (40.00%), elevated transaminase (24.40%), and elevated alkaline phosphatase (24.44%). Sixteen cases (35.56%) were classified as AEs of grades 3-5. No deaths attributed to treatment-related causes occurred in any patient during the trial. Conclusion: Combination chemotherapy is currently the first-line therapy for extensive small-cell lung cancer (ES-SCLC). Combining anlotinib with conventional platinum-based chemotherapy demonstrated promising therapeutic outcomes and prognosis in the management of ES-SCLC.

Radiomic signatures associated with tumor immune heterogeneity predict survival in locally recurrent nasopharyngeal carcinoma.

BACKGROUND: The prognostic value of traditional clinical indicators for locally recurrent nasopharyngeal carcinoma is limited because of their inability to reflect intratumor heterogeneity. We aimed to develop a radiomic signature to reveal tumor immune heterogeneity and predict survival in locally recurrent nasopharyngeal carcinoma. METHODS: This multicenter, retrospective study included 921 patients with locally recurrent nasopharyngeal carcinoma. A machine learning signature and nomogram based on pretreatment magnetic resonance imaging features were developed for predicting overall survival in a training cohort and validated in 2 independent cohorts. A clinical nomogram and an integrated nomogram were constructed for comparison. Nomogram performance was evaluated by concordance index and receiver operating characteristic curve analysis. Accordingly, patients were classified into risk groups. The biological characteristics and immune infiltration of the signature were explored by RNA-sequencing analysis. RESULTS: The machine learning signature and nomogram demonstrated comparable prognostic ability to a clinical nomogram, achieving concordance indexes of 0.729, 0.718, and 0.731 in the training, internal, and external validation cohorts, respectively. Integration of the signature and clinical variables statistically improved the predictive performance. The proposed signature effectively distinguished patients between risk groups with statistically distinct overall survival rates. Subgroup analysis indicated the recommendation of local salvage treatments for low-risk patients. Exploratory RNA-sequencing analysis revealed differences in interferon response and lymphocyte infiltration between risk groups. CONCLUSIONS: A magnetic resonance imaging-based radiomic signature predicted overall survival more accurately. The proposed signature associated with tumor immune heterogeneity may serve as a valuable tool to facilitate prognostic stratification and guide individualized management for locally recurrent nasopharyngeal carcinoma patients.

The Dynamic Mechanical Properties and Damage Constitutive Model of Ultra-High-Performance Steel-Fiber-Reinforced Concrete (UHPSFRC) at High Strain Rates.

A high strain rate occurs when the strain rate exceeds 100 s-1. The mechanical behavior of materials at a high strain rate is different from that at middle and low strain rates. In order to study the dynamic compressive mechanical properties of ultra-high-performance steel-fiber-reinforced concrete (UHPSFRC) at high strain rates, an electro-hydraulic servo universal testing machine and a separate Hopkinson pressure bar (SHPB) with a diameter of 120 mm were used, respectively. A quasi-static compression test (strain rate 0.001 s-1) and impact compression test with a strain rate range of 90~200 s-1 were carried out to study the failure process, failure mode, and stress-strain curve characteristics of UHPSFRC at different strain rates and quantify the strain rate strengthening effect and fiber toughening effect. Based on the statistical damage theory and energy conversion principle, a dynamic damage constitutive model considering the effects of strain rate and fiber content was constructed. The results showed that the rate correlation of UHPSFRC and the fiber toughening properties showed a certain coupling competition mechanism. When the fiber content was less than 1.5%, with an increase in the steel fiber content, the crack initiation and propagation time of the specimen was extended, and the strain rate sensitivity gradually decreased. When the fiber content was 2%, the impact compressive strength of the specimen was optimal. Compared with UHPC, the dynamic increase factor (DIF) of UHPSFRC was significantly lower. The dynamic damage constitutive model established in this paper, considering the influence of strain rate and fiber content, has a good applicability and can describe the mechanical behavior of UHPSFRC at a high strain rate.

Association Between Preoperative Sleep Disturbance and Postoperative Delirium in Elderly: A Retrospective Cohort Study.

Purpose: Postoperative sleep disturbance, characterized by diminished postoperative sleep quality, is a risk factor for postoperative delirium (POD); however, the association between pre-existing sleep disturbance and POD remains unclear. This study aimed to evaluate the association between preoperative sleep disturbance and POD in elderly patients after non-cardiac surgery. Patients and methods: This retrospective cohort study was conducted at a single center and enrolled 489 elderly patients who underwent surgery between May 1, 2020, and March 31, 2021. Patients were divided into the sleep disorder (SD) and non-sleep disorder (NSD) groups according to the occurrence of one or more symptoms of insomnia within one month or sleep- Numerical Rating Scale (NRS)≥6 before surgery. The primary outcome was the incidence of POD. Propensity score matching analysis was performed between the two groups. Multiple logistic regression analysis was performed to identify the risk factors for POD. Results: In both the unmatched cohort (16.0% vs 6.7%, P=0.003) and the matched cohort (17.0% vs 6.2%, P=0.023), the incidence of POD was higher in the SD group than in the NSD group. In addition, the postoperative sleep quality and the VAS score at postoperative 24 h were significantly lower in the SD group than in the NSD group. Multivariate logistic regression analysis indicated that age (Odds Ratio, 1.13 [95% CI: 1.04-1.23], P=0.003) and preoperative sleep disturbance (Odds Ratio, 3.03 [95% CI: 1.09-9.52], P=0.034) were independent risk factors for the development of POD. Conclusion: The incidence of POD was higher in patients with pre-existing sleep disturbance than those without it. Whether improving sleep quality for preoperative sleep disturbance may help prevent POD remains to be determined.

Investigation of the mutual crosstalk between ER stress and PI3K/AKT/mTOR signaling pathway in iron overload-induced liver injury in chicks.

Iron is an essential element for the normal functioning of living organisms, but excessive iron deposition can lead to organ damage. This study aims to investigate the interaction between the endoplasmic reticulum stress signaling pathway and the PI3K/AKT/mTOR signaling pathway in liver injury induced by iron overload in chicks. Rspectively, 150 one-day-old broilers were divided into three groups and supplemented with 50 (C), 500 (E1), and 1000 (E2) mg ferrous sulfate monohydrate/kg in the basal diet. Samples were taken after continuous feeding for 14 days. The results showed that iron overload could upregulate the levels of ALT and AST. Histopathological examination revealed bleeding in the central vein of the liver accompanied by inflammatory cell infiltration. Hoechst staining showed that the iron overload group showed significant bright blue fluorescence, and ultrastructural observations showed chromatin condensation as well as mitochondrial swelling and cristae disorganization in the iron overload group. RT-qPCR and Western blot results showed that iron overload upregulated the expression of Bax, Caspase-3, Caspase-9, GRP78, GRP94, P-PERK, ATF4, eIF2α, IRE1, and ATF6, while downregulating the expression of Bcl-2 and the PI3K/AKT/mTOR pathway. XBP-1 splicing experiment showed significant splicing of XBP-1 gene after iron overload. PCA and correlation analysis suggested a potential association between endoplasmic reticulum stress, the PI3K/AKT/mTOR signaling pathway, and liver injury in chicks. In summary, iron overload can induce cell apoptosis and liver injury by affecting endoplasmic reticulum stress and the PI3K/AKT/mTOR signaling pathway.

Unraveling the Role of Endothelial Dysfunction in Osteonecrosis of the Femoral Head: A Pathway to New Therapies.

Osteonecrosis of the femoral head (ONFH) is a disabling disease characterized by the disruption of the blood supply to the femoral head, leading to the apoptosis and necrosis of bone cells and subsequent joint collapse. Total hip arthroplasty is not optimal since most patients are young. Multiple risk factors contribute to osteonecrosis, including glucocorticoid (GC) usage, excessive alcohol intake, hypercholesterolemia, and smoking. Continuous stimulation by many variables causes a chronic inflammatory milieu, with clinical repercussions including endothelial dysfunction, leading to thrombosis, coagulopathy, and poor angiogenesis. Immune cells are the primary regulators of inflammation. Innate and adaptive immune cells interact with endothelial cells to hinder the regeneration and repair of bone lesions. An in-depth examination of the pathological drivers of ONFH reveals that endothelial dysfunction may be a major cause of osteonecrosis. Understanding the involvement of endothelial dysfunction in the chronic inflammation of osteonecrosis could aid in the development of possible therapies. This review summarizes the role of endothelial cells in osteonecrosis and further explains the pathophysiological mechanism of endothelial dysfunction in this disease from the perspective of inflammation to provide new ideas for the treatment of osteonecrosis.

Utilizing procalcitonin, C-reactive protein, and serum amyloid A in combination for diagnosing sepsis due to urinary tract infection.

OBJECTIVE: In this study, we aimed to evaluate the combined diagnostic value of procalcitonin (PCT), C-reactive protein (CRP), and serum amyloid A (SAA) in sepsis caused by urinary tract infection. METHOD: A total of 80 patients with urosepsis who were hospitalized were included in the study group, and 80 patients with urinary tract infection without sepsis were included in the control group. We collected the PCT, SAA, and CRP levels of patients following admission. Subsequently, we conducted a comparative analysis to assess the specificity, accuracy, and sensitivity of combined diagnostic approaches in contrast to individual diagnostic methods for blood PCT, SAA, and CRP. RESULTS: The levels of PCT, SAA, and CRP in the study group were significantly higher than those in the control group, and the differences were statistically significant (P < 0.01). Multi-factor logistic regression analysis revealed that the levels of PCT (P = 0.003) and SAA (P = 0.014) were associated with urosepsis. The sensitivity of PCT was 87.133% and the specificity was 93.066%, which were higher than that of SAA and CRP. The specificity of the combined detection of the three was 95.670%, which was higher than that of PCT, SAA, and CRP alone. Correlation analysis revealed that PCT had a significant positive correlation with CRP and SAA (P < 0.01), and a weak correlation with white blood cell count (WBC) and fibrinogen (FIB) (P = 0.03 for WBC, P = 0.04 for FIB). CONCLUSION: PCT, SAA, and CRP indicators in patients with urosepsis are significantly elevated, and all three are valuable in the diagnosis of urosepsis. PCT alone has good diagnostic efficiency for urosepsis, and a certain correlation with other inflammatory factors. The diagnostic efficacy of the three indicators in combination is better than that of any one of the three, and is worthy of widespread clinical application.

An Engineered Bionic Nanoparticle Sponge as a Cytokine Trap and Reactive Oxygen Species Scavenger to Relieve Disc Degeneration and Discogenic Pain.

The progressive worsening of disc degeneration and related nonspecific back pain are prominent clinical issues that cause a tremendous economic burden. Activation of reactive oxygen species (ROS) related inflammation is a primary pathophysiologic change in degenerative disc lesions. This pathological state is associated with M1 macrophages, apoptosis of nucleus pulposus cells (NPC), and the ingrowth of pain-related sensory nerves. To address the pathological issues of disc degeneration and discogenic pain, we developed MnO2@TMNP, a nanomaterial that encapsulated MnO2 nanoparticles with a TrkA-overexpressed macrophage cell membrane (TMNP). Consequently, this engineered nanomaterial showed high efficiency in binding various inflammatory factors and nerve growth factors, which inhibited inflammation-induced NPC apoptosis, matrix degradation, and nerve ingrowth. Furthermore, the macrophage cell membrane provided specific targeting to macrophages for the delivery of MnO2 nanoparticles. MnO2 nanoparticles in macrophages effectively scavenged intracellular ROS and prevented M1 polarization. Supportively, we found that MnO2@TMNP prevented disc inflammation and promoted matrix regeneration, leading to downregulated disc degenerative grades in the rat injured disc model. Both mechanical and thermal hyperalgesia were alleviated by MnO2@TMNP, which was attributed to the reduced calcitonin gene-related peptide (CGRP) and substance P expression in the dorsal root ganglion and the downregulated Glial Fibrillary Acidic Protein (GFAP) and Fos Proto-Oncogene (c-FOS) signaling in the spinal cord. We confirmed that the MnO2@TMNP nanomaterial alleviated the inflammatory immune microenvironment of intervertebral discs and the progression of disc degeneration, resulting in relieved discogenic pain.

One-stage jaw reconstruction and prosthetic rehabilitation with an iliac flap: a case report and literature review.

BACKGROUND: One-stage jaw reconstruction with fibular flap and prosthetic rehabilitation restores bony and dental continuity simultaneously. It was also called as "jaw-in-a-day (JIAD)" technique. However, bone volume and height of fibular flap may be insufficient for dental implant insertion. The provision of a considerable amount of bone makes an iliac flap the ideal choice in these cases. We present the first case report to document the use of one-stage jaw reconstruction and prosthetic rehabilitation with the iliac flap. CASE PRESENTATION: We modified the conventional JIAD workflow to make it suitable for iliac flap. Two cases were presented who both underwent segmental mandibulectomy for ameloblastoma. Virtual surgical planning was performed in all cases. The iliac crest was positioned upward to provide cortical bone for achieving primary stability of dental implants. Similar to the "all-on-4" procedure, the iliac bone was placed 12 to 15 mm below the occlusal plane to create adequate space for the implant-retained prosthesis. Immediate implant-based dental rehabilitation was performed at same stage. The surgery was successful in all cases without any short-term complications. In the first postoperative week, patients were given a liquid diet through a nasal feeding tube. The liquid diet is advised until 1 month after the surgery. Thereafter, a soft diet is recommended. Patients were advised to resume routine mastication and normal diet 3 months after the surgery. Peri-implantitis occurred in one patient, and additional gingival graft was required. Postoperative function and esthetics were satisfactory at the last follow-up visit. CONCLUSIONS: One-stage jaw reconstruction and prosthetic rehabilitation with the iliac flap are safe and useful for restoring postoperative function and esthetics. It should be used in more cases with a longer follow-up in further studies.

Secondary metabolites from the Actinomadura sp. and their cytotoxic activity.

Actinomadura sp., which is usually found in muddy habitats, produces various secondary metabolites with biological activities. In this study, five new compounds named formosensin A (1), formosensin B (2), oxanthroquinone-3-O-α-d-mannose (8), oxanthromicin A (9), and oxanthromicin B (10) were isolated from the culture of Actinomadura sp. together with five known compounds (3-7). Their structures were elucidated by extensive spectroscopic methods including NMR and MS. In particular, the absolute configurations of compounds 1 and 2 were determined using computational methods. Moreover, compounds 1-2 and 8-10 were screened for cytotoxic activity using a panel of human tumor cell lines. Compound 9 induced significant cytotoxicity in five human tumor cell lines (HL-60, A-549, SMMC-7721, MCF-7, and SW480) with IC50 values of 8.7, 17.5, 15.0, 17.8, and 14.6 µM, respectively. These findings suggested that compound 9 could provide therapeutic benefits in the treatment of tumor-related diseases.