OBJECTIVE: To compare the effectiveness of a zero-profile three-dimensiaonal (3D)-printed microporous titanium alloy Cage and a conventional titanium plate combined with a polyether-ether-ketone (PEEK)-Cage in the treatment of single-segment cervical spondylotic myelopathy (CSM) by anterior cervical discectomy and fusion (ACDF). METHODS: The clinical data of 83 patients with single-segment CSM treated with ACDF between January 2022 and January 2023 were retrospectively analyzed, and they were divided into 3D-ZP group (35 cases, using zero-profile 3D-printed microporous titanium alloy Cage) and CP group (48 cases, using titanium plate in combination with PEEK-Cage). There was no significant difference in gender, age, disease duration, surgical intervertebral space, and preoperative Japanese Orthopaedic Association (JOA) score, visual analogue scale (VAS) score, neck disability index (NDI), vertebral height at the fusion segment, Cobb angle, and other baseline data between the two groups (P>0.05). The operation time, intraoperative blood loss, hospital stay, complications, interbody fusion, and prosthesis subsidence were recorded and compared between the two groups. VAS score, NDI, and JOA score were used to evaluate the improvement of pain and function before operation, at 3 months after operation, and at last follow-up, and the vertebral height at the fusion segment and Cobb angle were measured by imaging. The degree of dysphagia was assessed by the Bazaz dysphagia scale at 1 week and at last follow-up. RESULTS: The operation was successfully completed in all the 83 patients. There was no significant difference in intraoperative blood loss and hospital stay between the two groups (P>0.05), but the operation time in the 3D-ZP group was significantly shorter than that in the CP group (P<0.05). Patients in both groups were followed up 24-35 months, with an average of 25.3 months, and there was no significant difference in the follow-up time between the two groups (P>0.05). The incidence and grade of dysphagia in CP group were significantly higher than those in 3D-ZP group at 1 week after operation and at last follow-up (P<0.05). There was no dysphagia in 3D-ZP group at last follow-up. There was no complication such as implant breakage or displacement in both groups. The intervertebral fusion rates of 3D-ZP group and CP group were 65.71% (23/35) and 60.42% (29/48) respectively at 3 months after operation, and there was no significant difference between the two groups [OR (95%CI)=1.256 (0.507, 3.109), P=0.622]. The JOA score, VAS score, and NDI significantly improved in the 3D-ZP group at 3 months and at last follow-up when compared with preoperative ones (P<0.05), but there was no significant difference between the two groups (P>0.05). There was no significant difference in the improvement rate of JOA between the two groups at last follow-up (P>0.05). At 3 months after operation and at last follow-up, the vertebral height at the fusion segment and Cobb angle significantly improved in both groups, and the two indexes in 3D-ZP group were significantly better than those in CP group (P<0.05). At last follow-up, the incidence of prosthesis subsidence in 3D-ZP group (8.57%) was significantly lower than that in CP group (29.16%) (P<0.05). CONCLUSION The application of zero-profile 3D-printed Cage and titanium plate combined with PEEK-Cage in single-segment ACDF can both reconstruct the stability of cervical spine and achieve good effectiveness. Compared with the latter, the application of the former in ACDF can shorten the operation time, reduce the incidence of prosthesis subsidence, and reduce the incidence of dysphagia.
Humans ; Spinal Fusion/instrumentation* ; Titanium ; Cervical Vertebrae/surgery* ; Diskectomy/instrumentation* ; Bone Plates ; Male ; Printing, Three-Dimensional ; Female ; Retrospective Studies ; Middle Aged ; Treatment Outcome ; Benzophenones ; Adult ; Spondylosis/surgery* ; Aged ; Polymers ; Ketones ; Polyethylene Glycols

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

Objective:To evaluate the clinical application effects of a domestic bone-level implant system for restoring single tooth loss, and provide clinical evidence for the promotion and application of domestic implants.Methods:A prospective, multicenter clinical trial was conducted from April 2018 to January 2020 in three institutions: Department of Oral Implantology, School & Hospital of Stomatology, Wuhan University, Department of Stomatology, The First Affiliated Hospital of Zhejiang University School of Medicine, and Department of Stomatology, The Third Hospital of Hebei Medical University. The trial planned to include 100 patients for single tooth implantation and restoration, followed up for 1 year, to evaluate the implantation success rate and other related outcomes.Results:This study screened a total of 142 patients and ultimately included 100, comprising 43 males and 57 females with age of (47.0±12.2) years. Ninety-eight out of 100 patients completed a one-year follow-up (98.0%), while 2 patients terminated the trial early due to implant loosening (2.0%). After a one-year follow-up, the implants of the 98 patients were all functioning successfully, with a success rate of 98.0% (98/100). The patients were satisfied with the overall restoration effect.Conclusions:This study indicates that the domestic bone-level implant system has achieved favorable short-term clinical outcomes for single-tooth implantation and restoration.

Endothelial-mesenchymal transition (EndMT) disrupts vascular endothelial integrity and induces atherosclerosis. Active integrin β1 plays a pivotal role in promoting EndMT by facilitating TGFβ/Smad signaling in endothelial cells. Here, we report a novel anthraquinone compound, Kanglexin (KLX), which prevented EndMT and atherosclerosis by activating MAP4K4 and suppressing integrin β1/TGFβ signaling. First, KLX effectively counteracted the EndMT phenotype and mitigated the dysregulation of endothelial and mesenchymal markers induced by TGFβ1. Second, KLX suppressed TGFβ/Smad signaling by inactivating integrin β1 and inhibiting the polymerization of TGFβR1/2. The underlying mechanism involved the activation of FGFR1 by KLX, resulting in the phosphorylation of MAP4K4 and Moesin, which led to integrin β1 inactivation by displacing Talin from its β-tail. Oral administration of KLX effectively stimulated endothelial FGFR1 and inhibited integrin β1, thereby preventing vascular EndMT and attenuating plaque formation and progression in the aorta of atherosclerotic Apoe^-/- mice. Notably, KLX (20 mg/kg) exhibited superior efficacy compared with atorvastatin, a clinically approved lipid-regulating drug. In conclusion, KLX exhibited potential in ameliorating EndMT and retarding the formation and progression of atherosclerosis through direct activation of FGFR1. Therefore, KLX is a promising candidate for the treatment of atherosclerosis to mitigate vascular endothelial injury.
Animals ; Atherosclerosis/prevention & control* ; Mice ; Receptor, Fibroblast Growth Factor, Type 1/metabolism* ; Signal Transduction/drug effects* ; Anthraquinones/pharmacology* ; Humans ; Integrin beta1/metabolism* ; Epithelial-Mesenchymal Transition/drug effects* ; Male ; Transforming Growth Factor beta/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Human Umbilical Vein Endothelial Cells/drug effects*

21-hydroxylase deficiency(21-OHD) is mainly characterized by cortisol deficiency with or without aldosterone deficiency and hyperandrogenemia.The disease requires lifelong exogenous glucocorticoid/salt supplementation.Excessive doses of exogenous glucocorticoids are often needed to control hyperandrogenemia, but the effect is not satisfactory.Corticotropin releasing factor (CRF) type 1 receptor antagonist can directly block the production of adrenocorticotropin, inhibit the generation of adrenogenic androgen, reduce the dose of glucocorticoid therapy, and thus lower the incidence of adverse reactions.In this article, the current research progress on 21-OHD therapy and CRF1 receptor antagonist was reviewed.

In recent years,increasing attention has been paid to the study on the pathogenesis of cerebral ischemia in terms of the overall structure and function of neurovascular unit(NVU),which has become one of the hot spots in the field of brain sciences and major brain diseases.This paper is intended to outline the roles of the four main NVU cells(neurons,astrocytes,microglia and cerebral microvascular endothelial cells)in brain function and pathogenesis of cerebral ischemia,which are closely related in structure,work together to maintain cerebral homeostasis in function,and play an important role in brain function and cerebral ischemic injuries.NVU injury leads to microvascular and blood brain barrier integrity impairment,neuronal cell death,glial reaction and immune cell infiltration,and even tissue injury and brain edema.This paper also aims to elucidate the roles of NVU structure and function in the pathogenesis of cerebral ischemia,and offer new ideas and strategies for the research related to drugs for prevention and treatment of cerebral ischemia based on NVU structure and function.

Tirzepatide is the first-in-class dual agonist of glucagon-like peptide-1 (GLP-1) receptor and glucose-dependent insulinotropic peptide (GIP) receptor, which plays a variety of physiological effects by imitating natural GLP-1 and GIP. In the completed large phase III series of clinical studies of SURPASS and SURMOUNT, Tirzepatide has demonstrated excellent effects in decreasing glycosylated hemoglobin, reducing weight, improving blood lipid and other metabolic indicators, and is superior to the currently approved GLP-1 receptor agonist. Gastrointestinal reaction is the most common adverse event of the drug, which is generally mild to moderate, and decreases with continuous administration. On May 13, 2022, Tirzepatide was approved for listing by FDA, the current indication is to improve glycemic control of adult patients with type 2 diabetes (T2D) as an adjunct of diet and exercise. In addition to T2D and obesity, there are also extensive and in-depth studies on other metabolic fields. This paper makes a systematic overview of this.

Objective: To analyze the quantitative features of coronary plaque and evaluate its diagnostic performance for myocardial ischemic injury in patient with coronary artery disease. Methods: Retrospectively enrolled 109 patients with suspected coronary artery disease, who successively underwent coronary CT angiography(CCTA) and coronary angiography in Shandong Provincial Hospital from June 2018 to September 2019. Elevated myocardial enzyme with segmental wall motion abnormalities (SWMA) in ultrasound was defined as myocardial ischemic injury, with which the subjects were divided into two groups, with and without myocardial ischemic injury (n=75,34) respectively. CCTA images of each target vessel were quantitatively analyzed by automated plaque analysis software to obtain the following indexes: minimal lumen area(MLA), plaque length(PL), total plaque volume(TPV), total plaque burden(TPB),calcified plaque volume(CPV), calcified plaque ratio(CPR), fibrous plaque volume(FPV), fibrous plaque ratio(FPR), lipid plaque volume(LPV), lipid plaque ratio(LPR), napkin-ring sign(NRS), spotty calcification(SC), remodeling index (RI) and eccentric index (EI). Chi-square, Mann-Whitney U tests, logistic regression and area under the receiver operating characteristics were determined. Results: For the degree of coronary artery stenosis, MAS% was 85.00% (80.00%, 92.00%) and 63.00% (60.00%, 65.00%) in myocardial ischemic group and without myocardial ischemic injury group, which was statistically significant (Z=-4.32, P=0.001). For the quantitative plaque features, TPV 150.13 (104.44,202.20) mm³, TPB (75.67%±9.90%), FPV 95.73 (66.57, 134.23)mm³, LPV 32.18 (18.93,54.55) mm³, LPR (25.13%±13.71%) in the group with myocardial ischemic injury were larger than those in group without myocardial ischemic injury 109.94 (79.39, 121.67) mm³, 65.37%±6.94%, 67.35 (57.67, 90.11) mm³, 16.64 (13.26, 24.73) mm³, 18.44%±7.09% respectively with statistically significant (Z=-2.59, P=0.010; t=3.11, P=0.003; Z=-2.16, P=0.031; Z=-2.18, P=0.029; t=2.19, P=0.037). In logistic regression analysis, MAS%(OR=1.55,P=0.021) was independent significant predictors of myocardial ischemic injury. The AUC of MAS%, LPV, LPR, TPV, TPB, FPV were 0.84, 0.82, 0.77, 0.72, 0.74, 0.67, respectively, which were all statistically significant (P<0.05). Conclusions In quantitative plaque analysis by coronary CT angiography, MAS%, TPV, TPB, FPV, LPV, LPR were affecting factors of myocardial ischemic injury, in which MAS% was independent predictors. MAS% and LPV have higher diagnostic accuracy in myocardial ischemic injury.

Acute pancreatitis is a local pancreatic and systemic inflammatory disease due to various living and environmental factors, such as alcohol, gallstones, high lipids, and smoking, and its pathogenesis remains unclear. Studies have shown that epigenetic regulation mechanisms, such as DNA methylation, histone modification, and non-coding RNA, play an important role in the development and progression of acute pancreatitis. This article introduces the association between the common causes of acute pancreatitis (including alcohol, gallstones, high lipids, and smoking) and epigenetic regulation mechanisms, as well as the association between inflammatory response and epigenetic regulation mechanisms. The preliminary exploration of epigenetic regulation mechanisms in acute pancreatitis provides new thoughts for further understanding the development, progression, and treatment of acute pancreatitis.

BACKGROUND: Tumor microenvironment is a complex and dynamic community, which plays a crucial role in tumor progression via the co-evolution of cancer cells and tumor stroma. Among them, tumor-associated macrophages (TAMs) and tumor neo-vessels are two key components in the tumor microenvironment during cancer invasion. In addition, programmed cell death ligand 1/programmed cell death ligand 1 (PD-1/PD-L1) also plays an important role in tumorigenesis and development, and the clinical strategies to block PD-1/PD-L1 pathway could have great benefits for cancer patients. This study was aimed at analyzing the quantitative expression and prognostic significance of TAMs, tumor neo-vessels and PD-L1 in tumor microenvironment and exploring the relations between the expression of above components with the patients' prognosis of non-small cell lung cancer (NSCLC). METHODS: Clinico-pathological data and surgical specimens of 92 patients with NSCLC were collected, and immunohistochemistry was used to stain the expression of TAMs, tumor neo-vessels and PD-L1 on tumor tissue and peri-tumor tissues. The inverted microscopy was used to take pictures and Image-pro Plus 6.0 software was used for quantitative analysis. The clinicopathological characteristics and overall survival (OS) were analyzed. RESULTS: The median OS of 92 NSCLC cases was 22.5 month. The expression of TAMs, tumor neo-vessels and PD-L1 in tumor tissue and peri-tumor tissues were not statistically significant (P>0.05). According to the cutoff of above key three components in tumor microenvironment, all the cases could be classified into high, middle and low expression groups. The survival analysis demonstrated that the OS in high expression group of TAMs (P=0.016) and PD-L1 (P=0.002) was shorter than the other two groups, respectively, with statistical significance. The OS in high tumor neo vessels group was shorter than the other two groups. However, there was no statistical significance between these three group (P=0.626). Combined with above the three components, all the cases could be classified into low, middle and high density groups. The survival analysis demonstrated that the median OS of combined high density group was shorter than the other two groups (P=0.001). Multivariate analysis by Cox regression indicated that pathological type, TAMs and PD-L1 expression were the independent prognostic factors. CONCLUSIONS The key components of TAMs and PD-L1 in tumor microenvironment are closely related to the prognosis of NSCLC patients.