Lipid nanoparticle: advanced drug delivery systems for promotion of angiogenesis in diabetic wounds.

Diabetic wound is one of the most challenge in healthcare, requiring innovative approaches to promote efficient healing. In recent years, lipid nanoparticle-based drug delivery systems have emerged as a promising strategy for enhancing diabetic wound repair by stimulating angiogenesis. These nanoparticles offer unique advantages, including improved drug stability, targeted delivery, and controlled release, making them promising in enhancing the formation of new blood vessels. In this review, we summarize the emerging advances in the utilization of lipid nanoparticles to deliver angiogenic agents and promote angiogenesis in diabetic wounds. Furthermore, we provide an in-depth exploration of key aspects, including the intricate design and fabrication of lipid nanoparticles, their underlying mechanisms of action, and a comprehensive overview of preclinical studies. Moreover, we address crucial considerations pertaining to safety and the translation of these innovative systems into clinical practice. By synthesizing and analyzing the available knowledge, our review offers valuable insights into the future prospects and challenges associated with utilizing the potential of lipid nanoparticle-based drug delivery systems for promoting robust angiogenesis in the intricate process of diabetic wound healing.

High-intensity interval training ameliorates postnatal immune activation-induced mood disorders through KDM6B-regulated glial activation.

Postnatal immune activation (PIA) induces persistent glial activation in the brain and causes various neuropathologies in adults. Exercise training improves stress-related mood disorders; however, the role of exercise in psychiatric disorders induced by early-life immune activation and the association between exercise training and glial activation remain unclear. We compared the effects of different exercise intensities on the PIA model, including high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT). Both HIIT and MICT in adolescent mice inhibited neuroinflammation, remodeled synaptic plasticity, and improved PIA-induced mood disorders in adulthood. Importantly, HIIT was superior to MICT in terms of reducing inflammation and increasing body weight. RNA-seq of prefrontal cortex (PFC) tissues revealed a gene expression pattern, confirming that HIIT was more effective than MICT in improving brain glial cell activation through epigenetic modifications of KDM6B. We investigated the role of KDM6B, a specific histone lysine demethylation enzyme - histone 3 lysine 27 demethylase, in inhibiting glial activation against PIA-induced depression and anxiety by regulating the expression of IL-4 and brain-derived neurotrophic factor (BDNF). Overall, our data support the idea that HIIT improves PIA-induced mood disorders by regulating KDM6B-mediated epigenetic mechanisms and indicate that HIIT might be superior to MICT in improving mood disorders with PIA in mice. Our findings provide new insights into the treatment of anxiety and depression disorders.

Melatonin improves mouse oocyte quality from 2-ethylhexyl diphenyl phosphate-induced toxicity by enhancing mitochondrial function.

2-Ethylhexyl diphenyl phosphate (EHDPP) is a representative organophosphorus flame retardant (OPFR) that has garnered attention due to its widespread use and potential adverse effects. EHDPP exhibits cytotoxicity, genotoxicity, developmental toxicity, and endocrine disruption. However, the toxicity of EHDPP in mammalian oocytes and the underlying mechanisms remain poorly understood. Melatonin is a natural free radical scavenger that has demonstrated cytoprotective properties. In this study, we investigated the effect of EHDPP on mouse oocytes in vitro culture system and evaluated the rescue effect of melatonin on oocytes exposed to EHDPP. Our results indicated that EHDPP disrupted oocyte maturation, resulting in the majority of oocytes arrested at the metaphase I (MI) stage, accompanied by cytoskeletal damage and elevated levels of reactive oxygen species (ROS). Nevertheless, melatonin supplementation partially rescued EHDPP-induced mouse oocyte maturation impairment. Results of single-cell RNA sequencing (scRNA-seq) analysis elucidated potential mechanisms underlying these protective effects. According to the results of scRNA-seq, we conducted further tests and found that EHDPP primarily disrupts mitochondrial distribution and function, kinetochore-microtubule (K-MT) attachment, DNA damage, apoptosis, and histone modification, which were rescued upon the supplementation of melatonin. This study reveals the mechanisms of EHDPP on female reproduction and indicates the efficacy of melatonin as a therapeutic intervention for EHDPP-induced defects in mouse oocytes.

Enhanced external counterpulsation treatment improves multi-organ hemodynamics for postoperative liver transplantation patient. A case report.

INTRODUCTION: Post liver transplantation (LT) patients endure high morbidity rate of multi-organ ischemic symptoms following reperfusion. We hypothesize that enhanced external counterpulsation (EECP) as a typical non-invasive assisted circulation procedure, which can efficiently inhibit the relative ischemic symptoms via the systemic improvement of hemodynamics. CASE PRESENTATION: A 51-year-old male patient, 76 kg, 172 cm, received orthotopic LT surgery for viral hepatitis B induced acute-on-chronic liver failure hepatic failure. His medical records revealed ischemic symptoms in multi-organ at the time of hospital discharge, including headache, refractory insomnia, abdominal paralysis, and lower limb pain. The EECP treatment was introduced for assisted rehabilitation and to improve the postoperative quality of life. Doppler Ultrasound examination showed significant augmentation of blood flow volume in the carotid arteries, the hepatic artery, the portal vein and the femoral artery during EECP intervention. A standard 35-hour EECP treatment led to significant improvement in quality of life, e.g. sleep quality and walking ability. CONCLUSION: We report a case of multi-organ ischemic symptoms in a post LT patient. EECP treatment can significantly improve the quality of life via the systematic promotion of hemodynamics.

The role of oxidative stress in intervertebral disc degeneration: Mechanisms and therapeutic implications.

Oxidative stress is one of the main driving mechanisms of intervertebral disc degeneration(IDD). Oxidative stress has been associated with inflammation in the intervertebral disc, cellular senescence, autophagy, and epigenetics of intervertebral disc cells. It and the above pathological mechanisms are closely linked through the common hub reactive oxygen species(ROS), and promote each other in the process of disc degeneration and promote the development of the disease. This reveals the important role of oxidative stress in the process of IDD, and the importance and great potential of IDD therapy targeting oxidative stress. The efficacy of traditional therapy is unstable or cannot be maintained. In recent years, due to the rise of materials science, many bioactive functional materials have been applied in the treatment of IDD, and through the combination with traditional drugs, satisfactory efficacy has been achieved. At present, the research review of antioxidant bioactive materials in the treatment of IDD is not complete. Based on the existing studies, the mechanism of oxidative stress in IDD and the common antioxidant therapy were summarized in this paper, and the strategies based on emerging bioactive materials were reviewed.

Sijunzi decoction, a classical Chinese herbal formula, improves fatigue symptoms with changes in gut microbiota in chronic fatigue syndrome: A randomized, double-blind, placebo-controlled, multi-center clinical trial.

BACKGROUD: Chronic fatigue syndrome (CFS) severely impact patients' quality of life and lacks well-acknowledged drug therapy. Sijunzi decoction (SJZD), a classical Chinese herbal formula, has been widely used for spleen deficiency syndrome like fatigue in China. However, there is a lack of evidence on the efficacy of SJZD in treating CFS. PURPOSE: To evaluate the efficacy and safety of SJZD for CFS. STUDY DESIGN: A multi-center, double-blinded, randomized controlled trial. METHODS: Participants with definite diagnoses of CFS and spleen deficiency syndrome were randomly assigned in 1:1 ratio to receive SJZD or placebo granules for 2 months. The primary outcome was the change of Chalder fatigue questionnaire (CFQ) scoring after treatment. Other outcomes included changes in short form-36 physical function (SF36-PF) score, spleen deficiency scale score, Euroqol Questionnaire-Visual Analogue Scale (ED-VAS) score, and clinical global impression (CGI) evaluating by corresponding questionnaires. Fecal metagenome sequencing was conducted to explore the potential mechanism of SJZD effect. RESULTS: From June 2020 to July 2021, 105 of 127 participants completed the study at four hospitals in China. After a 2-month treatment, intention-to-treat (ITT) analysis found participants who received SJZD had larger reduction than placebo control (mean change 6.65 [standard deviation (SD) 6.11] points vs. 5.31 [SD 5.19] points; difference 1.34, 95 % confidence interval [CI] -0.65 to 3.33). Per-protocol (PP) analysis reported confirmative results with a significant difference between SJZD and placebo groups (2.24, 95 % CI 0.10 to 4.39). SJZD also significantly improved overall health status compared with placebo in per-protocol population (p = 0.009). No significant difference was found between groups in changes of SF36-PF, spleen deficiency scale scoring, and CGI. Fecal metagenome sequencing and correlation analyses indicated that the beneficial effect of SJZD may be related to the abundance change of Pediococcus acidilactici. No serious adverse event or abnormal laboratory test was found during the whole study. CONCLUSION: Our results indicated that SJZD can improve fatigue symptom and overall health status in patients with CFS under good medication adherence. Potential therapeutic effects may be related to the regulation of gut microbiota. Large-scale trials with longer intervention period are encouraged to further support SJZD's application. CLINICAL TRIAL REGISTRATION: (ID, ISRCTN23930966, URL = https://www.isrctn.com/ISRCTN23930966).

MicroRNA expression as a prognostic biomarker of tongue squamous cell carcinoma (TSCC): a systematic review and meta-analysis.

BACKGROUND: Recent studies have indicated that microRNA (miRNA) expression in tumour tissues has prognostic significance in Tongue squamous cell carcinoma (TSCC) patients. This study explored the possible prognostic value of miRNAs for TSCC based on published research. METHODS: A comprehensive literature search of multiple databases was conducted according to predefined eligibility criteria. Data were extracted from the included studies by two researchers, and HR results were determined based on Kaplan‒Meier curves according to the Tierney method. The Newcastle‒Ottawa Scale (NOS) and GRADE (Grading of Recommendations Assessment, Development, and Evaluation) pro-GDT were applied to assess the quality of all studies. Publication bias was estimated by funnel plot, Egger's rank correlation test and sensitivity analysis. RESULTS: Eleven studies (891patients) were included, of which 6 reported up-regulated miRNAs and 7 mentioned down-regulated miRNAs. The pooled hazard ratio (HR) from the prognostic indicator overall survival (OS) was 1.34 (1.25-1.44), p < 0.00001, indicating a significant difference in miRNA expression between TSCC patients with better or worse prognosis. CONCLUSION: MiRNAs may have high prognostic value and could be used as prognostic biomarkers of TSCC.

Efflux pumps as potential targets for biofilm inhibition.

Biofilms account for a great deal of infectious diseases and contribute significantly to antimicrobial resistance. Efflux pumps confer antimicrobial resistance to microorganisms and involve multiple processes of biofilm formation. Efflux pump inhibitors (EPIs) are attracting considerable attention as a biofilm inhibition strategy. The regulatory functions of efflux pumps in biofilm formation such as mediating adherence, quorum sensing (QS) systems, and the expression of biofilm-associated genes have been increasingly identified. The versatile properties confer efflux pumps both positive and negative effects on biofilm formation. Furthermore, the expression and function of efflux pumps in biofilm formation are species-specific. Therefore, this review aims to detail the double-edged sword role of efflux pumps in biofilm formation to provide potential inhibition targets and give an overview of the effects of EPIs on biofilm formation.

Nicotinamide mononucleotide maintains cytoskeletal stability and fortifies mitochondrial function to mitigate oocyte damage induced by Triocresyl phosphate.

Triocresyl phosphate (TOCP) was commonly used as flame retardant, plasticizer, lubricant, and jet fuel additive. Studies have shown adverse effects of TOCP on the reproductive system. However, the potential harm brought by TOCP, especially to mammalian female reproductive cells, remains a mystery. In this study, we employed an in vitro model for the first time to investigate the effects of TOCP on the maturation process of mouse oocytes. TOCP exposure hampered the meiotic division process, as evidenced by a reduction in the extrusion of the first polar body from oocytes. Subsequent research revealed the disruption of the oocyte cell cytoskeleton induced by TOCP, resulting in abnormalities in spindle organization, chromosome alignment, and actin filament distribution. This disturbance further extended to the rearrangement of organelles within oocytes, particularly affecting the mitochondria. Importantly, after TOCP treatment, mitochondrial function in oocytes was impaired, leading to oxidative stress, DNA damage, cell apoptosis, and subsequent changes of epigenetic modifications. Supplementation with nicotinamide mononucleotide (NMN) alleviated the harmful effects of TOCP. NMN exerted its mitigating effects through two fundamental mechanisms. On one hand, NMN conferred stability to the cell cytoskeleton, thereby supporting nuclear maturation. On the other hand, NMN enhanced mitochondrial function within oocytes, reducing the excess reactive oxygen species (ROS), restoring meiotic division abnormalities caused by TOCP, preventing oocyte DNA damage, and suppressing epigenetic changes. These findings not only enhance our understanding of the molecular basis of TOCP induced oocyte damage but also offer a promising avenue for the potential application of NMN in optimizing reproductive treatment strategies.

Pcgf5: An important regulatory factor in early embryonic neural induction.

Polycomb group RING finger (PCGF) proteins, a crucial subunits of the Polycomb complex, plays an important role in regulating gene expression, embryonic development, and cell fate determination. In our research, we investigated Pcgf5, one of the six PCGF homologs, and its impact on the differentiation of P19 cells into neural stem cells. Our findings revealed that knockdown of Pcgf5 resulted in a significant decrease in the expression levels of the neuronal markers Sox2, Zfp521, and Pax6, while the expression levels of the pluripotent markers Oct4 and Nanog increased. Conversely, Pcgf5 overexpression upregulated the expression of Sox2 and Pax6, while downregulating the expression of Oct4 and Nanog. Additionally, our analysis revealed that Pcgf5 suppresses Wnt3 expression via the activation of Notch1/Hes1, and ultimately governs the differentiation fate of neural stem cells. To further validate our findings, we conducted in vivo experiments in zebrafish. We found that knockdown of pcgf5a using morpholino resulted in the downregulated expression of neurodevelopmental genes such as sox2, sox3, and foxg1 in zebrafish embryos. Consequently, these changes led to neurodevelopmental defects. In conclusion, our study highlights the important role of Pcgf5 in neural induction and the determination of neural cell fate.

Molybdenum disulfide nanosheet induced reactive oxygen species for high-efficiency luminol chemiluminescence.

BACKGROUND: Luminol chemiluminescence (CL) sensing system remains an excellent candidate for application in bioanalysis due to its good water solubility. However, traditional luminol CL system usually requires the addition of oxidizing agents and sensitizers to obtain high efficiency for the improvement of detection sensitivity. Although numerous studies on the nanomaterial-enhanced luminol CL systems have been carried out, there is still great potential to develop inexpensive, readily available and easily handled catalysts to construct simple and effective CL platform for biomolecular sensing. RESULTS: Few-layered MoS2 nanosheets (NS) prepared by sonication-assisted exfoliation of commercially available bulk MoS2 were found to significantly enhance the CL of luminol‒dissolved oxygen in the absence of additional oxidants. The mechanism study demonstrated that exfoliated MoS2 NS could catalyze the decomposition of dissolved oxygen by virtue of its exposed active sites on the surface, generating increased reactive oxygen intermediates, which then oxidize luminol and produce intense CL emission. The proposed high-efficiency luminol CL system was then employed for the extremely sensitive identification of dopamine based on the quenching of CL by dopamine. The limit of detection (LOD) for dopamine can be as low as 2.07 nM. Besides, it also works well in the actual urine sample with good recoveries (99.6-100.6 %), confirming the practicability of the method. SIGNIFICANCE: As a new type of CL catalyst, MoS2 NS developed in this work are easy to obtain, simple to prepare and can be produced in large quantities, which lays a foundation for extending applicability of MoS2 NS in the CL field, and provides a new idea for developing simple and highly sensitive CL sensing system.

[Comparison of the virtual surgical planning position of maxilla and condyle with the postoperative real position in patients with mandibular protrusion].

OBJECTIVE: To compare the difference between virtual surgical planning (VSP) position and postoperative real position of maxilla and condyle, and to explore the degree of intraoperative realization of VSP after orthognathic surgery. METHODS: In this study, 36 patients with mandibular protrusion deformity from January 2022 to December 2022 were included. All the patients had been done bilateral sagittal split ramus osteotomy (SSRO) combined with Le Fort Ⅰ osteotomy under guidance of VSP. The VSP data (T0) and 1-week postoperative CT (T1) were collected, the 3D model of postoperative CT was established and segmented into upper and lower jaws in CCMF Plan software. At the same time, accor-ding to the morphology of palatal folds, the virtual design was registered with the postoperative model, and the unclear maxillary dentition in the postoperative model was replaced. Then the postoperative model was matched with VSP model by registration of upper skull anatomy that was not affected by the operation. The three-dimensional reference plane and coordinate system were established. Selecting anatomical landmarks and their connections of condyle and maxilla for the measurement, we compared the coordinate changes of marker points in three directions, and the angle changes between the line connecting the marker points and the reference plane to analyze the positional deviation and the angle deviation of the postoperative condyle and maxilla compared to VSP. RESULTS: The postoperative real position of the maxilla deviates from the VSP by nearly 1 mm in the horizontal and vertical directions, and the anteroposterior deviation was about 1.5 mm. In addition, most patients had a certain degree of counterclockwise rotation of the maxilla after surgery. Most of the bilateral condyle moved forward, outward and downward (the average distance deviation was 0.15 mm, 1.54 mm, 2.19 mm, respectively), and rotated forward, outward and upward (the average degree deviation was 4.32°, 1.02°, 0.86°, respectively) compared with the VSP. CONCLUSION: VSP can be mostly achieved by assistance of 3D printed occlusal plates, but there are certain deviations in the postoperative real position of maxilla and condyle compared with VSP, which may be related to the rotation axis of the mandible in the VSP. It is necessary to use patient personalized condylar rotation axis for VSP, and apply condylar positioning device to further improve surgical accuracy.

Polysaccharide-Based Coating with Excellent Antibiofilm and Repeatable Antifouling-Bactericidal Properties for Treating Infected Hernia.

In recent years, the utilization of medical devices has gradually increased and implantation procedures have become common treatments. However, patients are susceptible to the risk of implant infections. This study utilized chemical grafting to immobilize polyethylenimine (QPEI) and hyaluronic acid (HA) on the surface of the mesh to improve biocompatibility while being able to achieve antifouling antimicrobial effects. From the in vitro testing, PP-PDA-Q-HA exhibited a high antibacterial ratio of 93% against S. aureus, 93% against E. coli, and 85% against C. albicans. In addition, after five rounds of antimicrobial testing, the coating continued to exhibit excellent antimicrobial properties; PP-PDA-Q-HA also inhibits the formation of bacterial biofilms. In addition, PP-PDA-Q-HA has good hemocompatibility and cytocompatibility. In vivo studies in animal implantation infection models also demonstrated the excellent antimicrobial properties of PP-PDA-Q-HA. Our study provides a promising strategy for the development of antimicrobial surface medical materials with excellent biocompatibility.

Enhanced external counterpulsation improves sleep quality in chronic insomnia: A pilot randomized controlled study.

PURPOSE: To investigate the short-term efficacy of enhanced external counterpulsation (EECP) on chronic insomnia. METHODS: This is a pilot randomized, participant-blind, and sham-controlled study. Forty-six participants with chronic insomnia were randomly assigned in a 1:1 ratio to receive EECP or sham EECP intervention (total of 35 sessions with 45 min each). The primary outcome was Pittsburgh Sleep Quality Index (PSQI). The secondary outcomes included sleep diary, Hospital Anxiety and Depression Scale (HADS), Short-Form Health Survey (SF12), flow mediated dilation (FMD), serum biomarkers of melatonin, cortisol, interleukin-6, and high sensitivity C-reactive protein. Outcomes were assessed after treatment and at 3-month follow-up. RESULTS: The PSQI was significantly decreased in both EECP and sham groups after 35-session intervention (13.74 to 6.96 in EECP and 13.04 to 9.48 in sham), and EECP decreased PSQI more than sham EECP (p = 0.009). PSQI in two groups kept improved at 3-month follow-up. After treatment, the total sleep time, sleep efficiency, FMD value and SF12 mental component of EECP group were significantly improved, and group differences were found for these outcomes. At follow-up, total sleep time, sleep efficiency and SF12 mental component of EECP group remained improved, and group difference for SF12 mental component was found. Post-treatment and follow-up HADS-A significantly decreased in both groups, with no differences between groups. Post-treatment serum biomarkers showed no differences within and between groups. LIMITATION: Lack of objective sleep measurement. CONCLUSION: EECP could improve sleep quality and mental quality of life in chronic insomnia and the therapeutic effect maintained for 3 months.

Generation of a Hydrophobic Protrusion on Nanoparticles to Improve the Membrane-Anchoring Ability and Cellular Internalization.

Controlling the nanoparticle-cell membrane interaction to achieve easy and fast membrane anchoring and cellular internalization is of great importance in a variety of biomedical applications. Here we report a simple and versatile strategy to maneuver the nanoparticle-cell membrane interaction by creating a tunable hydrophobic protrusion on Janus particles through swelling-induced symmetry breaking. When the Janus particle contacts cell membrane, the protrusion will induce membrane wrapping, leading the particles to docking to the membrane, followed by drawing the whole particles into the cell. The efficiencies of both membrane anchoring and cellular internalization can be promoted by optimizing the size of the protrusion. In vitro, the Janus particles can quickly anchor to the cell membrane in 1 h and be internalized within 24 h, regardless of the types of cells involved. In vivo, the Janus particles can effectively anchor to the brain and skin tissues to provide a high retention in these tissues after intracerebroventricular, intrahippocampal, or subcutaneous injection. This strategy involving the creation of a hydrophobic protrusion on Janus particles to tune the cell-membrane interaction holds great potential in nanoparticle-based biomedical applications.

Aesthetic effect evaluation of the xenogeneic collagen matrix in keratinized mucosa augmentation around dental implants / 口腔疾病防治

Objective@#To evaluate the stability and aesthetic effect of a xenogeneic collagen matrix (mucograft) on achieving an adequate keratinized mucosa width (KMW) around implants and to provide a reference basis for the clinical application of xenogeneic collagen matrix materials.@*Methods@#The hospital ethics committee approved the study protocol, and the patients provided informed consent. Twenty patients with a KMW<2 mm at the buccal implant site who were treated in Binzhou Medical University Affiliated Yantai Stomatological Hospital from July 2020 to September 2022 were included, and a total of 36 implants were included. The mean age of the patients was (52.0±10.4) years, of which 18 were females and 2 were males. They were divided into a free gingival graft group (FGG, control group) and a xenogeneic collagen matrix group (test group) according to different graft materials. The incremental effect of the KMW on the buccal side of the implant and the mucosal shrinkage rate was measured at 1 month and 3 months after the operation. The mucosal scar index (MSI) was evaluated after the operation.@*Results@#At 3 months postoperatively, the KMW was (3.67 ± 1.06) mm in the control group and (2.96 ± 0.98) mm in the test group, and the difference was statistically significant (t = 2.076, P<0.05). The KMW shrinkage rate was (33.34 ± 16.30) % in the test group and (22.05 ± 15.47) % in the control group at 1 month postoperatively and (51.95 ± 12.60) % in the test group and (37.44 ± 16.30) % in the control group at 3 months postoperatively, with statistically significant differences between the two groups at the same time points (P<0.05). Three months after surgery, the test group showed significantly better outcomes than the control group in terms of the five scar indicators (scar width, scar convexity, scar color, scar trace, and overall appearance), and the difference was statistically significant (P<0.05).@*Conclusion@#Xenogeneic collagen matrix can increase the peri-implant KMW and achieve a more natural and coordinated soft tissue aesthetic effect but with a higher shrinkage rate.

Expression and clinical diagnostic value of CCHE1 in breast cancer.

OBJECTIVE: Breast cancer is a malignant tumor in the epithelial tissue of the breast gland. This study aimed to unveil the expression and clinical diagnostic value of lncRNA cervical cancer high-expressed 1 (CCHE1) in breast cancer. METHODS: CCHE1 expression in breast cancer tissues was evaluated by RT-qPCR. The relationship between the CCHE1 expression and clinicopathological features of breast cancer was analyzed with the chi-square test, and the survival of breast cancer patients was evaluated with the Kaplan-Meier method. The diagnostic value of CCHE1 expression for breast cancer was evaluated by using the receiver operating characteristics (ROC) curve. Breast cancer cell lines (SKBR3, T47D, BT474, and MCF-7) were cultured for detecting CCHE1 expression in the cells. MCF-7 cells were selected for the subsequent experiments, and the small interfering RNA of CCHE1 (si-CCHE1) and CCHE1 overexpression vector (pcDNA-CCHE1) were transfected into MCF-7 cells. The proliferation, migration, and invasive ability were assessed by CCK-8 and Transwell assays. The influence of CCHE1 on the growth of tumors was validated by nude mice xenograft assay. RESULTS: CCHE1 was up-regulated in breast cancer tissues and breast cancer cells. The high expression level of CCHE1 in cancer tissues of breast cancer patients was correlated with larger tumor size, advanced TNM stage, Ki-67 status, and lymph node metastasis. The area under the ROC curve for CCHE1 in the diagnosis of breast cancer was 0.983 (95% CI: 0.966-1.000), with a sensitivity of 95.00% and a specificity of 91.70%. The 5-year survival rate was higher in patients with low CCHE1 expression than those with high CCHE1 expression. Furthermore, restrained CCHE1 impeded proliferation, invasion, and migration of MCF-7 cells, as well as tumor growth in mice. CONCLUSION: Our study highlights that elevated expression of CCHE1 in breast cancer tissues, which is closely related to clinicopathologic features, has some clinical value in the diagnosis of the disease.

Multi-disciplinary cooperation for the micro-elimination of hepatitis C in China: a hospital-based experience.

BACKGROUND: Hepatitis C virus (HCV) infection is one of the main causes of liver cancer and imposes an enormous social and economic burden. The blood-borne virus screening policy for preventing iatrogenic infections renders hospitals important for identifying individuals infected with hepatitis C. Therefore, we aimed to investigate the establishment of a multi-disciplinary cooperation model in medical institutions to leverage the screening results of patients with hepatitis C. Our objective is to ensure that patients receive timely and effective diagnosis and treatment, thereby enabling the elimination of hepatitis C by 2030. METHOD: A multi-disciplinary cooperation model was established in October 2021. This retrospective study was based on the establishment of antibody-positive and HCV RNA-positive patient databases. A Chi-square test was used to compare the HCV RNA confirmation rate in anti-HCV-positive patients, as well as the hepatitis C diagnosis rate and treatment rate in RNA-positive patients before and after the multi-disciplinary cooperation. A multivariable logistic regression was used to analyse the factors affecting the treatment of patients with hepatitis C. In addition, we examined changes in the level of hepatitis C knowledge among medical staff. RESULTS: After the implementation of the multi-disciplinary cooperation model, the RNA confirmation rate of hepatitis C antibody-positive patients increased from 36.426% to 88.737%, the diagnostic accuracy rate of RNA-positive patients increased from 67.456% to 98.113%, and the treatment rate of patients with hepatitis C increased from 12.426% to 58.491%. Significant improvements were observed among the clinicians regarding their ability to understand the characteristics of hepatitis C (93.711% vs. 58.861%), identify people at high risk (94.340% vs. 53.797%), manage patients with hepatitis C after diagnosis (88.679% vs. 67.089%), and effectively treat hepatitis C (84.277% vs. 51.899%). Multi-disciplinary cooperation in medical institutions was the most important factor for patients to undergo HCV treatment (odds ratio: 0.024, 95% confidence interval: 0.007-0.074). CONCLUSIONS: This study showed that the use of a multi-disciplinary cooperation model to utilise the results of HCV antibody screening fully in patients through further tracking, referral, and treatment may facilitate the detection and treatment of patients with hepatitis C and accelerate the elimination of HCV in China.

Pyruvate dehydrogenase kinase 1 protects against neuronal injury and memory loss in mouse models of diabetes.

Hyperglycemia-induced aberrant glucose metabolism is a causative factor of neurodegeneration and cognitive impairment in diabetes mellitus (DM) patients. The pyruvate dehydrogenase kinase (PDK)-lactic acid axis is regarded as a critical link between metabolic reprogramming and the pathogenic process of neurological disorders. However, its role in diabetic neuropathy remains unclear. Here, we found that PDK1 and phosphorylation of pyruvate dehydrogenase (PDH) were obviously increased in high glucose (HG)-stimulated primary neurons and Neuro-2a cell line. Acetyl-coA, a central metabolic intermediate, might enhance PDK1 expression via histone H3K9 acetylation modification in HG condition. The epigenetic regulation of PDK1 expression provided an available negative feedback pattern in response to HG environment-triggered mitochondrial metabolic overload. However, neuronal PDK1 was decreased in the hippocampus of streptozotocin (STZ)-induced diabetic mice. Our data showed that the expression of PDK1 also depended on the hypoxia-inducible factor-1 (HIF-1) transcriptional activation under the HG condition. However, HIF-1 was significantly reduced in the hippocampus of diabetic mice, which might explain the opposite expression of PDK1 in vivo. Importantly, overexpression of PDK1 reduced HG-induced reactive oxygen species (ROS) generation and neuronal apoptosis. Enhancing PDK1 expression in the hippocampus ameliorated STZ-induced cognitive impairment and neuronal degeneration in mice. Together, our study demonstrated that both acetyl-coA-induced histone acetylation and HIF-1 are necessary to direct PDK1 expression, and enhancing PDK1 may have a protective effect on cognitive recovery in diabetic mice. Schematic representation of the protective effect of PDK1 on hyperglycemia-induced neuronal injury and memory loss. High glucose enhanced the expression of PDK1 in an acetyl-coA-dependent histone acetylation modification to avoid mitochondrial metabolic overload and ROS release. However, the decrease of HIF-1 may impair the upregulation of PDK1 under hyperglycemia condition. Overexpression of PDK1 prevented hyperglycemia-induced hippocampal neuronal injury and memory loss in diabetic mice.