Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Nicotinamide adenine dinucleotide (NAD⁺) is a central and pleiotropic metabolite involved in multiple cellular energy metabolism, such as cell signaling, DNA repair, protein modifications, and so on. Evidence suggests that NAD⁺ levels decline with age, obesity, and hypertension, which are all significant CVD risk factors. In addition, the therapeutic elevation of NAD⁺ levels reduces chronic low-grade inflammation, reactivates autophagy and mitochondrial biogenesis, and enhances antioxidation and metabolism in vascular cells of humans with vascular disorders. In preclinical animal models, NAD⁺ boosting also extends the health span, prevents metabolic syndrome, and decreases blood pressure. Moreover, NAD⁺ storage by genetic, pharmacological, or natural dietary NAD⁺-increasing strategies has recently been shown to be effective in improving the pathophysiology of cardiac and vascular health in different animal models and humans. Here, we discuss NAD⁺-related mechanisms pivotal for vascular health and summarize recent research on NAD⁺ and its association with vascular health and disease, including hypertension, atherosclerosis, and coronary artery disease. This review also assesses various NAD⁺ precursors for their clinical efficacy and the efficiency of NAD⁺ elevation in the prevention or treatment of major CVDs, potentially guiding new therapeutic strategies.
Humans ; Cardiovascular Diseases/physiopathology* ; NAD/metabolism* ; Animals ; Hypertension/metabolism*

Successful cloning through somatic cell nuclear transfer (SCNT) faces significant challenges due to epigenetic obstacles. Recent studies have highlighted the roles of H3K4me3 and H3K27me3 as potential contributors to these obstacles. However, the underlying mechanisms remain largely unclear. In this study, we generated genome-wide maps of H3K4me3 and H3K27me3 in mouse pre-implantation NT embryos. Our analysis revealed that aberrantly over-represented broad H3K4me3 domain and H3K27me3 signal lead to increased bivalent marks at gene promoters in NT embryos compared with naturally fertilized (NF) embryos at the 2-cell stage, which may link to relatively low levels of H3K36me3 in NT 2-cell embryos. Notably, the overexpression of Setd2, a H3K36me3 methyltransferase, successfully restored multiple epigenetic marks, including H3K36me3, H3K4me3, and H3K27me3. In addition, it reinstated the expression levels of ZGA-related genes by reestablishing H3K36me3 at gene body regions, which excluded H3K27me3 from bivalent promoters, ultimately improving cloning efficiency. These findings highlight the excessive bivalent state at gene promoters as a potent barrier and emphasize the removal of these barriers as a promising approach for achieving higher cloning efficiency.
Animals ; Mice ; Histone-Lysine N-Methyltransferase/biosynthesis* ; Histones/genetics* ; Nuclear Transfer Techniques ; Female ; Gene Expression Regulation, Developmental ; Promoter Regions, Genetic ; Epigenesis, Genetic ; Embryo, Mammalian/metabolism*

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

Objective To develop a Traditional Chinese Medicine(TCM)syndrome diagnosis scale suitable for evaluating the overall health status of participants in long-term simulated weightlessness experiments,and preliminarily evaluate its reliability and validity.Methods Based on the understanding of the pathogenesis of TCM in different stages of long-term manned spaceflight,a scale was developed through literature research and expert consultation.Test-retest reliability and internal consistency coefficient were used to test the reliability of the scale.Item analysis and factor principal component analysis were used to evaluate the validity of the scale,and a rotating component matrix was used to analyze the correlation between each item and dimension using 36 volunteers in a 90 days head down bed rest experiment as the research subjects.Results The scale contains eight dimensions and 57 items.The reliability analysis showed that the correlation coefficient of the total score of the scale for the first and second tests of 30 participants was 0.889,indicating high stability of the scale.The Cronbach coefficient of the scale was 0.934,indicating very good internal consistency.The split half reliability after correction was 0.858,indicating a high reliability of the scale.The validity analysis showed that the difference between the high score group and the low score one for each of the 57 items was statistically significant(P<0.01),and the Pearson correlation coefficient between each item and the total score of the scale was greater than 0.4(P<0.001).The cumulative contribution rate of 8 common factors extracted using principal component factor analysis was 55.293%,and the results of rotating component matrix analysis,after applying TCM theory and expert feedback,had a coincidence of up to 87.5%with the initial 8 dimensions,indicating good structural validity of the scale.Conclusion The scale has good reliability and validity,and can diagnose TCM syndromes.It is suitable for long-term simulated weightlessness experiment and provides an objective and quantitative new method for evaluating the subjective feelings of participants.

ObjectiveTo investigate the clinical value of DR corneal suture ring localization and CT 3D reconstruction localization of orbital foreign bodies. MethodsRetrospective analysis was performed on patients （51 cases） suspected of ocular foreign bodies admitted to our hospital from January 2016 to December 2020 At the same time， DR corneal suture ring localization and CT three-dimensional reconstruction localization of orbital foreign bodies were performed， and the detection rate of foreign bodies by the two methods was calculated to analyze the location of ocular foreign bodies. ResultsThere were 38 cases of intraorbital foreign body identified by DR corneal suture ring localization method， and 46 cases of intraorbital foreign body identified by CT three-dimensional reconstruction localization method. The accuracy of CT three-dimensional reconstruction localization method was 90.20%， which was higher than that of DR corneal suture ring localization method 74.51% （P<0.05）. Intraocular foreign bodies in 23 cases could be distinguished by DR corneal suture ring localization， and 25 cases by CT 3D reconstruction localization. The maximum diameter of intraocular foreign bodies that could be distinguished by CT 3D reconstruction localization was （2.65±0.14） mm. The diameter of intraspherical foreign body was （2.94±0.36） mm （P<0.05） lower than that which could be distinguished by DR corneal suture ring localization method. The results of DR corneal suture ring localization of orbital foreign body showed no difference compared with the results of CT 3D reconstruction localization （P>0.05）. Forty cases of high density images inside and outside the eye could be clearly distinguished by CT 3D reconstruction. By using DR corneal suture ring localization method， 23 cases were confirmed to be intraocular high-density shadows， and 15 cases could not be confirmed to be intraocular high-density shadows （P < 0.05）. ConclusionsFor the location of intraorbital foreign bodies， CT three-dimensional reconstruction can be used as a conventional method for locating ocular foreign bodies with high resolution and accuracy， and can detect fine metal particles inside the eyeball. Meanwhile， for a few small foreign bodies in the iris root， ciliary body and lateral suspension ligament， it is necessary to locate orbital foreign bodies with DR corneal suture ring.

Ilizarov technique is designed based on the "tension-stress principle". Application of the Ilizarov technique can help form a stable mechanical structure through external fixation. It only creates small wounds, without peeling off the surrounding tissue and periosteum. It connects different types of fixation pins and bone or soft tissue to form a traction force, which continuously stimulates the regeneration of bone and tissue and improves the local blood supply and early functional rehabilitation exercises, forming a complete set of minimally invasive orthopedic treatment systems. Ilizarov technique has achieved good results in fracture healing, deformity correction, tissue repair, osteomyelitis, bone nonunion, bone defect, and bone tumor. This paper will summarize the clinical application and research of the Ilizarov technique in orthopedics and explore the key problems of the Ilizarov technique that need to be solved at present.

Objective:To investigate the early curative effects of robot-assisted total knee arthroplasty (TKA) in the treatment of valgus knee.Methods:A retrospective study was conducted to analyze the data of 40 patients with valgus knee who had been treated by TKA at Department of Orthopaedics, The 920th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army from January to December 2021. The patients were divided into 2 groups according to whether a robot had been used or not for TKA. In the observation group of 15 cases for which TKA was assisted by a robot, there were 4 males and 11 females with an age of (65.5±6.2) years, and the disease course was 42 (36, 54) months; in the control group of 25 cases for which conventional TKA was performed, there were 8 males and 17 females with an age of (65.8±7.5) years, and the disease course was 42 (36, 60) months. Surgical time, hemoglobin decrease, and knee joint range of motion, American Knee Society Score (KSS), hip-knee-ankle angle (HKA), lateral distal femoral angle (LDFA), and medial proximal tibial angle (MPTA) at 12 months after surgery were compared between the 2 groups.Results:There was no significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). The surgical time in the observation group was (148.0±21.2) min, significantly longer than that in the control group [(115.2±7.1) min], and the hemoglobin decreased by (11.8±1.1) g/L in the observation group, significantly less than that in the control group [(18.1±1.8) g/L] ( P<0.05). The observation group and the control group were followed up for 13 (13, 14) and 13 (13, 14) months after surgery, respectively, showing no statistically significant difference ( P>0.05). At 12 months after surgery, the KSS knee score, KSS functional score, and knee range of motion in the observation group were (86.1±4.6) points, (86.9±3.1) points, and 115.7°±5.0°, significantly larger than those in the control group [(82.2±3.5) points, (82.8±0.9) points, and 108.2°±5.0°] ( P<0.05). Reexamination of full-length radiographs of both lower limbs in all patients showed good positions of the prostheses and no such adverse events as loosening or sinking at 12 months after surgery. The HKA (178.5°±1.2°) and LDFA (89.1°±0.7°) at 12 months after surgery in the observation group were significantly larger than those in the control group (176.6°±1.5°, 88.2°±8.2°) ( P<0.05); there was no statistically significant difference in MPTA between the 2 groups ( P>0.05). Conclusions:In the treatment of valgus knee, robot-assisted TKA can correct joint deformity, and achieve precise osteotomy and functional alignment of lower limbs, leading to better early curative effects than conventional TKA.

This study aimed to investigate the neurotoxicity induced by trichloroacetic acid (TCA) and the possible protective mechanisms of boron (B). Mouse BV2 cells were treated with TCA (0, 0.39, 0.78, 1.56, 3.12, 6.25, or 12.5 mmol/L) and B (0, 7.8, 15.6, 31.25, 62.5, 125, 500, or 1,000 mmol/L) for 3 h and 24 h, respectively. Then, reactive oxygen species, and supernatant proinflammatory cytokine and protein levels were analyzed after 24 h of combined exposure. Beyond the dose-dependent decrease in the cellular viability, it clearly increased after B supplementation ( P < 0.05). Moreover, B decreased oxidative damage, and significantly down-regulated IL-6 levels and up-regulated TNF-β production ( P < 0.05). B also decreased apoptosis via the p53 pathway. The present findings indicated that TCA may induce oxidative damage, whereas B mitigates these adverse effects by decreasing cell apoptosis.
Animals ; Apoptosis ; Boron/toxicity* ; Mice ; Oxidative Stress ; Reactive Oxygen Species/metabolism* ; Trichloroacetic Acid/toxicity* ; Tumor Suppressor Protein p53/metabolism*

The composition of serum is extremely complex,which complicates the discovery of new pharmaco-dynamic biomarkers via serum proteome for disease prediction and diagnosis.Recently,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich low-abundance proteins in serum.Here,we synthesized a silica-coated iron oxide nanoparticle and devel-oped a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis.We identified 1,070 proteins with a median coefficient of variation of 12.56％using PC-based proteomic analysis,which was twice the number of proteins iden-tified by direct digestion.There were also more biological processes enriched with these proteins.We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with MTX.This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment.

Objective: To evaluate the associations of sarcopenia, handgrip strength and calf circumference with cognitive impairment among Chinese older adults. Methods: Totally 2,525 older adults were recruited from the Healthy Aging and Biomarkers Cohort Study. Cognitive impairment was assessed by the Chinese Mini-Mental State Examination. Handgrip strength was calculated from the means of the right and left hand values. Calf circumference was measured at the site of maximum circumference of the non-dominant leg. The formula developed by Ishii was used to define sarcopenia. Multiple logistic regression was performed to evaluate the associations of sarcopenia, handgrip strength, and calf circumference with cognitive impairment. Results: The prevalence of cognitive impairment was 34.36%. The adjusted odds ratio ( Conclusion Sarcopenia, identified by low handgrip strength and low calf circumference, was positively associated with cognitive impairment.
Aged ; Aged, 80 and over ; China/epidemiology* ; Cognitive Dysfunction/etiology* ; Female ; Hand Strength ; Humans ; Leg/anatomy & histology* ; Logistic Models ; Male ; Sarcopenia/pathology*