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*

This study investigated the effects of Rehmanniae Radix Praeparata on striatal neuronal apoptosis in rats with attention deficit hyperactivity disorder(ADHD) based on the B-cell lymphoma-2(Bcl-2)/Bcl-2-associated X protein(Bax)/caspase-3 signaling pathway. Twenty-four 3-week-old male spontaneously hypertensive rats(SHR) were randomly divided into a model group, a methylphenidate group(2 mg·kg~(-1)·d~(-1)), and a Rehmanniae Radix Praeparata group(2.4 mg·kg~(-1)·d~(-1)). Age-matched male Wistar Kyoto(WKY) rats were used as the normal control group, with 8 rats in each group. The rats were administered by gavage for 28 days. Body weight and food intake were recorded for each group. The open field test and elevated plus maze test were used to assess hyperactivity and impulsive behaviors. Nissl staining was used to detect changes in striatal neurons and Nissl bodies. Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) fluorescence staining was used to detect striatal cell apoptosis. Western blot was employed to detect the expression levels of Bcl-2, Bax, and caspase-3 proteins in the striatum. The results showed that compared with the model group, Rehmanniae Radix Praeparata significantly reduced the total movement distance, average movement speed, and central area residence time in the open field test, and significantly reduced the ratio of open arm entries, open arm stay time, and head dipping in the elevated plus maze test. Furthermore, it increased the number of Nissl bodies in striatal neurons, significantly downregulated the apoptosis index, significantly increased Bcl-2 protein expression and the Bcl-2/Bax ratio, and reduced Bax and caspase-3 protein expression. In conclusion, Rehmanniae Radix Praeparata can reduce hyperactivity and impulsive behaviors in ADHD rats. Its mechanism may be related to the regulation of the Bcl-2/Bax/caspase-3 signaling pathway in the striatum, enhancing the anti-apoptotic capacity of striatal neurons.
Animals ; Male ; Apoptosis/drug effects* ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Caspase 3/genetics* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; bcl-2-Associated X Protein/genetics* ; Rehmannia/chemistry* ; Attention Deficit Disorder with Hyperactivity/physiopathology* ; Signal Transduction/drug effects* ; Neurons/cytology* ; Rats, Inbred SHR ; Rats, Inbred WKY ; Humans ; Corpus Striatum/cytology* ; Plant Extracts

The phase changes and quantity-quality transfer of 17 batches of Ostreae Concha(Ostrea rivularis) during the raw material-calcined decoction pieces-standard decoction process were analyzed. The content of calcium carbonate(CaCO_3), the main component, was determined by chemical titration, and the extract yield and transfer rate were calculated. The CaCO_3 content in the raw material, calcined decoction pieces, and standard decoction was 94.39%-98.80%, 95.03%-99.22%, and 84.58%-90.47%, respectively. The process of raw material to calcined decoction pieces showed the yield range of 96.85% to 98.55% and the CaCO_3 transfer rate range of 96.92% to 99.27%. The process of calcined decoction pieces to standard decoction showed the extract yield range of 2.86% to 5.48% and the CaCO_3 transfer rate range of 2.59% to 5.13%. The results of X-ray fluorescence(XRF) assay showed that the raw material, calcined decoction pieces, and standard decoction mainly contained Ca, Na, Mg, Si, Br, Cl, Al, Fe, Cr, Mn, and K. The chemometric results showed an increase in the relative content of Cr, Fe, and Si from raw material to calcined decoction pieces and an increase in the relative content of Mg, Al, Br, K, Cl, and Na from calcined decoction pieces to standard decoction. X-ray diffraction(XRD) was employed to establish XRD characteristic patterns of the raw material, calcined decoction pieces, and standard decoction. The XRD results showed that the main phase of all three was calcite, and no transformation of crystalline form or generation of new phase was observed. Fourier transform infrared spectroscopy(FTIR) was employed to establish the FTIR characteristic spectra of the raw material, calcined decoction pieces, and standard decoction. The FTIR results showed that the raw material had internal vibrations of O-H, C-H, C=O, C-O, and CO■ groups. Due to the loss of organic matter components after calcination, no information about the vibrations of C-H, C=O, and C-O groups was observed in the spectra of calcined decoction pieces and standard decoction. In summary, this study elucidated the quantity-quality transfer and phase changes in the raw material-calcined decoction pieces-standard decoction process by determining the CaCO_3 content, calculating the extract yield and transfer rate, and comparing the element changes, FTIR characteristic spectra, and XRD characteristic pattern. The results were reasonable and reliable, laying a foundation for the subsequent process research and quality control of the formula granules of calcined Ostreae Concha(O. rivularis Gould), and providing ideas and methods for the quality control of the whole process of raw material-decoction pieces-standard decoction-formula granules of Ostreae Concha and other testacean traditional Chinese medicine.
Drugs, Chinese Herbal/isolation & purification* ; Calcium Carbonate/analysis* ; Quality Control

OBJECTIVE: To compare clinical efficacy of intermetatarsal incision and lateral soft tissue release of medial incision combined with Scarf osteotomy in treating moderate to severe hallux valgus (HV). METHODS: A retrospective analysis was conducted on clinical data of 42 patients with moderate to severe HV admitted from January 2022 to December 2022. According to different incisions, the patients were divided into medial incision group with 22 patients (22 feet) and intermetatarsal incision group with 20 patients (20 feet). In medial incision group, there were 3 males and 19 females, aged from 40 to 69 years old with an average of (55.0±11.4) years old;body mass index (BMI) ranged from 21 to 29 kg·m-2 with an average of (25.2±2.1) kg·m-2;the courses of disease ranged from 8 to 16 years with average of (12.0±2.2) years;11 patients with moderate deformity and 11 patients with severe deformity. In transplantar incision group, there were 3 males and 17 females, aged from 39 to 68 years old with an average of (53.0±7.5) years old;BMI ranged from 20 to 28 kg·m^-2 with an average of (24.8±1.9) kg·m^-2;the courses of disease ranged from 9 to 17 years with an average of (14.0±3.1) years;9 patients with moderate deformity and 11 patients with severe deformity. Hallux valgus angle (HVA) and the first-second intermetatarsal angle (IMA), American Orthopaedic Foot and Ankle Society (AOFAS) forefoot scores and complications between two groups before operation and 12 months after operation were observed and compared. RESULTS: All patients were successfully completed the surgery and were followed up for 12 to 15 months with an average of (13.52±1.65) months. There were no statistically significant difference in HVA and IMA between two groups before operation and 12 months after operation (P>0.05). AOFAS forefoot scores of medial incision group before operation and 12 months after operation were (45.0±6.8) and (86.0±6.7) respectively, and those of transmetatarsal incision group were (46.0±7.4) and (83.0±7.5) respectively. Postoperative AOFAS forefoot scores between two groups at 12 months were statistically significant compared with those of before operation (P<0.01). According to AOFAS forefoot scores, 8 patients got excellent result, 14 good in medial incision group;while 6 excellent and 14 good in transplantar incision group. At 12 months, postoperative AOFAS forefoot score of functional score of in medial incision group(38.0±2.5), was better than that in transplantar incision group (34.0±2.2), and the difference was statistically significant (P<0.05). One patient in medial incision group occurred HV deformity, mild numbness occurred in 3 toes in transplantar incision group, and 3 patients were dissatisfied with scar. No complications such as infection, nonunion of bones or ischemic necrosis of metatarsal heads occurred in either group. CONCLUSION Both intermetatarsal incision and lateral soft tissue release of medial incision combined with Scarf osteotomy can effectively treat moderate to severe HV. The functional recovery after medial incision is better than that after intermetatarsal incision.
Humans ; Male ; Female ; Hallux Valgus/physiopathology* ; Middle Aged ; Osteotomy/methods* ; Adult ; Aged ; Retrospective Studies ; Treatment Outcome ; Metatarsal Bones/surgery*

OBJECTIVES: To investigate the risk factors for the occurrence of cardiopulmonary dysfunction following ligation of hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. METHODS: A retrospective collection of clinical data was conducted on preterm infants with a gestational age of <34 weeks who were admitted to the Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology from January 2018 to August 2024. These infants underwent hsPDA ligation after 1-2 courses of failed ibuprofen treatment. Based on the occurrence of blood pressure changes and oxygenation or ventilation failure postoperatively, the infants were divided into a cardiopulmonary dysfunction group (19 cases) and a non-cardiopulmonary dysfunction group (40 cases). Binary logistic regression analysis was performed to explore risk factors for postoperative cardiopulmonary dysfunction. RESULTS: Binary logistic regression analysis indicated that a faster average weight gain rate preoperatively and low levels of free triiodothyronine (FT₃) within one week before surgery were risk factors for cardiopulmonary dysfunction following hsPDA ligation (P<0.05). Receiver operating characteristic curve analysis showed that an average weight gain rate >11.45 g/(kg·d) and FT₃ levels <2.785 pmol/L within one week before surgery had predictive value for postoperative cardiopulmonary dysfunction (P<0.05). The combination of these two indicators provided the highest predictive value (P<0.05), with an area under the curve of 0.825, a sensitivity of 79%, and a specificity of 75%. CONCLUSIONS An average weight gain rate exceeding 11.45 g/(kg·d) and FT₃ levels below 2.785 pmol/L within one week before surgery are risk factors affecting cardiopulmonary function after hsPDA ligation. Preoperative assessment and intervention should be strengthened to reduce the risk of postoperative complications.
Humans ; Ductus Arteriosus, Patent/physiopathology* ; Risk Factors ; Female ; Infant, Newborn ; Male ; Retrospective Studies ; Infant, Premature ; Ligation/adverse effects* ; Hemodynamics ; Postoperative Complications/etiology* ; Logistic Models ; Lung Diseases/etiology*

OBJECTIVE: To identify the gene mutation types of 4 suspected β-thalassemia patients in Yunnan Province, and to analyze the genotypes and hematological phenotypes. METHODS: Whole genome sequencing was performed on the samples of 4 suspected β-thalassemia patients from the Dai ethnic group in a thalassemia endemic area of Yunnan Province, whose hematological phenotypes were not consistent with the results of common thalassemia gene mutations. The mutations of β-globin gene clusters were confirmed by polymerase chain reaction (PCR) and Sanger DNA sequencing technology. RESULTS: The 3.5 kb deletion in β-globin gene cluster (NC_000011.10: g. 5224302-5227791del3490bp) was detected in 4 patients' samples, of which 1 case was also detected with HbE mutation and 1 case with CD17 mutation. These 2 patients displayed moderate anemia phenotype, while the two patients with only the 3.5 kb deletion presented with other mild anemia phenotype. CONCLUSION Heterozygous carriers with rare 3.5 kb deletion of the β-globin gene cluster may develop mild anemia, compound mutations of the 3.5 kb deletion with other mutations may led to intermediate thalasemia with moderate to sever anemia. In areas with a high incidence of thalassemia, suspected patients should undergo genetic testing to avoid missing or misdiagnosing rare mutations.
Humans ; beta-Globins/genetics* ; Multigene Family ; beta-Thalassemia/genetics* ; Mutation ; Genotype ; Sequence Deletion ; Phenotype ; Male ; Female

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*

Medical device related infections caused by bacteria are common complications in clinical practice,and preventing bacterial colonization on the surface of medical materials is one of the important challenges in the medical field.Therefore,there is an urgent need to construct medical coatings that combine antibacterial properties and biocompatibility.In this study,a γ-polyglutamic acid(γ-PGA)complex with long-chain alkyl quaternary ammonium salts formed by electrostatic and hydrophobic interactions was prepared,which was insoluble in water but soluble in organic solvents(e.g.,ethanol),and was capable of constructing antimicrobial coatings on the surfaces of medical materials in a simple and efficient manner.The bactericidal effect of the coating was verified using viable bacteria counting experiments,and the results showed that the bactericidal rate of the coated thermoplastic polyurethane(TPU)membrane against Staphylococcus aureus was greater than 99.9%compared with that of the uncoated TPU membrane.In addition,a cytotoxicity assay was performed using the L929 fibroblast and cell proliferation detection kit(CCK-8),which showed that the survival rate of L929 fibroblasts on coated TPU was greater than 90%.Meanwhile,the hemolysis rate of coated erythrocytes was tested using fresh rabbit red blood cells(RBCs),and the hemolysis rate on the coated TPU surface was 1.5%.The above results indicated that the coating had good biocompatibility.The preparation method of medical antibacterial coating reported in this study provided a new idea for preventing bacterial infections related to implantable/interventional medical devices.

Objective To investigate the changes in serum complement activation product(sC5b-9),serotonin(5-HT),and peripheral blood C1q mRNA levels in patients with bipolar disorder during manic episodes,and their correlation with cognitive impairment.Methods From January 2022 to December 2023,75 patients with bipolar disorder during manic episodes and 75 healthy individuals who were treated at Baoji Central Hospital were selected and divided into BD group and healthy group.Serum sC5b-9,5-HT,peripheral blood C1q mRNA levels,and Montreal Cognitive Assessment(MoCA)scores were detected and compared.Patients in the BD group were further grouped based on MoCA scores:cognitive impairment group(22～25 points)(n=40)and non-impairment group(≥26 points)(n=35).Differences in serum sC5b-9,5-HT,and peripheral blood C1q mRNA levels were compared,and multiple Logistic regression analysis was performed to identify influencing factors of cognitive impairment in bipolar disorder patients.Results Compared to the healthy group,the BD group showed significantly elevated serum sC5b-9,5-HT,and peripheral blood C1q mRNA expression levels(P<0.05).The BD group's 8 MoCA domain scores and total MoCA score were significantly lower than the healthy group(P<0.05).Compared to the non-impairment group,the cognitive impairment group demonstrated significantly higher serum sC5b-9,5-HT,and peripheral blood C1q mRNA expression levels(P<0.05).Serum sC5b-9,5-HT,and peripheral blood C1q mRNA expression levels were risk factors for cognitive impairment in patients with bipolar disorder during manic episodes(P<0.05).Conclusion Patients with bipolar disorder during manic episodes show abnormally elevated serum sC5b-9,5-HT,and peripheral blood C1q mRNA expression levels.Cognitive impairment in these patients is closely related to the expression levels of serum sC5b-9,5-HT,and peripheral blood C1q mRNA.

Objective To assess inter-observer variations(IOV)in the delineation of target volumes and organs-at-risk(OAR)for intensity-modulated radiotherapy(IMRT)of nasopharyngeal carcinoma(NPC)among physicians from different levels of cancer centers,thereby providing a reference for quality control in multi-center clinical trials.Methods Twelve patients with NPC of different TMN stages were randomly selected.Three physicians from the same municipal cancer center manually delineated the target volume(GTVnx)and OAR for each patient.The manually modified and confirmed target volume(GTVnx)and OAR delineation structures by radiotherapy experts from the regional cancer center were used as the standard delineation.The absolute volume difference ratio(△V_diff),maximum/minimum volume ratio(MMR),coefficient of variation(CV),and Dice similarity coefficient(DSC)were used to compare the differences in organ delineation among physicians from different levels of cancer centers and among the 3 physicians from the same municipal cancer center.Furthermore,the IOV of GTVnx and OAR among physicians from different levels cancer centers were compared across different TMN stages.Results Significant differences in the delineation of GTVnx were observed among physicians from different levels of cancer centers.Among the 3 physicians,the maximum values of △V_diff,MMR,and CV were 97.23%±83.45%,2.19±0.75,and 0.31±0.14,respectively,with an average DSC of less than 0.7.Additionally,there were considerable differences in the delineation of small-volume OAR such as the left and right optic nerves,chiasm,and pituitary,with average MMR>2.8,CV>0.37,and DSC<0.51.However,relatively smaller differences were observed in the delineation of large-volume OAR such as the brainstem,spinal cord,left and right eyeballs,and left and right mandible,with average△V_diff<42%,MMR<1.55,and DSC>0.7.Compared with the differences among physicians from different levels cancer centers,the differences among the 3 physicians from the municipal cancer center were slightly reduced.Furthermore,there were also differences in the delineation of target volumes for NPC among physicians from different levels cancer centers,depending on the staging of the disease.Compared with the delineation of target volumes for earlier stage patients(stages I or II),the differences among physicians in the delineation of target volumes for advanced stage patients(stages III or IV)were smaller,with average △V_diff and DSC of 98.31%±67.36%vs 69.38%±72.61%(P<0.05)and 0.55±0.08 vs 0.72±0.12(P<0.05),respectively.Conclusion There are differences in the delineation of GTVnx and OAR in radiation therapy for NPC among physicians from different levels of cancer centers,especially in the delineation of target volume(GTVnx)and small-volume OAR for early-stage patients.To ensure the accuracy of multicenter clinical trials,it is recommended to provide unified training to physicians from different levels of cancer centers and review their delineation results to reduce the effect of differences on treatment outcomes.