Objective:To investigate the protective effect of PSD95 on neurobehavioral abnormalities and synaptic damage in cortex induced by hypoxia exposure in mice.Methods:The 3-week-old C57BL/6 male mice were injected with neuron-specific adeno-associated virus through stereotaxic brain after 7 days of normal environment adaptation.The mice were divided into normoxia group(AAV-NC-Nor),control hypoxia group(AAV-NC-Hyp),normal oxygen group with over-expression of postsynaptic density-95(PSD95)(AAV-PSD95-Nor),and hypoxia group with over-expression of PSD95(AAV-PSD95-Hyp).Using a hypobaric hypoxia chamber,PSD95-overexpressing mice were continuously ex-posed to hypoxic conditions for 14 days to establish a hypoxia exposure model.The open field,elevated cross maze and conditioned fear tests were used to detect the neurobehavioral activities of mice,and Golgi staining was used to observe the density of neuronal dendritic spines in cortex.The expression of PSD95,SYN1 and N-methyl-D-aspartate receptor subtype 2A(NMDAR2A)were detected by Western blot.Result:Compared with the normal oxygen group,the total distance and average speed of exercise in the open field experiment of mice in hypoxia group increased(P＜0.01),the rigidity time of mice in the conditioned fear box decreased(P＜0.01),and the density of dendritic spines in cortical region decreased(P＜0.05).The expressions of PSD95,SYN1 and NMDAR2A were decreased(P＜0.05).After the over-expression of PSD95,the autonomic activity of mice was reduced,the fear memory was relieved(P＜0.05),the dendrite density was reversed(P＜0.05),and the expression of synaptic related protein was increased(P＜0.05).Conclusion:Over-expression of PSD95 can alleviate neurobehavioral abnormalities and decline of fear memory induced under hypoxia exposure,protect neuronal dendritic spine injury in cortical region,and up-regulate the expression of syn-aptic protein.

Objective:Analyze the risk factors for acute lung injury of postoperative acute lung injury(ALI)in patients with Stanford type A aortic dissection(STAAD),and construct a nomogram predictive model.Methods:A retrospective cohort study design was adopted.A total of 112 patients with STAAD who underwent surgical treatment in our hopital from January 2021 to August 2024 were included.They were divided into two groups according to the occurrence of ALI after the surgical:non-ALI group(73 cases)and ALI group(39 cases).Clinical data were collected from both groups of patients.The influencing factors of postoperative ALI in patients with STAAD were analyzed by multivariate logistic regression.Established nomogram prediction model based on influencing factors and validated.Results:Among 112 patients with STAAD who underwent surgical treatment,39 case postoperative ALI occurred,with an incidence rate of 34.82％.Age,preoperative creatinine,body mass index(BMI),preoperative white blood cell count,preoperative lactate and other aspects compared,The difference were statistically significant(P＜0.05).The length of stay in the intensive care unit(ICU)of the ALI group was longer than that of the non ALI group(P＜0.05).The intraoperative red blood cell transfusion volume and extracorporeal circulation time in the ALI group were higher than those in the non ALI group(P＜0.05).Long intraoperative cardiopulmonary bypass time,high BMI,high intraoperative red blood cell transfusion volume and high preoperative white blood cell count were risk factors for postoperative ALI(P＜0.05).The receiver operating characteristic(ROC)curve analysis results show that,the Area under the curve(AUC)of the nomogram prediction model was 0.871.When the optimal critical value was 0.472,its sensitivity and specificity wew 0.887 and 0.776,respectively.The internal validation results of Bootstrap show that,the C-index of the column chart prediction model was 0.862,with an absolute error of 0.032.The calibration curve is close to the ideal curve and the original curve,with a slope close to 1.Conclusions:Long intraoperative cardiopulmonary bypass time,high BMI,high intraoperative red blood cell transfusion volume and high preoperative white blood cell count are independent risk factors for postoperative ALI in patients with STAAD.The nomogram model constructed based on the above risk factors can effectively evaluate the risk of postoperative ALI in patients with STAAD.

Objective:To investigate the protective effect of PSD95 on neurobehavioral abnormalities and synaptic damage in cortex induced by hypoxia exposure in mice.Methods:The 3-week-old C57BL/6 male mice were injected with neuron-specific adeno-associated virus through stereotaxic brain after 7 days of normal environment adaptation.The mice were divided into normoxia group(AAV-NC-Nor),control hypoxia group(AAV-NC-Hyp),normal oxygen group with over-expression of postsynaptic density-95(PSD95)(AAV-PSD95-Nor),and hypoxia group with over-expression of PSD95(AAV-PSD95-Hyp).Using a hypobaric hypoxia chamber,PSD95-overexpressing mice were continuously ex-posed to hypoxic conditions for 14 days to establish a hypoxia exposure model.The open field,elevated cross maze and conditioned fear tests were used to detect the neurobehavioral activities of mice,and Golgi staining was used to observe the density of neuronal dendritic spines in cortex.The expression of PSD95,SYN1 and N-methyl-D-aspartate receptor subtype 2A(NMDAR2A)were detected by Western blot.Result:Compared with the normal oxygen group,the total distance and average speed of exercise in the open field experiment of mice in hypoxia group increased(P＜0.01),the rigidity time of mice in the conditioned fear box decreased(P＜0.01),and the density of dendritic spines in cortical region decreased(P＜0.05).The expressions of PSD95,SYN1 and NMDAR2A were decreased(P＜0.05).After the over-expression of PSD95,the autonomic activity of mice was reduced,the fear memory was relieved(P＜0.05),the dendrite density was reversed(P＜0.05),and the expression of synaptic related protein was increased(P＜0.05).Conclusion:Over-expression of PSD95 can alleviate neurobehavioral abnormalities and decline of fear memory induced under hypoxia exposure,protect neuronal dendritic spine injury in cortical region,and up-regulate the expression of syn-aptic protein.

Objective:Analyze the risk factors for acute lung injury of postoperative acute lung injury(ALI)in patients with Stanford type A aortic dissection(STAAD),and construct a nomogram predictive model.Methods:A retrospective cohort study design was adopted.A total of 112 patients with STAAD who underwent surgical treatment in our hopital from January 2021 to August 2024 were included.They were divided into two groups according to the occurrence of ALI after the surgical:non-ALI group(73 cases)and ALI group(39 cases).Clinical data were collected from both groups of patients.The influencing factors of postoperative ALI in patients with STAAD were analyzed by multivariate logistic regression.Established nomogram prediction model based on influencing factors and validated.Results:Among 112 patients with STAAD who underwent surgical treatment,39 case postoperative ALI occurred,with an incidence rate of 34.82％.Age,preoperative creatinine,body mass index(BMI),preoperative white blood cell count,preoperative lactate and other aspects compared,The difference were statistically significant(P＜0.05).The length of stay in the intensive care unit(ICU)of the ALI group was longer than that of the non ALI group(P＜0.05).The intraoperative red blood cell transfusion volume and extracorporeal circulation time in the ALI group were higher than those in the non ALI group(P＜0.05).Long intraoperative cardiopulmonary bypass time,high BMI,high intraoperative red blood cell transfusion volume and high preoperative white blood cell count were risk factors for postoperative ALI(P＜0.05).The receiver operating characteristic(ROC)curve analysis results show that,the Area under the curve(AUC)of the nomogram prediction model was 0.871.When the optimal critical value was 0.472,its sensitivity and specificity wew 0.887 and 0.776,respectively.The internal validation results of Bootstrap show that,the C-index of the column chart prediction model was 0.862,with an absolute error of 0.032.The calibration curve is close to the ideal curve and the original curve,with a slope close to 1.Conclusions:Long intraoperative cardiopulmonary bypass time,high BMI,high intraoperative red blood cell transfusion volume and high preoperative white blood cell count are independent risk factors for postoperative ALI in patients with STAAD.The nomogram model constructed based on the above risk factors can effectively evaluate the risk of postoperative ALI in patients with STAAD.

Articular cartilage is a crucial tissue structure in humans.With ongoing exploration of joint tissue structure and the emergence of innovative biotechnological organoids,various sources of stem cells can be selected for induction to differentiate into articular cartilaginous organoids based on the articular cartilage tissue structure,which can be applied to the treatment of cartilage defects,drug testing,and precision medicine and biological development.This article presents a review of the research progress concerning articular cartilaginous organoids,in order to provide a reference for clinical practice.

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.

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*

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

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*