OBJECTIVE: To explore the mechanism by which the extract of Semen Ziziphi Spinosae extract promotes bone growth in mice by modulation of the expression of miR-34a-5p in brain tissue. METHODS: Mice were assigned to four experimental groups:a normal control group, a drug administration group (receiving 0.320 mg·g^-1 body weight of Semen Ziziphi Spinosae extract via intragastric administration), a positive control group (receiving 0.013 mg·g^-1 body weight of jujube seed saponin via intragastric administration), and a combination group administration with Semen Ziziphi Spinosae extract plus a 5-hydroxytryptamine 2A receptor (5-HT2AR) agonist (intragastric administration of Semen Ziziphi Spinosae extract combined with intracerebroventricular injection of 8 μg P-MPPF per mice for the final three days of the experiment). Following a 20-day administration period, the effects of the interventions on bone growth, serum growth hormone (GH) levels, and 5-HT2AR expression in brain tissue were evaluated. MicroRNAs (miRNAs) that were differentially expressed in the brain tissues of mice exhibiting bone growth induced by Semen Ziziphi Spinosae extract, as compared to those in normal mice, were identified using a gene chip approach. The interaction between miR-34a-5p and 5-HT2AR was subsequently validated through quantitative reverse transcription polymerase chainreaction (RT-qPCR) and dual-luciferase reporter gene assays. Subsequently, by utilizing the miR-34a-5p inhibitor group and mimics group, along with the normal control group, the drug administration group, the positive control group, and the drug administration combined with miR-34a-5p inhibitor group, the variations in 5-HT2AR expression in mouse brain tissue across all groups were examined, and the binding activity of 5-hydroxytryptamine (5-HT) to the 5-hydroxytryptamine 1A receptor (5-HT1AR) in mice was assessed. RESULTS: The body lengths of the normal control group and the drug administration group were(8.9±0.3) and(10.4±0.4) cm;femur lengths were (8.5±0.3) and (9.1±0.5) mm;tibia lengths were (10.7±0.3) and (11.2±0.4) mm, respectively. The contents of GH levels were (58.6±8.2) and (72.9±6.1) ng·ml-1;and the contents of 5-HT2AR were (32.0±5.0) and (21.9± 5.5) ng·ml-1, respectively. Compared with the normal control group, the drug administration group promoted the growth of body length, femur, and tibia in mice, and increased GH secretion, showing statistically significant differences (P<0.05). Additionally, it significantly reduced the content of 5-HT2AR in brain tissue, with statistical significance (P<0.01). The gene chip analysis identified a total of 16 differentially expressed miRNAs, of which 13 were up-regulated and 3 were down-regulated. Bioinformatics analysis predicted that the up-regulated miR-34a-5p could regulate the expression of 5-HT2AR, a prediction that was confirmed through a dual-luciferase reporter gene assay, demonstrating a direct regulatory interaction between the two. Furthermore, in vivo experiments in mice revealed that overexpression and silencing of miR-34a-5p resulted in corresponding changes in the expression levels of 5-HT2AR in brain tissues/cells, as well as in the binding activity between 5-HT and 5-HT1AR. CONCLUSION The Semen Ziziphi Spinosae extract promotes animal bone growth by enhancing miR-34a-5p expression in brain tissue, downregulating the expression level of 5-HT2AR, improving the binding activity between 5-HT and 5-HT1AR, and extending slow-wave sleep duration, thereby stimulating GH secretion.
Animals ; MicroRNAs/metabolism* ; Mice ; Male ; Brain/metabolism* ; Ziziphus/chemistry* ; Bone Development/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Plant Extracts/pharmacology*

Objective To evaluate the clinical efficacy of Modified Buyang Huanwu Decoction combined with Ningxin Jieyu Electroacupuncture in treating post-stroke depression(PSD)and explore its potential mechanisms.Methods A total of 120 PSD patients diagnosed at Shaanxi Provincial Hospital of Traditional Chinese Medicine(inpatient and outpatient departments)from October 2021 to October 2023 were enrolled and randomly divided into an observation group and a control group using a random number table,with 60 cases in each group.Both groups received conventional therapy.The control group additionally received oral administration of Escitalopram Oxalate Tablets,while the observation group underwent Modified Buyang Huanwu Decoction combined with Ningxin Jieyu Electroacupuncture.Both groups were treated for 4 weeks.The clinical efficacy,24-item Hamilton Depression Scale(HAMD-24)scores,National Institutes of Health Stroke Scale(NIHSS)scores,cerebral blood volume(CBV),cerebral blood flow(CBF),serum neurotransmitter levels[norepinephrine(NE),dopamine(DA),5-hydroxytryptamine(5-HT)],and inflammatory cytokines[interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)]were evaluated after one-month treatment.Results(1)After treatment,the HAMD-24 scores and NIHSS scores of patients in the two groups significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the HAMD-24 scores and NIHSS scores,and the difference was statistically significant(P＜0.05).(2)After treatment,the cerebral blood flow and cerebral blood volume of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving cerebral blood flow and cerebral blood volume,with statistically significant differences(P＜0.05).(3)After treatment,the serum NE,DA,and 5-HT levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving serum NE,DA,and 5-HT levels,with statistically significant differences(P＜0.05).(4)After treatment,the serum TNF-α and IL-6 levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving serum TNF-α and IL-6 levels,with statistically significant differences(P＜0.05).(5)The total effective rate was 93.33%(56/60)in the observation group and 76.67%(46/60)in the control group.The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).Conclusion Modified Buyang Huanwu Decoction combined with Ningxin Jieyu Electroacupuncture effectively alleviates depressive symptoms,enhances neurological function,and improves cerebrovascular perfusion in PSD patients.The therapeutic mechanism may involve modulation of neurotransmitter levels and inflammatory cytokines.

Objective To explore the behavioral patterns and hippocampal neurogenesis of CHD8+mice,and to provide behavioral and morphological basis for improving autism like behavior and neurogenesis.Methods Genotype of wild type(WT)and CHD8+/-mice was identified.Weight measurement was conducted on both male and female mice of the WT and CHD8+/-strains.Subsequently,a battery of behavioral tests was administered,which included three-chamber test,self-grooming test,nesting test,Y-maze spontaneous alternation test,food burial test,open-field test and light-dark transition test.Afterwards,the mice were administered 2％pentobarbital sodium(2 ml/kg)to induce anesthesia.Their brains were frozen with 4％paraformaldehyde,removed for photography and analysis to identify any alterations in brain size.Western blotting and immunofluorescent labeling were used to detect changes in the process of hippocampus neurogenesis.Results Western blotting analysis demonstrated a decrease in the amounts of chromodomain helicase DNA binding protein 8(CHD8)protein in both male and female mice with CHD8+genotype,as compared to WT mice.There were no notable disparities in body weight between male and female WT and CHD8+mice,as well as in brain size.The three-chamber social behavior test revealed that both male and female CHD8+/-mice had social deficiencies(P＜0.05).During the open field test,there was no significant difference in the total distance moved by male and female WT and CHD8+/-mice.However,the amount of time spent in the central region was considerably lower in CHD8+/-mice compared to the WT mice(P＜0.01).Furthermore,the light-dark transition test revealed that both male and female CHD8+/-mice spent considerably less time investigating the white box compared to the WT mice(P＜0.05).Nevertheless,there were no notable alterations found in self-grooming,nesting,spontaneous alternation of Y-maze,and food burial experiments.In addition,Western blotting result demonstrated a significant drop in doublecortin(DCX)expression(P＜0.001),and immunofluorescent staining revealed a notable reduction in the number of DCX+cells(P＜0.01)in the hippocampus of CHD8+/-mice.Conclusion CHD8+/-mice exhibit social disorders and anxiety-like behaviors,with a decrease in the number of newly generated neurons in the hippocampus and neurogenesis disorders.

In this report, the protective effect and molecular mechanism of Chaihu Shugan San-containing serum on corticosterone(CORT)-induced mitochondrial damage in pheochromocytoma(PC12) cells was studied based on CORT-induced rat PC12 cell model. The cultured cells were divided into five groups: blank control group, CORT group(400 μmol·L~(-1) CORT), Chaihu Shugan San-containing serum group(400 μmol·L~(-1) CORT + 10% Chaihu Shugan San-containing serum), control serum group(400 μmol·L~(-1) CORT + 10% control serum), and fluoxetine group(400 μmol·L~(-1) CORT + 10% fluoxetine-containing serum). The study was carried out by cell activity detection, mitochondrial morphology observation, membrane potential measurement, energy metabolism analysis, and mitochondrial dynamics-related protein detection. The results showed that CORT treatment significantly reduced the survival rate of PC12 cells, altered mitochondrial morphology, and decreased mitochondrial membrane potential and adenosine triphosphate(ATP) synthetic rate. Both Chaihu Shugan San-and fluoxetine-containing serum significantly increased the survival rate of CORT-treated PC12 cells and the ATP synthetic rate in the mitochondria. Unlike fluoxetine, Chaihu Shugan San-containing serum significantly inhibited the decrease in mitochondrial membrane potential caused by CORT and increased the oxygen consumption rate(OCR) values of both mitochondrial maximum respiration and reserve respiration capacity. Western blot analysis showed that CORT induced upregulated protein expressions of dynamin-related protein 1(Drp1) and peroxisome proliferator-activated receptor gamma co-activator 1α(PGC-1α) in PC12 cells and specific protein expression of optic atrophy protein 1(OPA1), yet it repressed the protein expressions of silent information regulator 1(SIRT1) and mitochondrial fusion protein 1(Mfn1) in PC12 cells. Both Chaihu Shugan San-and fluoxetine-containing serum significantly inhibited the protein expression of Drp1. However, only Chaihu Shugan San-containing serum could significantly inhibit the CORT-induced upregulation protein of PGC-1α. RESULTS:: herein suggest that Chaihu Shugan San-containing serum can alleviate CORT-induced damage in PC12 cells, which may be related to the mitochondrial fragmentation/lipid peroxidation protection by Drp1 inhibition, as well as mitochondrial dynamics and energy metabolism mediated by PGC-1α/SIRT1 signaling pathway.
Animals ; PC12 Cells ; Rats ; Mitochondrial Dynamics/drug effects* ; Mitochondria/metabolism* ; Corticosterone/adverse effects* ; Membrane Potential, Mitochondrial/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Protective Agents/pharmacology* ; Cell Survival/drug effects*

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of alisol A,23-acetyl alisol B,alisol A-24-acetate,alisol B,alisol C,23-acetyl alisol C,alisol F,alisol G,atractylenolideⅠ,atractylenolide Ⅱ,atractylenolide Ⅲ,atractylon and ferulic acid in Zexie Decoction.METHODS The analysis was performed on a 30 ℃ thermostatic Waters ACQUITY UPLC HSS C18 column(100 mm×2.1 mm,1.8μm),with the mobile phase comprising of water(containing 0.1％formic acid)-acetonitrile(containing 0.1％formic acid)flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning with multiple reaction monitoring mode.RESULTS Thirteen constituents showed good linear relationships within their own ranges(r＞0.999 1),whose average recoveries were 95.05％-103.8％with the RSDs of 1.4％-6.7％.CONCLUSION This simple,rapid and accurate method can provide experimental basis for the quality control of Zexie Decoction.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

BACKGROUND:It has been confirmed that ferroptosis is closely related to the mechanism of various nervous diseases.However,the pathological mechanisms of ferroptosis and peripheral nerve injury need to be further studied and clarified.OBJECTIVE:To review the role and mechanism of ferroptosis in the treatment of peripheral nerve injury.METHODS:The articles related to ferroptosis and nervous system injuries were searched in CNKI and PubMed databases from database inception to May 2024.The keywords were"ferroptosis,peripheral nerve injury,antioxidant defense system,Schwann cells,macrophage,neuroinflammation,neuropathic pain"in Chinese and English,respectively.Sixty eligible articles were finally included for review.RESULTS AND CONCLUSION:The occurrence of ferroptosis is closely related to abnormal intracellular iron metabolism,reactive oxygen species accumulation and lipid peroxidation.Ferroptosis occurs in both Schwann cells and macrophages after peripheral nerve injury,leading to changes in the microenvironment and further inducing diseases such as neuroinflammation and neuropathic pain.Increasing studies have shown that nerve injury is closely related to ferroptosis,and inhibition of ferroptosis can promote tissue repair and functional recovery after peripheral nerve injury.Therefore,it is of great significance to study the mechanism underlying the occurrence and regulation of ferroptosis after peripheral nerve injury.Current research on the role and regulation of ferroptosis after peripheral nerve injury is still in its infancy,and more in-depth studies are needed to provide more strategies to promote repair after peripheral nerve injury.

Aim To systematically investigate the ac-tive components,targets,and regulatory pathways of Po-lygonum capitatum in intervening atherosclerosis(AS)through network pharmacology,molecular docking and animal experiments.Methods Active components of Polygonum capitatum and AS-related targets were screened and identified through database searches.Protein-protein interaction(PPI)network analysis was performed using the STRING database,followed by GO and KEGG enrichment analyses via the David plat-form.Molecular docking validation was conducted with AutoDock.An AS model was established in Syrian golden hamsters fed a high-fat diet.Predicted pathways and targets were validated using qPCR,ELISA,and histopathological assessment of aortic and hepatic tis-sues via HE staining.Results Network pharmacology identified 27 potential active components of Polygonum capitatum(primarily flavonoids such as quercetin and luteolin)and 110 drug-disease intersection targets,in-cluding core targets MMP-9,ALB,and AKT1.GO and KEGG analyses enriched 593 and 125 pathways,re-spectively,with the NF-κB inflammatory pathway,TNF signaling pathway and lipid metabolism/atherosclerosis pathways highlighted as key mechanisms.Animal ex-periments demonstrated that Polygonum capitatum im-proved serum lipid profiles(reduced TC,TG,LDL-C)in AS hamsters,suppressed the MMP-9/NF-κB signa-ling pathway(downregulated MMP-9,p65 phosphoryla-tion,TNF-α,and IL-6),and inhibited VSMC synthetic phenotypic transformation(upregulated α-SMA and myocardin)by downregulating MCPIP1.Additionally,Polygonum capitatum ameliorated aortic lesions and he-patic lipid deposition in AS hamsters.Conclusions Polygonum capitatum alleviates AS by synergistically regulating the MMP-9/NF-κB/MCPIP1 axis through flavonoid components,suppressing vascular inflammato-ry cascades and maintaining VSMC contractile pheno-types.This reflects Polygonum capitatum's multi-com-ponent,multi-pathway,and multi-target characteristics in combating AS.

Objective:To explore the clinical value of combination of contrast-enhanced ultrasound(CEUS)and magnetic reso-nance imaging(MRI)in the diagnosis of parotid gland tumors.Methods:167 patients with parotid gland tumors were diagnosed by CEUS and MRI respectively and in combination.With postoperative pathological diagnosis result as the gold standard,the diagnos-tic value of CEUS combined with MRI(CEUS+MRI)was analyzed.Results:171 tumors were confirmed by postoperative pathology in 167 patients,including 143 benign tumors(83.63％)and 28 malignant tumors(16.37％).The benign tumors were mainly pleo-morphic adenoma(65 tumors,45.45％),Warthin tumor(40 tumors,27.97％)and basal cell adenoma(13 tumors,9.09％).Among the malignant tumors,mucoepidermoid carcinoma(7 tumors,25.00％),adenoid cystic carcinoma(6 tumors,21.43％)and acinic cell carcinoma(3 tumors,10.71％)were the most common.CEUS showed 39 cases of malignant parotid gland tumors and 132 cases of benign parotid gland tumors.The sensitivity,specificity and accuracy rate of CEUS were 57.14％,83.92％and 79.53％respectively.The MRI ADC values were manifested as pleomorphic adenoma＞malignant tumor＞Warthin tumor(P＜0.05).MRI showed 53 cases of malignant parotid gland tumors and 118 cases of benign parotid gland tumors,and the sensitivity,specifici-ty and accuracy rate of MRI diagnosis were 67.86％,76.22％and 74.85％respectively.CEUS+MRI revealed 33 cases of malig-nant parotid gland tumors and 138 cases of benign parotid gland tumors,the sensitivity,specificity and accuracy rate of CEUS+MRI diagnosis were 78.57％,92.31％and 90.06％respectively.The specificity and accuracy rate of CEUS+MRI were significantly higher than those of single examination(x2=4.806,13.951,7.348,13.664,allP＜0.05).Conclusion:Both CEUS and MRI have certain clinical value in the diagnosis of parotid gland tumors,and the specificity and accuracy rate of CEUS+MRI are significantly higher than those of single examination.