Chronic pain has emerged as a prevalent medical challenge in contemporary society.Patients suffering from chronic pain frequently develop comorbid psychological disorders,including anxiety,depression,post-traumatic stress disorder,and various psychiatric syndromes.These psychological complications not only affect patients' pain perception and responses,but may also constitute critical obstacles during pain management interventions.Acupuncture is a long-established clinical practice that has demonstrated remarkable efficacy in alleviating diverse pain types and has shown favorable therapeutic outcomes in ameliorating emotional disturbances such as anxiety and depression.The precise mechanisms underlying acupuncture-induced analgesia and anxiolytic effects,however,remain to be fully elucidated.In this context,it is essential to establish suitable and stable animal models to allow in-depth investigations into the pathogenesis of pain-related emotional disorders and the mechanistic foundations of acupuncture.This article presents a comprehensive review of recent literature regarding the selection of experimental animals,model-establishment method ologies,and behavioral-assessment paradigms pertaining to animal model platforms of chronic pain with comorbid anxiety.We also provide an in-depth discussion of research advancements regarding acupuncture intervention parameters,including needling techniques,acupoint selection,treatment duration,and efficacy evaluation within these animal models.This review proposes comprehensive and reference strategies for constructing preclinical animal models to investigate the mechanisms of acupuncture in managing chronic pain with comorbid anxiety,thus supporting scientific advancements in related research fields.

Aim To investigate the effect of chrysoeriol on pulmonary vascular remodeling in pulmonary hyper-tension by animal experiments combined with cell ex-periments,and to explore its potential therapeutic tar-gets by network pharmacology.Methods The target of chrysoeriol was collected in Targetnet,SEA and SwissTargetPrediction database.Pulmonary arterial hy-pertension(PAH)targets were collected in the Dis-GeNET and GeneCards databases,and PPI network map was drawn in the STRING database,and key tar-gets were screened.The GO and KEGG pathway en-richment analysis was carried out through DAVID data-base and Weishengxing platform.AutoDock software was used for molecular docking of key core targets.The PAH model of rats was constructed,and the pulmo-nary hemodynamics and vascular remodeling were de-tected by echocardiography,HE and Masson staining.Primary pulmonary smooth muscle cells were extracted,and the effects of drugs on pathway proteins were de-tected in vitro.Results The results of network phar-macology showed that chrysoeriol exerted therapeutic effects on pulmonary hypertension by affecting key tar-gets such as AKT1,SRC,EGFR,MMP9 and gsk3 β,and signaling pathways such as EGFR and PI3K-AKT.Molecular docking showed that chrysoeriol had good binding ability with 5 key target genes.Animal experi-ments showed that the pulmonary hemodynamic func-tion of PAH rats was significantly improved after ad-ministration of chrysoeriol.The remodeling of small pulmonary arteries was significantly reduced.Cell ex-periments showed that chrysoeriol could inhibit the ex-pression of proliferation,migration and phenotypic transformation genes.Conclusion Chrysoeriol may play a role in the treatment of pulmonary hypertension through multiple targets.

This study was aimed at investigating the effects of demethylase fat mass and obesity-associated protein(FTO)and methyltransferase methyltransferase like protein 3(METTL3),key molecules in N6-methyladenosine(m6A)modification,on the replication and proliferation of Japanese encephalitis virus(JEV).Recombinant lentiviruses were generated by packaging the FTO and green fluorescent protein into lentiviral vectors.Neuro2a cells,a mouse neuroblastoma cell line,were infected with the lentivirus,and stable FTO-expressing cell lines were obtained through puromycin selection.Successful overexpression of FTO was confirmed through fluorescence microscopy,real-time quantitative PCR,and western blot analysis.When Neuro2a cells overexpressing FTO were infected with JEV,the overexpression of FTO decreased JEV replication in the cells,and increased the expression of interferon(IFN)and related molecules.Additionally,treatment of JEV-infected Neuro2a cells with the METTL3-specific inhibitor STM2457 resulted in a dose-dependent decrease in JEV replication and viral protein expression.These findings suggested that lowering m6A methylation levels inhibits JEV replication,thus shedding light on the regulatory role of methylation modification in JEV replication.

Objective:To investigate the effects of thoracolumbar vertebral fracture with incomplete spinal cord injury on male sexual function and postoperative prognosis.Methods:A retrospective review was conducted on data from 144 male patients with thoracolumbar vertebral fractures and incomplete spinal cord injuries treated between May 2009 and May 2021 in the Department of Traumatology and Orthopedics at Peking University Third Hospital. Patients ranged in age from 19 to 55 years (mean: 38.6±10.6 years) and underwent posterior incision and reduction internal fixation. The International Index of Erectile Function-5 (IIEF-5), the Premature Ejaculation Diagnostic Tool (PEDT), and the International Spinal Cord Injury Male Sexual Function Basic Data Set were used for sexual function evaluation. Based on the American Spinal Injury Association (ASIA) Spinal Cord Injury classification, changes in neurological and sexual function were assessed at the pre-injury stage, 3 months post-injury, 2 years postoperatively, and at the final follow-up. Factors influencing sexual dysfunction and recovery were analyzed. Spearman correlation analysis was used to identify factors affecting sexual function injury and recovery.Results:A total of 117 patients were included in the final analysis. Follow-up duration ranged from 26.2 to 161.7 months (mean: 74.6±40.5 months). After injury, ASIA grades were distributed as follows: 43 patients with grade B, 41 with grade C, and 33 with grade D. At the 2-year follow-up, 30 patients were grade E, 63 grade D, 19 grade C, and 5 grade B. Improvement in ASIA classification was observed in 90.6% (106/117) of patients: 79 improved by one grade, 27 by two grades, 8 remained unchanged, 1 worsened by one grade, and 2 worsened by two grades. Mean IIEF-5 scores were 19.5±6.4 pre-injury, 8.7±8.0 at 3 months post-injury, and 17.5±7.1 at 2 years postoperatively, with statistically significant differences ( F=123.247, P<0.001). Differences between 3 months post-injury vs. pre-injury and 2 years postoperatively vs. 3 months post-injury were statistically significant ( P<0.05). Mean PEDT scores were 5.3±3.1 pre-injury, 6.9±5.2 at 3 months post-injury, and 6.4±5.1 at 2 years postoperatively, with statistically significant differences ( F=17.014, P<0.001). The difference between 3 months post-injury and pre-injury was statistically significant ( P<0.05), but not between 2 years postoperatively and 3 months post-injury ( P>0.05). At the 2-year follow-up, 96 patients had their IIEF-5 classification restored to pre-injury levels, 85 restored PEDT classifications, and 83 restored both. Post-injury ASIA classification was positively correlated with a decrease in IIEF-5 score and an increase in PEDT score at 3 months post-injury ( P<0.05). Injury segment was positively correlated with the decrease in IIEF-5 score ( P<0.05). Time from injury to surgery showed a positive correlation with increased PEDT score at 3 months ( P<0.05). Post-injury ASIA grade, injury segment, time to surgery, age, intraoperative decompression, and spinal cord function recovery all showed significant correlations with changes in IIEF-5 and (or) PEDT scores at 2 years postoperatively ( P<0.05). According to the International Spinal Cord Injury Male Sexual Function Basic Data Set, the proportion of patients willing to discuss sexual issues increased from 29.9% at 3 months post-injury to 47.9% at 2 years postoperatively ( P<0.05). The proportion of patients with absent or diminished psychogenic erections remained stable (48.7% vs. 48.9%, P>0.05), while those with normal reflexive erections increased from 34.2% to 65.0% ( P<0.05). Conclusion:Thoracolumbar fractures with incomplete spinal cord injury result in reduced erectile function and increased incidence of premature ejaculation. The degree of spinal cord injury and the level of the injured segment are strongly correlated with the extent of sexual dysfunction. At the 2-year postoperative follow-up, 70.9% of patients had recovered sexual function to pre-injury levels.

Objective:To explore the diagnostic value of shear wave elastography(SWE)for clinically significant prostate cancer(csPCa).Methods:We retrospectively analyzed the clinical data of 359 cases with suspected prostate cancer(PCa)in Baoji Central Hospital from June 2017 to July 2023.All the patients underwent the following examinations in the order of serum prostate-spe-cific antigen(PSA)testing,transrectal ultrasonography(TRUS),measurement of the stiffness of the entire prostate gland by SWE,and TRUS-guided prostate puncture biopsy.The stiffness of the entire prostate gland was defined as the average of Young's modulus at both sides of the base,middle,and apex of the prostate,including the maximum Young's modulus(Emax),mean Young's modulus(Emean),and minimum Young's modulus(Emin).We analyzed the correlation of the parameters of the stiffness of the entire prostate gland with the pathological results,focusing on their diagnostic performance for csPCa.Results:Of the 359 cases,189 were diag-nosed by pathological puncture biopsy as BPH,26 as non-csPCa,and 144 as csPCa.The PSA level,Emax,Emean and Emin were significantly higher in the csPCa than those in the BPH and non-csPCa groups(all P＜0.01),but showed no statistically significant difference between the BPH and non-csPCa groups(all P＞0.05).The area under the receiver operating characteristic curve(AUC),optimal cut-off value,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV)and accura-cy of Emax in the diagnosis of csPCa were 0.852,143.92 kPa,72.22％,84.65％,75.91％,81.98％and 79.67％;those of Emean were 0.868,82.42 kPa,67.36％,91.16％,83.62％,80.66％and 81.62％;and those of Emin were 0.682,32.73 kPa,47.22％,89.30％,73.91％,71.54％and 72.14％,respectively.In the non-csPCa group,Emax,Emean and Emin were found be-low the optimal cut-off value in 73.08％(19/26),92.31％(24/26)and 88.46％(23/26),respectively.Conclusion:The stiff-ness of the entire prostate gland measured by SWE contributes to the diagnosis of csPCa,reduces unnecessary detection of non-csPCa,and provides some reference for its active surveillance.

Objective: To establish a machine learning-based precision blood donor recruitment model at the county level and assess its generalizability and applicability. Methods: A retrospective study was conducted using blood donation and SMS recruitment data from the Taicang Branch of the Suzhou Blood Center between 2019 and 2024. Multiple machine learning algorithms were employed, including extreme gradient boosting, support vector machine, k-nearest neighbor, logistic regression, decision tree, random forest, and multilayer perceptron. These were combined with techniques such as synthetic minority oversampling, undersampling, and cost-sensitive learning (using MFE and MSFE loss functions). Model parameters were optimized through grid search to identify the best-performing model. Results: In a prospective comparative study against conventional methods, the machine learning models increased the recruitment success rate among high-willingness donors by an average of 129.15%, and the recruitment efficiency per SMS improved by 125.02% compared with the traditional method. Under full-scale SMS sending, the recruitment rate per SMS increased by 42.61%, and SMS sending efficiency improved by 31.77%, significantly enhancing recruitment performance. Conclusion: This study represents the first application of a machine learning-based precision donor recruitment model at the county-level in China. The precise recruitment framework not only improves recruitment efficiency and reduces recruitment costs but also demonstrates strong scalability and generalizability. It provides a scientific and feasible intelligent pathway to ensure the safety and sustainability of the blood supply.

Investigating the correlation between micronucleus formation and male infertility has the potential to improve clinical diagnosis and deepen our understanding of pathological progression. Our study enrolled 2252 male patients whose semen was analyzed from March 2023 to July 2023. Their clinical data, including semen parameters and age, were also collected. Genetic analysis was used to determine whether the sex chromosome involved in male infertility was abnormal (including the increase, deletion, and translocation of the X and Y chromosomes), and subsequent semen analysis was conducted for clinical grouping purposes. The participants were categorized into five groups: normozoospermia, asthenozoospermia, oligozoospermia, oligoasthenozoospermia, and azoospermia. Patients were randomly selected for further study; 41 patients with normozoospermia were included in the control group and 117 patients with non-normozoospermia were included in the study group according to the proportions of all enrolled patients. Cytokinesis-block micronucleus (CBMN) screening was conducted through peripheral blood. Statistical analysis was used to determine the differences in micronuclei (MNi) among the groups and the relationships between MNi and clinical data. There was a significant increase in MNi in infertile men, including those with azoospermia, compared with normozoospermic patients, but there was no significant difference between the genetic and nongenetic groups in azoospermic men. The presence of MNi was associated with sperm concentration, progressive sperm motility, immotile spermatozoa, malformed spermatozoa, total sperm count, and total sperm motility. This study underscores the potential utility of MNi as a diagnostic tool and highlights the need for further research to elucidate the underlying mechanisms of male infertility.
Humans ; Male ; Infertility, Male/genetics* ; Adult ; Micronucleus Tests ; Semen Analysis ; Oligospermia/genetics* ; Azoospermia/genetics* ; Chromosome Aberrations ; Sperm Count ; Micronuclei, Chromosome-Defective ; Middle Aged

Extensive studies have identified potential adverse effects on semen quality of obesity, based on body mass index, but the association between body fat distribution, a more relevant indicator for obesity, and semen quality remains less clear. We conducted a longitudinal study of 4304 sperm donors from the Guangdong Provincial Human Sperm Bank (Guangzhou, China) during 2017-2021. A body composition analyzer was used to measure total and local body fat percentage for each participant. Generalized estimating equations were employed to assess the association between body fat percentage and sperm count, motility, and morphology. We estimated that each 10% increase in total body fat percentage (estimated change [95% confidence interval, 95% CI]) was significantly associated with a 0.18 × 10 6 (0.09 × 10 6 -0.27 × 10 6 ) ml and 12.21 × 10 6 (4.52 × 10 6 -19.91 × 10 6 ) reduction in semen volume and total sperm count, respectively. Categorical analyses and exposure-response curves showed that the association of body fat distribution with semen volume and total sperm count was stronger at higher body fat percentages. In addition, the association still held among normal weight and overweight participants. We observed similar associations for upper limb, trunk, and lower limb body fact distributions. In conclusion, we found that a higher body fat distribution was significantly associated with lower semen quality (especially semen volume) even in men with a normal weight. These findings provide useful clues in exploring body fat as a risk factor for semen quality decline and add to evidence for improving semen quality for those who are expected to conceive.
Humans ; Male ; Adult ; Semen Analysis ; China ; Body Fat Distribution ; Longitudinal Studies ; Sperm Count ; Sperm Motility ; Body Mass Index ; Tissue Donors ; Obesity/complications* ; Spermatozoa ; Young Adult ; Middle Aged ; East Asian People

OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
Animals ; Hesperidin/therapeutic use* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Male ; Stress, Psychological/drug therapy* ; Brain/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Serotonin/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Behavior, Animal/drug effects* ; Rats ; Brain-Gut Axis/drug effects* ; Chronic Disease ; Colon/drug effects*