OBJECTIVE To investigate the mechanisms of rutin in alleviating depressive symptoms associated with premenstrual dysphoric disorder （PMDD） characterized by liver qi stagnation syndrome. METHODS Network pharmacology was employed to identify the intersecting targets of action between PMDD and rutin. A protein-protein interaction network was constructed to screen core targets， followed by gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. Molecular docking simulations validated rutin’s binding affinity to core targets. The bilateral ovaries of female Wistar rats were removed， followed by artificial hormone induction. The rats were then randomly divided into normal group （10 rats） and modeling group （50 rats）. PMDD rat model with liver qi stagnation syndrome was established via restraint stress. The successfully modeled rats were further divided into model group， fluoxetine group （positive control） and rutin group， with 12 rats in each group. The corresponding drug solutions or water were administered by gavage at 9：00 a.m. every day， continuing for two estrous cycles. The open-field test， forced swimming test and Y-maze test were utilized to evaluate the effects of rutin on the behavioral indexes of model rats. Additionally， the density of neuronal dendritic spines in the hippocampal tissues of the rats was observed. Serum brain-derived neurotrophic factor （BDNF） levels and the expressions of BDNF， tyrosine kinase receptor type B （TrkB）， synuclein （Syn）， and postsynaptic density protein 95 （PSD95） in hippocampal tissues were quantified， respectively. RESULTS Network pharmacology and molecular docking revealed the core targets through which rutin ameliorated PMDD characterized by liver qi stagnation syndrome included BDNF， TrkB， PSD65， Syn， etc. The results of experimental validation demonstrated that rutin significantly increased the spontaneous alternation behavior scores of PMDD model rats with liver qi stagnation syndrome during the non-receptive phase， shortened their immobility time during the forced swimming test， and enhanced the density of neuronal dendritic spines in the hippocampal tissues. Additionally， rutin upregulated the levels of serum BDNF and the protein expressions of BDNF， TrkB and Syn in the hippocampal tissues （P＜0.05）. However， it had no significant effect on the above indexes in model rats during the receptive phase （P＞0.05）. CONCLUSIONS Rutin ameliorates depressive symptoms， enhances spatial memory capabilities， and reduces neuronal damage in PMDD model rats with liver qi stagnation syndrome. These effects may be associated with the activation of BDNF/TrkB signaling pathway and upregulation of Syn protein expression.

Immunoglobulin A nephropathy （IgAN） is a common primary glomerular disease and a frequent cause of chronic renal failure. Tripterygium wilfordii is a traditional Chinese herbal medicine， which possesses the effects of promoting blood circulation， relieving swelling and pain， and dispelling wind and dampness. Modern pharmacological studies have shown that T. wilfordii multiglucoside exhibit anti-inflammatory and immunomodulatory effects， inhibit mesangial cell proliferation， protect podocytes， ameliorate endothelial cell injury， and regulate gut microbiota disturbances. Triptolide also possesses anti-inflammatory and immunomodulatory properties， suppresses mesangial cell proliferation， and protects podocytes. Celastrol demonstrates anti- inflammatory and immunomodulatory functions as well as the ability to improve endothelial cell damage. Through these mechanisms， T. wilfordii and its active components can play a role in alleviating clinical symptoms and delaying disease progression in the treatment of IgAN. Future research should focus on in-depth analysis and mechanistic investigation of these active ingredients， promote high-quality clinical studies， systematically evaluate the synergistic effects among them， and emphasize strategies for reducing toxicity and enhancing efficacy， thereby providing more comprehensive and reliable evidence-based foundations for the clinical treatment of IgAN.

PURPOSE: We carried out the study aiming to explore and analyze the risk factors, the distribution of pathogenic bacteria, and their antibiotic-resistance characteristics influencing the occurrence of surgical site infection (SSI), to provide valuable assistance for reducing the incidence of SSI after traumatic fracture surgery. METHODS: A retrospective case-control study enrolling 3978 participants from January 2015 to December 2019 receiving surgical treatment for traumatic fractures was conducted at Tangdu Hospital of Air Force Medical University. Baseline data, demographic characteristics, lifestyles, variables related to surgical treatment, and pathogen culture were harvested and analyzed. Univariate analyses and multivariate logistic regression analyses were used to reveal the independent risk factors of SSI. A bacterial distribution histogram and drug-sensitive heat map were drawn to describe the pathogenic characteristics. RESULTS: Included 3978 patients 138 of them developed SSI with an incidence rate of 3.47% postoperatively. By logistic regression analysis, we found that variables such as gender (males) (odds ratio (OR) = 2.012, 95% confidence interval (CI): 1.235 - 3.278, p = 0.005), diabetes mellitus (OR = 5.848, 95% CI: 3.513 - 9.736, p < 0.001), hypoproteinemia (OR = 3.400, 95% CI: 1.280 - 9.031, p = 0.014), underlying disease (OR = 5.398, 95% CI: 2.343 - 12.438, p < 0.001), hormonotherapy (OR = 11.718, 95% CI: 6.269 - 21.903, p < 0.001), open fracture (OR = 29.377, 95% CI: 9.944 - 86.784, p < 0.001), and intraoperative transfusion (OR = 2.664, 95% CI: 1.572 - 4.515, p < 0.001) were independent risk factors for SSI, while, aged over 59 years (OR = 0.132, 95% CI: 0.059 - 0.296, p < 0.001), prophylactic antibiotics use (OR = 0.082, 95% CI: 0.042 - 0.164, p < 0.001) and vacuum sealing drainage use (OR = 0.036, 95% CI: 0.010 - 0.129, p < 0.001) were protective factors. Pathogens results showed that 301 strains of 38 species of bacteria were harvested, among which 178 (59.1%) strains were Gram-positive bacteria, and 123 (40.9%) strains were Gram-negative bacteria. Staphylococcus aureus (108, 60.7%) and Enterobacter cloacae (38, 30.9%) accounted for the largest proportion. The susceptibility of Gram-positive bacteria to Vancomycin and Linezolid was almost 100%. The susceptibility of Gram-negative bacteria to Imipenem, Amikacin, and Meropenem exceeded 73%. CONCLUSION Orthopedic surgeons need to develop appropriate surgical plans based on the risk factors and protective factors associated with postoperative SSI to reduce its occurrence. Meanwhile, it is recommended to strengthen blood glucose control in the early stage of admission and for surgeons to be cautious and scientific when choosing antibiotic therapy in clinical practice.
Humans ; Surgical Wound Infection/epidemiology* ; Male ; Female ; Risk Factors ; Retrospective Studies ; Middle Aged ; Adult ; Case-Control Studies ; Fractures, Bone/surgery* ; Aged ; Drug Resistance, Bacterial ; Logistic Models ; Anti-Bacterial Agents/therapeutic use* ; Incidence ; Bacteria/drug effects*

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

OBJECTIVE: To explore the correlation between chromosome 8 open reading frame 76 (C8orf76) and cyclin-dependent kinase 4 (CDK4) and the potential predictive effect of C8orf76 and CDK4 on the prognosis of colorectal cancer (CRC). METHODS: We constructed a protein-protein interaction network of C8orf76-related genes and analyzed the prognostic signatures of C8orf76 and CDK4. Clinicopathological features of C8orf76 and CDK4 were visualized using a nomogram. RESULTS: C8orf76 and CDK4 levels were positively correlated in two independent human CRC cohorts ( n = 83 and n = 597). A consistent positive correlation was observed between C8orf76 and CDK4 expression in the CRC cell lines. The nomogram included prognostic genes (C8orf76 and CDK4) and pathological N and M stages. The concordance index (C-index) in our cohort was 0.776, which suggests that the ability of the indicators to predict the overall survival of patients with CRC in our cohort was strong. CONCLUSION We found that C8orf76 was positively correlated with CDK4 in both the cohorts as well as in CRC cell lines. Therefore, C8orf76 and CDK4 can be used as potential biomarkers to predict the prognosis of CRC.
Humans ; Colorectal Neoplasms/diagnosis* ; Cyclin-Dependent Kinase 4/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/genetics* ; Aged ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

DNA genetic markers have always played important roles in individual identification, kinship analysis, ancestry inference and phenotype characterization in the field of forensic medicine. DNA methylation has unique advantages in biological age inference, body fluid identification and prediction of phenotypes. The majority of current studies independently examine DNA and DNA methylation markers using various workflows, and they use various analytical procedures to interpret the biological information these two markers present. Integrated methods detect DNA and DNA methylation markers simultaneously through a single experimental workflow using the same preparation of sample. Therefore, they can effectively reduce consumption of time and cost, streamline experimental procedures, and preserve valuable DNA samples taken from crime scenes. In this paper, the integrated detection approaches of DNA and DNA methylation markers on different detection platforms were reviewed. In order to convert methylation modifications to detectable forms, several options were available for pretreatment of genomic DNA, including digestion with methylation-sensitive restriction enzyme, affinity enrichment of methylated fragments, conversion of methylated or unmethylated cytosine. Multiplexed primers can be designed for DNA markers and converted DNA methylation markers for co-amplification. The schemes of using capillary electrophoresis platform for integrated detection add the pretreatment of genomic DNA on the basis of detecting DNA genetic markers. DNA and DNA methylation markers are then integrated by co-amplification. But the limited number of fluorescent options available and the length of amplicons restrict the type and quantity of markers that can be integrated into a panel. Pyrophosphate sequencing also supports integrated detection of DNA and DNA methylation markers. On this platform, due to the conversion of unmethylated cytosine to thymine after treatment with bisulfite, the methylation level of CpG site can be directly calculated using the peak height ratio of cytosine bases and thymine bases. Therefore, the methylation levels and SNP typing can be simultaneously obtained. However, due to the limited read length of sequencing, the detection of markers with longer amplicons is restricted. It is not conducive to fully interpret the complete information of the target sequence. Next-generation sequencing also supports integrated detection of DNA and DNA methylation markers. A preliminary experimental process including DNA extraction, pretreatment of genomic DNA, co-preparation of DNA and DNA methylation library and co-sequencing, has been formed based on the next-generation sequencing platform. It confirmed the feasibility of next-generation sequencing technology for integrated detection of DNA and DNA methylation markers. In field of biomedicine, various integrated detection schemes and corresponding data analysis approaches of DNA and DNA genetic markers developed based on the above detection process.Co-analysis can simultaneously obtain the genomic genetic and epigenetic information through a single analytic process. These schemes suggest that next-generation sequencing may be an effective method for achieving more accurate and highly integrated detection, helping to explore the potential for application in forensic biological samples. We finally explore the impact of interactions between sites and different pretreatment methods on the integrated detection of DNA and DNA methylation markers, and also propose the challenge of applying third-generation sequencing for integrated detection in forensic samples.

Objective To investigate the protective effect of silymarin extract(SME)and its complex preparation on ethanol liver injury.Methods An ethanol liver injury model was established by gavage of 12 mL·kg-1 50％ethanol.Male mice were divided into blank group(distilled water),model group(ethanol liver injury model),SME-L,-H groups(6,20 mg·mL-1 SME),SME+Ganoderma lucidum extract(GLE)-L,-H groups(10,30 mg·mL-1 SME+GLE,SME∶GLE=1∶1),Jian An Shi Silymarin Pueraria Mirifica and Tansy tablets(JAS)-L,-H groups(68,204 mg·mL-1 JAS),there were 12 mice in each group.The serum levels of glutamic-oxaloacetic transaminase(GOT)in mice were measured by fully automated biochemical analyzer assay;the serum levels of interleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α)in mice were measured by enzyme-linked immunosorbent assay(ELASA);the hepatic tissue of oxidative stress indexes[catalase(CAT)and total superoxide dismutase(T-SOD)]were measured by ultraviolet spectrophotometer.Results The T-SOD activity in the blank group,model group,SME-L,SME-H,SME+GLE-L,SME+GLE-H,JAS-L and JAS-H groups were(192.54±49.00),(141.65±34.72),(205.83±32.77),(191.68±25.83),(192.31±28.79),(177.82±32.61),(218.58±74.80)and(210.24±31.65)U·mg·prot-1;CAT activity were(37.78±5.73),(28.92±8.44),(44.12±11.52),(41.41±9.15),(47.01±10.48),(41.63±8.95),(47.14±8.91)and(48.29±10.06)U·mg-1;GPT levels were(47.61±13.00),(97.84±26.00),(62.33±18.92),(51.84±17.91),(70.77±28.00),(58.00±21.27),(52.28±18.78)and(45.55±9.27)U·L-1;IL-6 levels were(21.03±1.52),(28.43±5.75),(21.90±3.24),(21.23±1.55),(22.26±2.58),(21.24±2.91),(22.17±4.14)and(21.14±3.02)pg·mL-1.Comparing the above indexes in the model group with the blank group,and comparing the above indexes in the SME-L,SME-H,SME+GLE-L,SME+GLE-H,JAS-L,JAS-H groups with the model group,the differences were statistically significant(all P＜0.01).The TNF-α levels in blank,model,SME-L,SME-H,SME+GLE-L,SME+GLE-H,JAS-L and JAS-H groups were were(28.07±7.72),(69.02±16.34),(40.29±8.94),(48.84±10.17),(41.91±14.96),(40.07±12.75),(50.72±11.44)and(45.05±11.34)pg·mL-1.Comparing the model group with the blank group,the SME,SME+GLE-L,-M and JAS,-M groups with the model group,the differences were statistically significant(all P＜0.01).Conclusion Silybum marianum extract and its compound preparation can increase the antioxidant level and reduce the inflammation of mouse liver,and have a certain improvement effect on liver injury caused by acute ethanol poisoning.

ObjectiveTo evaluate the effectiveness of Lutongning granules in the treatment of trigeminal neuralgia in animal models and study its mechanism of action， so as to provide laboratory data support for the clinical application of Lutongning granules and precise treatment. MethodMale SD rats were randomly divided into normal group， model group， carbamazepine group （0.06 g·kg^-1·d^-1）， high-dose Lutongning group （2.70 g·kg^-1·d^-1）， and low-dose Lutongning group （1.35 g·kg^-1·d^-1） according to the stratified basic mechanical pain thresholds， with 10 rats in each group. A trigeminal neuralgia model of rats was prepared by injecting 30% talc suspension into the infraorbital foramen area of the rat. The drug groups were administered 10 mL·kg^-1 of drugs by gavage after 2 h of modeling. The normal group and the model group were administered distilled water by gavage under the same conditions once a day for 10 consecutive days. Von Frey brushes were used to determine the mechanical pain threshold of rats. A fully automated blood and body fluid analyzer was employed to detect the blood routine of rats. Hematoxylin and eosin （HE） staining was utilized to detect the pathological changes in the trigeminal ganglion and medulla oblongata tissue. Transmission electron microscopy was used to scan the ultrastructure of the medulla oblongata tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of inflammatory factors interleukin （IL）-1， IL-6， IL-8， tumor necrosis factor （TNF）-α， neuropeptide substance P， and β-endorphins （β-EP） in the serum of rats， and Western blot was used to detect the protein expression levels of IL-1β， purinergic receptor P2X7 （P2X7R）， and phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）. ResultCompared with that in the normal group， the pain threshold of rats in the model group was significantly lower （P<0.01）. The absolute value of neutrophils （NEUT#） and the percentage of neutrophils （NEUT） were significantly improved， and the percentage of lymphocytes （LYMPH） was significantly reduced （P<0.01）. The serum levels of IL-1， IL-6， IL-8， and TNF-α were significantly increased （P<0.01）. SP content in brain tissue was significantly increased， and β-EP content was significantly decreased （P<0.01）. The relative protein expression of IL-1β， P2X7R， and p-p38 MAPK was significantly increased （P<0.05）. HE staining and transmission electron microscopy results of medulla oblongata tissue revealed neuronal degeneration， mild proliferation of microglial cells， reduction in the number of myelinated nerves， and obvious demyelination. The trigeminal nerve fibers of rats were disarranged， and some nerve fibers showed vacuolization. Axons were swollen， and Schwann cells proliferated. Demyelination was observed. Compared with the model group， each administration group significantly increased the pain threshold of rats （P<0.05， P<0.01）， reduced NEUT# and NEUT， and elevated LYMPH （P<0.05， P<0.01）. The administration group significantly decreased the levels of IL-1， IL-6， IL-8， and TNF-α in serum and SP in brain tissue （P<0.01） and increased the level of β-EP （P<0.01）. They significantly down-regulated the protein expression of IL-1β， P2X7R， and p-p38 MAPK（P<0.05， P<0.01） and significantly ameliorated the pathological changes in medulla oblongata tissue and trigeminal nerves of rats. ConclusionLutongning Granules had significant therapeutic effects on trigeminal neuralgia induced by injection of talc into the infraorbital foramen of model rats， and the mechanism may be related to amelioration of P2X7R-mediated neuroinflammation and inhibition of demyelination of myelinated nerves.