ObjectiveTo investigate the optimal ratio of goat horn replacing antelope horn in Fufang Lingjiao Jiangya pills and the blood pressure-lowering mechanism of this medicine. MethodsThe blood pressure-lowering efficacy of Fufang Lingjiao Jiangya pills with varying proportions of goat horn replacing antelope horn was evaluated on spontaneous hypertensive rats （SHR）. In this experiment， 50 SHR rats were randomly grouped as follows： model （n=8）， captopril （0.01 g·kg^-1） （n=6）， low-dose blank Fufang Lingjiao Jiangya pills （0.342 g·kg^-1） （n=6）， high-dose blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1） （n=6）， low-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， high-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）， low-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， and high-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）. Additionally， 8 WKY rats were used as the normal group. Drugs were administered by gavage for 4 weeks while an equal volume of distilled water was administered for the normal and model groups. Blood pressure was measured before administration， 3 h post administration， and biweekly thereafter. In the experiment for Fufang Lingjiao Jiangya pills with goat horn replacing antelope horn in different proportions， 48 SHR rats were randomly grouped as follows： model， blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1）， antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1）， 2× goat horn-containing Fufang Lingjiao Jiangya pills （0.824 g·kg^-1）， 4× goat horn Fufang Lingjiao Jiangya pills （0.969 g·kg^-1）， and 6× goat horn Fufang Lingjiao Jiangya pills （1.112 g·kg^-1）. The normal group included 8 WKY rats， and the normal group and model group received an equal volume of distilled water. The treatment lasted for 2 weeks， and blood pressure was recorded at various time points （pre-administration， 3 h post administration， and on days 4， 7， 10， and 14 of administration）. Serum levels of angiotensin-converting enzyme （ACE）， angiotensin Ⅱ（Ang Ⅱ）， renin， and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay. Histopathological changes in the heart， kidney， and thoracic aorta were observed by hematoxylin-eosin staining. The protein levels of ACE2， angiotensin Ⅱ type 1 receptor （AT1R）， and angiotensinogen （AGT） in the kidney tissue were determined by Western blot， while the expression of nuclear factor （NF）-κB p65 and Toll-like receptor 4 （TLR4） in the thoracic aorta tissue was assessed by immunohistochemistry. ResultsCompared with the model group， all treatment groups showed lowered blood pressure （P<0.05， P<0.01）， and the 6× goat horn-containing Fufang Lingjiao Jiangya pills group showed consistent blood pressure-lowering effect with the antelope horn-containing Fufang Lingjiao Jiangya pills group. Compared with the normal group， the model group showed elevated serum levels of ACE， Ang Ⅱ， renin， and IL-6， while the elevations were declined in the Fufang Lingjiao Jiangya pills groups （P<0.05， P<0.01）. Pathological changes in the heart， kidney， and thoracic aorta were alleviated in all the treatment groups， with the 6× goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups exhibited the best effect. Western blot and immunohistochemistry results showed that all the treatment groups exhibited down-regulated protein levels of AT1R， AGT， NF-κB p65， and TLR4 and up-regulated protein levels of ACE2 （P<0.05， P<0.01） compared with model group， with the 6×goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups showcasing the best effect. ConclusionReplacing antelope horn with 6×goat horn in Fufang Lingjiao Jiangya pills can achieve consistent blood pressure-lowering effect with the original prescription. The prescription may exert the effect by inhibiting the renin-angiotensin-aldosterone system （RAAS） and TLR4/NF-κB signaling pathways.

BackgroundCurrently， the problem of depressed mood in college students is becoming more prominent. The experience of childhood maltreatment is a significant contributor to depression among college students. Although the association between the two has been confirmed， the specific psychosocial mechanisms underlying how childhood maltreatment affects college students' mental health remain insufficiently evidenced. ObjectiveTo explore the mediating role of emotion regulation difficulties in the relationship between childhood maltreatment and depression among college students， and to investigate the moderated effects of psychological resilience and family socioeconomic status， aiming to provide references for improving depressive symptoms in college students. MethodsOn 14 March 2024， a cluster sampling method was employed to recruit 751 college students from a university in Heilongjiang Province. Participants were assessed with Childhood Trauma Questionnaire （CTQ）， Difficulties in Emotion Regulation Scale （DERS）， Patients' Health Questionnaire Depression Scale-9 item （PHQ-9）， 10-item Connor-Davidson Resilience Scale （CD-RISC-10） and Family Socioeconomic Status Questionnaire. Pearson correlation analysis was adopted to examine the correlation between the scores of scales. Model 4 and model 7 in Process 4.2 were used to test the mediating effects of emotional regulation difficulties and the moderated effects of psychological resilience and family socioeconomic status. Results① A total of 712 （94.81%） valid questionnaires were collected. ② College students' CTQ score was positively correlated with DERS score and PHQ-9 score （r=0.296， 0.507， P<0.01）， and negatively correlated with CD-RISC-10 score and Family Socioeconomic Status Questionnaire score （r=-0.148， -0.229， P<0.01）. ③ The indirect effect value of difficulties in emotion regulation on the relationship between childhood maltreatment and depression was 0.091 （95% CI： 0.018~0.046）， accounting for 17.95% of the total effect. ④ The first half of the mediation model "childhood maltreatment → difficulties in emotion regulation → depression" （childhood maltreatment → difficulties in emotion regulation） was moderated by psychological resilience （β=-0.030， t=-6.147， 95% CI： -0.040~-0.020） and family socioeconomic status （β=-0.051， t=-3.929， 95% CI： -0.077~-0.026）. ConclusionChildhood maltreatment exerts both a direct effect on college students' depression and an indirect effect through emotion regulation difficulties. The childhood maltreatment → emotion regulation difficulties pathway in this mediation model is moderated by psychological resilience and family socioeconomic status. ［Funded by Qiqihar Medical University Graduate Student Innovation Fund Project （number， QYYCX2023-48）； Special Research Fund Project for Young Doctors of Qiqihar Academy of Medical Sciences （number， QMSI2021B-08）］

Objective： The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods： The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results： Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62－24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16－17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12－3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion： For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Retrospective Studies ; Nomograms ; Prostate-Specific Antigen/blood* ; Lymph Nodes/pathology* ; Pelvis ; Predictive Value of Tests ; Prostatectomy ; Lymph Node Excision ; Risk Factors ; Magnetic Resonance Imaging ; Logistic Models ; Middle Aged ; Aged

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BackgroundNon-suicidal self-injury （NSSI） behaviors have become a serious global public health issue.The detection rate of NSSI behaviors among college students in China ranges from 9.8% to 13.53%. Integrated theoretical models suggest that distal family risk factors influence NSSI behaviors through emotional regulation mechanisms. However， existing researches have predominantly focused on single family risks， leaving the relationship between cumulative family risks and NSSI behaviors， as well as the underlying pathways， remain unclear. ObjectiveTo explore the effects of cumulative family risk on NSSI behaviors among college students， analyze the chain mediating roles of emotional regulation difficulties and depression， and examine the moderating effect of gender， so as to provide references for targeted interventions for NSSI behaviors in college students. MethodsOn March 1， 2024， a cluster sampling method was employed to select 518 college students from two universities in Heilongjiang Province. Assessments were conducted using Chinese version of the Childhood Trauma Questionnaire （CTQ）， the Difficulties in Emotion Regulation Scale （DERS）， the Patient Health Questionnaire Depression Scale-9 item （PHQ-9） and the Adolescent Self-Injury Questionnaire. Logistic regression analysis was used to examine the impact of cumulative family risk factors on NSSI behaviors among college students. Model 6 in Process 4.1 was applied to test the chain mediating roles of emotional regulation difficulties and depression in the relationship between cumulative family risk and NSSI behaviors， while model 83 was utilized to analyze the moderating effects of gender on the path "cumulative family risk → emotion regulation difficulties". ResultsA total of 475 （91.70%） college students completed valid questionnaires. Logistic regression analysis revealed that childhood abuse （OR=2.561， 95% CI： 1.566-2.561）， non-parental family structure （OR=2.108， 95% CI：1.102-4.029） and left-behind experience （OR=2.356， 95% CI： 1.021-5.439） were risk factors for NSSI behaviors among college students. Cumulative family risk positively predicted NSSI behaviors （β=0.345，95% CI：1.059-4.286， P<0.01）， and this relationship was mediated by a chain pathway involving emotional regulation difficulties （β=0.136，95% CI： 0.882-4.681， P<0.05） and depression （β=0.160， 95% CI： 0.316-1.073， P<0.01）. Gender moderated the relationship between cumulative family risk and emotional regulation difficulties （β=0.103， 95% CI： 1.567-8.316， P<0.01）， with cumulative family risk significantly predicting emotional regulation difficulties in female students （β=0.374， 95% CI： 0.099-0.084， P<0.01）. ConclusionCumulative family risk can directly influence college students' NSSI behaviors， and may also indirectly affect NSSI behaviors through the mediating roles of emotional regulation difficulties and depression. The path "cumulative family risk → emotional regulation difficulties" in this mediating model is moderated by gender.［Funded by Heilongjiang Philosophy and Social Sciences Research Planning Project （number， 24SHB007）］

Objective To explore the mechanism of'homotherapy for heteropathy'Zhigancao Decoction in the treatment of coronary heart disease arrhythmia and pulmonary fibrosis by network pharmacology and molecular docking technology.Methods All the active components of Zhigancao Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Herbal Compendium(HERB).The SwissTargetPrediction database was used to predict the targets.Cytoscape software was used to construct the drugs-targets network diagram and network topology analysis was performed to obtain the core drug targets.The disease targets of coronary heart disease,arrhythmia and pulmonary fibrosis were obtained in GeneCards and OMIM databases,and the intersection targets of Chinese medicine and disease were obtained by Venny software.The intersection targets were imported into the STRING online database to construct a protein-protein interaction network,and the data were imported into Cytoscape software for visualization and screening of core targets.Gene ontology(GO)function enrichment analysis and kyto encyclo-pedia of genes and genomes(KEGG)pathway enrichment analysis were performed on the intersection targets using the Metascape database.Molecular docking verification and heat map visualization were performed on the core intersection target and the core drug target through the CB-DOCK2 online platform.Results A total of 137 active components of Zhigancao Decoction were screened out,and 848 corresponding drug targets were obtained by removing repeated values.A total of 9 962 targets of coronary heart disease,5 735 targets of arrhythmia and 7 722 targets of pulmonary fibrosis were obtained.A total of 362 drug-disease intersection targets were obtained by Venny platform processing.The potential core targets with higher degree values were GAPDH,IL-6,ALB,STAT3,TNF,MMP-9 and so on by network topology analysis.GO functional enrichment analysis showed that the main biological processes(BP)involved in Zhigancao Decoction'homotherapy for heteropathy'were the response to hormones,the positive regulation of circulatory system process,phosphorus metabolism process,the response to exogenous stimulation,and the response to organic matter,the main cellular components(CC)include lipid rafts,receptor complexes,cytoplasmic perinuclear regions,dendrites,membrane sides,etc.,the main molecular functions(MF)include protein kinase activity,kinase binding,protein homopolymerization activity,nuclear receptor activity,heme binding,etc..KEGG pathway enrichment analysis showed that the main signaling pathways involved in Zhigancao Decoction'homotherapy for heteropathy'were lipid and atherosclerosis,calcium signaling pathway,cAMP signaling pathway,insulin resistance,cGMP-PKG signaling pathway,JAK-STAT signaling pathway,NF-κB signaling pathway,etc..The results of molecular docking suggested that there was a good binding activity between the main active component targets of Zhigancao Decoction and the core targets of'homotherapy for heteropathy'.Conclusion Zhigancao Decoction mainly regulates JAK-STAT,NF-κB,cAMP and other signaling pathways,acts on IL-6,STAT3,TNF,MMP-9 and other gene targets,and exerts the effect of'homotherapy for heteropathy'on coronary heart disease arrhythmia and pulmonary fibrosis.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

The peroxisome proliferator-activated receptor gamma(peroxisome proliferator-activated receptor gamma,coactivator 1 beta,PPARGC1B)gene is an intranuclear receptor transcription fac-tor responsible for regulating the expression of target genes.To comprehend the characteristics and mutations of the PPARGC1B gene within the Sichuan yak population,the SNP loci of the PPARGC1B gene were identified through direct sequencing of PCR products.Additionally,the cod-ing region of the PPARGC1B gene was obtained via PCR amplification and sequencing.Bioinforma-tics analyses were conducted to predict protein-coding and mRNA secondary structure.This study identified four exon SNP mutation sites(E9-189A→C,E9-387G→A,E9-542C→T,and E9-554T→C)based on the single nucleotide polymorphism analysis of the PPARGC1B gene in Sichuan yaks.Notably,the E9-387G→A and E9-554T→C loci exhibited significant correlations with shear force and backfat thickness in Sichuan yaks.Subsequently,bioinformatics analysis of the four mutation sites revealed that the PPARGC1B protein is an acidic,unstable,non-transmembrane,and non-secretory hydrophilic protein with a coiled helix structure.It lacks a signal peptide and transmembrane region,predominantly functions in the nucleus,and features 106 phosphorylation sites,one glycosylation site,and one conserved RRM structure.The secondary structure comprises mainly α-helix and random coils.Although the protein structure of the PPARGC1B gene remained unchanged post-mutation,there were significant differences in mRNA secondary structure.These findings suggest that the polymorphic loci of the PPARGC1B gene in Sichuan yaks could serve as a theoretical basis for enhancing meat quality traits through molecular biological methods,presen-ting practical applications in breeding.

ObjectiveTo investigate the genetic polymorphism and structure of 47 autosomal microhaplotypes in the Han population in Changshu City, Jiangsu Province, and to evaluate the forensic efficiencies and forensic parameters. MethodsThe DNA library of unrelated individual samples was prepared according to MHSeqTyper47 kit manual and sequenced on the MiSeq FGx platform. Microhaplotype genotyping and sequencing depth statistics were processed using MHTyper. The genetic information of samples was then evaluated. The fixation index and genetic distance between the Jiangsu Changshu population and the reference populations in the 1000 Genomes Project phase 3 (1KG) were calculated, and forensic parameters were evaluated. ResultsThe fixation index and genetic distance between the Han population in Changshu, Jiangsu, and the CHB (Han Chinese in Beijing, China) reference population in 1KG were the lowest. The effective allele number (A_e) of each locus is also the closest between the two populations. The combined matching probability (CMP) of the Changshu Han population is close to the 5 populations of the East Asian reference super-population in 1KG, which is 1.25×10^-36, and the combined probability of exclusion reached 0.999 999 999 964 1. ConclusionThis study reported the genetic polymorphism and allele frequency of 47 microhaplotypes in a Han population in Changshu City, Jiangsu Province. This information provides a data basis for 47 microhaplotypes in forensic applications. In addition, the polymorphism differences between the 1KG reference population and the Han population in Changshu, Jiangsu were compared, and the genetic structure of 47 microhaplotypes in the Han population in Changshu, Jiangsu was revealed. In general, the reference data of the East Asian super-population in 1KG is more in line with the genetic characteristics of Han population in Changshu, Jiangsu.

Objective:To investigate the molecular mechanisms of chronic rhinosinusitis (CRS), to identify key cell subgroups and genes, to construct effective diagnostic models, and to screen for potential therapeutic drugs.Methods:Key cell subgroups in CRS were identified through single-cell transcriptomic sequencing data. Essential genes associated with CRS were selected and diagnostic models were constructed by hdWGCNA (high dimensional weighted gene co-expression network analysis) and various machine learning algorithms. Causal inference analysis was performed using Mendelian randomization and colocalization analysis. Potential therapeutic drugs were identified using molecular docking technology, and the results of bioinformatics analysis were validated by immunofluorescence staining. Graphpad Prism, R, Python, and Adobe Illustrator software were used for data and image processing.Results:An increased proportion of basal and suprabasal cells was observed in CRS, especially in eosinophilic CRS with nasal polyps (ECRSwNP), with P=0.001. hdWGCNA revealed that the "yellow module" was closely related to basal and suprabasal cells in CRS. Univariate logistic regression and LASSO algorithm selected 13 key genes ( CTSC, LAMB3, CYP2S1, TRPV4, ARHGAP21, PTHLH, CDH26, MRPS6, TENM4, FAM110C, NCKAP5, SAMD3, and PTCHD4). Based on these 13 genes, an effective CRS diagnostic model was developed using various machine learning algorithms (AUC=0.958). Mendelian randomization analysis indicated a causal relationship between CTSC and CRS (inverse variance weighted: OR=1.06, P=0.006), and colocalization analysis confirmed shared genetic variants between CTSC and CRS (PPH4/PPH3>2). Molecular docking results showed that acetaminophen binded well with CTSC (binding energy:-5.638 kcal/mol). Immunofluorescence staining experiments indicated an increase in CTSC +cells in CRS. Conclusion:This study integrates various bioinformatics methods to identify key cell types and genes in CRS, constructs an effective diagnostic model, underscores the critical role of the CTSC gene in CRS pathogenesis, and provides new targets for the treatment of CRS.