Objective:To investigate the risk factors for detecting clinically significant prostate cancer (CSPCa) in patients with Prostate Imaging Reporting and Data System (PI-RADS) score≤3 on multi-parameter magnetic resonance imaging (mpMRI).Methods:Retrospective analysis was performed on the case data of 335 patients with suspected prostate cancer and PI-RADS score ≤3 who were admitted to Beijing Friendship Hospital, Capital Medical University from January 2013 to October 2022. All patients underwent 24-needle prostate biopsy. Clinical data such as age, body mass index, past medical history, serological laboratory indicators, and mpMRI imaging data were collected. The patients were grouped according to whether the puncture pathology was CSPCa or not, and the differences in clinical data between the two groups were analyzed by t-test, rank sum test and Chi-test. Multivariate Logistic regression analysis was further used to determine independent risk factors for MRI invisible prostate cancer, and receiver operating characteristics (ROC) curves were drawn. At the same time, further subgroup analysis was conducted based on whether prostate-specific antigen (PSA) was positive before puncture and PI-RADS score, respectively, and the same statistical method was used to further determine the influence of different serological indicators and PI-RADS score on the analysis results of risk factors. Results:Among all patients, 81 were CSPCa patients and 254 were non-CSPCa patients. Multivariate Logistic regression analysis showed that prostate-specific antigen density (PSAD) and PI-RADS score of 3 were independent risk factors for MRI invisible prostate cancer. At the same time, compared with suspected lesions located only in the transitional zone, the incidence of CSPCa in patients with suspected lesions located in the peripheral zone would increase, and the incidence of CSPCa would further increase when suspected lesions were found in both the transitional zone and the peripheral zone. In PSA-negative patients, only suspected lesion location was an independent risk factor for MRI invisible prostate cancer, while in PSA-positive patients, prostate volume, PSAD, and PI-RADS scores were independent risk factors. In subgroup analysis with different PI-RADS scores, suspicious lesions in both the transitional zone and peripheral zone indicate a higher likelihood of CSPCa. For patients with PI-RADS scores of 1 to 2, suspicious lesions in the peripheral zone alone may also indicated CSPCa, while for patients with PI-RADS scores of 3, the lower free prostate-specific antigen/total prostate-specific anti-principle was more accurate in predicting CSPCa.Conclusions:For patients who are clinically suspected of prostate cancer but whose PI-RADS score is less than or equal to 3 points indicated by mpMRI, it is necessary to further focus on the results of different serological indicators according to whether their PSA is positive and PI-RADS score respectively to judge whether patients should receive systemic prostate puncture, instead of using PSA level as a single indication for puncture. At the same time, clinicians should also pay full attention to the location of suspected lesions, when they are located in the peripheral zone, or there are suspected lesions in both the peripheral zone and the transitional zone, the possibility of CSPCa should be fully considered.

Objective To investigate the critical role of macrophage M1 polarization in mediating the effect of periodontitis on the progression of chronic obstructive pulmonary disease(COPD).Methods Alveolar lavage fluid samples were collected from COPD patients with comorbid periodontitis,and gene expression analysis was performed to validate the changes in the expression of M1 polarization-related genes.A mouse model of COPD,with experimentally induced periodontitis,were established.Hematoxylin and eosin(HE)staining of pathological sections was performed to observe the effect of periodontitis on COPD progression.Flow cytometry,immunofluorescence staining,and reverse transcription quantitative polymerase chain reaction(RT-qPCR)were performed to analyze the effect of periodontitis on macrophage M1 polarization and the expression of relevant genes in the alveolar lavage fluid and lung tissues.Results In clinical samples of alveolar lavage fluid from COPD patients with periodontitis,the expression of macrophage M1 polarization-related genes,including CD86,inducible nitric oxide synthase(iNOS),interleukin(IL)-1β,tumor necrosis factor(TNF)-α,IL-23,and IL-6,was upregulated compared with that of COPD patients without periodontitis.Analysis of a mouse disease model revealed that periodontitis affected the growth of COPD mice,with the final body mass of mice in the periodontitis and COPD comorbid group([21.3±0.52]g,day 34)lower than that of the COPD group([23.93±0.45]g,day 34).Pathological sections of the lung tissue showed that periodontitis exacerbated COPD progression,with more pronounced alveolar expansion and alveolar wall destruction observed in the periodontitis and COPD comorbid group.Flow cytometry revealed a higher proportion of M1-polarized macrophages in alveolar lavage fluid from COPD and periodontitis comorbid mice([31.36±2.51]%)compared with the COPD mice([23.19±1.07]%).Immunofluorescence assays indicated that periodontitis also promoted macrophage M1 polarization in the lung tissue of COPD mice.Gene expression analysis demonstrated that M1 polarization-related gene expression was significantly upregulated in both the alveolar lavage fluid and lung tissue of mice in the COPD and periodontitis co-morbid group compared to the COPD group.Conclusion Periodontitis exacerbates COPD progression by promoting macrophage M1 polarization in the lungs.Enhancing oral hygiene management and targeting the inhibition of macrophage M1 polarization may represent new therapeutic strategies for the clinical prevention and control of COPD.

Natural products (NPs) have historically been a fundamental source for drug discovery. Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents, and corresponding targets. In the present study, an innovative natural product virtual screening-interaction-phenotype (NP-VIP) strategy that integrates virtual screening, chemical proteomics, and metabolomics to identify and validate the bioactive targets of NPs. This approach reduces false positive results and enhances the efficiency of target identification. Salvia miltiorrhiza (SM), a herb with recognized therapeutic potential against ischemic stroke (IS), was used to illustrate the workflow. Utilizing virtual screening, chemical proteomics, and metabolomics, potential therapeutic targets for SM in the IS treatment were identified, totaling 29, 100, and 78, respectively. Further analysis via the NP-VIP strategy highlighted five high-confidence targets, including poly [ADP-ribose] polymerase 1 (PARP1), signal transducer and activator of transcription 3 (STAT3), amyloid precursor protein (APP), glutamate-ammonia ligase (GLUL), and glutamate decarboxylase 67 (GAD67). These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM. The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research, proposing a comprehensive approach that could be adapted for broader pharmacological explorations.

Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.

Objective To explore the function of electroacupuncture(EA)on body mass,fasting blood glucose,heat pain threshold,and transient receptor potential vanilloid 4(TRPV4)in the dorsal root ganglia(DRG)of rats with diabetic neuropathic pain(DNP).Methods A DNP rat model was formed by intraperitoneally injecting the animals with STZ.From days 15 to 21,bilateral Zusanli and Kunlun points of the DNP rat model were treated with electroacupuncture once daily for 30 min.We then measured their body mass,fasting blood glucose,and heat pain threshold.The co-expression of TRPV4 and NeuN in the rat L4～L6 DRG was detected by immunofluorescence.The effects of the TRPV4 agonist GSK1016790A on body mass,fasting blood glucose,and the heat pain threshold of DNP rats treated with electroacupuncture were detected.Results After the 7th day,body mass was significantly decreased(P<0.01)and fasting glucose was significantly increased(P<0.01)in the model group compared with the normal group.After the 21st day,compared with the model group,heat pain threshold of the model+electroacupuncture group was significantly higher(P<0.01);the results of co-expression of TRPV4 and NeuN immunofluorescence on rat L4～L6 DRG showed that:the expression of positive cells in the model group was significantly higher(P<0.01)than that in the normal group,the co-expression of TRPV4 and NeuN positive cells in L4～L6 DRG of rats in the model+electroacupuncture group was significantly lower(P<0.01)than that in the model group.The TRPV4 agonist GSK1016790A can reverse the downregulation of thermal pain threshold induced by electroacupuncture in DNP rats(P<0.01).Conclusion Electroacupuncture alleviated the DNP induced by STZ,and its mechanism may involve the inhibition of TRPV4 protein expression in the DRG.

Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.

Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.

Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.

ObjectiveTo analyze the distribution characteristics of traditional Chinese medicine （TCM） syndrome elements in different risk populations of heart failure complicated with type 2 diabetes. MethodsClinical data of 675 type 2 diabetes patients were retrospectively collected. Lasso-multivariate Logistic regression was used to construct a clinical prediction nomogram model. Based on this， 441 non-heart failure patients were divided into a low-risk group （325 cases） and a high-risk group （116 cases） according to the median risk score of heart failure complicated with type 2 diabetes. TCM diagnostic information （four diagnostic methods） was collected for both groups， and factor analysis was applied to summarize the distribution of TCM syndrome elements in different risk populations. ResultsLasso-multivariate Logistic regression analysis identified age， disease duration， coronary heart disease， old myocardial infarction， arrhythmia， absolute neutrophil count， activated partial thromboplastin time， and α-hydroxybutyrate dehydrogenase as independent risk factors for heart failure complicated with type 2 diabetes. These were used as final predictive factors to construct the nomogram model. Model validation results showed that the area under the curve （AUC） of the receiver operating characteristic （ROC） curve for the modeling group and validation group were 0.934 and 0.935， respectively. The Hosmer-Lemeshow test （modeling group P = 0.996， validation group P = 0.121） indicated good model discrimination. Decision curve analysis showed that the curves for All and None crossed in the upper right corner， indicating high clinical utility. The low-risk and high-risk groups each obtained 14 common factors. Preliminary analysis revealed that the main disease elements in the low-risk group were qi deficiency （175 cases， 53.85%）， dampness （118 cases， 36.31%）， and heat （118 cases， 36.31%）， with the primary locations in the spleen （125 cases， 38.46%） and lungs （99 cases， 30.46%）. In the high-risk group， the main disease elements were yang deficiency （73 cases， 62.93%）， blood stasis （68 cases， 58.62%）， and heat （49 cases， 42.24%）， with the primary locations in the kidney （84 cases， 72.41%） and heart （70 cases， 60.34%）. ConclusionThe overall disease characteristics in different risk populations of type 2 diabetes patients with heart failure are a combination of deficiency and excess， with deficiency being predominant. Deficiency and heat are present throughout. The low-risk population mainly shows qi deficiency with dampness and heat， related to the spleen and lungs. The high-risk population shows yang deficiency with blood stasis and heat， related to the kidneys and heart.