Objective To investigate the role and molecular mechanism of ginsenoside Rb1(Rb1)in regulating neutrophil extracellular trapping networks(NETs)to intervene in atherosclerosis(AS).Methods In vivo:an AS model was constructed with ApoE knockout mice superimposed on a high-fat diet.The pathological and morphological changes of aortic root plaques were observed by HE staining and oil red O staining;Immunofluorescence labelling of neutrophils citrullinated histones(Cit-H3)and macrophages as well as IL-1β at the aortic root plaque site were used to assess the inflammatory infiltration.In vitro:NETs induced by PMA and cholesterol crystals were taken as models respectively.Direct effect of Rb1 against NETs formation assessed by Sytox staining and immunofluorescence staining with Cit-H3 and myeloperoxidase.Rb1 on ROS levels was assessed by DCFH-DA.Rb1 on histone H3 citrulline modification was assessed by Western blotting.Results In vivo:Rb1 significantly inhibited plaque formation,lipid deposition(P<0.05)and intra-plaque inflammatory infiltration(P<0.05).In vitro:Rb1 significantly inhibited NETs formation(P<0.05),neutrophil ROS levels(P<0.05),and Cit-H3 levels(P<0.05).Conclusions Rb1 significantly inhibited AS progression by inhibiting plaque NETs formation,which may be partly through the inhibition of histone H3 citrullination resulting from activation of the neutrophil oxidative stress pathway.

Objective To investigate the role and molecular mechanism of ginsenoside Rb1(Rb1)in regulating neutrophil extracellular trapping networks(NETs)to intervene in atherosclerosis(AS).Methods In vivo:an AS model was constructed with ApoE knockout mice superimposed on a high-fat diet.The pathological and morphological changes of aortic root plaques were observed by HE staining and oil red O staining;Immunofluorescence labelling of neutrophils citrullinated histones(Cit-H3)and macrophages as well as IL-1β at the aortic root plaque site were used to assess the inflammatory infiltration.In vitro:NETs induced by PMA and cholesterol crystals were taken as models respectively.Direct effect of Rb1 against NETs formation assessed by Sytox staining and immunofluorescence staining with Cit-H3 and myeloperoxidase.Rb1 on ROS levels was assessed by DCFH-DA.Rb1 on histone H3 citrulline modification was assessed by Western blotting.Results In vivo:Rb1 significantly inhibited plaque formation,lipid deposition(P<0.05)and intra-plaque inflammatory infiltration(P<0.05).In vitro:Rb1 significantly inhibited NETs formation(P<0.05),neutrophil ROS levels(P<0.05),and Cit-H3 levels(P<0.05).Conclusions Rb1 significantly inhibited AS progression by inhibiting plaque NETs formation,which may be partly through the inhibition of histone H3 citrullination resulting from activation of the neutrophil oxidative stress pathway.

Objective:To investigate the risk factors of skin adverse events associated with immune checkpoint inhibitor (ICI) therapy in patients with urologic neoplasms, and establish a predictive model.Methods:A single-center retrospective case-control study enrolled 91 advanced urologic neoplasms patients who received ICI therapy at the Department of Urology, Beijing Friendship Hospital, Capital Medical University from January 2020 to June 2025. Patients were divided into the skin lesion group ( n=44) and the control group ( n=47). Patients in the skin lesion group experienced related skin adverse events during ICI treatment, while patients in the control group did not experience such events during ICI treatment. The general data and laboratory indicators were compared between the two groups. The normally distributed measurement data were expressed as mean±standard deviation ( ± s), and the independent sample t-test was used for comparison between groups; the non-normally distributed measurement data were expressed as the median (interquartile range) [ M ( Q1, Q3)], and the Kruskal-Wallis test was used for comparison between groups. The count data were expressed as the number of cases and percentages, and the Chi-test was used for comparison between groups. First, a univariate analysis was conducted on the influencing factors of skin adverse events in patients with urologic neoplasms after ICI treatment. Then, the indicators with statistically significant differences in the univariate analysis were further included in the multivariate Logistic regression model to screen the independent risk factors for predicting skin adverse events. The R software was used to incorporate the factors with significant differences from multivariate analysis into the prediction model and construct a Nomogram. The calibration curve was utilized to evaluate the consistency between predicted values and actual observed results. Meanwhile, the discrimination of the model was verified by the receiver operating characteristic (ROC) curve and the area under the curve (AUC), so as to comprehensively verify the reliability and clinical application value of the prediction model. Results:The results of univariate analysis showed that there were statistically significant differences between the skin lesion group and the control group in terms of the proportion of other immune responses, serum albumin level, absolute eosinophil count, and C-reactive protein (CRP) levels ( P<0.05). These factors were included in multivariate Logistic regression, which identified elevated absolute eosinophil count and elevated CRP as the independent risk factors for related skin adverse events in patients with urologic neoplasms after ICI treatment. A predictive nomogram was built based on these factors. The calibration curve showed high consistency between predicted and actual probabilities, and ROC analysis confirmed the combined model had high predictive value (AUC=0.883, P<0.001). Conclusions:Elevated absolute eosinophil count and elevated CRP level are independent predictors of immune-related skin adverse events in urologic neoplasms patients after ICI treatment. The prediction model constructed based on these two factors facilitates early clinical screening and identification of high-risk patients.

Kidney stones are a disease with high incidence, high recurrence rate and heavy economic burden. Current clinical treatments clear formed stones but fail to target the pathophysiological core of recurrence. Beyond systemic risk factors like obesity and diabetes, diet-driven gut dysbiosis is a key potential mediator of stone recurrence. Moreover, the gut-kidney syndrome and gut-kidney axis theories reveal the bidirectional regulation between intestine and kidney, among these, the gut microbiota-metabolite axis as the core functional carrier of the gut-kidney axis has a regulatory mechanism key to resolving recurrence. Currently, 16S rRNA sequencing and metagenomic sequencing have identified gut microbiota differences between stone and non-stone groups: kidney stone patients show reduced alpha diversity, imbalanced Firmicutes/ Bacteroidetes ratio, significantly higher abundance of harmful bacteria (e.g., Escherichia- Shigella), and lower abundance of oxalate-degrading bacteria ( Oxalobacter formigenes, Lactobacillus) and short-chain fatty acid (SCFA)-producing bacteria ( Faecalibacterium). Notably, gut dysbiosis persists even after surgery.Meanwhile, targeted and non-targeted metabolomics show significant abnormalities in intestinal and urinary metabolites (e.g., SCFA tryptophan derivatives) in stone patients, along with downregulated pathways including purine metabolism, caffeine metabolism and aromatic amino acid metabolism. These abnormalities promote stone formation by disrupting the intestinal barrier, worsening renal inflammation and triggering renal oxidative stress. This article reviews the aforementioned gut microbiota, metabolites and related regulatory pathways with significant inter-group differences. Combined with advances in genomics and metabolomics, it aims to provide theoretical references for further clarifying the mechanism of gut microbiota-metabolite axis regulates kidney stone formation and recurrence, and for developing microecological interventions.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

MHNTs@PDA@ZIF-8 with rod-shaped core-shell structures was synthesized and used as sorbent in magnetic solid phase extraction(MSPE).MHNTs@PDA@ZIF-8-MSPE method coupled with gas chromatography-mass spectrometry(GC-MS)was employed to analyze sixteen kinds of polycyclic aromatic hydrocarbons(PAHs)in tea beverages.Vibrating sample magnetometer(VSM),Fourier transform infrared spectroscopy(FT-IR),X-ray diffraction(XRD),scanning electron microscopy(SEM)and nitrogen adsorption-desorption techniques were used to characterize the MHNTs@PDA@ZIF-8.The results demonstrated that the MHNTs@PDA@ZIF-8 exhibited significant magnetic properties and a large specific surface area.The experimental conditions that could affect MSPE were investigated,including adsorbent dosage,extraction time,desorption time,ionic strength,desorption solvent type,and desorption solvent volume.The optimal conditions were 10 mg of MHNTs@PDA@ZIF-8 as adsorbent,90 s under vortex extraction,and ultrasonic desorption for 60 s with 1 mL ofn-hexane.The sixteen kinds of PAHs showed good linearity in the concentration range of 5-500 μg/L(r2≥0.995).The limits of detection(S/N=3)and quantitation(S/N=10)were in the range of 0.1-0.8 μg/L and 0.3-2.6 μg/L,respectively.The recoveries of the method ranged from 60.9%to 114.7%,with relative standard deviations(n=3)ranging from 0.2%to 9.2%when the addition levels of sixteen kinds of PAHs were 10,50,and 100 μg/L.The method was simple,fast,sensitive and environmentally friendly,and suitable for detecting sixteen kinds of PAHs in tea beverages.

Objective:To evaluate the safety and effectiveness of incision and drainage with Holmium laser under flexible ureteroscope in the treatment of parapelvic cysts.Methods:The clinical data of 21 patients with parapelvic cysts in Beijing Friendship Hospital, Capital Medical University from January 2018 to December 2022 were retrospectively analyzed, including 10 males and 11 females. The average age was (62.86±5.38) years, and median age was 63.0 years, aged from 36-72 years. The maximum diameter of the cyst was 33-71 mm, with an average of (53.46±9.68) mm. There were 15 cases with homolateral hydronephrosis and 6 cases with homolateral renal calculus. The patients included in the study were treated with incision and drainage with Holmium laser under flexible ureteroscope. The double J ureteral catheter was removed and the urinary system ultrasound was repeated one month after surgery. CT on bilateral kidney was repeated every 6 months until 12 months after surgery. Subsequently, ultrasound on bilateral kidney was reviewed regularly every year. Prognostic indexes sunch as operation time, postoperative hospital stay, postoperative time of getting out of bed, intraoperative blood loss, recurrence and shrinkage of renal cysts were recorded.Results:Of the 21 patients who underwent incision and drainage with Holmium laser under flexible ureteroscope, 9 cases (42.9%) underwent the one-stage operation and 12 cases (57.1%) underwent the two-stage operation. The mean operative time was (41.57±10.86) min, the mean postoperative hospitalization time was (2.90±1.06) d, the mean time of getting out of bed was (0.53±0.30) d, and the mean intraoperative blood loss was (6.52±2.15) mL. No significant recurrence of cysts was observed in all patients after 6-60 months of follow-up, and the cysts disappeared completely or shrank significantly.Conclusion:Incision and drainage with Holmium laser under flexible ureteroscope is safe and reliable in patients with parapelvic cysts, with short operation time, minor blood loss, rapid postoperative recovery and low recurrence rate, which is one of the ideal treatment options for parapelvic cysts.

Objective Based on ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS),the potential biomarkers and metabolic mechanisms of adult calcium oxalate urolithiasis were identified to guide the diagnosis and treatment of calcium oxalate lithiasis.Methods Blood samples of 36 patients diagnosed with bilateral upper urinary tract calcium oxalate stones and 36 healthy controls admitted to our hospital during Oct.2017 and Jul.2018 were collected.Metabolic fingerprints were analyzed with UPLC-Q-TOF/MS.The multivariate data were analyzed with principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA).Potential biological markers were identified by comparing human metabolome datasets.Finally,the metabolic pathways of the identified compounds were analyzed and the metabolic network map was constructed.Results PCA and OPLS-DA showed significant differences in blood metabolites between patients and healthy controls,and identified 29 blood-related metabolites,including linoleic acid,citric acid,uric acid and so on.The most relevant blood metabolic pathways were bile acid synthesis pathway,fatty acid biosynthesis pathway,glycerophospholipid metabolism pathway,sphingolipid metabolism pathway and purine metabolism pathway.Conclusion Blood metabolomics analysis based on the UPLC-Q-TOF/MS platform identified 29 potential blood biomarkers of adult calcium oxalate urolithiasis,and purine and lipid metabolism may be related to the genesis of calcium oxalate stones.

Objective:To investigate the effect of astragaloside A (AS-A) on the photoreceptor degeneration induced by sodium iodate (NaIO 3) and its related mechanism. Methods:Sixty healthy male C57BL/6J mice, aged 6-8 weeks, were randomly divided into normal control (NC) group, NaIO 3 group, and ASA group, with twenty mice in each group. 30 min before modeling, AS-A group mice were intraperitoneally injected with 100 μl AS-A at a dose of 100 mg/kg body weight. 30 min later, mice in NaIO 3 group and AS-A group were intraperitoneally injected with 100 μl NaIO 3 at a dose of 30 mg/kg body weight. Subsequently, AS-A group mice were administered AS-A twice daily at 12 h intervals until the end of the experiment. On day 1 post-modeling, zonula occludens-1 (ZO-1) immunohistochemistry was performed to observe the structure of retinal pigment epithelium (RPE) cells; real-time quantitative polymerase chain reaction (qPCR) was conducted to detect the mRNA expression of various retinal chemokine ligand-2 ( Ccl2), interleukin-1 beta ( Il-1β), mixed lineage kinase domain-like protein ( Mlkl), receptor-interacting protein kinase 3 ( Ripk3), and tumor necrosis factor ( Tnf). On day 3 post-modeling, immunohistochemistry was performed to observe the expression of ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acid protein (GFAP) in the retina; TdT-mediated dUTP nick-end labeling (TUNEL) assay was used to detect photoreceptor cell death in each group. On day 4 post-modeling, fundus morphology of mice in each group was observed by fundus color photography and optical coherence tomography (OCT). Hematoxylin-eosin staining (HE) was used to observe the morphological structure of the retina in each group. Inter-group comparisons between two groups were conducted using independent samples t-test, while comparisons among three groups were performed using one-way ANOVA. Results:Fundus color photography and OCT examination showed that a large number of scattered yellow-white subretinal nodular structures in the fundus of NaIO 3 group mice, and a large number of strong reflection areas in the RPE layer. The number of strong reflection areas in the RPE layer was reduced in the AS-A group. Immunohistochemical analysis of ZO-1 showed that ZO-1 was largely lost on the RPE cell membrane in that NaIO 3 group; whereas in the AS-A group, ZO-1 was evenly distributed on the RPE cell membrane. HE staining results showed circular black deposits were visible in the RPE layer of the NaIO 3 group, and the inner and outer segments of photoreceptors were severely damaged, with a significant decrease in the number of outer nuclear layer (ONL) cell nuclei; whereas in the AS-A group, the RPE layer pigments were orderly, the inner and outer segments of photoreceptors were intact, and the number of ONL cell nuclei significantly increased. The results of TUNEL staining show that numerous TUNEL-positive cell nuclei were observed in the ONL of the retina in the NaIO 3 group, while the number of TUNEL-positive cell nuclei in the ONL of the retina was significantly reduced in the AS-A group, with statistically significant differences ( t=2.66, P<0.05). The analysis of qPCR data showed that compared with the AS-A group, the relative expression levels of Mlkl, Ripk3, Ccl2, Il-1β and Tnf mRNA in the retina were significantly increased in the NaIO 3 group, with statistically significant differences ( F=39.18, 10.66, 53.51, 41.40, 24.13; P<0.001). Immunohistochemical staining results showed that compared with NC group and AS-A group, the positive expression of GFAP in retina of NaIO 3 group was significantly increased, and the difference was statistically significant ( F=9.62, P<0.05). Conclusion:AS-A antagonizes NaIO 3-induced photoreceptor degeneration in part by inhibiting photoreceptor cell death and neuroinflammation. Meanwhile, AS-A treatment protects against NaIO 3-triggered perturbation of retinal homeostasis.