Objective To explore the feasibility of radiomics nomogram based on magnetic resonance diffusion weighted imaging for predicting the expression of Ki-67 in breast cancer.Methods A retrospective study was conducted on patients with breast cancer confirmed by surgery and pathology in the Second Affiliated Hospital of Guangdong Medical University.All patients were detected by Ki-67 expression staining,and then divided into group A(n=28,low-level expression of Ki-67)and group B(n=73,high-level expression of Ki-67).The apparent diffusion coefficient(ADC)graph was generated from diffusion weighted images,and the two groups were compared for radiomics features of ADC images and clinical data.The expression level of Ki-67 in breast cancer was predicted using the features of LASSO after dimensionality reduction,and a nomogram model was established,whose diagnostic efficiency was analyzed with receiver operating characteristic curve.Results No significant difference was observed in ADC value,age,carbohydrate antigen 199,carbohydrate antigen 153,carbohydrate antigen 125 and carcinoembryonic antigen between two groups(P>0.05).LASSO regression identified two radiomics features as predictors for the expression level of Ki-67 in breast cancer.The best tuning Lambda of LASSO was-0.125 690 135 478 682,and the included radiomics features for nomogram establishment were MinIntensity and Quantile95.The established nomogram had an area under ROC curve of 0.917,achieving a sensitivity of 91.7%and a specificity of 83.3%.Conclusion The expression of Ki-67 in breast cancer can be predicted based on the radiomics features of ADC images,which can provide a noninvasive detection method for evaluating the proliferation degree and treatment prognosis of breast cancer.

To summarize Professor DING Ying's clinical experience in treating children's IgA nephropathy from the perspective of "wind-induced water turbidity". It is believed that the core pathogenesis of IgA nephropathy in children is the wind stimμlating water to become turbidity， and the basic treatment principles are to eliminate wind and settle viscera， and to remove turbidity and drain water. For those with the syndrome of wind-heat invading the lungs and injury to blood collaterals， modified Yinqiao Powder （银翘散） combined with Xiaoji Decoction （小蓟饮子） could be used； for those with dampness-heat in Sanjiao， heavy dampness and light heat pattern， modified Sanren Decoction （三仁汤） combined with Bazheng Powder （八正散） could be used； for those with lung-spleen qi deficiency and kidney essence depletion pattern， modified Buzhong Yiqi Decoction （补中益气汤） combined with Wuzi Yanzong Pill （五子衍宗丸） could be used； for those with deficiency of both qi and yin， kidney deficiency with stasis pattern， self-prescribed Yishen Huazhuo Formula （益肾化浊方） could be used. Meanwhile on the basis of pattern identification and treatment， rattan-type herbs could be combined in use in order to unblock the meridians and collaterals.

Various therapeuti modailities have been engineered for lung cancer treatment, but their clinic application is severely impeded by the poor therapy efficiency and immunosuppressive microenvironment. Herein, we fabricated a library of small molecule redox-labile nanoparticles (NPs) (i.e., diPTX-2C NPs, diPTX-2S NPs, and diPTX-2Se NPs) by the self-assembly of dimer paclitaxel (PTX) prodrug, and then utilized these NPs with the traditional Chinese medicine (TCM) Qi-Yu-San-Long-Fang (Q) for effective chemoimmunotherapy on Lewis lung carcinoma (LLC)-bearing mice models. Under the high concentration of glutathione (GSH) and H₂O₂, diPTX-2Se NPs could specifically release PTX in cancer cells and exert a higher selectivity and toxicity than normal cells. In LLC tumor-bearing mice, oral administration of Q not only effectively downregulated programmed death ligand-1 (PD-L1) expression, but also remodeled the immunosuppressive tumor immune microenvironment via the increase of CD4⁺ T and CD8⁺ T cell proportion and the repolarization of M2 into M1 macrophages in tumor tissues, collectively achieving superior synergistic treatment outcomes in combination with intravenous PTX prodrug NPs. Besides, we found that the combination regimen also demonstrated excellent chemoimmunotherapeutic performances on low-dose small established tumor and high-dose large established tumor models. This study may shed light on the potent utilization of Chinese and Western-integrative strategy for efficient tumor chemoimmunotherapy.

Background:Rhei Radix et Rhizoma has been traditionally used as a potent laxative for centuries due to its remarkable efficacy.Raw pieces of Rhei Radix et Rhizoma(RP)are known for their strong laxative effects,often accompanied by side effects,while steamed Rhei Radix et Rhizoma pieces(SP)possess a milder laxative effect and are widely used clinically.However,there is a lack of comprehensive evidence examining the mechanisms underlying SP's effectiveness,particularly from a bioavailability perspective.Objective:This study aimed to investigate the impact of the steaming process on the in vivo disposition of RP and SP through pharmacokinetics,tissue distribution,and excretion assays.Methods:An ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous quantitative analysis of prototype anthraquinones and their glucuronide metabolites.Pharmacokinetic,tissue distribution,and excre-tion assays were conducted in constipation rats following oral administration of RP and SP.Blood,tissue,urine,and fecal samples were collected and analyzed to compare the absorption,distribution,metabolism,and excretion profiles of anthraquinones,high-lighting differences in bioavailability and safety between RP and SP.Results:Compared with the RP group,the SP group showed significantly reduced area under the plasma concentration-time curve,mean residence time,and half-life time values for rhein-8-O-β-D-glucopyranoside,rhein,emodin,aloe-emodin,and their glucuronide metabolites.The clearance values were significantly increased in the SP group.These results demonstrate that SP led to lower exposure levels and higher elimination rates of these components compared with RP.Additionally,these compo-nents were primarily distributed in the large intestine,where they exerted their laxative effects.Glucuronide metabolites were mainly excreted through urination,while prototype components were excreted in both urine and feces.Notably,the cumulative excretion of aloe-emodin,emodin,rhein,and their glucuronide metabolites was significantly higher in both urine and feces after SP administra-tion,indicating that SP enhances the excretion of these components compared with RP.Conclusion:The findings suggest that SP reduced anthraquinone exposure levels while enhancing their excretion,demonstrating that the steaming process significantly promotes the elimination of key components.This study provides a comprehensive analysis of how steaming alters the in vivo disposition of Rhei Radix et Rhizoma,offering a scientific basis for the improved safety and clinical use of SP.These insights not only clarify the mechanistic differences between RP and SP but also contribute to a broader understanding of processing-induced modifications in Chinese medicines.This research paves the way for optimizing Chinese medicine processing techniques to enhance the safety and efficacy of herbal therapies.

Background: Rhei Radix et Rhizoma has been traditionally used as a potent laxative for centuries due to its remarkable efficacy. Raw pieces of Rhei Radix et Rhizoma (RP) are known for their strong laxative effects, often accompanied by side effects, while steamed Rhei Radix et Rhizoma pieces (SP) possess a milder laxative effect and are widely used clinically. However, there is a lack of comprehensive evidence examining the mechanisms underlying SP's effectiveness, particularly from a bioavailability perspective. Objective: This study aimed to investigate the impact of the steaming process on the in vivo disposition of RP and SP through pharmacokinetics, tissue distribution, and excretion assays. Methods: An ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous quantitative analysis of prototype anthraquinones and their glucuronide metabolites. Pharmacokinetic, tissue distribution, and excretion assays were conducted in constipation rats following oral administration of RP and SP. Blood, tissue, urine, and fecal samples were collected and analyzed to compare the absorption, distribution, metabolism, and excretion profiles of anthraquinones, highlighting differences in bioavailability and safety between RP and SP. Results: Compared with the RP group, the SP group showed significantly reduced area under the plasma concentration-time curve, mean residence time, and half-life time values for rhein-8-O-β-D-glucopyranoside, rhein, emodin, aloe-emodin, and their glucuronide metabolites. The clearance values were significantly increased in the SP group. These results demonstrate that SP led to lower exposure levels and higher elimination rates of these components compared with RP. Additionally, these components were primarily distributed in the large intestine, where they exerted their laxative effects. Glucuronide metabolites were mainly excreted through urination, while prototype components were excreted in both urine and feces. Notably, the cumulative excretion of aloe-emodin, emodin, rhein, and their glucuronide metabolites was significantly higher in both urine and feces after SP administration, indicating that SP enhances the excretion of these components compared with RP. Conclusion: The findings suggest that SP reduced anthraquinone exposure levels while enhancing their excretion, demonstrating that the steaming process significantly promotes the elimination of key components. This study provides a comprehensive analysis of how steaming alters the in vivo disposition of Rhei Radix et Rhizoma, offering a scientific basis for the improved safety and clinical use of SP. These insights not only clarify the mechanistic differences between RP and SP but also contribute to a broader understanding of processing-induced modifications in Chinese medicines. This research paves the way for optimizing Chinese medicine processing techniques to enhance the safety and efficacy of herbal therapies.

Objective:To investigate the differences in cross-frequency coupling (CFC) characteristics of electroencephalography (EEG) between narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2).Methods:A total of 23 NT1 and 31 NT2 patients were included from the Chinese Clinical Sleep Database (CCSD) between October 2022 and September 2023. All participants underwent overnight polysomnography and a multiple sleep latency test. CFC features were extracted from EEG signals during polysomnography, encompassing various combinations of sleep stages, electrode pairs, frequency bands, and coupling types. Feature selection was performed using elastic net regularization. The Spearman correlation between key CFC features and the Epworth Sleepiness Scale (ESS) scores was analyzed. Finally, a support vector classification (SVC) model was constructed to distinguish NT1 from NT2, and leave-one-out cross-validation was used to assess the generalization performance.Results:Among all coupling features during non-rapid eye movement sleep stage 1 (N1), the fronto-occipital θ-α1 and central δ-α1 couplings showed the highest absolute coefficients, reaching 1.13 and 1.10, respectively. In the NT1 group, the α1-β2 imaginary part of phase-locking value (iPLV) of the F3-C3 pair during N1 was significantly positively correlated with ESS scores ( r=0.52, P=0.012). In the machine learning classification task, the SVC model achieved an accuracy of 85% using leave-one-out cross-validation. Conclusion:The CFC features during the sleep-wake transition stage play an important role in distinguishing NT1 from NT2 and show a significant correlation with excessive daytime sleepiness (EDS) in NT1. CFC may serve as a potential biomarker for differentiating narcolepsy subtypes and provide new insights into the mechanisms and clinical evaluation of EDS.

Objective To explore the feasibility of radiomics nomogram based on magnetic resonance diffusion weighted imaging for predicting the expression of Ki-67 in breast cancer.Methods A retrospective study was conducted on patients with breast cancer confirmed by surgery and pathology in the Second Affiliated Hospital of Guangdong Medical University.All patients were detected by Ki-67 expression staining,and then divided into group A(n=28,low-level expression of Ki-67)and group B(n=73,high-level expression of Ki-67).The apparent diffusion coefficient(ADC)graph was generated from diffusion weighted images,and the two groups were compared for radiomics features of ADC images and clinical data.The expression level of Ki-67 in breast cancer was predicted using the features of LASSO after dimensionality reduction,and a nomogram model was established,whose diagnostic efficiency was analyzed with receiver operating characteristic curve.Results No significant difference was observed in ADC value,age,carbohydrate antigen 199,carbohydrate antigen 153,carbohydrate antigen 125 and carcinoembryonic antigen between two groups(P>0.05).LASSO regression identified two radiomics features as predictors for the expression level of Ki-67 in breast cancer.The best tuning Lambda of LASSO was-0.125 690 135 478 682,and the included radiomics features for nomogram establishment were MinIntensity and Quantile95.The established nomogram had an area under ROC curve of 0.917,achieving a sensitivity of 91.7%and a specificity of 83.3%.Conclusion The expression of Ki-67 in breast cancer can be predicted based on the radiomics features of ADC images,which can provide a noninvasive detection method for evaluating the proliferation degree and treatment prognosis of breast cancer.

Background:Rhei Radix et Rhizoma has been traditionally used as a potent laxative for centuries due to its remarkable efficacy.Raw pieces of Rhei Radix et Rhizoma(RP)are known for their strong laxative effects,often accompanied by side effects,while steamed Rhei Radix et Rhizoma pieces(SP)possess a milder laxative effect and are widely used clinically.However,there is a lack of comprehensive evidence examining the mechanisms underlying SP's effectiveness,particularly from a bioavailability perspective.Objective:This study aimed to investigate the impact of the steaming process on the in vivo disposition of RP and SP through pharmacokinetics,tissue distribution,and excretion assays.Methods:An ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous quantitative analysis of prototype anthraquinones and their glucuronide metabolites.Pharmacokinetic,tissue distribution,and excre-tion assays were conducted in constipation rats following oral administration of RP and SP.Blood,tissue,urine,and fecal samples were collected and analyzed to compare the absorption,distribution,metabolism,and excretion profiles of anthraquinones,high-lighting differences in bioavailability and safety between RP and SP.Results:Compared with the RP group,the SP group showed significantly reduced area under the plasma concentration-time curve,mean residence time,and half-life time values for rhein-8-O-β-D-glucopyranoside,rhein,emodin,aloe-emodin,and their glucuronide metabolites.The clearance values were significantly increased in the SP group.These results demonstrate that SP led to lower exposure levels and higher elimination rates of these components compared with RP.Additionally,these compo-nents were primarily distributed in the large intestine,where they exerted their laxative effects.Glucuronide metabolites were mainly excreted through urination,while prototype components were excreted in both urine and feces.Notably,the cumulative excretion of aloe-emodin,emodin,rhein,and their glucuronide metabolites was significantly higher in both urine and feces after SP administra-tion,indicating that SP enhances the excretion of these components compared with RP.Conclusion:The findings suggest that SP reduced anthraquinone exposure levels while enhancing their excretion,demonstrating that the steaming process significantly promotes the elimination of key components.This study provides a comprehensive analysis of how steaming alters the in vivo disposition of Rhei Radix et Rhizoma,offering a scientific basis for the improved safety and clinical use of SP.These insights not only clarify the mechanistic differences between RP and SP but also contribute to a broader understanding of processing-induced modifications in Chinese medicines.This research paves the way for optimizing Chinese medicine processing techniques to enhance the safety and efficacy of herbal therapies.

Objective:To investigate the differences in cross-frequency coupling (CFC) characteristics of electroencephalography (EEG) between narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2).Methods:A total of 23 NT1 and 31 NT2 patients were included from the Chinese Clinical Sleep Database (CCSD) between October 2022 and September 2023. All participants underwent overnight polysomnography and a multiple sleep latency test. CFC features were extracted from EEG signals during polysomnography, encompassing various combinations of sleep stages, electrode pairs, frequency bands, and coupling types. Feature selection was performed using elastic net regularization. The Spearman correlation between key CFC features and the Epworth Sleepiness Scale (ESS) scores was analyzed. Finally, a support vector classification (SVC) model was constructed to distinguish NT1 from NT2, and leave-one-out cross-validation was used to assess the generalization performance.Results:Among all coupling features during non-rapid eye movement sleep stage 1 (N1), the fronto-occipital θ-α1 and central δ-α1 couplings showed the highest absolute coefficients, reaching 1.13 and 1.10, respectively. In the NT1 group, the α1-β2 imaginary part of phase-locking value (iPLV) of the F3-C3 pair during N1 was significantly positively correlated with ESS scores ( r=0.52, P=0.012). In the machine learning classification task, the SVC model achieved an accuracy of 85% using leave-one-out cross-validation. Conclusion:The CFC features during the sleep-wake transition stage play an important role in distinguishing NT1 from NT2 and show a significant correlation with excessive daytime sleepiness (EDS) in NT1. CFC may serve as a potential biomarker for differentiating narcolepsy subtypes and provide new insights into the mechanisms and clinical evaluation of EDS.

Objective:To assess the renal-protective effect of Elabela (Ela) on diabetic kidney disease (DKD), and explore its potential mechanism.Methods:db/db mice were randomly divided into diabetic group and Ela intervention group, while db/m mice were taken as normal control group. The mice in the Ela intervention group were intraperitoneally injected with Ela-21 5 mg·kg -1·d -1 for 8 weeks. At the end of the experiment, urinary albumin/creatinine ratio (UACR) was measured. The renal pathological changes were observed by HE and PAS staining. The expression of aquaporin 2(AQP2) examined by immunohistochemistry. The level of collage Ⅳ(Col-Ⅳ) and AQP2 in renal tissue was analyzed by Western blot. The human renal tubular epithelial cells (HK-2) were incubated with high glucose medium and further interfered with apelin receptors (APJ)-siRNA. Western blot analysis was used to detect the effect of Ela intervention on Col-Ⅳ and AQP2 expression. Finally, to clarify the possible mechanism of Ela regulating AQP2, the interaction between Ela-induced APJ activation and arginine vasopressin (AVP)-evoked arginine vasopressin receptor 2 (AVPR2) activation was investigated by NanoBit ? technology. Results:(1) Without affecting blood glucose and body weight, Ela intervention significantly reduced the UACR in db/db mice, and attenuate pathological changes of the kidney, as well as expression of Col-Ⅳ and AQP2. (2) Ela treatment could remarkably inhibit the high glucose-induced the expression of Col-Ⅳ and AQP2, which was reversed by interfering with APJ. (3) AVP-induced downstream β-Arrestin-2 signaling transduction via AVPR2 was obviously antagonized by interaction of Ela and APJ, further suggesting that the inhibitory effect of Ela on AQP2 may be related to antagonizing AVP/AVPR2 signaling.Conclusion:Ela exerts renal protection by inhibiting the expression of AQP2 through APJ.