ObjectiveIn traditional Chinese medicine (TCM), the foundational doctrine that the eyes reflect the essence of the internal viscera establishes ocular observation as a cornerstone of diagnostic practice. Specifically, the morphological characteristics and coloration variations of the scleral microvasculature serve as critical clinical indicators for assessing the dynamic balance of Qi and Blood, as well as the pathological status of internal organs. Historically, however, TCM eye diagnosis has relied predominantly on the subjective clinical experience and visual acuity of individual practitioners, leading to inherent challenges in standardization and reproducibility. While automated computer-aided diagnostic systems offer a promising solution, existing vessel segmentation algorithms encounter significant domain-specific bottlenecks when applied to scleral imagery. These challenges primarily stem from the highly reflective and moist nature of the ocular surface, which generates severe reflective interference. Furthermore, the inherent low contrast of fine capillary networks against complex background textures, compounded by non-uniform illumination, frequently results in high false-positive rates, misdetections, and severe vessel fragmentation. To address these critical limitations and advance the objective quantification of TCM diagnostics, this paper proposes a novel, highly robust sclera vessel segmentation framework that innovatively integrates Frangi-Sato dual-filter adaptive enhancement with pixel-level reflection detection. MethodsThe proposed methodology systematically addresses the segmentation pipeline through three synergistic stages. First, to overcome the structural limitations of single-filter approaches, a multi-scale weighted fusion strategy is meticulously designed to harness the complementary extraction capabilities of both Frangi and Sato filters. This adaptive enhancement optimally balances the preservation of main vessel trunk continuity with the heightened sensitivity required for delineating delicate, low-contrast peripheral capillaries. Second, to tackle the persistent issue of reflective highlights, a sophisticated multi-feature synergistic reflection detection module is introduced. By jointly analyzing local information entropy, gradient field variations, and intensity statistical distributions, this module achieves precise, pixel-level identification and elimination of reflective artifacts without compromising the underlying vascular structures. Finally, a dual-level adaptive thresholding strategy, featuring an innovative “core protection” mechanism, is implemented. This critical step effectively suppresses complex background noise while rigorously preserving the structural and topological integrity of the intricate vessel network, preventing the structural breaks often seen in conventional binarization methods. ResultsThe efficacy of the proposed framework was rigorously evaluated using both self-constructed clinical datasets specifically acquired for TCM research and standardized public datasets. Extensive experimental results demonstrate that the proposed method consistently outperforms state-of-the-art traditional approaches and contemporary deep learning models. Specifically, the proposed method achieves a Dice similarity coefficient of approximately 0.71 on the private clinical dataset, and secures the best performance across the majority of quantitative metrics on both datasets. Notably, the framework exhibits exceptional robustness and generalization capabilities in highly challenging scenarios characterized by intense reflective interference, low signal-to-noise ratios, and cross-domain image variations. ConclusionThis study successfully realizes the high-integrity, automated segmentation of scleral vessel networks under complex clinical imaging conditions. By overcoming the fundamental algorithmic challenges of reflection interference and micro-vessel loss, the proposed methodology provides potential support for the digitization, objective standardization, and intelligent advancement of modern TCM eye diagnosis systems.

ObjectiveIn traditional Chinese medicine (TCM), the foundational doctrine that the eyes reflect the essence of the internal viscera establishes ocular observation as a cornerstone of diagnostic practice. Specifically, the morphological characteristics and coloration variations of the scleral microvasculature serve as critical clinical indicators for assessing the dynamic balance of Qi and Blood, as well as the pathological status of internal organs. Historically, however, TCM eye diagnosis has relied predominantly on the subjective clinical experience and visual acuity of individual practitioners, leading to inherent challenges in standardization and reproducibility. While automated computer-aided diagnostic systems offer a promising solution, existing vessel segmentation algorithms encounter significant domain-specific bottlenecks when applied to scleral imagery. These challenges primarily stem from the highly reflective and moist nature of the ocular surface, which generates severe reflective interference. Furthermore, the inherent low contrast of fine capillary networks against complex background textures, compounded by non-uniform illumination, frequently results in high false-positive rates, misdetections, and severe vessel fragmentation. To address these critical limitations and advance the objective quantification of TCM diagnostics, this paper proposes a novel, highly robust sclera vessel segmentation framework that innovatively integrates Frangi-Sato dual-filter adaptive enhancement with pixel-level reflection detection. MethodsThe proposed methodology systematically addresses the segmentation pipeline through three synergistic stages. First, to overcome the structural limitations of single-filter approaches, a multi-scale weighted fusion strategy is meticulously designed to harness the complementary extraction capabilities of both Frangi and Sato filters. This adaptive enhancement optimally balances the preservation of main vessel trunk continuity with the heightened sensitivity required for delineating delicate, low-contrast peripheral capillaries. Second, to tackle the persistent issue of reflective highlights, a sophisticated multi-feature synergistic reflection detection module is introduced. By jointly analyzing local information entropy, gradient field variations, and intensity statistical distributions, this module achieves precise, pixel-level identification and elimination of reflective artifacts without compromising the underlying vascular structures. Finally, a dual-level adaptive thresholding strategy, featuring an innovative “core protection” mechanism, is implemented. This critical step effectively suppresses complex background noise while rigorously preserving the structural and topological integrity of the intricate vessel network, preventing the structural breaks often seen in conventional binarization methods. ResultsThe efficacy of the proposed framework was rigorously evaluated using both self-constructed clinical datasets specifically acquired for TCM research and standardized public datasets. Extensive experimental results demonstrate that the proposed method consistently outperforms state-of-the-art traditional approaches and contemporary deep learning models. Specifically, the proposed method achieves a Dice similarity coefficient of approximately 0.71 on the private clinical dataset, and secures the best performance across the majority of quantitative metrics on both datasets. Notably, the framework exhibits exceptional robustness and generalization capabilities in highly challenging scenarios characterized by intense reflective interference, low signal-to-noise ratios, and cross-domain image variations. ConclusionThis study successfully realizes the high-integrity, automated segmentation of scleral vessel networks under complex clinical imaging conditions. By overcoming the fundamental algorithmic challenges of reflection interference and micro-vessel loss, the proposed methodology provides potential support for the digitization, objective standardization, and intelligent advancement of modern TCM eye diagnosis systems.

The liver is a vital metabolic organ sustaining human life activities， and its dysfunction is closely associated with various liver diseases. In recent years， an increasing number of studies have shown that semaphorins （SEMA） play a significant role in pathological processes such as immune inflammatory response， tumor progression， and fibrosis in liver diseases by interacting with their receptors plexins and neuropilins. This article reviews the expression， functions， and molecular mechanisms of different SEMA in viral hepatitis， hepatocellular carcinoma， liver fibrosis， nonalcoholic fatty liver disease， and hepatic ischemia-reperfusion injury， and it also explores the potential application value of SEMA in the diagnosis and treatment of liver diseases， in order to provide new ideas for precise diagnosis and targeted treatment of liver diseases.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

ObjectiveTo investigate the urate-lowering effect of Shenling Qushi prescription in the mouse model of hyperuricaemia. MethodsSixty-three C57BL/6N mice were randomly assigned to the following groups （n=9）： Control， model， low-dose （6 g·kg^-1） Shenling Qushi prescription， medium-dose （12 g·kg^-1） Shenling Qushi prescription， high-dose （24 g·kg^-1） Shenling Qushi prescription， medium-dose Shenling Qushi prescription plus febuxostat （12+0.003 g·kg^-1）， and febuxostat （3 mg·kg^-1）. A mouse model of persistent hyperuricaemia was established via intraperitoneal injection of potassium oxazolamide （250 mg·kg^-1） combined with oral administration of allopurinol （300 mg·kg^-1） over a 28-day period. Concurrently， the prescription was administered orally at the specified doses once daily for 21 consecutive days. Throughout the experiment， mouse body weight， food intake， water consumption， and urine output were measured and recorded. Kidney and liver indices were calculated. Renal histopathological changes were observed by haematoxylin and eosin staining. Serum uric acid （SUA） and urinary uric acid （UUA） levels， along with xanthine oxidase （XOD） and adenosine deaminase （ADA）， alanine aminotransferase （ALT） and aspartate aminotransferase （AST） activities， were determined. Real-time PCR was employed to assess the mRNA levels of urate anion transporter 1 （URAT1） and glucose transporter 9 （GLUT9） in the renal tissue， alongside those of XOD and ADA in the liver tissue. The protein levels of URAT1 and GLUT9 in the renal tissue were determined by Western blot. ResultsCompared with the normal group， model mice exhibited reduced food intake and body weight （P<0.01）， decreased water consumption yet increased urine output， no significant change in the liver index but increased kidney index （P<0.01）. Pathological findings revealed renal tissue damage including glomerular atrophy， epithelial cell detachment， and inflammatory cell infiltration. Furthermore， the model group exhibited elevated UUA and SUA levels （P<0.01）， enhanced activities of ALT， AST， XOD， and ADA in the liver tissue （P<0.05， P<0.01）， upregulated mRNA and protein levels of URAT1 and GLUT9 in the renal tissue （P<0.05）， alongside markedly elevated mRNA levels of XOD and ADA in the liver （P<0.01）. Compared with the model group， the Shenling Qushi prescription groups showed no significant changes in body weight or food intake， with water consumption and urine output remaining within normal ranges， alleviated glomerular atrophy， with reduced pathological damage such as inflammatory infiltration， declined UUA and SUA levels （P<0.01）， and increased activities of ALT， AST， XOD， and ADA in the serum （P<0.01）. Real-time PCR results demonstrated that Shenling Qushi prescription downregulated the mRNA levels of URAT1 and GLUT9 in the renal tissue （P<0.05， P<0.01） and XOD and ADA in the hepatic tissue （P<0.05， P<0.01）. Western blot results demonstrated Shenling Qushi prescription reduced the protein levels of URAT1 and GLUT9 （P<0.05， P<0.01）. ConclusionShenling Qushi prescription modulates fluid balance and reduces uric acid levels， thereby alleviating renal injury in hyperuricaemic mice. This effect is highly likely mediated through inhibition of uric acid synthesis and reabsorption.

With the rapid advancement of medical technology and the increasing complexity of clinical environments, competence in clinical ethical decision-making has become an indispensable core competency for exemplary physicians. However, traditional medical ethics education has long been confronted with the persistent challenges of theory-practice dissociation and the disconnect between pedagogical settings and clinical realities. Thus, how to construct a "Clinical Ethics" curriculum that aligns with the objectives of training high-caliber medical professionals has emerged as a critical and challenging issue in current medical education reform. To effectively address this challenge, the Office of Education at Peking University Third Hospital, since 2021, has assembled a multidisciplinary "Clinical Ethics" teaching and management team comprising faculty from Peking University School of Humanities and key clinical specialists from the hospital. In 2022, the "Clinical Ethics" elective course was formally launched for fourth-year students in the eight-year MD program who had completed coursework in "Medical Ethics" and organ-system-based curricula, with the aim of exploring and operationalizing a pre-clinical ethics education model tailored for senior medical students. The course employs a modular instructional design encompassing "theoretical review-case-based deliberation-clinical workshop", which effectively facilitates the deep integration of medical humanities with clinical practice.Following four years of iterative refinement through the "plan-act-observe-reflect" cycle, the course has demonstrated positive outcomes in enhancing students' ethical awareness and decision-making capabilities, and has preliminarily established a sustainable collaborative mechanism among the multidisciplinary faculty team. This article systematically delineates the course development background, pedagogical model and methodological innovations, and the multidisciplinary collaborative framework, alongside reflections and summaries based on implementation outcomes, with the intent of providing references for the future development of "Clinical Ethics" curricula.

Objective To analyze the trends and changes in the burden of chronic kidney dis-ease(CKD)in China from 1990 to 2021.Methods Data related to the burden of CKD in China from the 2021 Global Burden of Disease(GBD)Study public database were downloaded.Descriptive analyses were conducted using indicators such as age-standardized incidence rates,mortality rates,years of life lost(YLL)rates,years lived with disability(YLD)rates,and disability-adjusted life years(DALY)rates.The Joinpoint regression model was employed to analyze the trends in CKD.The Nordpred model was used to predict the standardized mortality rates,prevalence rates,and inci-dence rates of CKD in China over the next 20 years.Results The age-standardized incidence rate of CKD in China increased from 147.29 per 100,000 in 1990 to 163.74 per 100,000 in 2021,while the age-standardized prevalence rates,mortality rates,YLL rates,YLD rates,and DALY rates all ex-hibited downward trends.The incidence and prevalence of CKD were higher in Chinese women than in men,while mortality rates and DALY rates were lower in women than in men.The burden of CKD increased with age.It is estimated that by 2045,the incidence and prevalence of CKD in China will continue to rise,but the standardized mortality rate and standardized prevalence rate will decline.Conclusion Based on the current status and trends in the burden of CKD in China,implementing precise health management for different populations can help reduce the burden of CKD in China.

Objective To establish a human intestinal organ-on-a-chip model using a multi-array chip array to simulate the microphysiological structure of the human intestine and to investigate the impact of ionizing radiation on radiation-induced damage to human intestinal cells.Methods Caco-2 and human umbilical vein endothelial cells(HUVECs)were co-cultured in an organ chip.The cells were subjected to fluid shear stress via a precision shaker.After 7 days of dynamic culture,the morphological structure of intestinal epithelial cells and venous endothelial cells within the intestinal organ chip was examined using phase contrast microscopy,immunofluorescence staining,and confocal microscopy for three-dimensional(3D)imaging.γ-H2AX and TUNEL immunofluorescence staining were employed to assess DNA damage and apoptosis in intestinal epithelial cells two days post-irradiation.Villin immunofluorescence staining was used to evaluate villus height three days post-irradiation.EdU incorporation assay and Ki67 immunofluorescence staining were conducted to observe the effects of ionizing radiation on the proliferation of intestinal epithelial cells.Results After 7 days of dynamic culture,phase contrast microscopy and immunofluorescence staining combined with confocal 3D imaging revealed that the upper intestinal epithelial cells in the middle compartment of the chip formed a 3D intestinal villus structure,while the vascular endothelial cells in the lower compartment developed a vascular network structure.The chip was subsequently irradiated by 10 Gy X-ray.Immunofluorescence staining results indicated that the mean fluorescence intensity of γ-H2AX and TUNEL in the irradiated group was significantly higher than in the non-irradiated group 2 days after irradiation(P＜0.01),and that the proportion of EDU+and Ki67+cells in the irradiated group was significantly lower than in the non-irradiated group three days after irradiation(P＜0.05).Conclusion Caco-2 cells and HUVECs co-culture on an organ chip can generate the biomimetic structure of human intestinal villus.Ionizing radiation has been found to shorten intestinal villus,increase DNA damage and apoptosis in intestinal epithelial cells,and inhibit the proliferation of these cells.

BACKGROUND:Developed by the esteemed Chinese medicine master Wei Guikang,Tongan Decoction has proven highly effective in treating knee osteoarthritis.However,the mechanism of action is yet unclear.OBJECTIVE:To elucidate how Tongan Decoction modulates synovial macrophage polarization as a therapeutic strategy for knee osteoarthritis in a rat model.METHODS:(1)We employed high-throughput microRNA sequencing and polymerase chain reaction to analyze the differentially expressed miRNA in synovial macrophages of normal and knee osteoarthritis rats.Predicted target genes of miR-27a were identified using bioinformatics databases,with subsequent validation through luciferase assays.A total of 68 Sprague-Dawley rats were randomly divided into normal control group(n=16),model group(n=16),miR-27a overexpression group(n=12),Tongan Decoction group(n=12),and Tongan Decoction+miR-27a inhibition group(n=12).The miR-27a overexpression group and the Tongan Decoction+miR-27a inhibition group were injected with miR-27a mimic and miR-27a inhibitor in the right knee joint cavity,respectively,once daily for 5 continuous days.On the 15th day after modeling,the Tongan Decoction group and the Tongan Decoction+miR-27a inhibition group were given Tongan Decoction by gastric lavage,and the other three groups were given saline by gastric lavage,once daily for 14 continuous days.After administration,behavioral tests,X-rays,hematoxylin-eosin staining of synovial and cartilage tissues of the knee joint and immunofluorescence staining of synovial tissues of the knee joint,RT-PCR,and Western blot were performed.RESULTS AND CONCLUSION:High-throughput sequencing of miRNA showed low expression of miR-27a in synovial tissues of rats with knee osteoarthritis.The target gene of miR-27a was nuclear factor κB,and luciferase assay showed that the two could bind to each other.Behavioral assays showed that miR-27a overexpression or Tongan Decoction alleviated joint dysfunction in rats with knee osteoarthritis,and miR-27a inhibition antagonized the effect of Tongan Decoction.X-ray films and hematoxylin-eosin staining showed that miR-27a overexpression or Tongan Decoction reduced the degree of knee osteoarthritis and miR-27a inhibition weakened the therapeutic effect of Tongan Decoction.The results of RT-PCR and western blot assay showed that compared with the normal control group,the expression of interleukin 10 was reduced in the model group(P＜0.05),and the expression of matrix metalloproteinase 13,interleukin 1β,and nuclear factor κB was elevated in the model group(P＜0.05).miR-27a overexpression or Tongan Decoction could differently reverse the changes in the above-mentioned indexes,while miR-27a inhibition weakened the effect of Tongan Decoction.Immunofluorescence staining results showed that CD86 protein expression in the model group was higher than that in the normal control group(P＜0.05),and CD206 protein expression was lower than that in the normal control group(P＜0.05);miR-27a overexpression group and Tongan Decoction had lower CD86 protein expression than that in the model group(P＜0.05),and higher CD206 protein expression than that in the model group(P＜0.05);in the Tongan Decoction+miR-27a inhibition group,CD86 protein expression was higher(P＜0.05)and CD206 protein expression was lower than that in the Tongan Decoction group(P＜0.05).Tongan Decoction mitigates knee osteoarthritis by upregulating miR-27a expression and suppressing nuclear factor κB activity,which improves knee joint function and further treats knee osteoarthritis.

Objective:To investigate the effect of mild moxibustion on transient receptor potential vanilloid type 1(TRPV1)channel expression in primary dysmenorrhea(PD)rats and explore its mechanism in alleviating central pain sensitization.Methods:Thirty-two female non-pregnant Wistar rats were randomized into a blank group,a model group,a mild moxibustion group,and a capsazepine group,with 8 rats in each group.Except for the blank group,the other three groups used estradiol benzoate,ice-water bath,and oxytocin to establish the rat PD model of cold-dampness stagnation pattern.The interventions began on day 1 of modeling,once a day,and lasted 10 d.The mild moxibustion group received mild moxibustion at Shenque(CV8)and Guanyuan(CV4),20 min/time;in the capsazepine group,capsazepine was injected at a dose of 2 mg/(kg·bw).The abdominal pain threshold was measured 10-30 min after oxytocin injection on day 11;enzyme-linked immunosorbent assay was used to detect serum prostaglandin F2α(PGF2α)level;the expression of TRPV1,cluster of differentiation 11B(CD11B),and proto-oncogene c-Fos in the spinal dorsal horn and hypothalamus was detected by immunofluorescence and Western blotting.Results:Compared to the blank group,the model group showed a decreased pain threshold(P<0.05)and an increased serum PGF2α level with elevated TRPV1,CD11B,and c-Fos protein expression in the spinal dorsal horn and hypothalamus(P<0.05).Compared to the model group,both the mild moxibustion group and capsazepine group showed significantly increased pain thresholds(P<0.05),along with decreased serum PGF2α levels and reduced protein expression levels of TRPV1,CD11B,and c-Fos in the spinal dorsal horn and hypothalamus(P<0.05).Rat pain threshold in the capsazepine group was higher than that in the mild moxibustion group(P<0.05).Serum PGF2α level,the expression levels of CD11B and c-Fos proteins in the spinal dorsal horn,as well as TRPV1,CD11B,and c-Fos proteins in the hypothalamus of the capsazepine group were lower than those in the mild moxibustion group(P<0.05).Conclusion:Mild moxibustion at Shenque(CV8)and Guanyuan(CV4)may alleviate the central pain sensitization in PD rats by down-regulating TRPV1 channel expression in the spinal dorsal horn and hypothalamus,thus playing an analgesic effect.