Renal lymphatic vessel density is clinically relevant in kidney disease but is still assessed by slow, subjective visual estimation. We evaluated a weakly supervised, attention-based multiple-instance learning framework for automated detection and quantification of renal lymphatic vessel density on D2-40-stained whole-slide images (WSIs). Methods: Two independent internal datasets from Tongji Hospital were collected, including 198 cases of chronic kidney disease (CKD) and 50 cases of hypertensive nephropathy (HTN). All biopsies were immunohistochemically stained for D2-40 and digitized as WSIs. Pathologists provided only slide-level labels (D2-40 high vs. D2-40 low). Tissue regions were automatically segmented, tiled into patches, and encoded using a pretrained convolutional neural network. Patch embeddings were then analyzed with a clustering-constrained attention multiple-instance learning (CLAM) model. Unlike conventional multiple-instance learning (MIL) methods that only weight instances, CLAM jointly performs attention-based instance selection and instance-level clustering to distinguish positive from negative evidence within each slide, yielding more discriminative slide-level features and interpretable attention maps. Performance was compared with a classic MIL model trained on the same features. Results: CLAM achieved area under the receiver operating characteristic curves of 0.942 and 0.858 on the CKD and HTN datasets, respectively, outperforming classic MIL (0.866 and 0.801). Attention maps highlighted lymphatic-rich regions consistent with renal pathologists’ assessments. Conclusions: This clustering-constrained, attention-based weakly supervised framework enables fully automated, reproducible quantification of renal lymphatic vessel density from WSIs, providing renal pathologists with rapid visual and numerical support for diagnosis and risk stratification in CKD and HTN.

Sepsis is a systemic inflammatory response caused by severe infection or trauma, and is one of the common causes of acute lung injury(ALI) and acute respiratory distress syndrome(ARDS). Sepsis-acute lung injury(SALI) is a critical clinical condition with high morbidity and mortality. Its pathogenesis is complex and not yet fully understood, and there is currently a lack of targeted and effective treatment options. Pyroptosis, a novel form of programmed cell death, plays a key role in the pathological process of SALI by activating inflammasomes and releasing inflammatory factors, making it a potential therapeutic target. In recent years, the role of traditional Chinese medicine(TCM) in regulating signaling pathways related to pyroptosis through multi-components and multi-targets has attracted increasing attention. TCM may intervene in pyroptosis by inhibiting the activation of NLRP3 inflammasomes and regulating the expression of Caspase family proteins, thus alleviating inflammatory damage in lung tissues. This paper systematically reviews the molecular regulatory network of pyroptosis in SALI and explores the potential mechanisms and research progress on TCM intervention in cellular pyroptosis. The aim is to provide new ideas and theoretical support for basic research and clinical treatment strategies of TCM in SALI.
Pyroptosis/drug effects* ; Humans ; Sepsis/genetics* ; Acute Lung Injury/physiopathology* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Inflammasomes/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics*

Recent studies have shown that shorter periods of ejaculatory abstinence may enhance certain sperm parameters, but the molecular mechanisms underlying these improvements are still unclear. This study explored whether reduced abstinence periods could improve semen quality, particularly for use in assisted reproductive technologies (ART). We analyzed semen samples from men with normal sperm counts ( n = 101) and those with low sperm motility or concentration ( n = 53) after 3-7 days of abstinence and then after 1-3 h of abstinence, obtained from the Reproductive & Genetic Hospital of CITIC-Xiangya (Changsha, China). Physiological and biochemical sperm parameters were evaluated, and the dynamics of transfer RNA (tRNA)-derived fragments (tRFs) were analyzed using deep RNA sequencing in five consecutive samples from men with normal sperm counts. Our results revealed significant improvement in sperm motility and a decrease in the DNA fragmentation index after the 1- to 3-h abstinence period. Additionally, we identified 245 differentially expressed tRFs, and the mitogen-activated protein kinase (MAPK) signaling pathway was the most enriched. Further investigations showed significant changes in tRF-Lys-TTT and its target gene mitogen-activated protein kinase kinase 2 ( MAP2K2 ), which indicates a role of tRFs in improving sperm function. These findings provide new insights into how shorter abstinence periods influence sperm quality and suggest that tRFs may serve as biomarkers for male fertility. This research highlights the potential for optimizing ART protocols and improving reproductive outcomes through molecular approaches that target sperm function.
Male ; Humans ; Spermatozoa/metabolism* ; RNA, Transfer/genetics* ; Sperm Motility/genetics* ; Adult ; Semen Analysis ; Sexual Abstinence/physiology* ; Sperm Count ; DNA Fragmentation

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

AIM:To observe the defocus state and myopia control in myopic children wearing single-vision, defocus, and orthokeratology lenses using multispectral refraction topography(MRT).METHODS: A total of 279 myopic patients aged 8-14 years old, with a spherical equivalent(SE)from -7.00 to -0.50 D, treated at the Chengdu Aier Eye Hospital from June 2022 to December 2023. Patients who volunteered for the study were assigned to three groups. A total of 94 cases were provided with single-vision spectacle lenses(SVL group), 90 cases received individualized ocular refraction customization(IORC group), and 95 cases received orthokeratology lenses(OK group). Simultaneously, the three groups were further categorized into low(-3.00 to -0.50 D), moderate(-6.00 to -3.25 D), and high myopia(-7.00 to -6.25 D)groups according to different SE. MRT was used to measure and compare the defocus changes of the retina in supperior, inferior, nasal, and temporal quadrants(RDV-S, RDV-I, RDV-N, RDV-T), and three angles of field of view, including 0-15°, 15°-30°, and 30°-45°(RDV-15, RDV-30, RDV-45)in the three groups(the data divide for the connected regions is grouped to the latter group). A one-way analysis of variance was used for intergroup comparisons. Univariate and multivariate linear regression analyses were used to analyze the factors related to changes in the axial length(AL)at 1 a after intervention.RESULTS:There were significant differences in 1-year SE and AL growth among patients in the SVL, IORC, and OK groups before and after intervention(P<0.001). The 1-year SE and the difference of AL growth in patients with low myopia was significantly different among SVL, IORC, and OK groups(P<0.001); however, there was no significant difference between the IORC and OK groups(P>0.05); there were significant differences in the SE and AL growth changes between the OK group and the IORC and SVL groups in moderate myopia(P<0.001); and there were significant differences between the OK group and the IORC and SVL groups in SE and AL growth of high myopia group after wearing lenses for 1 a(P<0.001), while there were no significant differences between the IORC and SVL groups(P>0.05). In addition, there were significant differences in the relative peripheral refractive errors(RPRE)of 4 quadrants and 3 eccentric regions among the three groups of patients in different degrees of myopia groups(P<0.001). Pair-wise comparison of the growth difference of eccentric D-RDV-15 in low myopia group after wearing lenses for 1 a showed significant differences between the SVL, IORC, and OK groups(P<0.001), but no significant differences between the IORC and OK groups(P>0.05). The angle of field of view D-RDV-30 in moderate myopia subgroups was statistically different between the SVL group and the IORC and OK groups after wearing lenses for 1 a(P<0.001), while the IORC and OK groups showed no significant differences(P>0.05); the angle of field of view D-RDV-15 in high myopia subgroups was statistically different between the OK group and the IORC and SVL groups after wearing lenses for 1 a(P<0.001), but there was no significant difference between the IORC and SVL groups(P>0.05). Univariate and multivariate linear regression model analysis showed that the changes in D-TRVD, D-RDV-45, D-RDV-N, and D-RDV-I correlated with the increase in the difference in 1 a AL.CONCLUSION: MRT can be used to guide the clinical control of myopia. Myopia development is related to the peripheral retinal defocus state, and the difference of defocus quantity in the inferior nasal side at 30°-45° eccentricity may be a factor regulating the rapid progression of myopia.

Objective To investigate the clinical efficacy of Yiqi Huoxue Prescription(derived from Shengyu Decoction)in the treatment of mild cervical spondylotic myelopathy(CSM)with qi deficiency and blood stasis type.Methods A total of 128 patients with mild CSM of qi deficiency and blood stasis type who admitted to Guangdong Provincial Hospital of Chinese Medicine from January 2022 to January 2024 were randomly divided into the control group and the trial group according to the random number table method,with 64 cases in each group.The control group was treated with oral administration of Mecobalamin Tablets,and the trial group was treated with Yiqi Huoxue Prescription orally on the basis of treatment for the control group.The two groups were all treated for four weeks,and then were followed up for three months after the completion of treatment.The CSM scores of the Japanese Orthopedic Association(JOA)and the traditional Chinese medicine(TCM)syndrome scores in the two groups were observed before treatment,after two weeks of treatment,after four weeks of treatment,and three months after the completion of treatment.And then the clinical efficacy,progression of CSM and the incidence of adverse reactions of the two groups were evaluated.Results(1)During the trial,two cases in the control group and three cases in the trial group fell off,and eventually a total of 123 cases were included,62 cases in the control group and 61 cases in the trial group.(2)Three months after the completion of treatment,the total effective rate of the trial group was 93.44%(57/61)and that of the control group was 82.26%(51/62),and the intergroup comparison(tested by chi-square test)showed that the efficacy of the trial group was significantly superior to that of the control group,the difference being statistically significant(P<0.05).(3)After two and four weeks of treatment as well as three months after the completion of treatment,JOA scores in the two groups were increased compared with those before treatment(P<0.05),and JOA scores of the trial group at various time points mentioned above were higher than those of the control group,the difference being statistically significant(P<0.05).(4)After two and four weeks of treatment as well as three months after the completion of treatment,TCM syndrome scores in the two groups were decreased compared with those before treatment(P<0.05),and TCM syndrome scores of the trial group at various time points mentioned above were lower than those of the control group,the difference being statistically significant(P<0.05).(5)During the follow-up period,there was none case of significant aggravation or progression to moderate-severe illness in the two groups,and there were no adverse events such as allergies and gastrointestinal reactions.Conclusion Yiqi Huoxue Prescription exerts certain efficacy in treating patients with mild CSM of the qi deficiency and blood stasis type,and the treatment method is effective on improving the spinal cord function and symptoms of qi deficiency and blood stasis type,and slowing down the progression of disease in the patients,with high safety.

19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Sepsis is a systemic inflammatory response triggered by infection and often leads to acute kidney injury(AKI).The pathogenesis of sepsis-associated AKI is complex,involving multiple factors such as renal ischemia,inflammation and oxidative stress.In recent years,pyroptosis,a pro-inflammatory form of programmed cell death,has gradually attracted the attention of researchers.Pyroptosis is activated by inflammasomes(e.g.,the NOD-like receptor pyrin domain-related protein 3 inflammasome,NLRP3 inflammasome),accompanied by Gas-dermin D(GSDMD)-mediated formation of cell membrane pores and release of cellular contents,which leads to exacerbation of local and systemic inflammatory responses.The mechanism of pyroptosis in sepsis-associated AKI has not been fully elucidated,but AKI is directly involved in the process of renal functional impairment by indu-cing the death of renal tubular epithelial cells and exacerbating the local inflammatory response.Blockade of key molecules in the pyroptosis pathway,such as GSDMD or NLRP3 inflammasome,can significantly alleviate renal injury,suggesting that the pyroptosis pathway may be a potential therapeutic target for sepsis-associated AKI.This review summarizes the recent research progress on pyroptosis in sepsis-associated AKI,and discuss its cen-tral role in the pathogenesis,particularly focusing on the inflammasome and GSDMD pathways.Additionally,this paper analyzes the potential of focal death inhibition as a therapeutic strategy and proposes future research direc-tions with the expectation of providing references for the treatment of sepsis-related AKI.

Post-stroke spasticity is a series of symptoms after stroke,such as hand and foot urgency,unflexion and extension of muscles,etc.In order to deeply understand the cognition of post-stroke spasticity of ancient Chinese physicians and comb out their therapeutic thoughts,this study took the General Catalogue of Chinese Ancient Books of Traditional Chinese Medicine as a bibliographic reference,all the ancient Chinese literature on spasms after stroke was retrieved manually and by computer,and then sorted and analyzed,and classified them by longitudinal time,and extracted the description about post-stroke spasticity,including medical classics,prescriptions,clinical evidence,medical records and so on.And this paper verified and summarized the etiology,pathogenesis,functional and indications and prescription characteristics of spasticity after stroke,in order to deeply understand systematic theories and treatment ideas of the ancient medical practitioners in the bud,development and mature stages of their understanding of spasticity after stroke,and provide the theoretical basis for the later doctors to understand this disease and the modern clinical treatment of traditional Chinese medicine.

Sepsis is a systemic inflammatory response triggered by infection and often leads to acute kidney injury(AKI).The pathogenesis of sepsis-associated AKI is complex,involving multiple factors such as renal ischemia,inflammation and oxidative stress.In recent years,pyroptosis,a pro-inflammatory form of programmed cell death,has gradually attracted the attention of researchers.Pyroptosis is activated by inflammasomes(e.g.,the NOD-like receptor pyrin domain-related protein 3 inflammasome,NLRP3 inflammasome),accompanied by Gas-dermin D(GSDMD)-mediated formation of cell membrane pores and release of cellular contents,which leads to exacerbation of local and systemic inflammatory responses.The mechanism of pyroptosis in sepsis-associated AKI has not been fully elucidated,but AKI is directly involved in the process of renal functional impairment by indu-cing the death of renal tubular epithelial cells and exacerbating the local inflammatory response.Blockade of key molecules in the pyroptosis pathway,such as GSDMD or NLRP3 inflammasome,can significantly alleviate renal injury,suggesting that the pyroptosis pathway may be a potential therapeutic target for sepsis-associated AKI.This review summarizes the recent research progress on pyroptosis in sepsis-associated AKI,and discuss its cen-tral role in the pathogenesis,particularly focusing on the inflammasome and GSDMD pathways.Additionally,this paper analyzes the potential of focal death inhibition as a therapeutic strategy and proposes future research direc-tions with the expectation of providing references for the treatment of sepsis-related AKI.