Objective Objective To analyze the potential spatial factors affecting the genetic differentiation of Oncomelania hupensis robertsoni in Yunnan Province. Methods A total of 13 administrative villages were selected from schistosomiasis-endemic areas of Yunnan Province as O. hupensis snail sampling sites. At least 200 snails were collected in each site, and the spatial variable data of each site were recorded, including longitude, latitude and altitude. Thirty active and Schistosoma japonicum uninfected O. hupensis snails were selected from each sampling site by means of the crawling method and the cercarial shedding method. Genomic DNA was extracted from O. hupensis snails. Following PCR amplification, purification of PCR amplification products and sequencing, the gene sequences of O. hupensis snail samples were spliced and edited using the DNAstar software and the NCBI database to yield the complete mitochondrial sequences of O. hupensis snails at each sampling site, and the mitochondrial genetic distance matrix of O. hupensis robertsoni was calculated at each sampling site. The geographical coordinates of each sampling site were marked using the software ArcGIS 10.2, and the straight-line geographical distance between each sampling site was calculated. The altitude difference, longitude difference and latitude difference between each sampling site were calculated using the Excel software, and the correlation between the mitochondrial genetic distance matrix of O. hupensis robertsoni and each spatial variable matrix was examined by using the Mantel test at 13 sampling sites in Yunnan Province. Results Among the 13 O. hupensis snail sampling sites in Yunnan Province, the largest mitochondrial genetic distance of O. hupensis robertsoni snail populations was seen between Anding Village, Nanjian Yi Autonomous County and Caizhuang Village, Midu County (26.244 2), and the largest geographical distance was seen between Dongyuan Village, Gucheng District and Cangling Village, Chuxiong County (272.64 km). The highest altitude difference was seen between Anding Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1 086.10 m), and the largest longitude difference was found between Qiandian Village, Eryuan County and Cangling Village, Chuxiong County (1.86°), while the largest latitude difference was measured between Leqiu Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1.81°). In addition, the mitochondrial genetic distance of O. hupensis robertsoni snail populations was positively correlated with altitude at 13 snail sampling sites in Yunnan Province (r = 0.542 8, P < 0.001), and showed no significant correlations with geographical distance (r = 0.093 4, P > 0.05), longitude (r = −0.199 5, P > 0.05) or latitude (r = 0.205 7, P > 0.05). Conclusion Altitude may be a potential spatial factor affecting the genetic differentiation of O. hupensis robertsoni in Yunnan Province.

Tumor angiogenesis is a core pathological driver of malignant growth, invasion, and metastasis, and represents a major obstacle to effective anticancer therapy. Conventional antiangiogenic agents, including neutralizing monoclonal antibodies and small-molecule tyrosine kinase inhibitors, are constrained by drug resistance, on-target toxicity, and the compensatory activation of alternative pro-angiogenic pathways. Targeted protein degradation (TPD) has emerged as a promising strategy that may overcome these limitations. Unlike traditional inhibitors that operate through an occupancy-driven mechanism, degraders function through an event-driven catalytic mechanism in which a single degrader molecule can catalytically promote the ubiquitination and subsequent proteasomal or lysosomal degradation of multiple molecules of the same target protein, thereby eliminating the target protein together with all of its functions rather than merely blocking a single active site. This review systematically delineates the pathophysiological basis of tumor angiogenesis, encompassing the angiogenic switch driven by hypoxia-inducible factor-1α (HIF-1α), the aberrant structural and functional features of the tumor vasculature, and the self-reinforcing vicious cycles that sustain malignant progression. We then categorize the principal TPD modalities, with particular emphasis on proteolysis-targeting chimeras (PROTACs) and lysosome-targeting chimeras (LYTACs), and describe their design principles and mechanisms of action. PROTACs recruit E3 ubiquitin ligases to direct intracellular targets to the ubiquitin-proteasome system for degradation, whereas LYTACs engage lysosome-targeting receptors to route extracellular and membrane proteins to the lysosome, thereby expanding the degradable target space beyond the intracellular proteome. We further summarize recent advances in the application of TPD to antiangiogenic intervention at four distinct levels. First, at the signaling initiation level, degradation of vascular endothelial growth factor (VEGF) and its receptor vascular endothelial growth factor receptor 2 (VEGFR2) by aptamer-engineered PROTACs, antibody-based LYTACs, and small-molecule VEGFR2 degraders blocks the upstream trigger of the angiogenic cascade. Second, at the signal transduction level, degradation of focal adhesion kinase (FAK), B-Raf proto-oncogene serine/threonine kinase (BRAF), phosphodiesterase 4 (PDE4), and bromodomain-containing protein 4 (BRD4) interrupts intracellular signaling cascades and transcriptional responses. Third, at the microenvironment level, degradation of proviral integration site for Moloney murine leukemia virus (PIM) kinases curtails the pro-angiogenic signals secreted by tumor-associated macrophages. Fourth, multi-target synergistic strategies, exemplified by bispecific degraders that simultaneously target human epidermal growth factor receptor 2 (HER2) and VEGF-A, represent a preliminary exploration of cooperative intervention. Representative degraders reviewed herein elicit diverse antiangiogenic phenotypes, ranging from the direct inhibition of endothelial cell proliferation, migration, and tube formation to reductions in microvessel density and the suppression of vasculogenic mimicry. Finally, we discuss the major challenges that remain, including the precise matching of degradation kinetics with the vascular normalization window, target selectivity and tissue specificity, and the activation of compensatory networks and the emergence of resistance. Since the application of TPD in this setting remains at an early stage, the clinical translation of these approaches will require careful optimization of degradation efficiency, spatiotemporal control, and delivery strategies. We also envision future directions toward immunotherapy-based combination regimens and precision-degradation approaches guided by single-cell and spatial transcriptomics. In our view, TPD should not be regarded merely as a substitute for conventional antiangiogenic drugs, but rather as a molecular tool capable of systematically remodeling the tumor vascular microenvironment. When precise control of degradation efficiency and spatiotemporal regulation are integrated with a thorough understanding of the heterogeneity and compensatory capacity of tumor vessels, the full clinical potential of this strategy can be realized.

Objective:To construct a decision tree model to predict the risk of breast cancer in patients with pathological nipple discharge.Methods:A total of 157 patients with pathological nipple discharge,who were diagnosed and treated at Weifang Municipal Hospital of Traditional Chinese Medicine from January 2019 to April 2024 and met the inclusion criteria,were selected.A risk prediction model for concurrent breast cancer in patients with pathological nipple discharge was developed using Logistic regression analysis.A decision tree was then constructed,and the predictive performance of the model was assessed based on the area under the receiver operating characteristic curve(AUC).Re-sults:The incidence of concurrent breast cancer among patients with pathological nipple discharge was 24.2%.Accord-ing to the results of binary Logistic regression analysis,elevated CEA and CA 153 levels in nipple discharge,as well as bloody discharge,emerged as independent risk factors for the development of breast cancer in such patients(P<0.05).Based on these findings,a decision tree model was constructed to predict the risk of concurrent breast cancer in patients with pathological nipple discharge.The validation results showed that the Logistic regression model had an AUC value of 0.800,while the decision tree model achieved an AUC value of 0.889.Conclusions:The decision tree model,built upon the identified influencing factors,exhibits strong predictive power for the risk of developing concurrent breast can-cer in patients with pathological nipple discharge,thus facilitating more precise preoperative diagnoses by clinicians for these patients.

Objective To propose a dynamic electrical impedance tomography imaging algorithm based on complementary information fusion network(CIFN)to enhance image quality of dynamic electrical impedance imaging.Methods There were three modules for initialization,multi-frame complementary information extraction and information fusion involved in the CIFN.Firstly,multi-frame dynamic conductivity distribution images were obtained by the initialization module;secondly,spatial complementary information was extracted from the images by using the multi-frame complementary information extraction module;finally,the fusion of lesion target distribution information and target re-reconstruction were realized by the information fusion module to aquire high-quality EIT images.With a 16-electrode multilayer cranial simulation model,the CIFN-based imaging method was compared with Tikhonov regularization algorithm,spectral constraint algorithm and U-Net algorithm in terms of imaging results of types of lesions to verify its performance.Results Compared with the Tikhonov regularization algorithm,spectral constraint algorithm and U-Net algorithm,the proposed CIFN-based algorithm exhibited the lowest mean absolute error(MAE)and the highest structural similarity(SSIM)when used to image different lesion targets,which accurately reconstructed the distribution of lesion targets and gained high imaging stability under common noise levels.Conclusion The proposed CIFN-based imaging algorithm obtains high imaging quality on a cranial simulation model and reconstruction results close to the real model distribution,which provides algorithmic support for subsequent clinical studies on electrical impedance imaging.[Chinese Medical Equipment Journal,2025,46(6):1-6]

OBJECTIVE: To explore the safety and efficacy of high-dose etoposide (VP-16) combined with recombinant human granulocyte colony-stimulating factor (rhG-CSF) as salvage mobilization for peripheral blood stem cells (PBSC) in newly diagnosed multiple myeloma (NDMM) patients. METHODS: From April 2021 to May 2023, eight NDMM patients who had failed to yield sufficient PBSC during initial mobilization with high-dose cyclophosphamide (CTX) combined with rhG-CSF underwent salvage mobilization with 1.2 g/m2 etoposide combined with rhG-CSF 10 μg/(kg·d). The effects and adverse reactions of initial mobilization and salvage mobilization were analyzed. RESULTS: For salvage mobilization and initial mobilization, the numbers of PBSC collections were 16 and 18, respectively. The mean value of total collected CD34⁺ cells were (11.90±5.75)×10⁶/kg and (1.67±0.75)×10⁶/kg (P =0.0010) in salvage mobilization group and initial mobilization group, respectively. The proportion of patients with a total collection of CD34⁺ cell count≥2×10⁶/kg were 100% and 37.5% (P =0.0625), and the proportion of patients with a total collection of CD34⁺ cell count≥5×10⁶/kg were 87.5% and 0% (P =0.0156) in salvage mobilization group and initial mobilization group, respectively. For five patients who underwent high-dose CTX initial mobilization but had a total CD34⁺ cell count < 2×10⁶/kg, successful collection was achieved through salvage mobilization with high-dose VP-16. Salvage mobilization with high-dose VP-16 was scheduled 2-3 weeks after failure of CTX mobilization. Adverse reactions of high-dose VP-16 mobilization did not increase compared to the initial mobilization with high-dose CTX. CONCLUSION As a salvage mobilization regimen, VP-16 1.2 g/m² combined with rhG-CSF is safe and highly effective in NDMM patients who failed to initial mobilization with high-dose CTX combined with rhG-CSF.
Humans ; Multiple Myeloma/therapy* ; Etoposide/therapeutic use* ; Hematopoietic Stem Cell Mobilization/methods* ; Cyclophosphamide/therapeutic use* ; Granulocyte Colony-Stimulating Factor ; Salvage Therapy ; Peripheral Blood Stem Cells ; Male ; Middle Aged ; Female ; Peripheral Blood Stem Cell Transplantation

Objective To propose a dynamic electrical impedance tomography imaging algorithm based on complementary information fusion network(CIFN)to enhance image quality of dynamic electrical impedance imaging.Methods There were three modules for initialization,multi-frame complementary information extraction and information fusion involved in the CIFN.Firstly,multi-frame dynamic conductivity distribution images were obtained by the initialization module;secondly,spatial complementary information was extracted from the images by using the multi-frame complementary information extraction module;finally,the fusion of lesion target distribution information and target re-reconstruction were realized by the information fusion module to aquire high-quality EIT images.With a 16-electrode multilayer cranial simulation model,the CIFN-based imaging method was compared with Tikhonov regularization algorithm,spectral constraint algorithm and U-Net algorithm in terms of imaging results of types of lesions to verify its performance.Results Compared with the Tikhonov regularization algorithm,spectral constraint algorithm and U-Net algorithm,the proposed CIFN-based algorithm exhibited the lowest mean absolute error(MAE)and the highest structural similarity(SSIM)when used to image different lesion targets,which accurately reconstructed the distribution of lesion targets and gained high imaging stability under common noise levels.Conclusion The proposed CIFN-based imaging algorithm obtains high imaging quality on a cranial simulation model and reconstruction results close to the real model distribution,which provides algorithmic support for subsequent clinical studies on electrical impedance imaging.[Chinese Medical Equipment Journal,2025,46(6):1-6]

Objective:To construct a decision tree model to predict the risk of breast cancer in patients with pathological nipple discharge.Methods:A total of 157 patients with pathological nipple discharge,who were diagnosed and treated at Weifang Municipal Hospital of Traditional Chinese Medicine from January 2019 to April 2024 and met the inclusion criteria,were selected.A risk prediction model for concurrent breast cancer in patients with pathological nipple discharge was developed using Logistic regression analysis.A decision tree was then constructed,and the predictive performance of the model was assessed based on the area under the receiver operating characteristic curve(AUC).Re-sults:The incidence of concurrent breast cancer among patients with pathological nipple discharge was 24.2%.Accord-ing to the results of binary Logistic regression analysis,elevated CEA and CA 153 levels in nipple discharge,as well as bloody discharge,emerged as independent risk factors for the development of breast cancer in such patients(P<0.05).Based on these findings,a decision tree model was constructed to predict the risk of concurrent breast cancer in patients with pathological nipple discharge.The validation results showed that the Logistic regression model had an AUC value of 0.800,while the decision tree model achieved an AUC value of 0.889.Conclusions:The decision tree model,built upon the identified influencing factors,exhibits strong predictive power for the risk of developing concurrent breast can-cer in patients with pathological nipple discharge,thus facilitating more precise preoperative diagnoses by clinicians for these patients.

Diabetes, hypertension, and dyslipidemia, collectively referred to the " Three Highs, " represent increasingly prevalent metabolic risk factors in China. Many individuals experience all three conditions concurrently, significantly heightening the risk of cardiovascular disease and mortality. Although the National Metabolic Management Center(MMC) has been established for over eight years and has its unique features, the awareness, treatment, and control rates of these diseases in China remain low, and the efficiency of community management is insufficient. According to the previous two editions of management guidelines and the most recent domestic and international diagnostic and treatment guidelines, this paper conducts an in-depth analysis of the operational experience and management strategies of the MMC. Its aim is to improve the efficiency of grassroots MMC mode management for " Three Highs" patients and ensure that patients receive more standardized management.

Objective To explore the regulatory role of transient receptor potential channel 6(TRPC6)on podocyte autophagy under the influence of homocysteine(Hcy)in mouse kidney.Methods Mouse renal podocytes were divided into control group and Hcy groups(stimulated by Hcy at 40,60,80 and 100 μmol/L for 48 h).The level of TRPC6 mRNA was assessed using quantitative reverse transcription polymerase chain reaction(qRT-PCR)to identify the optimal Hcy concentration for subsequent experiments.Western blotting was employed to evaluate the expression levels of autophagy-related proteins LC3 Ⅱ and p62,as well as the expression levels of podocyte structural proteins Nephrin and Podocin.The expression levels of TRPC6 mRNA and protein in both groups were determined using qRT-PCR,Western blotting and immunofluorescence.Transfections of cells with TRPC6 overexpression or interference were set as follows:(1)control group(untreated),negative control group of TRPC6 overexpression,and TRPC6 overexpression group;(2)control group(untreated),negative control group of TRPC6 interference,and TRPC6 interference group(si-1,si-2,si-3).The expression level of TRPC6 was detected using qRT-PCR.The cells after overexpressing or interfering of TRPC6 were further set as follows:(1)control group(untreated),Hcy group(80 μmol/L Hcy added),TRPC6 overexpression control+Hcy group,TRPC6 overexpression+Hcy group;(2)control group(untreated),Hcy group,TRPC6 interference control+Hcy group,and TRPC6 interference+Hcy group.The expression levels of p62,LC3 Ⅱ,and TRPC6 proteins were detected using Western blotting.Results qRT-PCR detection results showed that compared with control group,the expression level of TRPC6 mRNA in Hcy group increased with the increase of Hcy concentration,with the highest expression level observed at 80 μmol/L Hcy.Therefore,80 μmol/L Hcy was selected as the optimal concentration for intervention.At this time,the expression level of autophagy-related protein LC3 Ⅱ increased,and the expression level of p62 decreased(P<0.05).Western blotting results showed that compared with control group,the expression levels of podocyte-related proteins Nephrin and Podocin in Hcy group were significantly decreased(P<0.05).qRT-PCR results showed that compared with control group,the expression level of TRPC6 mRNA in Hcy group was significantly increased(P<0.05).Compared with negative control group for TRPC6 overexpression,both mRNA and protein expression levels of TRPC6 in TRPC6 overexpression group were significantly higher(P<0.05).Compared with negative control group for TRPC6 interference,both mRNA and protein expression levels of TRPC6 in TRPC6 interference group were significantly decreased(P<0.05).Western blotting results showed that compared with negative control group for TRPC6 overexpression,the expression level of autophagy-related protein LC3 Ⅱ in TRPC6 overexpression+Hcy group was significantly increased,and the expression level of p62 was significantly decreased(P<0.05).Compared with TRPC6 negative control+Hcy group for TRPC6 interference+Hcy,the expression level of autophagy-related protein LC3 Ⅱ in TRPC6 interference+Hcy group was significantly decreased,and the expression level of p62 was significantly increased(P<0.05).Conclusion Hcy can induce autophagy of renal podocytes.Inhibiting the expression of TRPC6 can significantly reduce the autophagy damage to podocytes.

Efficiency in pharmacodynamic study and evaluation is the critical issue in current drug research and development of non-alcoholic steatohepatitis(NASH).Resmetirom,the first marketed medicine for NASH,is approved by pathological surrogate endpoints,meanwhile several clinical trials suspended due to failure to achieve the liver histologic surrogate endpoints.The well-done non-clinical pharmacodynamic study basing on pathological features(ballooning degeneration,lobular inflammation,fibrosis)of NASH,is a great support to the whole research and development projects of new medicines for NASH.In this article,we discussed the necessity and feasibility of the NASH non-clinical pharmacodynamic study combining the clinical trials of NASH drug,the pathological features and the animal models of NASH,in order to facilitate the high-quality research and development of NASH drugs.