ObjectiveTo verify the association between the Ddit3-Trib3-Akt signaling pathway and rat spermatogenesis by constructing an in vitro co-culture system of testis. MethodsTesticular tissue blocks from 20-25-day-old male rats were placed in an in vitro culture system， and the culture medium was replaced every 2 to 3 days. PCR was used to verify the expression of marker genes of various spermatogenic cells. RNA interference technology was employed to verify the correlation between the Ddit3-Trib3-Akt signaling pathway and rat spermatogenesis. ResultsThe co-culture system could be continuously cultured for more than 2.5 months in vitro. RT-PCR showed that specific marker genes of spermatogonia， spermatocyte and spermoblast were expressed. The RNA and protein expression of Trib3 and Akt changed after the knocking down of Ddit3 and Trib3， respectively. It demonstrated the existence of Ddit3-Trib3-Akt signaling pathway in rat spermatogenesis. ConclusionThe culture time of more than 2.5 months indicates that the culture system can temporarily maintain the proliferation and differentiation of stem cells， and simultaneously maintain and stabilize spermatogenesis in a simple system. The successful validation of the Ddit3-Trib3-Akt signaling pathway also confirms that this culture system can be used to study possible molecular mechanisms of spermatogenesis in vitro.

Cancer remains a leading cause of global mortality, necessitating the development of advanced therapeutic strategies with enhanced efficacy and reduced systemic toxicity. Among promising bioactive agents, lactoferrin (LF)—a multifunctional iron-binding glycoprotein abundantly found in mammalian milk and exocrine secretions—has garnered significant interest for its potent and multifaceted anti-cancer properties. This review provides a comprehensive analysis of the current understanding of LF’s role in oncology, encompassing its structural biology, diverse mechanisms of action, and groundbreaking advancements in its application through nano-engineering. LF exerts anti-tumor effects through multiple pathways, including extracellular action, intracellular action, and immune regulation. It demonstrates a remarkable affinity for cancer cell membranes, binding to overexpressed anionic components such as glycosaminoglycans and sialic acids, as well as to specific receptors including the low-density lipoprotein receptor-related protein-1 (LRP-1). This selective binding facilitates targeted uptake. Upon internalization, LF orchestrates a direct assault by inducing cell-cycle arrest in phases such as G0/G1 or S phase through the modulation of key regulators including cyclins, CDKs, and p53. Furthermore, it promotes programmed cell death via apoptotic pathways, involving caspase activation and downregulation of anti-apoptotic proteins such as survivin. A more recently elucidated mechanism is the induction of ferroptosis, an iron-dependent form of cell death characterized by overwhelming lipid peroxidation. Beyond direct cytotoxicity, LF acts as a potent immunomodulator. It enhances natural killer (NK) cell activity, modulates T-lymphocyte populations, and crucially reprograms tumor-associated macrophages (TAMs) from a pro-tumor M2 state to an anti-tumor M1 state, thereby reversing the immunosuppressive tumor microenvironment (TME). The translation of LF’s potential has been significantly accelerated by nanotechnology. The inherent biocompatibility and natural tumor-targeting capabilities of LF make it an ideal platform for sophisticated drug-delivery systems. This review details various fabrication strategies for LF-based nanoparticles (NPs), including self-assembly, sol-in-oil emulsion, and electrostatic nanocomplexes, among others. Research demonstrates that nano-formulations not only protect LF from degradation but also enhance its bioactivity and anti-cancer potency. More importantly, LF NPs serve as versatile carriers for a wide array of therapeutic agents, including conventional chemotherapeutics, natural compounds, and imaging agents. These engineered systems enable synergistic therapy and facilitate site-specific delivery. Notably, the ability of LF to bind to receptors on the blood-brain barrier (BBB) has been leveraged to develop nano-systems for glioblastoma treatment. Other innovative designs utilize LF to modulate the TME—for instance, by alleviating tumor hypoxia to sensitize cells to radiotherapy and chemotherapy. Despite compelling pre-clinical evidence, the clinical translation of LF and its nano-formulations remains nascent. While early-phase trials have established a favorable safety profile for recombinant human LF, larger Phase III studies have yielded mixed results, underscoring the complexity of its action in humans. Key challenges include enhancing drug targeting, optimizing loading efficiency, ensuring batch-to-batch reproducibility, and achieving deep tumor penetration. Future research must focus on the rational design of next-generation LF-NPs. This entails developing standardized manufacturing protocols, engineering “smart” stimuli-responsive systems for targeted drug release in the TME, and constructing multi-targeting platforms. A concerted interdisciplinary effort is paramount to bridge the gap between bench and bedside. In conclusion, LF, particularly in its nano-engineered forms, represents a highly promising and versatile agent in the oncological arsenal, holding immense potential for precise and effective cancer therapy.

Cancer remains a leading cause of global mortality, necessitating the development of advanced therapeutic strategies with enhanced efficacy and reduced systemic toxicity. Among promising bioactive agents, lactoferrin (LF)—a multifunctional iron-binding glycoprotein abundantly found in mammalian milk and exocrine secretions—has garnered significant interest for its potent and multifaceted anti-cancer properties. This review provides a comprehensive analysis of the current understanding of LF’s role in oncology, encompassing its structural biology, diverse mechanisms of action, and groundbreaking advancements in its application through nano-engineering. LF exerts anti-tumor effects through multiple pathways, including extracellular action, intracellular action, and immune regulation. It demonstrates a remarkable affinity for cancer cell membranes, binding to overexpressed anionic components such as glycosaminoglycans and sialic acids, as well as to specific receptors including the low-density lipoprotein receptor-related protein-1 (LRP-1). This selective binding facilitates targeted uptake. Upon internalization, LF orchestrates a direct assault by inducing cell-cycle arrest in phases such as G0/G1 or S phase through the modulation of key regulators including cyclins, CDKs, and p53. Furthermore, it promotes programmed cell death via apoptotic pathways, involving caspase activation and downregulation of anti-apoptotic proteins such as survivin. A more recently elucidated mechanism is the induction of ferroptosis, an iron-dependent form of cell death characterized by overwhelming lipid peroxidation. Beyond direct cytotoxicity, LF acts as a potent immunomodulator. It enhances natural killer (NK) cell activity, modulates T-lymphocyte populations, and crucially reprograms tumor-associated macrophages (TAMs) from a pro-tumor M2 state to an anti-tumor M1 state, thereby reversing the immunosuppressive tumor microenvironment (TME). The translation of LF’s potential has been significantly accelerated by nanotechnology. The inherent biocompatibility and natural tumor-targeting capabilities of LF make it an ideal platform for sophisticated drug-delivery systems. This review details various fabrication strategies for LF-based nanoparticles (NPs), including self-assembly, sol-in-oil emulsion, and electrostatic nanocomplexes, among others. Research demonstrates that nano-formulations not only protect LF from degradation but also enhance its bioactivity and anti-cancer potency. More importantly, LF NPs serve as versatile carriers for a wide array of therapeutic agents, including conventional chemotherapeutics, natural compounds, and imaging agents. These engineered systems enable synergistic therapy and facilitate site-specific delivery. Notably, the ability of LF to bind to receptors on the blood-brain barrier (BBB) has been leveraged to develop nano-systems for glioblastoma treatment. Other innovative designs utilize LF to modulate the TME—for instance, by alleviating tumor hypoxia to sensitize cells to radiotherapy and chemotherapy. Despite compelling pre-clinical evidence, the clinical translation of LF and its nano-formulations remains nascent. While early-phase trials have established a favorable safety profile for recombinant human LF, larger Phase III studies have yielded mixed results, underscoring the complexity of its action in humans. Key challenges include enhancing drug targeting, optimizing loading efficiency, ensuring batch-to-batch reproducibility, and achieving deep tumor penetration. Future research must focus on the rational design of next-generation LF-NPs. This entails developing standardized manufacturing protocols, engineering “smart” stimuli-responsive systems for targeted drug release in the TME, and constructing multi-targeting platforms. A concerted interdisciplinary effort is paramount to bridge the gap between bench and bedside. In conclusion, LF, particularly in its nano-engineered forms, represents a highly promising and versatile agent in the oncological arsenal, holding immense potential for precise and effective cancer therapy.

Persistent atrial fibrillation and other factors can cause mitral and tricuspid annular dilation and leaflet regurgitation,leading to severe functional mitral and tricuspid regurgitation.Patients often experience significant heart failure symptoms and poor prognosis.For patients with severe mitral or tricuspid regurgitation who are at high risk or contraindicated for surgical procedures,transbronchial repair(TEER)is an important alternative therapy that can effectively reduce valve regurgitation and improve cardiac function;Although there is a lack of large-scale data on atrial functional reflux,existing experience still shows that TEER can significantly reduce reflux and improve patients'quality of life.However,double valve intervention therapy poses challenges,especially when combined with TEER repair,which is technically more complex,time-consuming,and carries higher risks.Foreign data shows that simultaneous or staged double valve intervention can safely improve cardiac function and increase survival rates,but the optimal intervention strategy still needs further research.Due to the fact that tricuspid TEER devices have not yet been launched in China,only staged treatment can be adopted at present.This case report shows a patient with severe atrial functional mitral and tricuspid regurgitation who underwent staged transcatheter edge to edge repair surgery successfully.During a 1-year follow-up,bilateral valve regurgitation continued to improve,indicating that staged repair of bilateral atrioventricular valve regurgitation through the catheter margin is a feasible and effective treatment option.

Objective:To explore the RNA expression and alterations in brain structure in individuals who have experienced stressful life events (SLE), as well as the correlation patterns between them and their association with the occurrence of depression.Methods:Prospectively, a total of 80 SLE subjects were recruited from the psychiatry and psychology clinic of the Jiangsu University Affiliated Yixing Hospital between January 2021 and December 2022, with 16 normal controls (NC) enrolled concurrently. The 17 items Hamilton depression scale (HAMD-17) and social readjustment rating scale (SRRS) were used to assess depressive symptoms and stress levels. RNA sequencing information of peripheral blood and imaging data at baseline were collected. Based on whether depression occurred during the 2-year follow-up period, SLE subjects were divided into the SLE-depression group ( n=15) and the SLE-non-depression group ( n=65). Differentially expressed genes (DEGs) were screened using differential analysis and protein-protein interaction (PPI) networks. Fractional anisotropy (FA) of white matter tracts and gray matter volume (GMV) were extracted using tract-based spatial statistics and voxel-based morphometry.Using analysis of variance compared inter-group differences in gene expression, GMV and white matter FA values. Partial correlation analysis was used to explore correlations between DEGs, altered GMV and white matter microstructure. Gene set enrichment analysis (GSEA) was performed on key genes to identify potential biological pathways. Propensity score matching constructed sensitivity subgroups to verify result robustness. Results:The SLE-depression group showed significantly higher SRRS and HAMD-17 scores at baseline and at the end of follow-up compared to the SLE-non-depression group and the NC group ( H=47.773, 35.427, 41.114, all P<0.05). Expression levels of IL-10 (2.12±0.28, 2.43±0.44), EZH2 (2.11±0.43, 2.45±0.51), NCAM1 (3.60±0.30, 3.03±0.39), CD3E (4.95±0.37, 4.57±0.48), CCK (3.29±0.28, 3.02±0.42), and CX3CR1 (5.55±0.40, 5.91±0.34) were significantly different between the SLE-depression group and SLE-non-depression group( F=5.549~28.371, all P<0.05). Compared with the SLE-non-depression group, the SLE-depression group exhibited significantly lower FA values in the genu of the corpus callosum (0.29±0.04, 0.31±0.04) and the left uncinate fasciculus (0.31±0.02, 0.33±0.02), as well as significantly smaller GMV in the right hippocampus (0.29±0.07, 0.33±0.06), bilateral middle frontal gyrus (left: 0.27±0.05, 0.31±0.05; right: 0.28±0.06, 0.32±0.06), right insula (0.36±0.03, 0.38±0.04), and left precentral gyrus (0.19±0.04, 0.24±0.05) ( F=4.593-12.064, all P<0.05, FDR correction). GMV in the right anterior cingulate and paracingulate gyri was significantly larger than that in the SLE-non-depression group (0.34±0.05, 0.29±0.06) ( F=6.704, P=0.034, FDR correction). Partial correlation analysis revealed significantly stronger correlations between hub DEGs and altered brain regions in the SLE-depression group ( r=0.017-0.801) compared to the SLE-non-depression group ( r=0.002-0.382), with a statistically significant difference ( U=629, P<0.001; Cliff's Delta=0.454). GSEA indicated that the aforementioned genes were primarily involved in pathways including the ribosome, spliceosome, ribosome biogenesis in eukaryotes, and neuroactive ligand-receptor interaction. Sensitivity analysis confirmed that the above results remained statistically significant after balancing sample sizes (all P<0.05). Conclusion:The SLE-depression group showed specific RNA expression and brain structure alterations compared to the SLE-non-depression group, and the correlation between RNA and brain structure was significantly enhanced in the SLE-depression group. This suggests that the correlation between genes and brain structure in the SLE population may be related to their susceptibility to depression.

Chemotherapy-induced nausea and vomiting (CINV) is one of the common adverse reactions in cancer patients undergoing chemotherapy, with a relatively high incidence. This article reviews the research progress on risk prediction models for CINV, introduces the basic information of related risk prediction models, and compares differences in research methods and risk factors, aiming to provide reference for the establishment of a prevention and assessment system for CINV in cancer patients.

Objective To investigate the influence of helical tomographic radiotherapy plans with different combinations of lead gate width,pitch and algorithms on threading effects.Methods A target model was established with a Cheese Phantom used as the simulated human body,then three lead gate widths(1.0,2.5,and 5.0 cm),six screw pitches(0.143,0.172,0.215,0.287,0.430,and 0.500)and two computational grids(Fine algorithm and Normal algorithm)were respectively combined for designing the helical tomography radiotherapy plans.The radiotherapy plans with a pitch of 0.143,0.172,0.215,0.287 or 0.430 were enrolled into an experimental group,and the plans with a pitch of 0.500 were divided into a control group.The dosimetric parameters including maximum dose(Dmax),minimum dose(Dmin)and mean dose(Dmean)of the target area PTV1 and PTV2 were evaluated by the dose volume histogram(DVH).The dose homogeneity index(HI)of the target area was calculated,and the single rotation time and total treatment time of each plan were recorded and counted.SPSS 27.0 software was used for statistical analysis.Results No significant threading effect appeared regardless of the pitch value when the lead gate width was 1.0 cm.The threading effects in the experimental group were weaker than those in the control group when the lead gate width was 2.5 or 5.0 cm.The threading effect gradually rose with the pitch increased when the lead gate width was 5.0 cm.The most significant difference was found between the threading effect in case of the screw pitch being 0.500 and that with the screw pitch being 0.143,with the differenes being statistically obvious(P<0.05).The lead gate width had significant effects on the Dmax,Dmin,Dmean and HI of PTV1 and PTV2.When the lead gate width was 5.0 cm,high HI value and uneven dose distribution were detected and lowered screw pitch weakened the threading effect.The single rotation time first remained constant and then increased with the screw pitch was enlarged,with the changing points occurring in case of the screw pitches of 0.287 and 0.430.With a certain lead gate width,the treatment time for plans was shortened with the decrease of the pitches in case of the pritches lower than 0.287,and tended to be constant after the screw pitches reached 0.287.The changes of the computational grid had no significant effects on the results of radiotherapy plans when the lead gate width and screw pitch were kept constant.Conclusion When designing a spiral tomotherapy plan with conventional doses,a lead gate width of 1.0 or 2.5 cm and a screw pitch of 0.287 or 0.430 should be selected in order to minimize the threading effect while ensuring the efficiency of plan implementation.[Chinese Medical Equipment Journal,2025,46(8):58-66]

Objective To investigate the influence of helical tomographic radiotherapy plans with different combinations of lead gate width,pitch and algorithms on threading effects.Methods A target model was established with a Cheese Phantom used as the simulated human body,then three lead gate widths(1.0,2.5,and 5.0 cm),six screw pitches(0.143,0.172,0.215,0.287,0.430,and 0.500)and two computational grids(Fine algorithm and Normal algorithm)were respectively combined for designing the helical tomography radiotherapy plans.The radiotherapy plans with a pitch of 0.143,0.172,0.215,0.287 or 0.430 were enrolled into an experimental group,and the plans with a pitch of 0.500 were divided into a control group.The dosimetric parameters including maximum dose(Dmax),minimum dose(Dmin)and mean dose(Dmean)of the target area PTV1 and PTV2 were evaluated by the dose volume histogram(DVH).The dose homogeneity index(HI)of the target area was calculated,and the single rotation time and total treatment time of each plan were recorded and counted.SPSS 27.0 software was used for statistical analysis.Results No significant threading effect appeared regardless of the pitch value when the lead gate width was 1.0 cm.The threading effects in the experimental group were weaker than those in the control group when the lead gate width was 2.5 or 5.0 cm.The threading effect gradually rose with the pitch increased when the lead gate width was 5.0 cm.The most significant difference was found between the threading effect in case of the screw pitch being 0.500 and that with the screw pitch being 0.143,with the differenes being statistically obvious(P<0.05).The lead gate width had significant effects on the Dmax,Dmin,Dmean and HI of PTV1 and PTV2.When the lead gate width was 5.0 cm,high HI value and uneven dose distribution were detected and lowered screw pitch weakened the threading effect.The single rotation time first remained constant and then increased with the screw pitch was enlarged,with the changing points occurring in case of the screw pitches of 0.287 and 0.430.With a certain lead gate width,the treatment time for plans was shortened with the decrease of the pitches in case of the pritches lower than 0.287,and tended to be constant after the screw pitches reached 0.287.The changes of the computational grid had no significant effects on the results of radiotherapy plans when the lead gate width and screw pitch were kept constant.Conclusion When designing a spiral tomotherapy plan with conventional doses,a lead gate width of 1.0 or 2.5 cm and a screw pitch of 0.287 or 0.430 should be selected in order to minimize the threading effect while ensuring the efficiency of plan implementation.[Chinese Medical Equipment Journal,2025,46(8):58-66]

Objective:To investigate the impact of blood pressure outcomes on the risk of arteriosclerosis in non-hypertensive populations.Methods:This study was a retrospective cohort study. All data were derived from Kailuan Cohort. Non-hypertensive individuals who completed two brachial-ankle pulse wave velocity (baPWV) measurements between January 2014 and December 2019 (using the first measurement as the baseline and the second as the follow-up) were enrolled, and clinical data such as blood pressure and baPWV were collected. According to the blood pressure level at baseline and follow-up, participants were divided into new-onset hypertension group (no hypertension at baseline but diagnosed at follow-up) and non-hypertension group (no hypertension at both baseline and follow-up). Multiple linear regression and multivariate logistic regression were used to analyze the impact of new-onset hypertension on arteriosclerosis progression. Subgroup analysis further classified participants into six blood pressure transition categories: normal-maintained, normal-to-high-normal, normal-to-hypertensive, high-normal-to-normal, high-normal-maintained, and high-normal-to-hypertensive groups. Multivariate logistic regression analysis was used to assess the impact of different blood pressure outcomes on arteriosclerosis progression.Results:A total of 7 049 participants were enrolled, with the age of (40.45±9.04) years, including 3 645 males (51.71%). There were 800 cases in the new-onset hypertension group and 6 249 individuals in the non-hypertension group. During follow-up, arteriosclerosis occurred in 2 154 cases (30.56%). Multivariable linear regression analysis revealed a positive correlation between new-onset hypertension and baPWV levels. The baPWV in the new-onset hypertension group was significantly higher by 63.94 cm/s compared to the non-hypertension group ( β=63.94, P<0.01). Additionally, the risk of arteriosclerosis in the new-onset hypertension group was 2.09 times that of the non-hypertension group ( OR=2.09, 95% CI: 1.77-2.46, P<0.01). Subgroup analysis revealed significantly higher arteriosclerosis risks in normal-to-high-normal ( OR=1.65, 95% CI 1.38-1.98, P<0.01), normal-to-hypertensive ( OR=2.47, 95% CI 1.70-3.59, P<0.01), high-normal-maintained ( OR=1.50, 95% CI 1.21-1.86, P<0.01), and high-normal-to-hypertensive groups ( OR=2.86, 95% CI 2.20-3.73, P<0.01) than normal-maintained group, except for a non-significant difference in high-normal-to-normal group ( OR=0.95, 95% CI 0.74-1.20, P>0.05). Conclusion:Blood pressure outcome in non-hypertensive populations is closely related to arteriosclerosis risk. Progression to or maintenance of high-normal blood pressure or higher levels substantially increases arteriosclerosis risk, while regression from high-normal to normal blood pressure shows no significant increase in arteriosclerosis risk.

Objective To retrospectively analyze the association between metabolic factors and high-risk colorectal adenoma(CRA).Methods The medical records of patients aged 18-75 years who underwent their initial colonoscopy at Karamay Central Hospital of Xinjiang Uygur Autonomous Region from Jul 2000 to Mar 2017 were collected.The comparison between normal colonoscopy(NC)and high-risk CRA patients was conducted using an unpaired t-test,while chi-square test was used for categorical variables.Least absolute shrinkage and selection operator(LASSO)regression and Logistic regression were utilized to analyze the association between metabolic factors and high-risk CRA.Results A total of 1 798 patients meeting the inclusion and exclusion criteria were enrolled and divided into normal colonoscopy(NC)findings group(n=972)and high-risk CRA group(n=826).The high-risk CRA group exhibited significantly lower levels of high-density lipoprotein cholesterol(HDL-C)in comparison to the NC group,while uric acid and fibrosis 4(FIB-4)index levels were significantly higher than those observed in the NC group(all P<0.05).Based on LASSO regression analysis,we identified 12 variables that potentially influence the occurrence of high-risk CRA,including age,gender,smoking history,alcohol consumption history,non-alcoholic fatty liver disease(NAFLD),hypertension,coronary artery disease,hyperglycemia,hypercholesterolemia,low levels of HDL-C,elevated alanine aminotransferase,and elevated gamma-glutamyl transferase.Multivariate analysis revealed that individuals aged over 50 years,male gender,cigarette and alcohol consumption,low HDL-C levels,history of NAFLD and hypertension were identified as independent risk factors associated with high-risk CRA(P<0.05).In addition,without or with adjusting for age,sex,smoking,and drinking history,patients with a high TG/HDL-C ratio(the ratio≥2.68)had a significantly higher risk of high-risk CRA than those with a low TG/HDL-C ratio(the ratio<2.68)[odds ratios(ORs)were1.430 and 1.235 respectively,all P<0.05)].Without or with adjusting variables,the ORs for NAFLD patients with FIB-4 index>2.67 were 1.849(P=0.466)and 1.435(P=0.707),respectively.Conclusion A significant association exists between metabolic factors and high-risk CRA.Independent risk factors for high-risk CRA include older age(≥50 years),male,smoking history,alcohol consumption history,low levels of HDL-C,and a history of NAFLD and hypertension.Individuals exhibiting a TG/HDL-C ratio exceeding 2.68 manifest a significantly heightened susceptibility to the development of high-risk CRA.Therefore,elderly males with one or more aforementioned metabolic abnormalities should be considered a priority population for colorectal screening.