It has been 131 years since Halsted reported radical mastectomy to treat breast cancer in 1894. The concept of “R0 resection” as the most important treatment strategy has significantly contributed to improving the survival rate of patients with breast cancer. With deep understanding of the mechanism of tumorigenesis and advancements in systematic treatment since the 20th century,modified radical mastectomy proposed by Patey and Auchincloss,aimed to improve quality of life,replaced radical mastectomy and became the mainstream surgery for breast cancer. Based on NSABP-B06 trial,the 2025 St. Gallen consensus persisted in the principle of preserving breast-conserving surgery whenever possible. Additionally,the guidelines recommend axillary lymph node dissection can be omitted in patients with negative sentinel lymph nodes,supported by high-level evidence. The AJCC Cancer Staging System (8th Edition) showed the evaluation of breast cancer burden has transcended TNM stage,leading to the level of detecting microscopic tumor burden. Pathological test is no longer limited to pathomorphology, instead,immunohistochemistry,molecular pathology testing,and next-generation sequencing technologies have laid a scientific foundation for categorized treatment of breast cancer. The evolution of breast cancer surgery is undergoing a shift from “maximal resection” to “minimal effective treatment” de-escalation. On this basis,promoting the standardization and homogenization of breast surgery suited to China′s national conditions is the common goal of breast surgeons at this stage.

BACKGROUND:Living microecological hydrogels are a hot topic in the field of wound dressing and have received widespread attention.OBJECTIVE:To summarize the basic features and advantages of living microecological hydrogels,review the progress in the application of hydrogels loaded with different living organisms in skin wound repair in recent years.METHODS:The articles published from database inception to 2024 were retrieved from Web of Science,PubMed,CNKI,and WanFang databases with"cell,probiotics,phage,chlorella,algae,living microecological,hydrogel,skin,wound healing,wound repair"as search terms in English and Chinese.The articles for inclusion were screened according to the inclusion and exclusion criteria.Finally,108 articles were included for review.RESULTS AND CONCLUSION:The living microecological hydrogels have good biocompatibility,and the hydrogel can provide a suitable living environment for the loaded organisms,and play a barrier role between the living organisms and the wound to avoid potential threats.Compared with traditional wound dressings,the effect of living microecological hydrogels is sustainable and renewable.Biological regulation can keep the microenvironment at the wound site relatively stable,which can provide suitable conditions for wound healing for a long time and reduce the additional trauma caused by frequent dressing changes.Compared with the direct use of living organisms to promote wound healing,living microecological hydrogels can improve the survival rate of organisms and ensure their biological regulation.Living microecological hydrogels promote wound healing mainly by regulating the"inflammation"and"proliferation"stages in the wound healing process.The existing living microecological hydrogels mainly load organisms such as cells,probiotics,algae,and phages,which give hydrogels with different biological properties,so that they can promote wound healing by releasing substances required for wound healing or improving the wound environment,and have great application potential.To further expand the actual clinical application of living microecological hydrogels,it is necessary to further control the biosafety risks of active organisms in hydrogels in the future,avoid potential biological threats,and research the hydrogel matrix that can better adapt to the complex changes of human skin wounds and can support living organisms.

BACKGROUND:3D-printed bone tissue engineering scaffolds have obvious advantages in the research and clinical treatment of bone defect repair.As one of the important raw materials for 3D printed bone scaffolds,poly-L-lactic acid has a great potential for application in performing bone defect repair,but clinical patients with different bone defect causative factors have different requirements for the comprehensive performance of poly-L-lactic acid bone scaffolds.OBJECTIVE:To summarize and review the development of 3D printing technology and poly-L-lactic acid scaffolds and the design strategies chosen for scaffolds for bone repair in the setting of bone diseases such as osteomyelitis,bone tumor,osteonecrosis,and osteoporosis.METHODS:Literature from CNKI,WanFang,PubMed,Science Direct,and Web of Science databases were searched and screened from 1994 to 2024.Search terms were"3D printing,polylactic acid,bone tissue engineering scaffold,osteomyelitis,bone tumor,osteonecrosis,osteoporosis,bone defect"in Chinese and English.The screened 62 articles were systematically summarized and analyzed.RESULTS AND CONCLUSION:(1)Poly-L-lactic acid is considered to be an ideal raw material for artificial bone scaffold design due to its non-toxicity,processability,biocompatibility,and ability to self-degrade in the human environment.The application of 3D printing technology has enabled poly-L-lactic acid bone scaffolds to meet the multilayered and porous structural design requirements of biomimetic artificial bone repair materials,and to optimize the mechanical properties for better bone repair.(2)According to different bone disease microenvironments,timely adjustment of the functional design of poly-L-lactic acid scaffolds is important for the comprehensive osteogenic efficacy of the scaffolds.The article discusses the application of poly-L-lactic acid scaffolds in bone disease environments such as osteomyelitis,bone tumor,osteonecrosis,and osteoporosis,and highlights the importance of rationally grasping the timing of bone disease treatment and bone tissue regeneration for bone defects caused by different bone diseases.(3)Although poly-L-lactic acid scaffolds show potential in bone repair,there are still some problems,such as the need to further optimize the structural design of the scaffolds to fit new bone regeneration,enhance the bioactivity of the scaffolds,and take into account other functions(e.g.,antimicrobial,anti-tumor,and anti-osteoporosis)in order to adapt to the needs of bone tissue repair in different pathological environments.

BACKGROUND:Age-related macular degeneration and deep vein thrombosis may share common pathophysiological mechanisms,but there is a lack of direct evidence regarding their relationship.Traditional studies are confounded by confounding factors and reverse causation.OBJECTIVE:To investigate the causal relationship between age-related macular degeneration and deep vein thrombosis based on Mendelian randomization design.METHODS:Through a two-way Mendelian randomization analysis,single nucleotide polymorphisms of exposure and outcomes were obtained from publicly available genome-wide association studies,with deep vein thrombosis data from the FinnGen database in a European population with a sample size of 363 612 and 1 048 575 single nucleotide polymorphisms.In addition,we obtained data on age-related macular degeneration from the IEUOpenGWAS project,also from a European population sample of 105 248 cases covering 11 304 110 single nucleotide polymorphisms.In R4.4.1,we used the TwoSampleMR package(version 0.6.8)to explore the causal effects of exposure factors on outcomes.At the same time,we also conducted a sensitivity analysis via MR-Egger regression,weighted median,weighted model and simple model methods to ensure that the assessment results were robust and reliable.In addition,we used the"heterogeneity"function to test for heterogeneity,and the"horizontal pleiotropy"function and the MR-PRESSO test to further assess horizontal pleotropy.The Cochran's Q test was used to determine whether there was statistical heterogeneity between single nucleotide polymorphisms,and the leave-one-out method was used to assess whether single nucleotide polymorphisms would significantly interfere with Mendelian randomization analysis.Funnel plots were drawn to assess the potential bias of single nucleotide polymorphisms.Forest plots were plotted to show the effect estimates of single nucleotide polymorphisms on exposure and outcomes,and their confidence intervals were plotted.Scatter plots were plotted to evaluate the relationship between the potency of single nucleotide polymorphisms and their causal effect size on outcome estimates.RESULTS AND CONCLUSION:Both forward and reverse studies showed that there was no causal association between age-related macular degeneration and the occurrence of deep vein thrombosis(P＞0.05).Sensitivity analysis showed that the main analysis results were reliable and robust,with no outliers,heterogeneity,and horizontal pleiotropy,and no single nucleotide polymorphism significantly affected the overall effect estimate.Although it is based on European population data,it has methodological reference value for Chinese biomedical research on complex disease associations.In this field,China can carry out multi-center large-sample studies,accurately analyze the internal links between Chinese population-related diseases,and provide a basis for prevention and treatment strategies and clinical practice.

BACKGROUND:Living microecological hydrogels are a hot topic in the field of wound dressing and have received widespread attention.OBJECTIVE:To summarize the basic features and advantages of living microecological hydrogels,review the progress in the application of hydrogels loaded with different living organisms in skin wound repair in recent years.METHODS:The articles published from database inception to 2024 were retrieved from Web of Science,PubMed,CNKI,and WanFang databases with"cell,probiotics,phage,chlorella,algae,living microecological,hydrogel,skin,wound healing,wound repair"as search terms in English and Chinese.The articles for inclusion were screened according to the inclusion and exclusion criteria.Finally,108 articles were included for review.RESULTS AND CONCLUSION:The living microecological hydrogels have good biocompatibility,and the hydrogel can provide a suitable living environment for the loaded organisms,and play a barrier role between the living organisms and the wound to avoid potential threats.Compared with traditional wound dressings,the effect of living microecological hydrogels is sustainable and renewable.Biological regulation can keep the microenvironment at the wound site relatively stable,which can provide suitable conditions for wound healing for a long time and reduce the additional trauma caused by frequent dressing changes.Compared with the direct use of living organisms to promote wound healing,living microecological hydrogels can improve the survival rate of organisms and ensure their biological regulation.Living microecological hydrogels promote wound healing mainly by regulating the"inflammation"and"proliferation"stages in the wound healing process.The existing living microecological hydrogels mainly load organisms such as cells,probiotics,algae,and phages,which give hydrogels with different biological properties,so that they can promote wound healing by releasing substances required for wound healing or improving the wound environment,and have great application potential.To further expand the actual clinical application of living microecological hydrogels,it is necessary to further control the biosafety risks of active organisms in hydrogels in the future,avoid potential biological threats,and research the hydrogel matrix that can better adapt to the complex changes of human skin wounds and can support living organisms.

BACKGROUND:3D-printed bone tissue engineering scaffolds have obvious advantages in the research and clinical treatment of bone defect repair.As one of the important raw materials for 3D printed bone scaffolds,poly-L-lactic acid has a great potential for application in performing bone defect repair,but clinical patients with different bone defect causative factors have different requirements for the comprehensive performance of poly-L-lactic acid bone scaffolds.OBJECTIVE:To summarize and review the development of 3D printing technology and poly-L-lactic acid scaffolds and the design strategies chosen for scaffolds for bone repair in the setting of bone diseases such as osteomyelitis,bone tumor,osteonecrosis,and osteoporosis.METHODS:Literature from CNKI,WanFang,PubMed,Science Direct,and Web of Science databases were searched and screened from 1994 to 2024.Search terms were"3D printing,polylactic acid,bone tissue engineering scaffold,osteomyelitis,bone tumor,osteonecrosis,osteoporosis,bone defect"in Chinese and English.The screened 62 articles were systematically summarized and analyzed.RESULTS AND CONCLUSION:(1)Poly-L-lactic acid is considered to be an ideal raw material for artificial bone scaffold design due to its non-toxicity,processability,biocompatibility,and ability to self-degrade in the human environment.The application of 3D printing technology has enabled poly-L-lactic acid bone scaffolds to meet the multilayered and porous structural design requirements of biomimetic artificial bone repair materials,and to optimize the mechanical properties for better bone repair.(2)According to different bone disease microenvironments,timely adjustment of the functional design of poly-L-lactic acid scaffolds is important for the comprehensive osteogenic efficacy of the scaffolds.The article discusses the application of poly-L-lactic acid scaffolds in bone disease environments such as osteomyelitis,bone tumor,osteonecrosis,and osteoporosis,and highlights the importance of rationally grasping the timing of bone disease treatment and bone tissue regeneration for bone defects caused by different bone diseases.(3)Although poly-L-lactic acid scaffolds show potential in bone repair,there are still some problems,such as the need to further optimize the structural design of the scaffolds to fit new bone regeneration,enhance the bioactivity of the scaffolds,and take into account other functions(e.g.,antimicrobial,anti-tumor,and anti-osteoporosis)in order to adapt to the needs of bone tissue repair in different pathological environments.

BACKGROUND:Age-related macular degeneration and deep vein thrombosis may share common pathophysiological mechanisms,but there is a lack of direct evidence regarding their relationship.Traditional studies are confounded by confounding factors and reverse causation.OBJECTIVE:To investigate the causal relationship between age-related macular degeneration and deep vein thrombosis based on Mendelian randomization design.METHODS:Through a two-way Mendelian randomization analysis,single nucleotide polymorphisms of exposure and outcomes were obtained from publicly available genome-wide association studies,with deep vein thrombosis data from the FinnGen database in a European population with a sample size of 363 612 and 1 048 575 single nucleotide polymorphisms.In addition,we obtained data on age-related macular degeneration from the IEUOpenGWAS project,also from a European population sample of 105 248 cases covering 11 304 110 single nucleotide polymorphisms.In R4.4.1,we used the TwoSampleMR package(version 0.6.8)to explore the causal effects of exposure factors on outcomes.At the same time,we also conducted a sensitivity analysis via MR-Egger regression,weighted median,weighted model and simple model methods to ensure that the assessment results were robust and reliable.In addition,we used the"heterogeneity"function to test for heterogeneity,and the"horizontal pleiotropy"function and the MR-PRESSO test to further assess horizontal pleotropy.The Cochran's Q test was used to determine whether there was statistical heterogeneity between single nucleotide polymorphisms,and the leave-one-out method was used to assess whether single nucleotide polymorphisms would significantly interfere with Mendelian randomization analysis.Funnel plots were drawn to assess the potential bias of single nucleotide polymorphisms.Forest plots were plotted to show the effect estimates of single nucleotide polymorphisms on exposure and outcomes,and their confidence intervals were plotted.Scatter plots were plotted to evaluate the relationship between the potency of single nucleotide polymorphisms and their causal effect size on outcome estimates.RESULTS AND CONCLUSION:Both forward and reverse studies showed that there was no causal association between age-related macular degeneration and the occurrence of deep vein thrombosis(P＞0.05).Sensitivity analysis showed that the main analysis results were reliable and robust,with no outliers,heterogeneity,and horizontal pleiotropy,and no single nucleotide polymorphism significantly affected the overall effect estimate.Although it is based on European population data,it has methodological reference value for Chinese biomedical research on complex disease associations.In this field,China can carry out multi-center large-sample studies,accurately analyze the internal links between Chinese population-related diseases,and provide a basis for prevention and treatment strategies and clinical practice.

ObjectiveTo explore the effects of Yimei Baijiang formula （YMBJF） on colitis-associated colorectal cancer （CAC） and the nuclear factor kappaB （NF-κB） signaling pathway in mice. MethodsSixty male Balb/c mice of 4-6 weeks old were randomized into 6 groups： Normal， model， capecitabine （0.83 g·kg^-1）， and low-， medium-， and high-dose （4.63， 9.25， 18.50 g·kg^-1， respectively） YMBJF. The mouse model of CAC was established by combining azoxymethane （AOM， 10 mg·kg^-1） and dextran sulfate sodium （DSS， 2%）. At the 5^th week after the start of modeling， the capecitabine group and the YMBJF groups were respectively administrated with the corresponding doses of drugs by gavage once a day for a total of 6 weeks. The body weights and general conditions of mice were measured and observed， and the disease activity index （DAI） was scored. The tumors in the colorectal tissue were counted， and the colorectal length was measured. The histological features of the colorectal tissue in each group of mice were observed by hematoxylin-eosin （HE） staining. The levels of inflammatory cytokines including interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the serum were determined by enzyme-linked immunosorbent assay （ELISA）. The expression and localization of proliferating cell nuclear antigen-67 （Ki67）， proliferating cell nuclear antigen （PCNA）， and phosphorylated nuclear transcription factor-κB p65 （p-NF-κB p65） proteins were observed by immunohistochemistry （IHC）. The apoptosis of tumor cells was observed by the TUNEL assay. The mRNA levels of IL-6，IL-1β， TNF-α， nuclear transcription factor-κB p65 （NF-κB p65）， NF-κB inhibitor alpha （IκBα）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the colorectal tissue were quantified by Real-time polymerase chain reaction（Real-time PCR）. The protein levels of NF-κB p65， phosphorylated （p）-NF-κB p65， IκBα， p-IκBα， Bcl-2， and Bax in the colorectal tissue were determined by Western blot. ResultsCompared with the model group， each YMBJF group showed decreases in DAI and tumor number （P0.01）， and the medium-dose and high-dose YMBJF groups showed increases in colorectal length （P0.05）. In addition， each YMBJF group showed alleviated colorectal mucosal pathological injury， declined levels of IL-6， IL-1β， and TNF-α in the serum （P0.05）， reduced expression of Ki67 and PCNA （P0.01）， and down-regulated expression of p-NF-κB p65 （P0.05）. The apoptosis in the medium-dose and high-dose YMBJF groups increased （P0.01）. Each YMBJF group and the capecitabine group showed down-regulated mRNA levels of IL-1β， TNF-α， IL-6， NF-κB p65， and Bcl-2 （P0.05） and up-regulated mRNA levels of IκBα and Bax （P0.05）. The mRNA level of IκBα was up-regulated， and that of Bcl-2 was down-regulated （P0.05） in the high-dose YMBJF group. The protein levels of p-IκBα and Bcl-2 were down-regulated （P0.05） in each YMBJF group. The protein levels of IκBα and Bax were up-regulated in the medium-dose and high-dose YMBJF groups （P0.01）， while those of NF-κB p65 and p-NF-κB p65 were down-regulated （P0.05）. ConclusionYMBJF can reduce the number of tumors， reduce the levels of inflammatory factors， promote tumor cell apoptosis， and inhibit tumor cell proliferation by regulating the direct effector molecules of the NF-κB signaling pathway in the mouse model of CRC.

Chronic obstructive pulmonary disease （COPD） is a chronic respiratory disease that poses a significant threat to global health， exhibiting high morbidity， disability and mortality rate， with its prevention and treatment situation becoming increasingly critical. The pathogenesis of COPD is complex， and the underlying cellular and molecular biological mechanisms remain incompletely elucidated. Programmed cell death （PCD） is the process wherein cells actively undergo demise to maintain internal environmental stability in response to certain signals or specific stimuli. Contemporary medical research indicates that the dysregulation of PCD patterns such as apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis is closely related to the onset and progression of COPD. Clarifying the molecular mechanisms of PCD in COPD may provide novel perspectives for in-depth understanding and prevention of the disease. Traditional Chinese medicine （TCM） is characterized by holistic regulation. In recent years， extensive research has been conducted in the TCM field focusing on modulating apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis for the treatment of COPD， yielding remarkable achievements. Therefore， this study systematically explored the molecular mechanism of PCD in COPD and reviewed the potential mechanisms and intervention status of TCM targeting PCD in COPD， aiming to provide insights and references for the clinical prevention， treatment and in-depth research of COPD.

ObjectiveTo explore the effects of Yimei Baijiang formula （YMBJF） on colitis-associated colorectal cancer （CAC） and the nuclear factor kappaB （NF-κB） signaling pathway in mice. MethodsSixty male Balb/c mice of 4-6 weeks old were randomized into 6 groups： Normal， model， capecitabine （0.83 g·kg^-1）， and low-， medium-， and high-dose （4.63， 9.25， 18.50 g·kg^-1， respectively） YMBJF. The mouse model of CAC was established by combining azoxymethane （AOM， 10 mg·kg^-1） and dextran sulfate sodium （DSS， 2%）. At the 5^th week after the start of modeling， the capecitabine group and the YMBJF groups were respectively administrated with the corresponding doses of drugs by gavage once a day for a total of 6 weeks. The body weights and general conditions of mice were measured and observed， and the disease activity index （DAI） was scored. The tumors in the colorectal tissue were counted， and the colorectal length was measured. The histological features of the colorectal tissue in each group of mice were observed by hematoxylin-eosin （HE） staining. The levels of inflammatory cytokines including interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the serum were determined by enzyme-linked immunosorbent assay （ELISA）. The expression and localization of proliferating cell nuclear antigen-67 （Ki67）， proliferating cell nuclear antigen （PCNA）， and phosphorylated nuclear transcription factor-κB p65 （p-NF-κB p65） proteins were observed by immunohistochemistry （IHC）. The apoptosis of tumor cells was observed by the TUNEL assay. The mRNA levels of IL-6，IL-1β， TNF-α， nuclear transcription factor-κB p65 （NF-κB p65）， NF-κB inhibitor alpha （IκBα）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the colorectal tissue were quantified by Real-time polymerase chain reaction（Real-time PCR）. The protein levels of NF-κB p65， phosphorylated （p）-NF-κB p65， IκBα， p-IκBα， Bcl-2， and Bax in the colorectal tissue were determined by Western blot. ResultsCompared with the model group， each YMBJF group showed decreases in DAI and tumor number （P0.01）， and the medium-dose and high-dose YMBJF groups showed increases in colorectal length （P0.05）. In addition， each YMBJF group showed alleviated colorectal mucosal pathological injury， declined levels of IL-6， IL-1β， and TNF-α in the serum （P0.05）， reduced expression of Ki67 and PCNA （P0.01）， and down-regulated expression of p-NF-κB p65 （P0.05）. The apoptosis in the medium-dose and high-dose YMBJF groups increased （P0.01）. Each YMBJF group and the capecitabine group showed down-regulated mRNA levels of IL-1β， TNF-α， IL-6， NF-κB p65， and Bcl-2 （P0.05） and up-regulated mRNA levels of IκBα and Bax （P0.05）. The mRNA level of IκBα was up-regulated， and that of Bcl-2 was down-regulated （P0.05） in the high-dose YMBJF group. The protein levels of p-IκBα and Bcl-2 were down-regulated （P0.05） in each YMBJF group. The protein levels of IκBα and Bax were up-regulated in the medium-dose and high-dose YMBJF groups （P0.01）， while those of NF-κB p65 and p-NF-κB p65 were down-regulated （P0.05）. ConclusionYMBJF can reduce the number of tumors， reduce the levels of inflammatory factors， promote tumor cell apoptosis， and inhibit tumor cell proliferation by regulating the direct effector molecules of the NF-κB signaling pathway in the mouse model of CRC.