[摘 要] 目的：探讨高良姜素（Gal）调控AMPK/mTOR/ULK1信号通路对胃癌细胞凋亡和自噬的影响及其机制。方法：将胃癌NCI-N87细胞分为对照组、多索吗啡（DM）组、Gal低剂量（Gal-L）组、Gal高剂量（Gal-H）组、Gal-H + DM组。采用MTT法、流式细胞术、划痕愈合实验和Transwell实验分别检测各组细胞的增殖、凋亡、迁移和侵袭能力，WB法检测PCNA、C-caspase-3、免疫逃逸相关蛋白（B7H1）、EMT和AMPK/mTOR/ULK1信号通路蛋白的表达水平。建立裸鼠NCI-N87细胞移植瘤模型，观察Gal和5-FU对移植瘤的抑制效果。结果：与对照组比较，DM组NCI-N87细胞增殖活性、划痕愈合率和侵袭细胞数、N-cadherin、vimentin、PCNA、B7H1、p62和p-mTOR/mTOR蛋白表达均显著升高（均P < 0.05），细胞凋亡率、C-caspase-3、E-cadherin、LC3Ⅱ/LC3Ⅰ、p-AMPK/AMPK和p-ULK1/ULK1蛋白表达均显著降低（均P < 0.05）；Gal-L组和Gal-H组NCI-N87细胞的增殖活性、划痕愈合率和侵袭细胞数、N-cadherin、vimentin、PCNA、B7H1、p62和p-mTOR/mTOR蛋白表达均显著降低（均P < 0.05），细胞凋亡率、C-caspase-3、E-cadherin、LC3Ⅱ/LC3Ⅰ、p-AMPK/AMPK和p-ULK1/ULK1蛋白表达均显著升高（均P < 0.05）；DM可部分逆转Gal对NCI-N87细胞恶性生物学行为的抑制作用（P < 0.05）；与对照组比较，Gal组和5-FU组裸鼠移植瘤体积和质量均显著降低，肿瘤组织细胞凋亡率显著升高（P < 0.05）。结论：Gal可促进胃癌NCI-N87细胞自噬和凋亡，抑制其增殖、迁移和侵袭，可能与激活AMPK/mTOR/ULK1信号通路有关。

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.

Objective: To investigate the clinical characteristics, the types of unexpected antibodies, and their impacts on immunological risks among patients with different frequencies of cross-matching incompatibility, so as to propose corresponding solutions. Methods: Data of cross-matching incompatibility samples from 92 medical institutions during 2022 to 2024 were collected and divided into three groups based on the frequency of cross-matching. Statistical analysis was performed on disease types, distribution of hematologic diseases, alloantibody detection rates, and proportions of alloantibody types. Results: The 858 patients were divided into three groups based on the frequency of blood cross-matching incompatibility: ≥5 times (8.28%, 71/858), 2 to 4 times (28.21%, 242/858); 1 time (63.52%, 545/858). There was a clustered distribution of disease types in the ≥5 cross-matchings group, with 71.83% (51/71) of patients having tumors or hematologic and hematopoietic diseases. In contrast, the disease types in the 2 to 4 cross-matchings and 1 cross-matching groups were more diverse. An analysis of 249 patients with hematologic diseases found that multiple myeloma was the most common disease in all three groups, accounting for 31.43% (11/35), 35.37% (29/82), and 37.88% (50/132) respectively. In the ≥5 cross-matchings group, myelodysplastic syndrome (14.29%, 5/35) and thalassemia (14.29%, 5/35) were the second most common diseases. In contrast, in the 2 to 4 cross-matchings group and 1 cross-matching group, autoimmune hemolytic anemia was the second most common disease, with prevalence rates of 20.73% (17/82) and 24.24% (32/132), respectively. Alloantibodies were detected in 54.66% of the patients, with antibodies against Rh blood group being most frequent (>50%) in all three groups. The detection rates of alloantibodies/alloantibodies with coexisting autoantibodies decreased across groups: the ≥5 cross-matchings group (70.42%, 50/71) > the 2 to 4 cross-matchings group (54.96%, 133/242) > the 1 cross-matching group (52.48%, 286/545). Conclusion: The risk of alloantibody production increases in patients with multiple cross-matching incompatibilities, especially in those with tumors or hematologic diseases. For handling of cross-matching incompatibility cases, it is recommended to optimize the cross-matching process, implement individualized transfusion plans, and enhance the technical capabilities of clinical transfusion departments and blood group reference laboratories to ensure the safety and effectiveness of transfusions.

Mental state is an important part of the normal life activities of the human body, and it is also the most external expression and the most easily obtained information of the physical condition. The normal activities of the mind depend on the normal operation of the viscera, qi, and blood, and are a unified whole that prospers together and suffers together. The theory of the five-spirit-viscera in the Yellow Emperor’s Inner Classic revealed that the normal mental activities of the human body were dominated by the five internal organs, that is, the five internal organs were the body and the five spirits were the function. And it highlighted the viewpoint that the five internal organs store the spirits and are actually one. The heart governs the spirit and belongs to the four internal organs. On this basis, Synopsis of Golden Chamber used the internal organs to diagnose and treat mental diseases, integrating the theory of the five spirits into it, forming a unique method of diagnosis and treatment with the heart as the leading factor and regulating the qi and blood of the four internal organs. It identified the pathogenesis of diseases such as pathogenic crying, lily disease, and hysteria from five levels: heart deficiency and weak qi, heart-lung disharmony, heart-liver disharmony, the heart of the loss of the spleen nourishment, and disharmony between heart and kidney. The treatment was mainly to replenish the deficiency of the viscera and eliminate the pathogens, reflecting the characteristics of regulating the mind and calming the four internal organs. This unique view on diagnosis and treatment has profoundly influenced the diagnosis and treatment theories of mental illnesses by later doctors, and is of great significance to the current clinical treatment of such illnesses.

Objective To analyze the active screening results on bacteria from neonates from different sources in the neonatal ward of a tertiary general hospital in Shanghai,provide a basis for the prevention and control of neo-natal infections.Methods The monitoring results of active screening on all neonates admitted to the neonatal ward of the hospital from 2017 to 2023 were collected retrospectively.Changes in bacterial detection among neonates ad-mitted from the obstetrics department and the community were compared and analyzed.Results From 2017 to 2023,a total of 4 265 neonates were admitted to the hospital,including 3 339 from department of obstetrics(obste-trics source group)and 926 from community(community source group).Active screening showed that 490 and 572 neonates were detected with bacteria,respectively.Bacterial detection rate of neonates in obstetrics source group was lower than community source group(14.68％vs 61.77％,P＜0.001);detection rates of bacteria from pha-rynx and umbilical site of neonates in community source group were both higher than obstetrics source group(both P＜0.001);detection rate of bacteria from neonates'umbilical site was higher than that from pharynx of both ob-stetrics source group and community source group(both P＜0.001).A total of 1 348 bacterial strains were detec-ted,detection rates of Escherichia coli,Staphylococcus epidermidis,Enterococcus faecalis,Streptococcus agalac-tiae,and Acinetobacter baumannii in the obstetrics source group were all higher than community source group(all P＜0.05),detection rates of Staphylococcus aureus and Enterobacter cloacae in the obstetrics source group were both lower than community source group(both P＜0.05).66 neonates were detected multidrug-resistant organism(MDRO),14 were from obstetrics source group and 52 from community source group,63 neonates were detected methicillin-resistant Staphylococcus aureus(MRSA).The detection rates of MDRO and MRSA from community source group were both higher than obstetrics source group(both P＜0.001);detection rate of MDRO from neo-nates'umbilical site was higher than that from the pharynx of the community source group(P＜0.001).Conclusion Bacteria detected in the obstetrics source group is mainly Escherichia coli,while that detected from community source group is mainly Staphylococcus aureus.MRSA is the main MDRO from neonates,and bacterial screening of neonates admitted from the community should be strengthened to prevent and control the spread of MDRO,espe-cially community-acquired MRSA in neonatal wards.

AIM:This study aims to investigate the role of histone methyltransferase SET and MYND domain containing 2(SMYD2)in facilitating renal fibrosis through the macrophage-myofibroblast transition in diabetic kidney dis-ease(DKD).METHODS:(1)C57BL/6J mice were intraperitoneally administered 55 mg/kg of streptozotocin to induce diabetes mellitus(DM).The experimental groups were categorized as follows:normal control,DM(20 weeks),DM(28 weeks),and DM(36 weeks).Blood glucose(BG),serum creatinine(SCr)and blood urea nitrogen(BUN)levels were determined using a biochemical analyzer.Hematoxylin-eosin(HE)staining and Masson staining were performed to assess morphological and fibrotic changes in renal tissues.Western blot analysis was used to measure the protein levels of SMYD2,histone H3 lysine 4 trimethylation(H3K4me3),arginase-1,matrix metalloproteinase 9(MMP9),collagen type Ⅰ(Col Ⅰ)and α-smooth muscle actin(α-SMA).Immunofluorescence staining was conducted to examine the localization and expression of F4/80,α-SMA,SMYD2,CD86,CD206 and CD163.(2)Mouse monocyte/macrophage RAW264.7 cells were cultured in vitro and assigned to groups as follows:normal glucose(NG)+negative control siRNA(siNC),high glucose(HG)+siNC,NG+SMYD2 siRNA(siSMYD2),and HG+siSMYD2.Western blot analysis was used to assess the expression of relevant proteins.RESULTS:(1)Compared with normal control group,the levels of BG,SCr and BUN were significantly elevated in DM(28 weeks)and DM(36 weeks)groups(P＜0.05).Renal tissue exhibited tubular atro-phy,dilation,and collagen fiber deposition.The levels of H3K4me3,arginase-1,MMP9,Col Ⅰ and α-SMA proteins were up-regulated(P＜0.05).The CD86,CD206,CD163 and F4/80 were primarily localized in the interstitial macrophages of the renal tubules,α-SMA was predominantly detected in the renal interstitium,and SMYD2 was mainly expressed in renal tubular epithelial cells and the renal interstitium.(2)Compared with NG+siNC group,the protein levels of SMYD2,H3K4me3,arginase-1,CD163,Col Ⅰ,α-SMA,transforming growth factor-β1(TGF-β1)and p-Smad3 in the cells of HG+siNC group were significantly increased(P＜0.05).Knockdown of SMYD2 resulted in a reduction of these indicators(P＜0.05).CONCLUSION:The SMYD2 protein appears to facilitate renal fibrosis in DKD by promoting the macrophage-myofibroblast transition,potentially through the modulation of TGF-β1/Smad3 signaling pathway.

Objective To explore the current status of penile erection hardness and its influencing factors in patients with non-obstructive azoospermia.Methods From January to December 2024,450 patients with non-obstructive azoospermia were surveyed at the Reproductive Medicine Center of Hospital.A self-made general information questionnaire was used to collect their demographic data.The Erectile Hardness Scale(EHS)was employed to investigate the current status of their penile erection hardness,and a self-made questionnaire was utilized to explore the influencing factors.Results Among the 450 patients with non-obstructive azoospermia,during sexual intercourse,35.3%of the patients reported that their penile erection hardness could reach grade 4(normal state),54.5%reported that it only reached grade 3(sub-optimal state),9.3%reported that it only reached grade 2(slight penile erection),and 0.9%reported that it only reached grade 1(inability to achieve an erection).In the survey of satisfaction with sexual life quality,among the 450 patients,only 24.9%were very satisfied with their sexual life quality;57.3%were basically satisfied;9.6%considered it average;4.0%were dissatisfied;3.1%were very dissatisfied;and 1.1%had no sexual life.alcohol consumption(OR=2.393,95%CI:1.493～3.836),satisfaction with the quality of sexual life(OR=1.455,95%CI:1.118～1.894),educational attainment(OR=0.709,95%CI:0.549～0.917),and the sleep quality in the past month(OR=0.641,95%CI:0.452～0.907).Conclusions Clinical studies have shown that factors such as drinking habits,sexual life satisfaction,sleep quality,and educational attainment collectively influence the penile erection hardness in patients with non-obstructive azoospermia.Therefore,the medical team needs to customize personalized intervention plans and educational materials based on individual differences among patients.Through psychological counseling and lifestyle guidance,they can improve erectile function and the quality of sexual life,promote harmonious marital relationships,and enhance the overall life experience of the patients.

Aim To investigate the effect of p-AMPK activity on autophagy in different subtypes of MDA-MB-231(triple-negative breast cancer cells)and MCF-7(estrogen receptor-positive cells)and its regulatory mechanism.Methods MDA-MB-231 cells were trea-ted with EBSS,Baf-A1,and EBSS+Baf-A1 for four hours,and MCF-7 cells for eight hours.The effects of autophagy on cell proliferation and apoptosis were ob-served,mitochondrial morphology was examined,and the expression of autophagy markers LC3B,P62,LAMP1,TOM20,AMPK,p-AMPK,ULK1,and Bec-lin1/VPS34 proteins was detected.The autophagy pathway was validated by inhibiting AMPK activity.Results Breast cancer cells underwent autophagy af-ter starvation induction(EBSS),with inconsistent au-tophagy processes observed in different subtypes of breast cancer cells.Autophagy inhibited cell prolifera-tion.In MDA-MB-231 cells,autophagy led to an in-crease in p-AMPK levels and a decrease in ULK1 lev-els,initiating autophagy through p-AMPK activation of ULK1.In MCF-7 cells,both p-AMPK and ULK1 levels decreased after autophagy,suggesting that autophagy might not be mediated by p-AMPK activation.Conclu-sions MDA-MB-231 cells primarily initiate autophagy by directly activating ULK1 by p-AMPK,independent of the MTOR pathway.In MCF-7 cells autophagy might be triggered by inhibiting MTOR through AMPK activity or directly activating MTOR through other up-stream factors.Regulating p-AMPK activity based on the autophagy pathways in different cell subtypes could enable more precise targeting and treatment of different types of breast cancer.

Objective:To conduct a scoping review of risk prediction models for the development of intraoperative hypothermia in patients undergoing cancer surgery to inform clinical nursing practice and future research.Methods:Relevant literature on constructing or validating intraoperative hypothermia risk prediction models for cancer surgery patients in five foreign language databases (PubMed, Embase, Web of Science, Cochrane Library, CINAHL) and four Chinese language databases (China National Knowledge Infrastructure, Wanfang, VIP, Chinese Biomedical Database) were searched from the time of library construction to June 1, 2024, extracted information on the applicable target, incidence of intraoperative hypothermia, methodology of model construction, predictors and performance, etc. The Prediction model Risk Of Bias Assessment Tool was used to evaluate the risk of bias of the studies, and the included literature was analyzed and discussed.Results:A total of 15 pieces of literature involving 18 models were included, with the study population focussing on patients undergoing surgery for colorectal cancer. The rate of intraoperative hypothermia ranged from 15.14% to 61.5%. Model construction methods included 2 types of Logistic regression models and machine learning, and model presentation was based on column-line plots. There were 8 predictors that appeared with a frequency of ≥5, including age, body mass index, operation time, anaesthesia time, operating room temperature, intraoperative rehydration volume, intraoperative bleeding volume, and heat preservation method.Conclusions:The performance of the included model was good, but the risk of bias was high for the predictors and the analysis part, and nursing staff should pay close attention to the risk factors of intraoperative hypothermia in patients undergoing cancer surgery, construct a risk prediction model with low bias and high applicability, and validate and improve the existing risk prediction model.