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.

Polycystic ovary syndrome(PCOS)is a complex disease that significantly impacts women's reproductive and metabolic health.The reprogramming of glucose metabolism points to fundamental changes in energy metabolism,which are central to the imbalance in energy metabolism,hormonal abnormalities,increasing insulin resistance,and chronic inflammatory states observed in PCOS.This represents a core pathological link in the pathogenesis of PCOS.The theory of"Spleen Qi to Dispersing Essence"provides a comprehensive overview of spleen function,essential for ensuring the normal operation of organs and the distribution of Qi,blood,and bodily fluids.It serves as a crucial theoretical support for the treatment of PCOS with traditional Chinese medicine.This article explores the role of regulating PCOS based on the theory of"Spleen Qi to Dispersing Essence"with a focus on the reprogramming of glucose metabolism.The mechanism of traditional Chinese medicinal treatments that assist Spleen Qi to Dispersing Essence is closely related to regulating glucose metabolism reprogramming,offering a novel research direction for the treatment of PCOS with TCM.

Objective:To explore the clinical effect on the treatment of radiation induced deep ulcers in the inguinal region with ipsilateral anterolateral thigh chimeric perforator flap.Methods:From March 2020 to March 2024, retrospective analysis of 8 patients with radiation induced deep ulcers in the inguinal region were treated with ipsilateral anterolateral thigh chimeric perforator flap in the Medical Centre of Burn Plastic and Wound Repair, the First Affiliated Hospital of Nanchang University. All ulcers induced by radiation were caused by postoperative radiotherapy in the inguinal region, of which 4 were of vulvar or penile cancer, 2 of urinary tract tumour, 1 of inguinal protuberant dermatofibrosarcoma and 1 of myofibroblastic sarcoma in lower abdominal wall. The course of the radiation induced ulcer was 0.5-11.0 years, with an average of 2.9 years. The sizes of the ulcerative wound were 2.5 cm × 3.0 cm - 5.5 cm × 7.5 cm. Preoperative biopsies of the tissues around wound and pelvic CT scans were performed to preliminarily exclude a tumour recurrence or an ulcerative malignancy, as well as to confirm the depth of radiation ulcer. The wound size after debridement was 4.5 cm × 6.0 cm-13.5 cm × 19.0 cm, with a depth of 2.0-4.0 cm. An ipsilateral anterolateral thigh chimeric perforator flap was transferred to reconstruct the wound, after the wound edges were cleared from tumour through intraoperative frozen section examinations. The flaps were 5.5 cm × 7.0 cm - 14.0 cm × 20.0 cm in size, with the volumes of muscle flap at 7.0 cm × 4.0 cm × 3.0 cm - 14.0 cm × 7.0 cm × 3.0 cm. After having the deep defect at the base of wound filled with a muscle flap, the wound surface was covered by the flap. Four patients had direct suture of the donor sites and 4 received a thick skin graft of head or contralateral thigh grafting. Survival of the anterolateral thigh chimeric perforator flaps and the healing of donor sites were observed after surgery through scheduled postoperative follow-up by the visits of outpatient clinic and distant interviews via telephone, WeChat or the internet hospital.Results:One of the ipsilateral anterolateral thigh chimeric perforator flaps had venous occlusion within 24 hours after surgery. Emergency surgical exploration revealed that it was caused by a haematoma compression due to haemorrhage in the muscle flap. Further debridement, haemostasis and suture were performed, then the wound healed. The rest of 7 flaps all survived. All donor sites healed primarily. The postoperative follow-up lasted for 5-17 months with all of the 8 patients, at 8.4 months in average. Both the donor and recipient sites healed well without recurrence of radiation ulcer in the affected sites. The appearance and texture of the flaps were good, and there was no obvious functional impairment at the donor sites.Conclusion:The treatment of radiation induced deep ulcer in the inguinal region with an ipsilateral anterolateral thigh chimeric perforator flap has shown good results, without recurrence of ulcer after surgery. The appearance and texture of the affected sites are good, and there is no secondary functional impairment at the donor site.

OBJECTIVE To investigate the current status of prevalence of hand eczema(HE)among the health care workers,explore the influencing factors and analyze the association with hand hygiene.METHODS A questionnaire survey was conducted for the health care workers.The health care workers who had HE were followed up by the dermatology department and were completed the assessment of severity.Logistic regression analysis was per-formed for the influencing factors.RESULTS The questionnaires were distributed to the health care workers of Shanghai First Peoples Hospital in Jul.2024,and 659 valid questionnaires were recycled.The prevalence rate of HE by self-report was 37.03％in recent almost one year.The finger and dorsal hand were the predilection sites of skin damage,with the symptom dominated by itching;dryness,desquamation and vesicles were the primary man-ifestations of skin damage,most of which(64.81％)were moderate.Wearing gloves in work environment and contact with hand sanitizer and disinfectants could make the HE symptoms ever more severe.The use of hand san-itizer/frequent hand washing with soap lye and prolonged glove-wearing were the leading causes of HE.The nurses were dominant among the health care workers with HE(P=0.003),and the proportion of those with allergic his-tory was even higher(P＜0.001).As for the health care workers who washed hands for surgeries,high volume of daily surgical procedures(OR=1.325,95％CI:1.121 to 1.567)and glove-wearing duration more than 120 min(OR=3.177,95％CI:1.087 to 9.281)were the risk factors for HE.As for the common hand-washing health care workers,daily hand washing more than 15 times(OR=3.199,95％CI:1.014 to 10.137),glove-wearing dura-tion more than 120 min(OR=2.216,95％CI:1.117 to 4.391)and use of powdered latex glove(OR=1.591,95％CI:1.058 to 2.390)were the risk factors for HE.CONCLUSION The prevalence rate of HE is high among the health care workers.It is necessary to attach great importance to the hand skin health of the health care work-ers and take comprehensive intervention measures for prevention of HE such as optimization of hand hygiene pro-cedure,enhancement of barrier protection and stress on occupational health education so as to achieve the dual goals of infection control and skin health.

Polycystic ovary syndrome(PCOS)is one of the main causes of ovulatory dysfunction-induced female infertility.The dysfunction of the hypothalamic-pituitary-ovarian axis(HPOA)is a key factor promoting reproductive damage and metabolic abnormalities in PCOS.This article explored the correlation between HPOA dysfunction and the pathogenesis of heart-kidney disharmony in TCM based on Ye Tianshi's theory of"simultaneous upper and lower diseases,treating the middle energizer".It is believed that the treatment of PCOS should aim at restoring the ascending and descending of qi in the middle energizer,with the main therapeutic approach being soothing the liver and strengthening the spleen,which can provide ideas for the clinical treatment of PCOS.

Dental implantology has developed rapidly for over half a century,since pure titanium(99.7％)dental cylindrical threaded implants were exploited and osseointegration was introduced in 1960s by Prof.Br?nemark.The long term retention rates of 10 years or more are over 95％.However,the biological complications jeopardize the long term effects of dental implant treatment seriously.The prevalence of dental implant biological complications varies greatly among different reports resulting from the disparities on the defini-tions of dental implant biological complications.After analyzing and summarizing the major opinions proposed internationally in recent years,the consensus for the definition of dental implant biological complications has been reached.Generally the dental implant biologi-cal implications can be classified into early stage(before restoration)biological complications and late stage(after restoration)biological complications.The early stage biological complications include acute and chronic infections,pain,soft tissue deficiency,and osseointegration failure,etc.The late stage complications include peri-implant diseases(peri-implant mucositis and peri-implantitis),soft tissue deficiency around implant,implant loosening and dropping off,etc.The various risk factors related to different dental implant biological complications,the strategies of the prevention and treatment for the dental implant biological complications have been discussed comprehensively,and the consensus has been reached.It is aimed to advocate the dentist to pay more attention to the early prevention of the biological implant complications,to promote more researches on the implant biological complications,and to help elevate the level of dental implantology in our country.

Objective:To explore the factors influencing the incidence and duration of delirium in ICU patients, so as to provide a reference for early identification and prevention of delirium in these patients.Methods:A retrospective analysis was conducted on the medical records of 1, 500 patients admitted to the ICU of the Affiliated Jiangning Hospital of Nanjing Medical University from January 2020 to December 2024. The data collected included gender, age, anesthesia method, surgical duration, infection duration, extubation time, duration of mechanical ventilation and hypoxia, Acute Physiology and Chronic Health EvaluationⅡ (APACHEⅡ) score, Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) score, duration of sedative medication, and ICU length of stay. Binary Logistic regression and multiple linear regression analysis were employed to investigate the factors influencing the incidence and duration of delirium in ICU patients.Results:The incidence of delirium among 1 500 ICU patients was 38.4% (576/1 500), with a duration of 1.10 (1.00, 3.20) d. Binary Logistic regression analysis revealed that infection duration, APACHEⅡ score, mechanical ventilation duration, and sedative medication duration were statistically significant factors influencing delirium incidence in ICU patients ( P<0.05). Multiple linear regression analysis revealed that delirium type, duration of hypoxia, use of sedative medications, and length of ICU stay were statistically significant factors influencing the duration of delirium in ICU patients ( P<0.05) . Conclusions:ICU patients have a relatively high incidence of delirium, and numerous factors influence the incidence and duration of delirium. Clinical nursing professionals should identify risk factors early and develop corresponding intervention measures to reduce the incidence of delirium in ICU patients and promote their recovery.

Objective:To analyze the predictive value of platelet parameters and prognostic nutritional index(PNI)in activity of ulcerative colitis(UC).Methods:This retrospective study included 158 UC patients from the Department of anorectal medicine of our hospital from January 2020 to June 2022.Mayo total score and Truelove-Witts score were used to evaluate clinical activity.Patients with Mayo score>2 was defined as clinically active UC,and patients with Mayo score≤2 was defined as clinically remission.The histological activity was evaluated by Riley score.Evaluation of endoscopic activity of UC patients by Mayo endoscopic score.Results:Among the 158 patients included in the analysis,111 were in remission phase and the remaining 47 were in clinical active phase.Compared with the remission group,the levels of albumin,lymphocytes,and PNI in the clinically active group reduced significantly(P<0.05),while the levels of CRP,fecal calprotectin,neutrophils,white blood cells,NPR,and NLR increased significantly(P<0.05).Fecal calprotectin,CRP,NPR,NLR were significantly positively correlated with Mayo endoscopic score,Riley score,Truelove Witts score,and Mayo total score(P<0.05),while PNI was significantly negatively correlated with Mayo endoscopic score,Truelove Witts score,and Mayo total score(P<0.05).The ROC curve analysis results showed that fecal calprotectin and NPR had similar performance in predicting clinical activity in UC patients(AUC=0.868,0.850),followed by PNI(AUC=0.770)and NLR(AUC=0.756);Fecal calprotectin had the highest performance in predicting endoscopic activity in UC patients(AUC=0.840),followed by NPR(AUC=0.731),NLR(AUC=0.677),and PNI(AUC=0.671).Conclusions:NPR has demonstrated sufficient diagnostic utility in identifying UC patients with clinical and endoscopic activity,and is comparable in diagnostic performance to the fecal biomarker calprotectin.However,PNI has lower performance as a monitoring tool for UC disease activity.

Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins