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.

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.

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.

AIM: To evaluate the necessity of slit-lamp biomicroscopy(referred to here as “slit-lamp”)training from the student's perspective and reach a consensus on slit-lamp training in medical students during ophthalmology clerkship.METHODS: A controlled before-after clerkship study was performed on 117 students of the class of 2017 enrolled in clinical medicine at Sun Yat-sen University. All medical students underwent slit-lamp training during ophthalmology clerkship. We evaluated the students' cognition, perceived need and recommendations for slit-lamp teaching, using a self-completed questionnaire survey and compared the students' scores in these aspects before and after their ophthalmology clerkships. Additionally, the efficiency of slit-lamp training was evaluated by subjective student assessment after the ophthalmology clerkship. Each item was scored on a five-point Likert Scale. Statistical analysis was performed by IBM SPSS(Version 20.0; SPSS Inc., Chicago, IL, USA).RESULTS: A total of 116(99.1%)medical students completed the survey. The average score before clerkship was 19.99±3.03, which indicated a high level of cognition regarding slit-lamp utility; However, this score significantly increased to 22.97±2.37 after clerkship(P<0.001). The average score regarding perceived need was also higher for post-clerkship students than for pre-clerkship students(24.62±3.15 vs. 23.60±2.36, P=0.009). Moreover, 86.2% of post-clerkship students reported that hands-on slit-lamp practice could help promote clerkship quality. More than three-quarters of the surveyed students tended to agree that slit-lamp practice time should be increased(76.7% and 77.6% before and after clerkship, respectively).CONCLUSION: A hands-on approach to slit-lamp training is more favored by medical students in ophthalmology clerkships, and this training should be recommended in ophthalmology clerkships given its potential usefulness for improving clerkship quality.

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

This study investigated the effect of rhein(RH) on the apoptosis and autophagy of human umbilical vein endothelial cells(HUVECs) induced by hydrogen peroxide(H_2O_2) and its underlying mechanism. The oxidative damage model in HUVECs was established and the cells were divided into different treatment groups. Cell survival rate was detected by MTT assay, apoptosis by Annexin V-FITC/PI double staining and Hoechst 33258 fluorescence staining, autophagy by Ad-mCherry-GFP-LC3 B adenovirus transfection, and protein expression by Western blot. The results showed that RH could protect cells by increasing the cell survival rate in a dose-dependent manner, decreasing the expression of apoptosis-related proteins(Bax and cleaved caspase-3) and the ratio of Bax/Bcl-2, elevating the expression of Bcl-2, up-regulating the expression of microtubule-associated protein 1 light chain 3(LC3)-Ⅱ, and down-regulating the expression of p62. Adenovirus transfection results showed that RH could increase the green and red spots, as well as the yellow spots. However, after the addition of autophagy inhibitor 3-MA, autophagy was reduced and apoptosis was increased. RH could enhance the expression of silent information regulator 2 related enzyme 1(SIRT1). The addition of SIRT1 inhibitor EX-527 reduced the protective effect of RH and cell viability. The addition of 3-MA had no effect on the expression of SIRT1 protein, but the expression of SIRT1 and LC3-Ⅱ proteins decreased and the expression of p62 increased after the addition of EX-527. After RH treatment, the phosphorylation of adenosine monophosphate-activated protein kinase(AMPK) increased, while that of the mechanistic target of rapamycin(mTOR) decreased in a dose-dependent manner. Moreover, this effect could be weakened by the AMPK inhibitor compound C. RH may enhance autophagy through SIRT1/AMPK/mTOR pathway to reduce H_2O_2-induced apoptosis of HUVECs.
Anthraquinones ; Apoptosis ; Autophagy ; Human Umbilical Vein Endothelial Cells ; Humans ; Hydrogen Peroxide ; Signal Transduction

Objective:To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology.Methods:This was a retrospectively study. Newborn screening data ( n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results:A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion:An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.

The current study was aimed to investigate the potential effects of perinatal exposure to therapeutic dose of penicillin and cefixime on the cognitive behaviors, gastrointestinal (GI) motility and serum 5-hydroxytryptamine (5-HT) level in the offspring. Pregnant rats were continuously treated with cefixime or penicillin in the period between 1 week before and 1 week after labor. Behavior tests, including social preference, self-grooming and elevated plus maze tests, and intestinal motility tests were carried out on the offspring at age of 4 to 10 weeks. Serum 5-HT levels were detected with ELISA, and potassium/sodium hyperpolarization activated cyclic nucleotide-gated channel 2 (HCN2) and tryptophan hydroxylase 1 (TPH1) expression levels in colon epithelium of offspring were detected by Western blot and RT-qPCR. The results showed that, compared with the naive group, cefixime increased social behavior in the female offspring, but did not affect the male offspring. Compared with the naive group, cefixime significantly decreased colonic and intestinal transits, and increased cecum net weight and standardized cecum net weight in the male offspring, but did not affect the female offspring. The serum 5-HT levels in the male offspring, rather than the female offspring, in cefixime and penicillin groups were significantly increased compared with that in the naive group. The protein expression level of HCN2 in colon epithelium of the offspring in cefixime group was significantly down-regulated, and the TPH1 expression level was not significantly changed, compared with that in the naive group. These results suggest that perinatal antibiotics exposure may affect neural development and GI functions of the offspring, and the mechanism may involve peripheral 5-HT and gender-dependent factor.
Animals ; Anti-Bacterial Agents ; pharmacology ; Colon ; Female ; Gastrointestinal Motility ; Male ; Mice ; Pregnancy ; Rats ; Serotonin ; Tryptophan Hydroxylase

DNA barcode technology was used to establish a rapid identification method of Chrysanthemum indicum based on ITS2 sequences. The total DNA was extracted from 22 collected samples,and the ITS2 sequence was amplified by PCR and sequenced,and the information of ITS2 sequence was obtained. Another 14 items of the same family or the same genus were downloaded from Gen Bank.We aligned all 36 sequences,calculated the intraspecific and interspecific distances,and constructed Neighbor Joining( NJ) phylogenetic tree,using MEGA 7. 0. The difference of the secondary structure between the ITS2 sequences was compared. The results showed that the genetic distance of Ch. indicum and Ch. morifolium was overlapped,but the maximum intraspecific distance was far less than the minimum interspecific distance between and among Ch. indicum and other species,with an obvious barcoding gap. The NJ tree showed that Ch. indicum and Ch. morifolium shared a clade,and most of Ch. morifolium with some Ch. indicum were shared a subclade,while Inula lineariifolia,Sinosenecio oldhamianus and Senecio scandens belonged to one clade separately. ITS2 secondary structures for I. lineariifolia,S. oldhamianus and S. scandens were significantly different enough to identify completely but Ch. indicum and Ch. morifolium shared two secondary structures of A and B. It was proved that Ch. indicum was one of the evolutionary sources of Ch.morifolium. Therefore ITS2 sequence as DNA barcode can identify Ch. indicum and its adulterants accurately and quickly. The study provides an important basis for Ch. indicum for the identification of germplasm resources and the safety of clinical medication.
Chrysanthemum ; DNA Barcoding, Taxonomic ; DNA, Plant ; DNA, Ribosomal Spacer ; Drugs, Chinese Herbal ; Phylogeny ; Quality Control