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 explore the prevalence of depressive symptoms in postoperative patients with ovarian cancer and to analyze its influencing factors from multiple dimensions, including clinical characteristics, psychological factors, and laboratory indicators. Methods A cross-sectional study was conducted, which enrolled 235 postoperative patients with ovarian cancer. Depressive status was assessed using the patient health questionnaire, and the demographic, pathological, and medical record data of the patients were collected using the generalized anxiety disorder scale, Pittsburgh sleep quality index, European organization for research and treatment of cancer quality of life questionnaire core 30, and ECOG performance status score. Peripheral blood tumor marker (CA125), routine blood test, lymphocyte subsets, and serum cytokine levels were measured. Univariate and multivariate binary logistic regression analysis were used for statistical analysis. Results The prevalence of depression in postoperative patients with ovarian cancer was 39.15% (92/235). Univariate analysis showed that ECOG score ≥ 2 points, pain, anxiety, poor sleep quality, low quality of life, low life satisfaction, tumor recurrence, six or more cycles of chemotherapy, as well as higher levels of CA125, NLR, and NAR, and lower hemoglobin levels were significantly associated with depression (all P<0.05). Multivariate binary Logistic regression analysis showed that anxiety (OR=1.975, 95%CI: 1.231-3.170), sleep efficiency (OR=4.181, 95%CI: 1.211-14.43), sleep latency (OR=34.806, 95%CI: 4.258-284.542), ECOG performance status score, cognitive function (OR=0.918, 95%CI: 0.868-0.97), and life satisfaction were independent risk factors for depression (all P<0.05). Laboratory indicators were not independent influencing factors in the multivariate Logistic regression model. Conclusion Depression in postoperative patients with ovarian cancer is influenced by physiological, psychological, and social factors. Clinical management should focus on patients with anxiety, sleep disorders, poor physical condition, and low life satisfaction, and a comprehensive prevention and treatment strategy centered on psychological intervention and taking into account symptom management and social support should be implemented.

[Objective] To assess the data characteristics of quality monitoring indicators for red blood cell (RBC) preparations, so as to provide reference for continuous improvement of blood quality. [Methods] The quality inspection data of 6 types of RBC preparations from Chongqing blood center from 2019 to 2023 were summarized. For the same indicators, the numerical range of quality indicators was monitored by comparing different types of preparations with the national standard GB18469. The loss and/or damage to RBCs caused by different preparation process were compared, and the impact of different preparation processes on the quality of RBCs was discussed. [Results] The appearance and sterility test compliance rates of the six types of RBC preparations were both 100%, while the compliance rates of other items were all ≥75%. The compliance rate of hematocrit for suspended RBCs was the lowest at 75%, with a median of 0.52, which was close to the lower limit of GB18469, while the medians of hematocrit for the other types were all at the midline level of GB18469. The Hb content for different types of RBCs was significantly higher than the corresponding requirements of GB18469 (P<0.05). The hemolysis rate at the end of storage for different types of RBCs was significantly lower than the requirements of GB18469 (P<0.05). The 1 U leukoreduction process resulted in a hemoglobin content loss of about 5% and had a significant impact on the hemolysis rate at the end of storage (P<0.05). The washing process resulted in a hemoglobin content loss of <3% and had no significant impact on the hemolysis rate at the end of storage (P>0.05). The concentration process resulted in a hemoglobin content loss of <3% and had a significant impact on the hemolysis rate at the end of storage (P<0.05). [Conclusion] The impact of different processes on RBC preparations is within a controllable range and meets the requirements of GB18469. The quality monitoring data can provide a reference for clinical blood selection, effectiveness evaluation and revision of related standards.

Objective To compare the analgesic effects and adverse reactions between intercostal nerve block (ICNB) and patient controlled intravenous analgesia (PCIA). Methods From August 2022 to January 2023, 180 patients with lung cancer who underwent thoracoscopic surgery were randomly divided into two groups: ICNB group (n=90) and PCIA group (n=90). The postoperative pain degree (VAS), location, nature; adverse events, such as nausea, vomiting, and dizziness; and other clinical symptoms were analyzed. Results The most common site of postoperative pain in both groups was surgical incision, and the nature of pain was distending pain. At 12 and 24 h after the operation, the pain degree in the ICNB group (1.10±0.91, 3.12±1.29) was markedly lower than that in PCIA group (1.44±0.86, 4.32±1.30, P=0.010, P<0.001). The incidence of nausea, vomiting, and dizziness in the ICNB group (5.56%, 23.33%) was noticeably lower than that in the PCIA group (35.56%, 51.11%, P<0.001, P<0.001). Total hospitalization expense in the ICNB group (41 043.16±10 885.63 yuan) was significantly lower than that in PCIA group (45 283.99±11 036.36 yuan, P=0.010). Conclusion The analgesic effect of intercostal nerve block is better than that of patient-controlled intravenous analgesia pump in patients with lung cancer after minimally invasive surgery, and the incidence of adverse reactions is low.

Organ damage from cancer treatment remarkably effects patients’ prognosis and quality of life. In recent years, preventive organ protection strategies, such as interdisciplinary collaboration, early prevention, precision interventions, psychological support, and the integrated application of traditional Chinese medicine, have demonstrated substantial clinical value and achieved notable progress. However, these approaches still encounter multiple challenges. Establishing multidisciplinary teams, optimizing therapeutic balance, and strengthening evidence-based research are essential for addressing the challenges related to treatment balance optimization, multidisciplinary coordination, and clinical translation of novel technologies. This review systematically summarizes recent advancements in preventive organ protection, analyzes existing challenges and potential solutions, and offers forward-looking recommendations. It aims to provide valuable insights for optimizing comprehensive cancer treatment strategies and improving long-term patient outcomes.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by radical surgery has been a common practice for patients with locally advanced rectal cancer, but the response rate varies among patients. This study aimed to develop a ResNet-Vision Transformer based magnetic resonance imaging (MRI)-endoscopy fusion model to precisely predict treatment response and provide personalized treatment. METHODS: In this multicenter study, 366 eligible patients who had undergone neoadjuvant chemoradiotherapy followed by radical surgery at eight Chinese tertiary hospitals between January 2017 and June 2024 were recruited, with 2928 pretreatment colonic endoscopic images and 366 pelvic MRI images. An MRI-endoscopy fusion model was constructed based on the ResNet backbone and Transformer network using pretreatment MRI and endoscopic images. Treatment response was defined as good response or non-good response based on the tumor regression grade. The Delong test and the Hanley-McNeil test were utilized to compare prediction performance among different models and different subgroups, respectively. The predictive performance of the MRI-endoscopy fusion model was comprehensively validated in the test sets and was further compared to that of the single-modal MRI model and single-modal endoscopy model. RESULTS: The MRI-endoscopy fusion model demonstrated favorable prediction performance. In the internal validation set, the area under the curve (AUC) and accuracy were 0.852 (95% confidence interval [CI]: 0.744-0.940) and 0.737 (95% CI: 0.712-0.844), respectively. Moreover, the AUC and accuracy reached 0.769 (95% CI: 0.678-0.861) and 0.729 (95% CI: 0.628-0.821), respectively, in the external test set. In addition, the MRI-endoscopy fusion model outperformed the single-modal MRI model (AUC: 0.692 [95% CI: 0.609-0.783], accuracy: 0.659 [95% CI: 0.565-0.775]) and the single-modal endoscopy model (AUC: 0.720 [95% CI: 0.617-0.823], accuracy: 0.713 [95% CI: 0.612-0.809]) in the external test set. CONCLUSION The MRI-endoscopy fusion model based on ResNet-Vision Transformer achieved favorable performance in predicting treatment response to neoadjuvant chemoradiotherapy and holds tremendous potential for enabling personalized treatment regimens for locally advanced rectal cancer patients.
Humans ; Rectal Neoplasms/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Neoadjuvant Therapy/methods* ; Aged ; Adult ; Chemoradiotherapy/methods* ; Endoscopy/methods* ; Treatment Outcome

The present study aimed to explore whether hydrogen sulfide (H₂S) improved hypoxic pulmonary hypertension (HPH) in rats by inhibiting aerobic glycolysis-pyroptosis. Male Sprague-Dawley (SD) rats were randomly divided into normal group, normal+NaHS group, hypoxia group, and hypoxia+NaHS group, with 6 rats in each group. The control group rats were placed in a normoxic (21% O₂) environment and received daily intraperitoneal injections of an equal volume of normal saline. The normal+NaHS group rats were placed in a normoxic environment and intraperitoneally injected with 14 μmol/kg NaHS daily. The hypoxia group rats were placed in a hypoxia chamber, and the oxygen controller inside the chamber maintained the oxygen concentration at 9% to 10% by controlling the N₂ flow rate. An equal volume of normal saline was injected intraperitoneally every day. The hypoxia+NaHS group rats were also placed in an hypoxia chamber and intraperitoneally injected with 14 μmol/kg NaHS daily. After the completion of the four-week modeling, the mean pulmonary artery pressure (mPAP) of each group was measured using right heart catheterization technique, and the right ventricular hypertrophy index (RVHI) was weighed and calculated. HE staining was used to observe pathological changes in lung tissue, Masson staining was used to observe fibrosis of lung tissue, and Western blot was used to detect protein expression levels of hexokinase 2 (HK2), pyruvate dehydrogenase (PDH), pyruvate kinase isozyme type M2 (PKM2), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), GSDMD-N-terminal domain (GSDMD-N), Caspase-1, interleukin-1β (IL-1β) and IL-18 in lung tissue. ELISA was used to detect contents of IL-1β and IL-18 in lung tissue. The results showed that, compared with the normal control group, there were no significant changes in all indexes in the normal+NaHS group, while the hypoxia group exhibited significantly increased mPAP and RVHI, thickened pulmonary vascular wall, narrowed lumen, increased collagen fibers, up-regulated expression levels of aerobic glycolysis-related proteins (HK2 and PKM2), up-regulated expression levels of pyroptosis-related proteins (NLRP3, GSDMD-N, Caspase-1, IL-1β, and IL-18), and increased contents of IL-1β and IL-18. These changes of the above indexes in the hypoxia group were significantly reversed by NaHS. These results suggest that H₂S can improve rat HPH by inhibiting aerobic glycolysis-pyroptosis.
Animals ; Rats, Sprague-Dawley ; Male ; Hypertension, Pulmonary/metabolism* ; Glycolysis/drug effects* ; Hydrogen Sulfide/therapeutic use* ; Hypoxia/complications* ; Rats ; Pyroptosis/drug effects*

ObjectiveTo understand the infection characteristics and drug resistance of carbapenem-resistant Serratia marcescens (CRSM) in a general hospital in Shanghai, and to provide a theoretical basis for clinical anti-infective treatment and prevention of drug-resistant bacteria. MethodsClinical data on cases with CRSM infections detected in clinical specimens at a gradeⅢ level A general hospital in Shanghai from June 2022 to June 2024 were retrospectively collected, and their clinical distributions, factors of hospital-acquired infections, prognosis, and drug-resistant situation were analyzed simultaneously. ResultsA total of 38 cases with CRSM were detected from June 2022 to June 2024, and the number of CRSM strains accounted for 25.00% (38/152) of the number of SM strains. The 38 CRSM infection samples were all derived from sputum. CRSM were distributed in 9 clinical departments, and the top 3 departments having the highest percentages of CRSM among SM strains, were intensive care unit (ICU) (78.79%, 26/33), gastrointestinal surgery department (57.14%, 4/7), and thyroid hernia surgery department (50.00%, 1/2). Among the 38 patients with CRSM infections, 8 cases were identified as hospital-acquired infection, resulting in a hospital-acquired infection rate of 21.05. The mortality rate of the 38 cases of CRSM infected patients within 30 days after detection of CRSM was 23.68% (9/38). The results of multivariate logistic regression analysis showed that sequential organ failure assessment (SOFA) score ≥6.5 points (OR=15.33, P<0.001), septic shock (OR=4.85, P=0.032), and suffering from neoplastic diseases (OR=0.12, P=0.018) were the related factors for death within 30 days after the detection of CRSM in patients with CRSM infection. The results of drug sensitivity test showed that the 38 cases of CRSM exhibited 100.00% (38/38) sensitivity to trimethoprim/sulfamethoxazole, tigecycline, or ceftazidime/avibactam; demonstrated high resistance toβ-lactams except for ceftazidime (18.42%, 7/38), the latter of which was one of the third-generation of cephalosporins; showed elevated resistance to fluoroquinolones [levofloxacin (89.47%, 35/38), ciprofloxacin (94.74%, 36/38)]; maintained good tetracycline sensitivity [doxycycline (97.37%, 37/38), minocycline (76.32%, 29/38)]; and displayed high susceptibility to the aminoglycoside gentamicin (94.74%, 36/38) and elevated resistance to tobramycin (86.84%, 34/38). The detection rate of serine carbapenemase in the 38 strains of CRSM was 100.00%, while all strains tested negative for metallo-β-lactamases. ConclusionFrom June 2022 to June 2024, the detection rate of CRSM in a gradeⅢ level A general hospital in Shanghai was relatively high, especially in the ICU. CRSM has a high resistance rate to commonly used antibacterial drugs such as the first and second-generation cephalosporins, quinolones, and polypeptide antibacterial drugs. Therefore the dynamics of drug-resistant bacteria should be tracked in a timely manner to guide the rational clinical application of antibacterial drugs.

Objective To investigate the impact of COVID-19 infection on the early clinical outcomes of patients undergoing valve replacement. Methods Perioperative data of patients who underwent single valve replacement at the Second Affiliated Hospital of Chinese People's Liberation Army Medical University from January to February 2023 were consecutively collected. Based on COVID-19 infection status, patients were divided into a COVID-19 group and a non-COVID-19 group. The perioperative data were compared between the two groups. Results A total of 136 patients were included, comprising 53 males and 83 females, with a mean age of (53.4±10.2) years. There were 32 patients receiving aortic valve replacements, 102 mitral valve replacements, and 2 tricuspid valve replacements. The COVID-19 group comprised 70 patients, and the non-COVID-19 group included 66 patients. No statistical difference was observed in the incidence of postoperative complications between the two groups [9.09% (6/66) vs. 11.43% (8/70), P=0.654]. However, the COVID-19 group had longer postoperative mechanical ventilation duration [1 201.00 (1 003.75, 1 347.75) min vs. 913.50 (465.50, 1 251.00) min, P=0.001] and ICU stay [3 (2, 3) days vs. 2 (2, 3) days, P<0.001] compared to the non-COVID-19 group. Additionally, troponin I [4.76 (2.55, 7.93) ng/mL vs. 2.66 (1.19, 5.65) ng/mL, P=0.001] and brain natriuretic peptide [608.50 (249.75, 1 150.00) pg/mL vs. 192.00 (100.93, 314.75) pg/mL, P<0.001] levels were significantly higher in the COVID-19 group. Conclusion For patients with single valve disease undergoing elective surgery, short-term outcomes after recovery from COVID-19 infection are favorable, with no significant increase in in-hospital mortality or postoperative complication rates.