1.Mechanism of Action of Guishenwan in Treatment of Ovarian Insufficiency Diseases: A Review
Yao CHEN ; Sainan TIAN ; Bin'an WANG ; Shengyu WANG ; Wen'e LIU ; Lei LEI ; Li TANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):317-324
Guishenwan (GSW), originating from Jingyue Quanshu (Zhang Jingyue's Complete Works), is a classic traditional Chinese medicine (TCM) formula with a history of over 400 years. Designed for kidney essence deficiency syndrome, it is clinically applied to treat diseases associated with essence-blood deficiency, such as ovarian insufficiency diseases in women, oligospermia-induced infertility in men, and lumbar disc herniation. Numerous studies have confirmed its significant efficacy and advantages in managing ovarian insufficiency diseases, including diminished ovarian reserve (DOR), premature ovarian insufficiency (POI), and premature ovarian failure (POF). According to recent literature, the therapeutic mechanisms of GSW in treating ovarian insufficiency diseases involve regulating the hypothalamic-pituitary-ovarian axis (HPOA) function, ameliorating reproductive endocrine disorders, improving ovarian function, modulating relevant signaling pathways, and exerting immunoregulatory and anti-inflammatory effects. A review of GSW in clinical treatment revealed that clinical applications of GSW, particularly in combination with Western medicine, not only alleviate symptoms but also compensate for the limitations of hormone replacement therapy, thereby reducing recurrence, minimizing adverse reactions, and enhancing safety. This review aims to provide a scientific basis for the rational clinical use of GSW in ovarian insufficiency diseases, offer innovative TCM strategies for developing novel ovarian-protective drugs, promote the integration of TCM and Western medicine in reproductive medicine, and ultimately contribute a Chinese approach to global management of ovarian insufficiency diseases.
2.Pathogenic Mechanisms of Spleen Deficiency-Phlegm Dampness in Obesity and Traditional Chinese Medicine Prevention and Treatment Strategies:from the Perspective of Immune Inflammation
Yumei LI ; Peng XU ; Xiaowan WANG ; Shudong CHEN ; Le YANG ; Lihua HUANG ; Chuang LI ; Qinchi HE ; Xiangxi ZENG ; Juanjuan WANG ; Wei MAO ; Ruimin TIAN
Journal of Traditional Chinese Medicine 2026;67(1):31-37
Based on spleen deficiency-phlegm dampness as the core pathogenesis of obesity, and integrating recent advances in modern medicine regarding the key role of immune inflammation in obesity, this paper proposes a multidimensional pathogenic network of "obesity-spleen deficiency-phlegm dampness-immune imbalance". Various traditional Chinese medicine (TCM) herbs that strengthen the spleen, regulate qi, and resolve phlegm and dampness can treat obesity by improving spleen-stomach transport and transformation, promoting water-damp metabolism, and regulating immune homeostasis. This highlights immune inflammation as an important entry point to elucidate the TCM concepts of "spleen deficiency-phlegm dampness" and the therapeutic principle of "strengthening the spleen and eliminating dampness to treat obesity". By systematically analyzing the intrinsic connection between "spleen deficiency generating dampness, internal accumulation of phlegm dampness" and immune dysregulation in obesity, this paper aims to provide theoretical support for TCM treatment of obesity based on dampness.
3.Mechanism of Electroacupuncture Alleviating Inflammatory Pain in Rats by Regulating ErbB Subtypes in the Spinal Dorsal Horn
Yuxin WU ; Shuxin TIAN ; Zhengyi LYU ; Dingru JI ; Xingzhen LI ; Yue DONG ; Binyu ZHAO ; Yi LIANG ; Jianqiao FANG
Journal of Traditional Chinese Medicine 2026;67(1):69-78
ObjectiveTo observe the changes in the levels of different subtypes of epidermal growth factor receptor (ErbB), namely ErbB1, ErbB2, ErbB3, and ErbB4, in the spinal dorsal horn of inflammatory pain model rats, and to explore their mechanism of mediating hyperalgesia as well as the intervention mechanism of electroacupuncture at "Zusanli (ST 36)" and "Kunlun (BL 60)". MethodsThe study was divided into five parts. In experiment 1, 14 Sprague Dawley (SD) rats were randomly divided into control and inflammatory pain group (7 rats each group) to observe the pain behavior and the protein expression of different ErbB receptor subtypes in the spinal dorsal horn. In experiment 2, 30 rats were randomly divided into control group 1, inflammatory pain group 1, and low-, medium-, and high-concentration TX1-85-1 groups, with 6 rats in each group, to observe the effect of inhibiting spinal ErbB3 on inflammatory pain. In experiment 3, 12 rats were randomly divided into control virus group and ErbB3 knockdown virus group, with 6 rats in each group, to observe the effect of knocking down ErbB3 in the spinal dorsal horn on inflammatory pain. In experiment 4, 44 rats were randomly divided into control group 2, inflammatory pain group 2, electroacupuncture group, and sham electroacupuncture group, with 11 rats in each group, to observe the effect of electroacupuncture. In experiment 5, 40 rats were randomly divided into control group 3, inflammatory pain group 3, electroacupuncture group 1, and electroacupuncture + NRG1 group, with 10 rats in each group, to observe the effect of activating ErbB3 on electroacupuncture. A rat model of inflammatory pain was established by subcutaneous injection of 100 μl of complete Freund's adjuvant into the sole of the unilateral hind foot of SD rats. Rats in the low-, medium-, and high-concentration TX1-85-1 groups were intrathecally injected with ErbB3 inhibitor TX1-85-1 on day 5 to day 7 after modeling. Rats in the ErbB3 knockdown virus group were injected with ErbB3 knockdown virus packaged with adenovirus vector-based short hairpin RNA (shRNA) into the spinal dorsal horn in situ 3 weeks before modeling. Rats in each electroacupuncture group received electroacupuncture at bilateral "Zusanli (ST 36)" and "Kunlun (BL 60)" from day 1 to day 7 after modeling, with dense-sparse waves at a frequency of 2 Hz/100 Hz and a current of 0.5-1.5 mA for 30 minutes once a day. Rats in the electroacupuncture + NRG1 group were intrathecally injected with ErbB3 ligand recombinant human neuregulin-1 (NRG1) after electroacupuncture intervention from day 5 to day 7 after modeling. The mechanical withdrawal threshold and thermal withdrawal latency of rats were measured on day 1, 3, 5, and 7 after modeling to evaluate behavior, and Western Blot was used to detect the protein and phosphorylation levels of each ErbB subtype in the spinal dorsal horn. ResultsCompared with the control group, rats in the inflammatory pain group showed decreased mechanical withdrawal threshold and thermal withdrawal latency of rats, and increased expression of phosphorylated ErbB3 (p-ErbB3) protein in the spinal dorsal horn on days 1, 3, 5, and 7 after modeling (P<0.01). On day 5 and day 7 after modeling, compared with the inflammatory pain group 1, the mecha-nical withdrawal threshold and thermal withdrawal latency of rats in the medium- and high-concentration TX1-85-1 groups increased, and the expression of p-ErbB3 protein decreased (P<0.05). On day 1, 3, 5, and 7 after modeling, compared with the control virus group, the mechanical withdrawal threshold and thermal withdrawal latency of rats in the ErbB3 knockdown virus group increased (P<0.05). On day 5 and day 7 after modeling, compared with the inflammatory pain group 2 and the sham electroacupuncture group, the mechanical withdrawal threshold and thermal withdrawal latency of rats in the electroacupuncture group increased, and the expression of p-ErbB3 protein decreased (P<0.05). On day 5 and day 7 after modeling, compared with the electroacupuncture + NRG1 group, the mechanical withdrawal threshold and thermal withdrawal latency of rats in the electroacupuncture group 1 increased (P<0.05). ConclusionThe p-ErbB3 in the spinal dorsal horn involved in hyperalgesia in rats with inflammatory pain, and electroacupuncture at "Zusanli (ST 36)" and "Kunlun (BL 60)" can alleviate inflammatory pain by inhibiting the expression of p-ErbB3 protein in the spinal dorsal horn of rats.
4.Treatment Principles and Paradigm of Diabetic Microvascular Complications Responding Specifically to Traditional Chinese Medicine
Anzhu WANG ; Xing HANG ; Lili ZHANG ; Xiaorong ZHU ; Dantao PENG ; Ying FAN ; Min ZHANG ; Wenliang LYU ; Guoliang ZHANG ; Xiai WU ; Jia MI ; Jiaxing TIAN ; Wei ZHANG ; Han WANG ; Yuan XU ; .LI PINGPING ; Zhenyu WANG ; Ying ZHANG ; Dongmei SUN ; Yi HE ; Mei MO ; Xiaoxiao ZHANG ; Linhua ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):272-279
To explore the advantages of traditional Chinese medicine (TCM) and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications (DMC), refine key pathophysiological insights and treatment principles, and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine, hosted by the China Association of Chinese Medicine, was held in Beijing, 2024. Experts in TCM, Western medicine, and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis, diagnostic and treatment challenges, and mechanism research related to DMC, ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development, research prioritization, and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM, strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.
5.Analysis of related factors for the comorbidity of allergic rhinitis and obesity among primary and secondary school students in Inner Mongolia
Chinese Journal of School Health 2026;47(1):27-31
Objective:
To investigate the factors influencing the co-prevalence of allergic rhinitis and obesity among primary and secondary school students in Inner Mongolia, so as to provide a data foundation and theoretical basis for developing targeted intervention measures.
Methods:
In September and October 2024, a stratified cluster random sampling method was employed to select 139 102 students from 539 schools across 12 leagues/cities and 103 banners/counties in Inner Mongolia Autonomous Region. Participants who were diagnosed with allergic rhinitis by a doctor at least once within one year and had a body mass index ≥ 28 kg/m 2 were considered to have comorbid conditions.
Results:
The coprevalence rate of allergic rhinitis and obesity among primary and secondary school students in Inner Mongolia was 6.4% (8 931 cases). Lasso-Logistic regression revealed that nonboarding status, higher maternal education, consuming high protein foods ≥1 time daily, occasionally or never eating breakfast, engaging in moderate to vigorous physical activity for ≥60 minutes on fewer than half of holidays, and having been exposed to second hand smoke in person within the past seven days were associated with higher odds ratios for co-prevalence of allergic rhinitis and obesity( OR = 1.23 , 1.22-1.63, 1.20, 1.19, 1.38, 1.35); being female, higher grade level, residence in flag/county/district areas, non only child status, never having consumed a full glass of alcohol, non hypertensive status, and households without pets were associated with lower co-prevalence risks ( OR =0.65, 0.67-0.77, 0.81, 0.87, 0.73, 0.41, 0.68) (all P <0.05). The ROC curve indicated an area under the curve of 0.64 for the predictive model, demonstrating satisfactory discriminatory ability. The calibration curve showed consistency between predicted and actual occurrence probabilities.
Conclusions
The co-prevalence of allergic rhinitis and obesity among primary and secondary school students in Inner Mongolia is closely associated with demographic characteristics, dietary behaviours, and lifestyle habits. Future prevention and control strategies should prioritize these factors to implement targeted interventions.
6.Mechanism of Danggui Shaoyaosan in Improving Inflammatory Response in Mice with Diabetic Kidney Disease Based on TLR4/p65/NLRP3 Signaling Pathway
Shilong GUO ; Ruijia LI ; Zixuan WANG ; Xinai WANG ; Luyu HOU ; Wenjing SHI ; Mengyuan TIAN ; Dengzhou GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):19-27
ObjectiveTo investigate the effect of Danggui Shaoyaosan on the expression of Toll-like receptor 4/nuclear factor-kappa B p65/NOD-like receptor protein 3 (TLR4/NF-κB p65/NLRP3) signaling pathway in the renal tissues of db/db mice with spontaneous diabetes, and to explore the potential mechanism by which Danggui Shaoyaosan alleviates inflammation in diabetic kidney disease (DKD). MethodsThirty db/db mice were divided into five groups: A model group, Danggui Shaoyaosan low- (16.77 g·kg-1·d-1), medium- (33.54 g·kg-1·d-1), and high-dose (67.08 g·kg-1·d-1) intervention groups, as well as an irbesartan group (0.025 g·kg-1·d-1) by the random number table method, with 6 mice in each group. Additionally, 6 db/m mice were assigned to the normal group. After 8 weeks of intervention, the following parameters were determined by corresponding methods: body weight, fasting blood glucose (FBG), 24-hour urinary protein (24 h-UTP), and serum creatinine (SCr) levels, renal histopathological analysis by hematoxylin-eosin (HE) staining, Masson staining, and periodic acid-Schiff (PAS) staining, the protein and mRNA expression levels of TLR4, NF-κB p65, NLRP3, tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-18 (IL-18) by Western blot and Real-time quantitative polymerase chain reaction (Real-time PCR), as well as TLR4, NF-κB p65, and NLRP3 protein expression in renal tissues by immunohistochemistry (IHC). ResultsCompared with the normal group, the model group exhibited increased body weight, FBG, 24 h-UTP, and SCr levels (P<0.05); disordered renal structure, thickened basement membrane, and interstitial inflammatory cell infiltration, elevated TLR4, NF-κB p65, NLRP3, TNF-α, IL-1β, IL-6, and IL-18 expression; as well as decreased IL-10 expression (P<0.05). Compared with the model group, these pathological changes and biochemical abnormalities were reversed in the medicine intervention groups to varying degrees (P<0.05). ConclusionDanggui Shaoyaosan may delay DKD progression by alleviating renal inflammatory response and reducing urinary protein excretion via modulating the TLR4/NF-κB p65/NLRP3 signaling pathway.
7.Analysis of serological and molecular genetic characteristics of a Chinese pedigree with a B(A)06 subtype.
Dongdong TIAN ; Ding ZHAO ; Wei LI ; Zhihao LI ; Jiali YANG ; Yongfang ZHANG ; Liuchuang ZHENG
Chinese Journal of Medical Genetics 2026;43(3):220-227
OBJECTIVE:
To explore the serological and molecular genetic characteristics of a family with subtype B(A)06.
METHODS:
A neonatal hyperbilirubinemia patient who was treated at Henan Children's Hospital on June 15, 2023 due to "yellowing of the skin and gradual aggravation", and was found to have inconsistent ABO forward and reverse typing through blood type testing, was selected as the research subject. Six milliliters of peripheral blood were collected from the newborn and her family members (grandfather, grandmother, father, mother and aunt) respectively. ABO blood group identification was performed by the blood group serological method. Human genomic DNA was extracted using the nucleic acid extraction or purification reagent BT-01. ABO gene exons 2 to 7 were amplified by PCR. The PCR-specific products that were successfully amplified were sequenced by Sanger method. Taking ABO*A1.01 as the reference sequence, the ABO gene sequences of the newborn and her family members were analyzed to determine the ABO genotype. The procedures followed in this study were approved by the Ethics Committee of Henan Children's Hospital (Ethics No.: 2022-K-L036).
RESULTS:
The serological results of ABO blood group showed that the newborn, her grandfather, father and aunt were all incompatible with the forward and reverse typing. The blood group phenotype of the newborn was AwB or B(A), the blood group phenotype of the grandfather was A2B or B(A), the blood group phenotype of the father and aunt were A2B, and the blood group phenotype of the grandmother and mother were both O. The screening test results of hemolytic disease of the newborn showed that the free test detected IgG anti-A1 antibody, while the elution test, direct antiglobulin test and antibody screening results were all negative. The Sanger sequencing results showed that the newborn had variations of c.261delG, c.297A>G, c.526C>G, c.657C>T, c.703G>A, c.796C>A and c.930G>A. Her grandfather had variations of c.297A>G, C.526C>G, c.657C>T, c.703G>A, c.796C>A, c.803G>C and c.930G>A. Her grandmother had variations of c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.261delG, c.297A>G, c.646T>A, c.681G>A, c.771C>T and c.829G>A. Her father and aunt had variations of c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.261delG, c.297A>G, c.526C>G, c.646T>A, c.657C>T, c.681G>A, c.703G>A, c.771C>T, c.796C>A, c.829G>A and c.930G>A. Her mother had variations of c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.261delG, c.297A>G, c.646T>A, c.681G>A, c.771C>T, and c.829G>A.The genotype of the newborn was ABO*BA.06/ABO*O.01.01, her grandfather was ABO*BA.06/ABO*B.01, her grandmother was ABO*O.01.02/ABO*O.01.02, her father and aunt were ABO*BA.06/ABO*O.01.02, and her mother was ABO*O.01.01/ABO*O.01.02. The ABO*BA.06 allele of the newborn, grandfather, father and aunt was caused by the c.803C>G variation in exon 7 based on the ABO*B.01 allele. The ABO*BA.06 allele can be stably inherited in this family.
CONCLUSION
The blood type of neonatal patients with B(A)06 subtype can be accurately determined by gene sequencing technology. If the forward typing is ≤ 3+ agglutination intensity in newborn ABO blood group identification, the reason should be carefully analyzed, and the molecular biology technology and family gene sequencing results should be used to jointly determine if necessary.
Humans
;
ABO Blood-Group System/genetics*
;
Female
;
Pedigree
;
Male
;
Infant, Newborn
;
Asian People/genetics*
;
Genotype
;
China
;
Blood Grouping and Crossmatching
;
Hyperbilirubinemia, Neonatal/blood*
;
East Asian People
8.Genetic disease diagnosis and treatment in Shanghai: Survey and countermeasures for clinical genetics specialist training.
Xiaoju HUANG ; Lin HAN ; Li CAO ; Taosheng HUANG ; Duan MA ; Jian WANG ; Wenjuan QIU ; Fanyi ZENG ; Luming SUN ; Chenming XU ; Songchang CHEN ; Xinyu KUANG ; Hong TIAN
Chinese Journal of Medical Genetics 2026;43(4):241-247
OBJECTIVE:
To investigate the current status of clinical genetics specialization development and the diagnostic and therapeutic capabilities for hereditary diseases across medical institutions in Shanghai, and to assess the necessity and feasibility of establishing training bases for clinical genetics specialists.
METHODS:
By employing a cross-sectional survey design, the Clinical Genetics Committee of Shanghai Medical Association has conducted questionnaire surveys from March to April 2025 across 54 healthcare institutions in Shanghai (including 33 tertiary hospitals and 21 secondary hospitals). The survey involved administrative departments and medical personnel from 15 clinical specialties. The survey has covered current genetic disease diagnosis and treatment practices, relevant and specialised disease types, genetic department establishment, testing capabilities, personnel teams, and training requirements.
RESULTS:
The results revealed that 78.0% of clinical departments surveyed had treated patients with hereditary disorders. Shanghai possesses diagnostic and therapeutic expertise for over 95% of hereditary diseases listed in its rare disease catalogue, reflecting both the practical clinical demand for such conditions and the city's overall diagnostic and therapeutic strengths in this field. Nevertheless, significant disparities exist in the development of genetics departments across different tiers of healthcare institutions. Resources for genetic testing capabilities (including molecular, cellular, and biochemical testing) are also unevenly distributed across different tiers of hospitals. The survey further revealed that only 26.0% of departments believe that their current physician structure fully meets the diagnostic and treatment demands. Over 90% of departments consider standard training for clinical genetic specialists necessary, with 74.0% expressing willingness to participate in establishing training bases. Based on above findings and thorough deliberation, the Clinical Genetics Committee of the Shanghai Medical Association proposes advancing specialist training and discipline development through establishing a standard training system. The committee has drafted a three-year training protocol featuring a "joint training"-centered model, recommending a pilot-first, dynamically optimized strategy for steadily advancing training base development.
CONCLUSION
Shanghai faces substantial demand for genetic disease diagnosis and treatment, yet exhibits shortcomings in clinical genetics specialization development, resource allocation, and talent pipeline cultivation. To establish a standard training system holds significant practical importance and is underpinned by a broad demand.
Humans
;
China
;
Surveys and Questionnaires
;
Genetic Diseases, Inborn/genetics*
;
Cross-Sectional Studies
;
Genetics, Medical/education*
;
Genetic Testing
9.Association between sunshine duration and hospitalization risk for mental and behavioral disorders in Zigong City, Sichuan Province
Xianyan JIANG ; Fengyuan TIAN ; Yang LI ; Shijuan RUAN ; Yue WEN ; Chunli SHI
Journal of Environmental and Occupational Medicine 2026;43(4):485-492
Background Sunshine duration is closely associated with population mental health and emotional states, although its relationship with mental and behavioral disorders (MBD) remains insufficiently studied. Objective To analyze the effect of sunshine duration on hospital admissions for MBD in Zigong City, Sichuan Province. Methods Hospital admission records for MBD from 10 medical institutions, meteorological data, and ambient air pollutant concentrations were collected in Zigong City from January 1, 2019 to December 31, 2024. A distributed lag non-linear model (DLNM) was employed to calculate single-day and cumulative lag effects of different sunshine duration exposures—0 h (P0, P5, P25), 6 h (P75), and 10.4 h (P95)—on hospitalization risks for MBD, stratified by diagnostic category, sex, and age groups. Results This study analyzed
10.Applications of Lactoferrin and Its Nanoparticles in Cancer Therapy
Wen-Tian YUE ; Shu-Rong HE ; Qin AN ; Yun-Xia ZOU ; Wen-Wen DONG ; Qing-Yong MENG ; Ya-Li ZHANG
Progress in Biochemistry and Biophysics 2026;53(2):342-355
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.


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