Alzheimer’s disease (AD) is pathologically characterized by cerebral amyloid β‑protein (Aβ) aggregation, neurofibrillary tangles and progressive cognitive deterioration. There is an urgent clinical demand for targeted therapeutic agents against AD, whereas the blood-brain barrier (BBB) acts as a critical physical barrier that blocks over 98% small-molecule drugs and nearly all biomacromolecules from entering brain parenchyma. Nanomedicine-based drug delivery systems (NDDSs) with tunable physicochemical properties can cross the BBB via multiple transcytosis pathways including adsorptive-mediated, receptor-mediated and transporter-mediated routes, opening a promising avenue for targeted AD treatment. A core academic viewpoint proposed herein is that robust in vitro endothelial penetration of nanocarriers cannot guarantee effective accumulation in brain target cells. Comprehensive evaluation of BBB-crossing delivery efficiency should not merely rely on in vitro permeability tests, but cover the full multi-step transcytosis cascade, cellular tropism in brain tissues and in vivo therapeutic outcomes. This review systematically sorts out diverse nanoplatforms applicable to BBB penetration for AD intervention. Inorganic nanomaterials such as gold and ceria nanoparticles possess large specific surface areas and intrinsic antioxidant capacity, which eliminate reactive oxygen species and hinder Aβ fibrillization. Liposomal formulations and solid lipid nanoparticles exhibit superior biocompatibility with biomimetic phospholipid bilayer architectures, capable of co-loading hydrophilic nucleic acids for Tau regulation and lipophilic Aβ inhibitors; relying on receptor-mediated transcytosis, they achieve sustained drug retention in the brain. Polymeric nanocarriers including nanogels and polyamidoamine dendrimers enable multi-target combinatorial therapy, and can be engineered to release cargo in response to inflammatory microenvironments, thereby suppressing excessive microglial activation and protecting neuronal mitochondria. Beyond conventional nanocarriers, this work elaborates two cutting-edge BBB-crossing delivery platforms: biomimetic nanosystems and metal-organic frameworks (MOFs). Biomimetic nanoparticles camouflaged with erythrocyte, platelet or macrophage membranes, as well as natural exosomes, evade immune clearance, prolong systemic circulation and inherently home to inflammatory lesions. Serving as “nano-decoys”, they neutralize Aβ neurotoxins and remodel cerebral inflammatory microenvironments simultaneously. MOFs feature high porosity and customizable pore channels for co-delivery of multiple therapeutics, and can be integrated with near-infrared photothermal and photooxidation modalities to facilitate focal brain lesion therapy. This review highlights a transformative paradigm shift in the field of BBB-targeted AD therapy: research focus has shifted from simply maximizing cerebral drug penetration toward active modulation and functional restoration of the BBB. Impaired BBB transporters intrinsically impede endogenous Aβ clearance. Accordingly, BBB-regulating nanocarriers are designed to remodel the low-density lipoprotein receptor-related protein 1 (LRP1) trafficking cascade, redirecting endocytic vesicles from lysosomal degradation to non-degradable transcytosis and restoring the intrinsic Aβ efflux capacity of the BBB. Distinct from conventional strategies that only exert local lesion inhibition, this systemic clearance strategy eliminates cerebral Aβ deposits by accelerating peripheral excretion.

AIM To investigate the impact of varying dosages of Supplemented Wendan Decoction on the PI3K/Akt/FOXO1 glycolipid metabolic pathway in 3T3-L1 adipocytes.METHODS The CCK-8 assay was used to determine the concentration of Supplemented Wendan Decoction-medicated serum.The mature adipocytes differentiated from 3T3-L1 preadipocytes after induction were further divided into the blank control group,the model group,the rosiglitazone group(10 mg/L),and the Supplemented Wendan Decoction groups(5％,10％,and 20％),followed by the sample collections after 48 hours of treatment.Oil red O staining quantified lipid accumulation in 3T3-L1 adipocytes;extracellular glucose levels were measured using glucose oxidase(GOD)assay;RT-qPCR analyzed mRNA expressions of IRS-1,PI3K,Akt,GLUT4,IL-6,TNF-α and IL-1β;Western blot assessed protein expressions of INSR,IRS-1,PI3K-p85,Akt,FOXO1 and GLUT4.RESULTS No significant changes in cell viability(P＞0.05)were observed in 3T3-L1 preadipocytes exposed to serum containing supplemented Wendan Decoction at different concentrations for 24,48,or 72 hours.The 3T3-L1 preadipocytes held the capacity to differentiate into mature adipocytes within a 14-day induction period.Compared to the model group,all supplemented Wendan Decoction groups exhibited reduced lipid accumulation in adipocytes and downregulated mRNA expression of IRS-1,IL-6,TNF-α and IL-1β(P＜0.01);the low-dose group demonstrated increased mRNA expressions of PI3K and GLUT4(P＜0.05,P＜0.01),alongside elevated protein expressions of INSR,IRS-1,PI3K-p85,Akt and GLUT4(P＜0.05,P＜0.01);the medium-dose group showed enhanced GLUT4 mRNA expression,and upregulated protein expressions of INSR and FOXO1(P＜0.01).After 24 hours intervention,the high-dose Supplemented Wendan Decoction group exhibited increased glucose consumption in adipocytes(P＜0.01),and elevated protein expression of INSR,Akt and FOXO1(P＜0.05,P＜0.01).CONCLUSION Supplemented Wendan Decoction reduces lipid accumulation in adipocytes,regulates glucose and lipid metabolism,and promotes metabolic homeostasis through PI3K/Akt/FOXO1 signaling pathway.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

[Purpose]To analyze the incidence and mortality rates of female breast cancer in Henan Province in 2020 and the trends from 2010 to 2020.[Methods]Breast cancer incidence and mor-tality data stratified by urban and rural areas and age groups were collected from Henan Provincial tumor registry,and the province's household population statistics were used.The crude incidence/mortality rate,age-standardized incidence/mortality rate by Chinese standard population(ASIRC/ASMRC)and world standard population(ASIRW/ASMRW),cumulative rate(0～74 year old)were calculated.The annual percentage change(APC),average annual percentage change(AAPC)and 95％confidence interval(CI)were calculated using Joinpoint software to analyze the trends of the incidence and mortality from 2010 to 2020.[Results]In 2020,24 744 new cases and 4 989 deaths of female breast cancer were documented in Henan Province,with a crude incidence rate of 46.96/105,ASIRC of 38.43/105 and ASIRW of 35.71/105;a crude mortality rate of 9.47/105,ASMRC of 6.80/105 and ASMRW of 6.72/105,respectively.The above indicators in urban areas were signifi-cantly higher than those in rural areas.The highest incidence was observed in the age group of 50～54 years old,while the highest mortality reached in the age group of 85 years old and above.From 2010 to 2020,the overall incidence of female breast cancer showed a slow upward trend(AAPC=2.09％,95％CI:0.62％～3.58％,P=0.010),while the mortality rate exhibited a signif-icant downward trend(AAPC=-3.49％,95％CI:-5.62％～-1.30％,P=0.005).[Conclusion]The incidence and mortality rates of female breast cancer in Henan Province are still at a high level,and corresponding preventive measures and control strategies are needed to effectively reduce the health hazards of breast cancer to women.

Objective To investigate the prognostic value of serum interferon-γ(IFN-γ),mannose-binding lectin(MBL)and soluble Fas(sFas)expression levels in patients with multiple myeloma(MM).Methods A total of 150 MM patients diagnosed in our hospital were included in this study and used as the research subjects.According to ISS staging,patients were separated into the stage Ⅰ group(46 cases),the stage Ⅱ group(54 cases)and the stage Ⅲ group(50 cases).According to the survival status of MM patients,they were assigned into the survival group(n=98)and the death group(n=52).Enzyme linked immunosorbent assay(ELISA)was applied to detect expression levels of serum IFN-γ,MBL and sFas.The influencing factors of prognostic mortality in MM patients were analyzed by Cox proportional hazard regression model.The receiver operating curve(ROC)was plotted to analyze the diagnostic value of serum IFN-γ,MBL and sFas expression levels in the prognostic mortality of MM patients.Results With the improvement of ISS stage,the serum Ca level of patients increased significantly(P＜0.05).With the improvement of ISS staging,the expression level of serum IFN-γ was greatly decreased,while the levels of serum MBL and sFas were significantly increased(P＜0.05).The serum IFN-γ level was significantly lower in the death group than that of the survival group,while the serum MBL and sFas levels were significantly higher(P＜0.05).The proportion of ISS Ⅲ stage and the level of serum Ca were significantly higher in the death group than those in the survival group(P＜0.05).Elevated serum levels of MBL,sFas and Ca and ISS stage Ⅲ were risk factors for death within three years in patients with MM,and elevated serum IFN-γ level was protective factor for death within three years in patients with MM(P＜0.05).The AUC of prognostic mortality in patients with combined serum IFN-γ,MBL and sFas in the diagnosis of MM was 0.977,which was better than that of patients diagnosed alone(Z=3.481,3.952 and 3.832,P＜0.05).Conclusion The decreased serum IFN-γ expression and the increased MBL and sFas levels are related to the three-year prognosis of MM patients,and the combination of the three has predictive value for death of MM patients,and which can be used as a biomarker for the prognosis evaluation of MM patients.

Objective:Based on value orientation,it aimed to scientifically define the concept and connotation of accessibility to novel anticancer drugs,in order to deeply understand the nature and current status of the accessibility issues of novel anticancer drugs,and to provide a reference for the formulation and optimization of policies related to novel anticancer drugs.Methods:Data was collected through literature review and expert interviews,and the concept of drug accessibility was defined using the atomic diagram method.Results:The core images include"affordability","availability","high quality"and"patients".The concept of accessibility to novel anticancer drugs is defined as"the process of ensuring the sustainable supply,equitable access,affordability,and rational use of high-quality anticancer drugs to safeguard the realization of patient benefit goals."The connotation of the value orientation in policies on the accessibility of novel anticancer drugs is profoundly reflected in the multi-dimensional value-driven approach to ensure the ultimate benefit of patients,which includes quality,sustainability,equity,affordability,and rational use.Conclusion:The proposal of the concept and connotation of accessibility provides a theoretical basis for a deep understanding of the accessibility of novel anticancer drugs and offers valuable references for subsequent policy-making and practical operations.

Alzheimer’s disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory loss. As the incidence of AD continues to rise annually, researchers have shown keen interest in the active components found in natural plants and their neuroprotective effects against AD. Quercetin, a flavonol widely present in fruits and vegetables, has multiple biological effects including anticancer, anti-inflammatory, and antioxidant. Oxidative stress plays a central role in the pathogenesis of AD, and the antioxidant properties of quercetin are essential for its neuroprotective function. Quercetin can modulate multiple signaling pathways related to AD, such as Nrf2-ARE, JNK, p38 MAPK, PON2, PI3K/Akt, and PKC, all of which are closely related to oxidative stress. Furthermore, quercetin is capable of inhibiting the aggregation of β‑amyloid protein (Aβ) and the phosphorylation of tau protein, as well as the activity of β‑secretase 1 and acetylcholinesterase, thus slowing down the progression of the disease.The review also provides insights into the pharmacokinetic properties of quercetin, including its absorption, metabolism, and excretion, as well as its bioavailability challenges and clinical applications. To improve the bioavailability and enhance the targeting of quercetin, the potential of quercetin nanomedicine delivery systems in the treatment of AD is also discussed. In summary, the multifaceted mechanisms of quercetin against AD provide a new perspective for drug development. However, translating these findings into clinical practice requires overcoming current limitations and ongoing research. In this way, its therapeutic potential in the treatment of AD can be fully utilized.

[Purpose]To analyze the incidence and mortality rates of female breast cancer in Henan Province in 2020 and the trends from 2010 to 2020.[Methods]Breast cancer incidence and mor-tality data stratified by urban and rural areas and age groups were collected from Henan Provincial tumor registry,and the province's household population statistics were used.The crude incidence/mortality rate,age-standardized incidence/mortality rate by Chinese standard population(ASIRC/ASMRC)and world standard population(ASIRW/ASMRW),cumulative rate(0～74 year old)were calculated.The annual percentage change(APC),average annual percentage change(AAPC)and 95％confidence interval(CI)were calculated using Joinpoint software to analyze the trends of the incidence and mortality from 2010 to 2020.[Results]In 2020,24 744 new cases and 4 989 deaths of female breast cancer were documented in Henan Province,with a crude incidence rate of 46.96/105,ASIRC of 38.43/105 and ASIRW of 35.71/105;a crude mortality rate of 9.47/105,ASMRC of 6.80/105 and ASMRW of 6.72/105,respectively.The above indicators in urban areas were signifi-cantly higher than those in rural areas.The highest incidence was observed in the age group of 50～54 years old,while the highest mortality reached in the age group of 85 years old and above.From 2010 to 2020,the overall incidence of female breast cancer showed a slow upward trend(AAPC=2.09％,95％CI:0.62％～3.58％,P=0.010),while the mortality rate exhibited a signif-icant downward trend(AAPC=-3.49％,95％CI:-5.62％～-1.30％,P=0.005).[Conclusion]The incidence and mortality rates of female breast cancer in Henan Province are still at a high level,and corresponding preventive measures and control strategies are needed to effectively reduce the health hazards of breast cancer to women.

OBJECTIVES: To evaluate the application value of genetic newborn screening (gNBS) in the Yunnan region. METHODS: A prospective study was conducted with a random selection of 3 001 newborns born in the Yunnan region from February to December 2021. Traditional newborn screening (tNBS) was used to test biochemical indicators, and targeted next-generation sequencing was employed to screen 159 genes related to 156 diseases. Positive-screened newborns underwent validation and confirmation tests, and confirmed cases received standardized treatment and long-term follow-up. RESULTS: Among the 3 001 newborns, 166 (5.53%) were initially positive for genetic screening, and 1 435 (47.82%) were genetic carriers. The top ten genes with the highest variation frequency were GJB2 (21.29%), DUOX2 (7.27%), HBA (6.14%), GALC (3.63%), SLC12A3 (3.33%), HBB (3.03%), G6PD (2.94%), SLC25A13 (2.90%), PAH (2.73%), and UNC13D (2.68%). Among the initially positive newborns from tNBS and gNBS, 33 (1.10%) and 47 (1.57%) cases were confirmed, respectively. A total of 48 (1.60%) cases were confirmed using gNBS+tNBS. The receiver operating characteristic curve analysis demonstrated that the areas under the curve for tNBS, gNBS, and gNBS+tNBS in diagnosing diseases were 0.866, 0.982, and 0.968, respectively (P<0.05). DeLong's test showed that the area under the curve for gNBS and gNBS+tNBS was higher than that for tNBS (P<0.05). CONCLUSIONS gNBS can expand the range of disease detection, and its combined use with tNBS can significantly shorten diagnosis time, enabling early intervention and treatment.
Humans ; Infant, Newborn ; Neonatal Screening ; Genetic Testing ; Female ; Male ; Follow-Up Studies ; Prospective Studies ; China

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.