This article reviews the research advances in the characteristics and application progress of various new models for preclinical cancer research on pancreatic cancer， analyzes and discusses the history， current research status， and advantages and disadvantages of new models of pancreatic cancer， including patient-derived tissue xenograft， conditional reprogramming， and patient derived organoids， and it also reviews the studies that have achieved clinical transformation from preclinical models and proposes possible research prospects in the future.

Gene therapy, harnessing the power of CRISPR-Cas9 and/or DNAzyme systems, stands as a pivotal approach in cancer therapy, enabling the meticulous manipulation of genes pivotal to tumorigenesis and immunity. However, the pursuit of precise gene therapy encounters formidable hurdles. Herein, a near-infrared upconversion theranostic nanomachine is devised and tailors for CRISPR-Cas9/DNAzyme systems mediate precise gene therapy. An ingenious logic DNAzyme system consists of Chain 1 (C1)/Chain 2 (C2) and endogenous lncRNA is designed. We employ manganese modified upconversion nanoparticles for carrying ultraviolet-responsive C1-PC linker-C2 (C₂P) chain and Cas9 ribonucleoprotein (RNP), with outermost coats with hyaluronic acid. Upon reaching tumor microenvironment (TME), the released Mn²⁺ ions orchestrate a trifecta: facilitating endosomal escape, activating cGAS-STING signaling, and enabling T1-magnetic resonance imaging. Under near-infrared irradiation, Cas9 RNP/C₂P complex dissociates, releasing Cas9 RNP into the nucleus to perform gene editing of Ptpn2, while C1/C2 chains self-assemble with endogenous lncRNA to form a functional DNAzyme system, targeting PD-L1 mRNA for gene silencing. This strategy remodels the TME by activating cGAS-STING signaling and dual immune checkpoints blockade, thus realizing tumor elimination. Our theranostic nanomachine armed with the CRISPR-Cas9/DNAzyme logic systems, represents a resourceful and promising strategy for advancing cancer systemic immunotherapy and precise gene therapy.

OBJECTIVE: To analyze the clinical effectiveness of veno-venous extracorporeal membrane oxygenation (VV-ECMO) in rescuing children with severe pulmonary contusion. METHODS: A retrospective analysis was conducted on the clinical data of four children with severe pulmonary contusion who were treated with VV-ECMO in the pediatric intensive care unit of Xi'an Children's Hospital from April 2021 to December 2024. The general data, laboratory indicators within 24 hours after admission, imaging features, bronchoscopic findings, diagnostic and treatment processes, as well as therapeutic outcomes of the children were analyzed. RESULTS: All four pediatric cases were male, aged 4 years and 9 months, 6 years and 5 months, 8 years and 10 months, and 9 years and 7 months, respectively. One case resulted from a high-altitude fall and three from traffic accidents, all presenting with multiple fractures. All four cases progressed to dyspnea within 1-4 hours post-injury and received endotracheal intubation with invasive ventilator support within 2-5 hours. Three cases exhibited tachycardia upon admission and were treated with norepinephrine, all four cases presented with fine moist rales in the lungs. Imaging studies revealed diffuse exudative changes in all four cases. Bronchoscopy identified diffuse pulmonary hemorrhage, with one case additionally showing rupture of the right intermediate bronchus. Conventional mechanical ventilation failed to correct oxygenation in all cases, prompting initiation of VV-ECMO therapy within 8-22 hours post-injury. One case underwent right thoracic exploration under ECMO support. Following treatment, all four cases demonstrated gradual reduction in bloody airway secretions, resolution of pulmonary exudative changes on imaging, and absence of hemorrhage on bronchoscopy. They were successfully weaned off ECMO and ultimately discharged as cured. CONCLUSIONS Severe pulmonary contusion rapidly leads to respiratory distress, requiring ventilator-assisted ventilation within hours of injury. When conventional ventilator support is ineffective, ECMO can be life-saving, with timely intervention yielding favorable prognosis.
Humans ; Extracorporeal Membrane Oxygenation/methods* ; Male ; Retrospective Studies ; Child, Preschool ; Child ; Contusions/therapy* ; Lung Injury/therapy* ; Treatment Outcome

Wastewater-based epidemiology has emerged as a transformative surveillance tool for estimating substance consumption and monitoring disease prevalence, particularly during the COVID-19 pandemic. It enables the population-level monitoring of illicit drug use, pathogen prevalence, and environmental pollutant exposure. In this perspective, we summarize the key challenges specific to the Chinese context: (1) Sampling inconsistencies, necessitating standardized 24-hour composite protocols with high-frequency autosamplers (≤ 15 min/event) to improve the representativeness of samples; (2) Biomarker validation, requiring rigorous assessment of excretion profiles and in-sewer stability; (3) Analytical method disparities, demanding inter-laboratory proficiency testing and the development of automated pretreatment instruments; (4) Catchment population dynamics, reducing estimation uncertainties through mobile phone data, flow-based models, or hydrochemical parameters; and (5) Ethical and data management concerns, including privacy risks for small communities, mitigated through data de-identification and tiered reporting platforms. To address these challenges, we propose an integrated framework that features adaptive sampling networks, multi-scale wastewater sample banks, biomarker databases with multidimensional metadata, and intelligent data dashboards. In summary, wastewater-based epidemiology offers unparalleled scalability for equitable health surveillance and can improve the health of the entire population by providing timely and objective information to guide the development of targeted policies.
China/epidemiology* ; Humans ; Wastewater/analysis* ; COVID-19/epidemiology* ; Public Health ; Wastewater-Based Epidemiological Monitoring ; SARS-CoV-2

Objective To deposit degradable amino-hybrid mesoporous silica(AHMS)in situ on the surface of tita-nium nanotube(TNT)and explore its protective effect on nanomorphology and osteogenesis.Methods TNT and TNT@AHMS were sequentially prepared via an anodizing method:the oil-water two-phase method(experimental group)and the acid-etched titanium method[control group(Ti)].The parameters for synthesis were explored by changing the silicon source dosage ratio(3∶1,1∶1,1∶3);the surface morphology was observed by scanning electron microscope(SEM),hydrophilicity was detected by Water Contact Angle Tester,elemental composition was detected by X-ray photo-electron spectroscopy(XPS);nanoindentation test and ultrasonic oscillator were used to observe the morphological hold-ing effect as mechanical strength of TNT@AHMS in vitro;simulated immersion experiments in vitro was used to observe the degradation behavior of the material.the MC3T3-E1 cell line was used to observe the effect of cell adhesion,prolif-eration and differentiation on the material;and an SD rat femoral implant model and micro-CT were used to verify the protective effect and osseointegration effect of AHMS on TNT morphology.Results The morphologies of TNT and TNT@AHMS were successfully prepared,and the silicon source ratio was 1∶3.SEM showed that the titanium nanotubes were uniformly covered with AHMS coating,and the mesoporous pore size was about 4 nm.After AHMS was incorporat-ed,the surface of the material was hydrophilic(12.78°),the presence of amino groups(NH2-)was detected,the material was completely degraded within 12 h in vitro,and the active morphology of the TNT was re-exposed with a cumulative silicon release of 10 ppm.Nanoindentation test showed that TNT@AHMS exhibited more ideal surface mechanical strength.SEM revealed that TNT maintains its own morphology under the protection of AHMS,and the TNT group suf-fered severe exfoliation.In addition,the early adhesion and proliferation rates,ALP activity,and bone volume fraction of cells on the TNT@AHMS surface 4 weeks after implantation were significantly higher than those in the TNT group.Con-clusion By depositing AHMS on the surface of TNT,the nanotopography can be protected.It not only prevents the ac-tive base topography from exerting subsequent biological effects but also further endows the material with the ability to promote bone regeneration,laying a foundation for the future development of nanotopography-modified titanium im-plants.

Diabetic kidney disease(DKD)is one of the most important complications of diabetes.In recent years,domestic and foreign studies have found that mammalian target protein of rapamycin(mTOR)related signaling pathway is a classic pathway involved in the regulation of autophagy,which can achieve the therapeutic effect of DKD by targeting the autophagy pathway,and plays a crucial role in the prevention and treatment of DKD.In this paper,we reviewed the mechanism of mTOR-related signaling pathway targeted autophagy in the prevention and treatment of DKD,in order to provide a new reference and basis for clinical prevention and treatment of DKD.

Objective: To explore the association of tobacco/alcohol-excessive Internet usage and insufficient sleep with depressive symptoms among middle school students, so as to provide a reference for improving mental health of middle school students. Methods: In accordance with the cluster random sampling method, a total of 18 484 middle school students in Shanghai were surveyed from September to November 2022. Tobacco/alcohol-excessive Internet usage and sleep duration with depressive symptoms were assessed using the relevant scale items included in the questionnaire of Surveillance for Common Disease and Health Risk Factors among Students. The χ 2 test was used for inter group comparison, Logistic regression analysis and likelihood ratio test were used to analyze the independent and aggregated associations of tobacco/alcohol-excessive Internet use and insufficient sleep wiht depressive symptoms. Results: Self reported rates of tobacco/alcohol-excessive Internet usage, insufficient sleep and depressive symptoms among adolescents were 14.7%, 73.5% and 16.3%, respectively. Tobacco/alcohol-excessive Internet usage ( OR=2.69, 95%CI =2.44-2.97) and insufficient sleep ( OR=1.76, 95%CI =1.58-1.95) were associated with depressive symptoms ( P <0.05). Compared to middle school students with no tobacco/alcohol-excessive Internet usage and sufficient sleep, those with both tobacco/alcohol-excessive Internet usage and insufficient sleep showed the higher rate of depressive symptoms ( OR=4.71, 95%CI =4.08-5.44, P <0.05). Further stratified analysis results showed that, compared to the boys and the high school students, the separate and joint association of tobacco/alcohol-excessive Internet usage and insufficient sleep with depressive symptoms were more pronounced in the girls and the middle school students [ OR (95% CI ) for tobacco/alcohol-excessive Internet usage were 3.09 (2.68-3.56) and 4.74 (3.86-5.83), respectively; OR (95% CI ) for insufficient sleep were 1.86 (1.60-2.17) and 2.00 (1.58-2.53), respectively; and the OR (95% CI ) for the joint association were 6.05 (5.01-7.31) and 9.15 (6.98-11.99), respectively, P <0.05]. Conclusions Tobacco/alcohol-excessive Internet usage and insufficient sleep are associated with depressive symptoms in middle school students. Prevention and control strategies for adolescent mental health should be developed with consideration of health related behaviors, and also need to be tailored by focusing on gender and grade differences.

Objectives:To report a novel mutation site in the pathogenic gene TTR of transthyretin cardiac amyloidosis(ATTR-CA),and to identify family members at risk,and provide suitable clinical diagnosis and treatment. Methods:A retrospective analysis was conducted on the clinical data of the proband with ATTR-CA who visited the Department of Cardiology,the First Affiliated Hospital of Zhengzhou University in March 2021.The proband underwent whole exome sequencing using high-throughput methods to detect mutation genes.Sanger sequencing was used to test candidate pathogenic loci in suspected family members,and relevant literature was reviewed. Results:Among 51 individuals spanning 5 generations in the pedigree,10 family members(including the proband)carried the heterozygous TTR gene c.163A>G mutation,resulting in the amino acid residue at position 55 changing from lysine(Lys)to glutamic acid(Glu).This mutation follows an autosomal dominant inheritance pattern,with early onset in adulthood,rapid progression,and presenting as a mixed-type ATTR-CA.Five mutation carriers had different clinical manifestations,while the remaining 5 mutation carriers,who are at younger age,have not yet shown symptoms.Within the pedigree,7 individuals died(the proband's uncle[Ⅱ-1]who died from stroke at 65 years old,the rest 6 family members died from heart disease before the age of 50). Conclusions:According to the American College of Medical Genetics and Genomics guidelines,TTR gene Lys55Glu mutation is classified as likely pathogenic,this mutation site has not been reported in the literature before.Present study adds clinical evidence that might broaden the spectrum of TTR mutations.

Objective:To establish an HPLC method for benzyl benzoate related substances and propose revision suggestions for the quality standard of this excipient.Methods:Phenylsilane bond and silica gel were used as fill-ers,and methanol-1％acetic acid(60:40)was used as the mobile phase at the flow rate of 1.0 mL·min-1.The detection wavelength was 254 nm and the injection amount was 20 μL.Results:Based on the results of the de-struction test and taking into account the separation requirements,the chromatographic conditions for benzyl benzo-ate related substances were confirmed and methodological validation was conducted.The detection limits for benzoic acid and benzaldehyde in related substances were 0.2 μg·mL-1 and 0.01 μg·mL-1.The correction factors for benzoic acid and benzaldehyde were 1.0 and 0.1,respectively.According to the newly established method,six batches of benzyl benzoate samples from four enterprises were inspected for related substances,and benzaldehyde was detected with content from 0.02％to 0.1％.The total amount of impurities was from 0.02％to 0.9％.Conclusion:The newly established method can be added to the quality standards of benzyl benzoate,and different impurity limits can be formulated according to the different administration routes in order to better control drug quality.