Lung cancer， with persistently high incidence and mortality rates， remains a significant global health challenge. By taking the study on the experience in diagnosis and treatment of lung cancer with phlegm-dampness and blood stasis syndrome by distinguished traditional Chinese medicine physicians of the Sichuan School as an example， the diagnosis and treatment system for lung cancer with phlegm-dampness and blood stasis syndrome， which was formed in response to the humid and foggy environment of the Sichuan Basin， possesses unique value. However， traditional inheritance modes face challenges such as fragmentation， lack of standardization， and insufficient quantification， which hinder the promotion and application of this experience. This research focused on how to leverage multimodal data and artificial intelligence-generated content （AIGC） to achieve precise analysis， intelligent inheritance， and clinical innovation of the experience in diagnosis and treatment of lung cancer with phlegm-dampness and blood stasis syndrome by distinguished traditional Chinese medicine physicians of the Sichuan School. By integrating multimodal data （encompassing four diagnostic methods of traditional Chinese medicine， modern medical imaging， clinical laboratory tests， molecular biology， and regional environmental information）， a precise diagnosis and treatment system integrating macro and micro perspectives for the "disease， syndrome， and pathogenesis" was constructed. The research yielded the following results： （1） In precise syndrome differentiation， the objective quantification of the phlegm-dampness and blood stasis syndrome was achieved. By constructing a "four diagnostic methods， imaging， and molecule" correlation model， the study revealed intrinsic links between tongue and pulse parameters and the tumor microenvironment， as well as between regional climatic factors and syndrome characteristics， enabling real-time dynamic monitoring of efficacy. （2） In elucidating patterns， the study systematically explored the syndrome differentiation thoughts of Sichuan School physicians， such as the timing of purgation and tonification. A "pathogenesis， syndrome complex， and prescriptions and herb" network model was constructed， which accurately elucidated the synergistic action mechanisms of core herb pairs and quantified the dynamic compatibility patterns of reinforcing healthy Qi and eliminating pathogenic factors. （3） In intelligent empowerment， an auxiliary system integrating intelligent syndrome differentiation， treatment plan generation， and efficacy evaluation was built. This system can fuse regional characteristics with individual data， dynamically generate and optimize personalized prescriptions aligned with the experience of Sichuan School， and predict efficacy trends and potential adverse reactions. The integration of multimodal data and AIGC can effectively facilitate the structured inheritance and clinical translation of distinguished physicians' experience. The established intelligent diagnosis and treatment model integrating traditional Chinese medicine and Western medicine demonstrates clear potential in prolonging patients' progression-free survival， alleviating symptoms， and reducing adverse reactions to treatment. This study provides a referential methodological framework for the traditional Chinese medicine experience in diagnosis and treatment of lung cancer， especially the empirical inheritance and modernized development of regional academic schools. It contributes to advancing clinical diagnosis and treatment toward greater precision and personalization.

BACKGROUND:Formononetin demonstrates potent anti-inflammatory and antioxidant abilities.However,its protective effect on nucleus pulposus mesenchymal stem cells is not yet clear.OBJECTIVE:To investigate the effect and mechanism of formononetin on nucleus pulposus mesenchymal stem cells under an inflammatory microenvironment.METHODS:(1)Primary nucleus pulposus mesenchymal stem cells were isolated from the intervertebral discs of SD rats,and flow cytometry was performed to identify the surface markers of mesenchymal stem cells.(2)The CCK-8 assay was employed to evaluate the impact of lipopolysaccharide and formononetin on the proliferation viability of nucleus pulposus mesenchymal stem cells,aiming to determine the appropriate concentration of formononetin for subsequent cell treatments.(3)An inflammatory microenvironment was simulated by adding 5 μg/mL lipopolysaccharide to the DMEM/F-12 culture medium,and nucleus pulposus mesenchymal stem cells were treated with different concentrations of formononetin for 24 hours.Levels of inflammation markers were detected using western blot assay,real-time quantitative PCR,and immunofluorescence.Western blot assay was conducted to measure the protein levels of the nuclear factor kappa B signaling pathway.RESULTS AND CONCLUSION:(1)The nucleus pulposus mesenchymal stem cells cultured in adherent wall were shuttle-shaped with good growth status.The results of flow cytometry showed that the surface markers of mesenchymal stem cells were positive for CD29,CD44,and CD90,and the surface markers of hematopoietic stem cells were negative for CD34 and CD45.(2)The treatment with formononetin at 12.5,25,50,100,and 200 μmol/L concentrations for 24 hours had no significant proliferation inhibitory effect on nucleus pulposus mesenchymal stem cells.Compared with the lipopolysaccharide group,the cell viability of nucleus pulposus mesenchymal stem cells treated with 12.5,25,and 50 μmol/L formononetin for 24 hours was significantly increased,so formononetin at 12.5,25,and 50 μmol/L concentrations was subsequently selected as the low,medium,and high concentrations for treating nucleus pulposus mesenchymal stem cells.(3)Compared with the lipopolysaccharide group,the protein and mRNA expressions of matrix metalloproteinase-3,matrix metalloproteinase-13,and tumor necrosis factor-α in nucleus pulposus mesenchymal stem cells in the low,medium,and high concentrations of formononetin groups were significantly decreased(P＜0.05)in a dose-dependent manner.(4)Compared with the lipopolysaccharide group,the expressions of phosphorylated nuclear factor kappa B and phosphorylated nuclear factor kappa B inhibitor protein in nucleus pulposus mesenchymal stem cells in the low,medium,and high concentrations of formononetin groups were significantly decreased(P＜0.05)in a dose-dependent manner.The above results suggest that formononetin may attenuate lipopolysaccharide-induced inflammation in rat nucleus pulposus mesenchymal stem cells by inhibiting the activation of the nuclear factor kappa B signaling pathway.

Objective:To explore the differences in early clinical features between Kawasaki disease shock syndrome (KDSS) and septic shock (SS).Methods:A retrospective case-control study was conducted. Clinical data was collected from 64 children who were diagnosed with KDSS or SS and admitted to the Department of Critical Care Medicine of Capital Center for Children′s Health, Capital Medical University from January 2018 to February 2025. Mann-Whitney U test, χ2 test, or Fisher′s exact test were used to compare the differences in clinical features, treatment, and outcomes between children with KDSS and SS. Lasso regression was applied to screen predictive variables, and multivariable logistic regression analysis was performed to identify factors associated with KDSS. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of parameters for KDSS. Results:Among the 64 children (30 males and 34 females), the age was 3.6 (1.2, 6.5) years. There were 51 cases in the SS group and 13 cases in the KDSS group. Compared to children with SS, children with KDSS had a longer pre-shock fever duration, lower lactate levels and serum albumin levels, and higher soluble interleukin-2 receptor (sIL-2R) levels (all P<0.05). Additionally, they exhibited a higher incidence of coronary involvement, pericardial effusion, and ascites, a higher utilization rate of intravenous immunoglobulin, and a lower utilization rate of invasive mechanical ventilation (all P<0.05). There was no significant difference in in-hospital mortality between KDSS and SS ( P=0.574). Multivariate logistic regression analysis identified pre-shock fever duration and sIL-2R as independent factors associated with KDSS ( OR=1.52 and 1.54 per 1 000 U increase, 95% CI 1.12-2.05 and 1.06-2.24, respectively; both P<0.05). ROC curve analysis showed that the areas under the curve for pre-shock fever duration and sIL-2R in identifying KDSS were 0.83 (95% CI 0.73-0.94, P=0.001) and 0.70 (95% CI 0.53-0.87, P=0.042), respectively. The optimal cutoff values were 3.5 d and 3.8×10 6 U/L, with sensitivities of 0.91 and 0.82, and specificities of 0.71 and 0.62, respectively. Conclusions:Children with KDSS have higher incidences of coronary involvement, pericardial effusion, and ascites compared to those with SS. Pre-shock fever duration and sIL-2R may serve as potential early indicators for distinguishing KDSS from SS.

Objective:To investigate the value of targeted three-dimensional contrast-enhanced ultrasound（3D-tCEUS）in efficacy evaluation of non-surgical treatments for renal cell carcinoma（RCC）.Methods:Forty nude mice with subcutaneous xenograft tumor model of human RCC（786-O cells）were divided into four groups based on different treatment methods：control，thermal ablation（TA），sunitinib（Suni），and TA+Suni. 3D-tCEUS were performed on days 1，3，7，and 14 post-treatment using self-developed vascular endothelial growth factor receptor 2（VEGFR2）targeted microbubbles. Tumor overall volume（V T）and non-enhanced volume（V N）were measured，from which the volume of the active（enhanced）region was calculated as V A = V T - V N. The tumor total and active area volume was standardized as V T st and V A st（standardized tumor volume = tumor volume after treatment / tumor volume at the beginning of treatment）. Tumor growth curves were plotted and tumor inhibition rates calculated for V T and V A respectively. Quantitative parameters，including the area under the curve（AUC）and the difference in peak intensity before and after burst（dTE），were obtained from the viable tumor enhanced region，and the standardized targeted quantitative parameters were derived by calculating the ratios of parameters at various time points post-treatment to those pre-treatment. The differences in V T st，V A st，AUC and dTE between different treatment groups at different time points were compared. At the end of the experiment，tumor tissues were obtained for immunohistochemical staining to observe the expression of VEGFR2 and CD31 antigens. Results:During the treatment period，no statistically significant differences in weight changes were observed among groups（all P > 0.05）. When V T was taken as the research object，V T st increased across all groups during the treatment period，with the TA group showing the most significant growth，while the TA + Suni group exhibited the smoothest increase in growth curve. When analyzing the tumor enhanced region，tumor growth trend of V A st was different with V T st for all groups；the Suni group showed a slow upward trend，whereas the TA + Suni group showed a continuous decline. Significant differences in tumor inhibition rate originated from V T and V A were noted within the same experimental group（ P < 0.05 for all experimental groups）. One day post-treatment，the AUC and dTE of the TA group were higher than that of the Control group，while the dTE of the TA + Suni group was lower than that of the Control group（all P < 0.05）. By day 3，statistically significant differences in AUC and dTE were observed between each experimental group and Control groups（all P < 0.05）. At day 14，the TA group showed increased AUC and dTE compared with those before treatment，while all other groups，particularly Suni group and TA + Suni group，demonstrated significant reductions（all P < 0.05）. Immunohistochemical results revealed the highest VEGFR2 and CD31 positivity in the TA group，followed by the Control group，while the Suni and TA + Suni groups exhibited lower rates. Conclusions:The combination of TA and targeted therapy effectively induces RCC cells death，demonstrating superior efficacy compared to monotherapy. 3D-tCEUS serves as a accurate and reliable tool for early evaluating the efficacy of non-surgical RCC treatments.

Objective To investigate the relationship of serum levels of neurofilament light chain protein(NFL)and chemerin with cerebral ischemia after interventional therapy in elderly patients with unruptured intracranial aneurysms.Methods A total of 258 patients with unruptured in-tracranial aneurysms undergoing stent-assisted coil embolization in our hospital from January 2020 to January 2024 were enrolled.They were divided into a cerebral ischemia group(52 cases)and a non-cerebral ischemia group(206 cases).The serum NFL and chemerin levels were detected.Multivariate logistic regression analysis was conducted to analyze the risk factors for cerebral is-chemia in the patients after interventional surgery.Results The cerebral ischemia group had sig-nificantly higher ratio of implantation of 3 stents,larger diameter of aneurysms,increased levels of NFL and chemerin before operation,10 min from the start of operation and 24 h after operation,and longer operation time than the non-cerebral ischemia group(P＜0.05,P＜0.01).Larger aneu-rysm diameter,longer operation time,and higher NFL and chemerin levels were the risk factors for cerebral ischemia in patients with unruptured intracranial aneurysm after interventional sur-gery(P＜0.05,P＜0.01).The AUC value of aneurysm diameter,operation time,NFL and chemerin,and combination of these indicators in predicting cerebral ischemia in patients with un-ruptured intracranial aneurysm after interventional surgery was 0.772,0.794,0.826,0.837,and 0.920,respectively,with that of the combination higher than that of each indicator alone(P＜0.05).Conclusion For the elderly patients with unruptured intracranial aneurysms,the increases of serum NFL and chemerin levels are associated with cerebral ischemia after stent-assisted coil embolization,which can predict the risk of cerebral ischemia after interventional therapy.

Objective:To explore the current implementation status and challenges of family doctor contract services (FDCS) from the perspective of contracted residents.Methods:This qualitative study used purposive sampling to select contracted residents from 11 primary healthcare institutions across five cities in China. Semi-structured interviews were conducted from March to December 2024, covering topics such as awareness of contracting, service experience, health needs, service continuity, and policy recommendations. Thematic framework analysis was applied to organize, code, and summarize the data.Results:A total of 25 contracted residents were interviewed (6 men, 19 women; 11 from central urban areas, 14 from suburban or rural towns; 8 with chronic diseases). Three main themes and ten sub-themes emerged: Theme Ⅰ: Pathways to improved service accessibility (optimized chronic disease management, more efficient referrals, and improved health education). Theme Ⅱ: Structural misalignment between supply and demand (limited specialty services despite patient needs, insufficient coverage and public awareness of home-based medical care, imbalanced human resources, and service disruption due to clinician turnover). Theme Ⅲ: Challenges in service awareness and communication mechanisms (information asymmetry and public misperception regarding FDCS, perverse incentives in administrative performance evaluation, and communication barriers in building patient-doctor trust).Conclusions:While FDCS has shown progress in chronic disease management, referral coordination, and health education, structural supply-demand gaps and communication challenges continue to hinder service quality. Improvements in resource allocation and service models are needed to support high-quality development.

DiGeorge(DGS)syndrome is an autosomal dominant disorder caused by 22q11.2 microdeletions,most patients developed the disease in childhood.22q11.2 deletion syndrome,and the mutation types are dominated by haploid deletion of this gene.We report a young patient with hypoparathyroidism(parathyroidism)induced by DGS syndrome combined with hypocalcemic heart failure.Genetic testing revealed pathogenic copy number variants associated with the clinical phenotype of the subject.About 2 674 kb of deletion variation was detected at q11.21 position on chromosome 22,which contained the TBX1 gene and was a pathogenic mutation.This paper discusses the clinical features,pathogenesis and current treatment of DGS,and emphasizes the importance of early screening,early diagnosis and treatment,and regular follow-up of heart failure,aiming to enhance the awareness of clinicians and geneticists on DGS syndrome.

Objective:To explore the mechanism through which the Ginkgo biloba extract(EGb)ameliorates depres-sion-like behaviors in chronic copper-exposed mice.Methods:A mouse model with depression was induced by chronic oral administration of copper sulfate solution(200 mg/L),followed by oral administration of the EGb(120 mg/L)for one month.Elevated plus-maze test,forced swimming test,and sucrose preference test were employed to detect the de-pression-like behaviors of mice.TUNEL staining was utilized to examine apoptosis in the hippocampal region of mice.Immunohistochemistry was adopted to detect the in situ expression of pro-brain-derived neurotrophic factor(proBDNF)and brain-derived neurotrophic factor(BDNF)in the hippocampal region.RT-qPCR was used to measure the expression of the BDNF mRNA.Western blot was utilized to determine the expressions of proteins such as proBDNF,mature BDNF(mBDNF),cAMP response element binding protein(CREB),phospho-CREB(p-CREB),tyrosine kinase receptor B(TrkB),p75 neurotrophin Receptor(p75NTR),furin,proprotein convertase subtilisin/kexin type 1(PCSK1),and matrix metalloproteinase-9(MMP9).Results:Chronic copper exposure led to depression-like behaviors in mice,in-creased neuronal apoptosis in the hippocampal region,enhanced proBDNF expression and reduced mBDNF expression(P＜0.05),decreased the expression of the downstream receptor protein TrkB and increased the expression of p75NTR(P＜0.05),and decreased the level of CREB and p-CREB(P＜0.05).Meanwhile,the expressions of intracellular proteases furin and PCSK1 in the hippocampal region of mice with depression-like behaviors decreased(P＜0.05),while the expression of extracellular protease MMP9 increased(P＜0.05).EGb was capable of alleviating depression-like behaviors and neuronal apoptosis in mice and partially reversing the abnormal expressions of BDNF,proBDNF,TrkB,p75NTR,CREB,p-CREB,furin,and PCSK1 proteins caused by copper exposure.Conclusion:Chronic copper exposure can lead to depression-like behaviors and apoptosis in mice.EGb can reverse these manifestations and corre-late with the balance of proBDNF/BDNF in the hippocampal region,which may offer novel insights for the treatment of depression.

Objective To investigate the correlation between G protein-coupled receptor family C group 6 member A(GPRC6A)gene polymorphisms and their expression and pulmonary infections in elderly patients with chronic heart failure(CHF).Methods 138 elderly CHF patients admitted to the Xianyang First People's Hospital from January 2021 to January 2024 were selected as the research subjects,and were divided into an infected group(n=42)and an uninfected group(n=96)based on their lung infection status.Polymerase chain reaction(PCR)was used to detect polymorphisms at the rs6901250 and rs1606365 loci of the GPRC6A gene.The allele and genotype frequency distributions of the infected and uninfected groups were compared.Logistic regression modeling was used to analyze the s6901250 and rs1606365 loci under three genetic models(co-dominant,dominant and reces-sive)and lung infections in elderly patients with CHF.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression level of GPRC6A gene.The predictive value of the mRNA expression level of the GPRC6A gene for the development of pulmonary infections in elderly patients with CHF was analyzed by applying the receiver operator characteristic(ROC)curve.Results The distribution of genotypes at loci rs6901250 and rs1606365 of the GPRC6A gene in both the infected and uninfected groups of the lungs of elderly CHF patients conformed to the Hardy-Weinberg equilibrium law(χ2=0.199～0.376,all P>0.05),which was representative of the population.Compared with the uninfected group,the frequency of allele A at locus rs6901250(57.14%vs 41.67%)was significantly higher in the infected group,Allele G(54.76%vs.37.50%)and genotype GG(14.06%vs 29.99%)frequencies were significantly higher at locus rs1606365,and the differences were statistically significant(χ2=5.628,7.114,6.849,all P<0.05).At locus rs6901250,in the co-dominant model(GG vs AA)and the dominant model(GA+AA vs GG),the elderly CHF patients with AA genotype the risk of lung infection was higher than that of GG genotype(OR=1.753,1.546,all P<0.05);.rs1606365 locus showed that the risk of lung infection was higher than that of CC genotype in el-derly CHF patients with GG genotype under all three genetic models of co-dominant model(CC vs GG),dominant model(CG+GG vs CC)and recessive model(CG+CC vs GG)(OR=1.833,1.741,0.695,all P<0.05).The mRNA expression level of GPR-C6A gene in the lung-infected group of elderly CHF patients(1.43±0.35)was significantly higher than that in the uninfected group(1.02±0.21),and the difference was statistically significant(t=8.515,P<0.001).The results of the ROC curve analysis showed that the GPRC6A gene expression level predicted lung infection in elderly CHF patients with an AUC value of 0.895,a cut-offvalue of 1.37,and sensitivity and specificity of 85.7%and 66.7%,respectively.Conclusion The AA genotype at the rs6901250 locus and the GG genotype at the rs1606365 locus of the GPRC6A gene increased the risk of developing lung infec-tions in elderly patients with CHF.MRNA expression levels of the GPRC6A gene were elevated in the infected group,and its ex-pression level could be used as a predictive indicator for the development of lung infections in elderly patients with CHF.

BACKGROUND:Studies have shown that upregulation of heme oxygenase-1 expression enhances cellular antioxidant and anti-apoptotic abilities.However,the effects of upregulating heme oxygenase-1 expression on the proliferation and differentiation of neural stem cells under oxidative stress conditions remain unclear.OBJECTIVE:To investigate the influence of heme oxygenase-1 overexpression on the survival and differentiation capacity of neural stem cells under oxidative stress conditions.METHODS:(1)Mouse primary neural stem cells were isolated and cultured from newborn Balb/c mice.Immunofluorescence was used to detect the neural stem cell marker Nestin.(2)Lentivirus was used to infect neural stem cells to induce heme oxygenase-1 overexpression.Flow cytometry was used to assess green fluorescent protein fluorescence.Western blot assay was performed to detect the expression levels of heme oxygenase-1.(3)H2O2 was added to the lentivirus-infected neural stem cell culture medium to simulate the oxidative stress microenvironment after spinal cord injury.Effects of heme oxygenase-1 overexpression on neural stem cell proliferation and apoptosis levels were analyzed using cell proliferation assay kits,cell apoptosis assay kits,and TUNEL staining kits.(4)The levels of lipid oxidation markers malondialdehyde,catalase,superoxide dismutase,and glutathione peroxidase were detected using assay kits.(5)Flow cytometry was used to measure intracellular reactive oxygen species levels,and neural stem cell differentiation into astrocytes and neurons.(6)The effect of heme oxygenase-1 overexpression on neuronal axon growth during neural stem cell differentiation was observed under optical and fluorescence microscopes.RESULTS AND CONCLUSION:(1)Mouse neural stem cells exhibited stable morphology,good growth status,and high expression of Nestin as detected by immunofluorescence.(2)Western blot analysis showed that the overexpression of heme oxygenase-1 in the overexpression group was significantly higher than that in the empty carrier control group.Flow cytometry was used to detect the expression of green fluorescent protein in the neural stem cells of the heme oxygenase-1 overexpression group and empty vector control group.(3)Overexpression of heme oxygenase-1 maintained the proliferative activity of neural stem cells and significantly reduced the number of apoptotic cells under oxidative stress conditions.(4)Overexpression of heme oxygenase-1 inhibited lipid peroxidation of neural stem cells under oxidative stress microenvironment,enhanced the expression of enzymes related to maintaining the oxidative-reductive balance,and significantly reduced intracellular reactive oxygen species levels.(5)Overexpression of heme oxygenase-1 promoted the differentiation of neural stem cells into neurons and reduced differentiation into astrocytes.(6)The heme oxygenase-1 overexpression group exhibited longer axons,and more intercellular connections.The above results indicate that overexpression of heme oxygenase-1 can alleviate oxidative damage of H2O2-induced neural stem cells,reduce neural stem cell apoptosis,promote proliferation,and facilitate differentiation of neural stem cells into neurons.