Diabetic nephropathy （DKD）， as a common microvascular complication of diabetes mellitus （DM）， is a major cause of end-stage renal disease （ESRD）. Its clinical manifestations include increased urinary protein excretion， thickening of the glomerular basement membrane， and renal tubulointerstitial fibrosis. The pathogenesis of DKD is complex and involves multiple factors， including disordered glucose metabolism， hemodynamic alterations， and oxidative stress. Although modern medical approaches can alleviate certain symptoms， they still have limitations such as insufficient therapeutic targeting and prominent adverse effects. The transforming growth factor-β/Smad （TGF-β/Smad） signaling pathway is not only a tissue fibrosis pathway that has attracted considerable attention in recent years， but also regulates multiple protein molecules， including the glomerular podocyte slit diaphragm protein Podocin， interleukin-1β （IL-1β）， and superoxide dismutase （SOD）， thereby participating in various pathological processes and ultimately mediating renal injury. Flavonoid compounds， owing to their sustained pharmacological effects， broad spectrum of action， and high safety profile， have become ideal candidates for targeted therapy research in DKD. Existing studies have shown that these compounds can exert inhibitory effects on renal fibrosis， alleviate inflammatory responses， protect podocytes， and reduce oxidative stress by regulating the interactions between the TGF-β/Smad signaling pathway and the aforementioned protein molecules， thereby maintaining renal structure and function， reducing proteinuria， and significantly improving DKD lesions. This review briefly outlines the composition and functions of the TGF-β/Smad signaling pathway， elucidates the mechanisms by which this pathway regulates DKD， and focuses on summarizing major studies from the past decade on flavonoid-based interventions in DKD through targeted inhibition of the TGF-β/Smad signaling pathway. Furthermore， it discusses the considerable therapeutic potential of flavonoids in the treatment of this disease， aiming to provide a scientific basis for future clinical prevention and treatment of DKD and to promote the development of targeted drugs.

Numerous techniques for C2 screw fixation have been recently reported. However, concerns remain regarding the risk of spinal cord or vertebral artery injury and inadequate biomechanical stability. To our knowledge, the specific transforaminal “in-out-in” screw fixation technique has not been previously reported. This study aimed to investigate the feasibility and preliminary clinical outcomes of a transforaminal “in-out-in” multi-cortical purchase screw for posterior C2 screw fixation. Between October 2022 and March 2023, 10 patients underwent posterior atlantoaxial internal fixation. All patients had severe hypoplasia of the C2 pedicle on at least one side, precluding the use of standard C2 pedicle screws. A transforaminal “in-out-in” screw was used as an alternative. No spinal cord injury, vascular injury, or other major complications were observed. No implant failure was noted at the final follow-up. In conclusion, the transforaminal “in-out-in” screw may achieve rigid three-column fixation with multiple cortical purchases. It represents a safe and effective alternative for posterior C2 fixation in patients with severely narrow C2 pedicles where traditional pedicle screw placement is not feasible.

With the continuous deepening of the concept of precision diagnosis and treatment for lung cancer, how to achieve higher efficiency and accuracy in the screening, diagnosis, and treatment pathways in clinical practice has become an important issue that urgently needs to be overcome. The current clinical difficulty lies in the fact that despite continuous advancements in imaging and molecular diagnostic technologies, there are still limitations in manual efficiency and subjective experience when it comes to massive data analysis and multi-scale feature extraction. Artificial intelligence (AI), especially algorithm systems based on deep learning, is an innovative technology capable of deeply empowering medical big data. This method utilizes algorithms such as convolutional neural networks, combined with radiomics, pathomics, and multi-modal data fusion analysis, demonstrating immense potential in early precise detection and benign-malignant differentiation of pulmonary nodules, digital pathological subtype recognition and non-invasive prediction of driver genes, precise 3D surgical planning and automatic delineation of radiotherapy target volumes, as well as dynamic risk warning during follow-up. This innovative technology provides a brand-new solution for realizing intelligent and individualized lung cancer diagnosis and treatment models. This consensus, based on the latest evidence from evidence-based medicine and combined with the development trends in the AI field and real-world clinical needs, was ultimately formed by gathering the consensus opinions of multidisciplinary experts in radiology, pathology, thoracic surgery, and other fields. The main content covers the application specifications of AI in the three core scenarios of lung cancer screening, diagnosis, and treatment, the technical standards for data collection and algorithm validation, as well as the ethical and regulatory challenges faced at the current stage. It aims to clarify the applicable boundaries of AI as a clinical auxiliary decision support tool, providing scientific guidance and standardized exploration directions for peers currently engaged in or planning to carry out AI-assisted clinical diagnosis, treatment, and translation of lung cancer.

Objective This study conducted molecular biological identification of the viruses carried by Culex pipiens pallens specimens collected in Shunyi District, Beijing in 2023, and observed the changes in the infection rate of the viruses carried by Cx. pipiens pallens at different collection times. Methods Cx. pipiens pallens were collected using carbon dioxide mosquito traps. The mosquito samples were ground in batches and analyzed by molecular biology technologies. The virus infection rate at different collection times was analyzed statistically. Results 17 strains of Culex pipiens pallens densovirus(CppDNV)were identified from Cx. pipiens pallens samples collected in Shunyi District, Beijing, in 2023. The nucleotide sequence analysis of the virus genome coding region showed that CppDNV was a single-stranded DNA virus with a total length of 3 335 nt, encoding 2 non-structural proteins(NS1, NS2)and 1 capsid protein(VP). The nucleotide(amino acid)sequence lengths of the three proteins were 2 376 nt(791 aa),1 092 nt(363 aa)and 1 071 nt(356 aa), respectively. Phylogenetic analysis showed that CppDNV was located in genus Brevihamaparvovirus. Statistical analysis showed no significant difference in infection rates across collection times(χ2=4.429, P=0.194). Conclusions CppDNV was identified in Cx. pipiens pallens in Beijing, and it was stably maintained in this natural population.

Objective:To evaluate the cost-effectiveness and impact on mortality of health management services for the elderly aged 65 years and older in national essential public health service project.Methods:Based on the data of county-level medical institutions in Henan Province from 2019 to 2024,the Random Forest Method was used to construct a counterfactual framework to predict the hospitalization expenses under the unmanaged scenario,and then the cost-benefit ratio(BCR)and net income were calculated.Time-dependent Cox proportional hazards model was used to evaluate the effect of health management on all-cause mortality and cardiovascular and cerebrovascular disease mortality in the elderly.Results:A total of 962 955 elderly patients were included,451 119(46.85%)were included in the management group.The average hospitalization cost of the management group was significantly lower than that of the non-management group(P<0.05).Except for 2020-2021,BCRS in 2019 and 2022-2024 were 6.34,2.05,4.45 and 6.60,respectively.The risk of all-cause death was reduced by 76.96%,and the risk of cardiovascular and cerebrovascular death was reduced by 75.57%in the elderly patients included in the management group compared with those not included in the management group.Suggestions:It is necessary to establish a health outcomes-based evaluation system and promote the transformation and upgrading of the service model from single chronic disease management to"integrated health services with multi-disease management".

To construct a recombinant fowl adenovirus 4(FAdV-4)expressing the Cap protein of goose astrovirus genotype 2(GoAstV-2),the expression cassette of Cap gene was inserted into the natural 1 966 bp deletion region of the FAdV-4 genome in the infectious clone p15A-cm-FAdV4-HNJZ.The resulted recombinant plasmid p15A-cm-FAdV4-HNJZ-Cap/GoAstV-2 was linearized with restriction enzyme and transfected into chicken hepatoma cell line(LMH)to rescue the recombinant FAdV-4 expressing the Cap protein of GoAstV-2,rF Ad V4-Cap/GoAstV-2.After 15 passages in LMH cells,the recombinant rFAdV4-Cap/GoAstV-2 was identified by PCR using primers flanking the insertion site of the Cap gene expression cassette and using viral genome DNA extracted from rFAdV4-Cap/GoAstV-2 infected LMH cells as template.LMH cells were in-fected with 15th passage rFAdV4-Cap/GoAstV-2 and indirect immunofluorescence was performed with a polyclonal antibody against Cap protein as the primary antibody.Western blot was carried out with lysates of rFAdV4-Cap/GoAstV-2 infected LMH cells.The in vitro replication dynamic of the 15th passage of the rFAdV4-Cap/GoAstV-2 was also investigated in LMH cells.The results demonstrated that the Cap gene of GoAstV-2 was presented in the genome of the recombinant vi-rus rF AdV4-Cap/Go Ast V-2,and could be expressed stably.The prepared recombinant virus in this study will lay a foundation for developing inactivated bivalent vaccine candidate against co-in-fection of FAdV-4 and GoAstV-2 in goose.

This study was aimed at exploring the interaction between the nucleoprotein(NP)of influenza A virus(IAV)and TRIM25.The physicochemical properties and protein structure of IAV NP protein were analyzed through bioinformatics methods.The interaction between IAV NP and TRIM25 proteins was simulated with molecular docking techniques,and the in-teraction sites were predicted.With the cDNA of the A/Puerto Rico/8/1934(H1N1)PR8 strain as the template,the NP pro-tein was cloned into the eukaryotic expression vector pCMV-C-Flag through PCR amplification,the eukaryotic expression re-combinant plasmid pCMV-Flag-NP was constructed,and the expression was further verified.The protein expression levels of pCMV-Flag-NP and pCMV-HA-TRIM25 were detected at various time periods.The interaction between NP protein and TRIM25 protein was verified by co-immunoprecipitation.The co-localization of NP protein and TRIM25 protein in cells was ob-served with laser confocal microscopy.Bioinformatics analysis revealed that the NP protein consists of 498 amino acids and 20 amino acids,and is an unstable hydrophilic protein.The NP protein has multiple phosphorylation sites,as well as N-glycosyla-tion and O-glycosylation sites,but no transmembrane domain or signal peptide domain.Additionally,the NP protein's second-ary structure consists of a high proportion of alpha-helices and random coils.The molecular docking prediction results indicated that IAV NP interacts with TRIM25 protein and has multiple potential interaction sites,including the 233rd alanine,234th ala-nine,236th lysine,and 440th alanine of the NP protein.After successfully constructing and expressing the IAV NP protein,we verified the interaction between IAV NP and TRIM25 protein by immunoprecipitation and laser confocal microscopy obser-vations.Our results together suggested that the structure of the IAV NP protein is closely related to its function,and its im-portance to the virus is clear.In addition,the interaction between IAV NP and TRIM25 protein may be associated with TRIM25's anti-influenza virus mechanism.Further in-depth research may provide new ideas for anti-influenza virus strategies.

Aim To explore the mechanism of Epimedii folium-Astmgali radix activating the SCF/c-kit signa-ling pathway to activate the PI3K/Akt signaling path-way and its effect on sperm production and vitality in oligoasthenospermia.Methods Sixty male SD rats were used to establish a model of oligoasthenospermia with cyclophosphamide.They were randomly divided into six groups:experimental group(further divided into high,medium,and low dose group),model group,control group and blank group.The oligoasthenosper-mia model was established by using cyclophosphamide in experimental group,levocarnitine group and model group.The rats in the high,medium,and low dose group of the experimental group were orally adminis-tered Epimedii folium-Astmgali radix extract at doses of 800,400,and 200 mg·kg-1,respectively,Once daily for 35 days.Rats of the control group were orally ad-ministered 250 mg·kg-1·d-1 of levocarnitine,Once daily for 35 days.ELISA was used to detect serum of T,E2,FSH,and LH.Western blot and IHC staining were used to detect the expression of SCF,c-kit,Bcl-2,Bax,PI3K,and Akt proteins in rat testicular tissues.Sperm activity is examined by microscopy.The testicu-lar tissue structure and cell morphology of rats in each group were observed.Results Compared with the model group,Epimedii folium-Astmgali radix increased the sperm density,total viability rate,and vitality(P＜0.05,P＜0.01),decreased sperm apoptosis rate and LH,T,and E2 levels(P＜0.05,P＜0.01),decreased Bax protein expression in testicular tissue(P＜0.01),and increased Bcl-2,SCF,c-Kit,PI3K,and Akt protein expression(P＜0.05,P＜0.01);it increased the number of germ cells,thickened basement membrane,and significantly improved seminiferous tubule mor-phology,even showing germ cells at different develop-mental stages and mature sperm.Conclusions Epi-medii folium-Astmgali radix has a significant therapeu-tic effect on oligoasthenospermia in rats.Its mechanism may be related to the activation of the SCF/c-kit signa-ling pathway to activate the PI3K/Akt signaling path-way promoting the proliferation and differentiation of germ cells,and promoting sperm production,maturation and motility.

Aim To explore the mechanism of Epimedii folium-Astmgali radix activating the SCF/c-kit signa-ling pathway to activate the PI3K/Akt signaling path-way and its effect on sperm production and vitality in oligoasthenospermia.Methods Sixty male SD rats were used to establish a model of oligoasthenospermia with cyclophosphamide.They were randomly divided into six groups:experimental group(further divided into high,medium,and low dose group),model group,control group and blank group.The oligoasthenosper-mia model was established by using cyclophosphamide in experimental group,levocarnitine group and model group.The rats in the high,medium,and low dose group of the experimental group were orally adminis-tered Epimedii folium-Astmgali radix extract at doses of 800,400,and 200 mg·kg-1,respectively,Once daily for 35 days.Rats of the control group were orally ad-ministered 250 mg·kg-1·d-1 of levocarnitine,Once daily for 35 days.ELISA was used to detect serum of T,E2,FSH,and LH.Western blot and IHC staining were used to detect the expression of SCF,c-kit,Bcl-2,Bax,PI3K,and Akt proteins in rat testicular tissues.Sperm activity is examined by microscopy.The testicu-lar tissue structure and cell morphology of rats in each group were observed.Results Compared with the model group,Epimedii folium-Astmgali radix increased the sperm density,total viability rate,and vitality(P＜0.05,P＜0.01),decreased sperm apoptosis rate and LH,T,and E2 levels(P＜0.05,P＜0.01),decreased Bax protein expression in testicular tissue(P＜0.01),and increased Bcl-2,SCF,c-Kit,PI3K,and Akt protein expression(P＜0.05,P＜0.01);it increased the number of germ cells,thickened basement membrane,and significantly improved seminiferous tubule mor-phology,even showing germ cells at different develop-mental stages and mature sperm.Conclusions Epi-medii folium-Astmgali radix has a significant therapeu-tic effect on oligoasthenospermia in rats.Its mechanism may be related to the activation of the SCF/c-kit signa-ling pathway to activate the PI3K/Akt signaling path-way promoting the proliferation and differentiation of germ cells,and promoting sperm production,maturation and motility.

Objective:To evaluate the cost-effectiveness and impact on mortality of health management services for the elderly aged 65 years and older in national essential public health service project.Methods:Based on the data of county-level medical institutions in Henan Province from 2019 to 2024,the Random Forest Method was used to construct a counterfactual framework to predict the hospitalization expenses under the unmanaged scenario,and then the cost-benefit ratio(BCR)and net income were calculated.Time-dependent Cox proportional hazards model was used to evaluate the effect of health management on all-cause mortality and cardiovascular and cerebrovascular disease mortality in the elderly.Results:A total of 962 955 elderly patients were included,451 119(46.85%)were included in the management group.The average hospitalization cost of the management group was significantly lower than that of the non-management group(P<0.05).Except for 2020-2021,BCRS in 2019 and 2022-2024 were 6.34,2.05,4.45 and 6.60,respectively.The risk of all-cause death was reduced by 76.96%,and the risk of cardiovascular and cerebrovascular death was reduced by 75.57%in the elderly patients included in the management group compared with those not included in the management group.Suggestions:It is necessary to establish a health outcomes-based evaluation system and promote the transformation and upgrading of the service model from single chronic disease management to"integrated health services with multi-disease management".