With the accelerating trend of population aging, the number of elderly patients with lung cancer continues to rise, and the disease burden is becoming increasingly heavy. The clinical management of these patients faces severe challenges due to their decreased physiological reserve, complex comorbidities, and significant individual heterogeneity. Consequently, under traditional diagnosis and treatment models, doctors often struggle to identify the individualized risks of elderly patients in a timely and comprehensive manner, which can easily lead to decision biases such as undertreatment or overtreatment. In view of this, this study advocates for the establishment of an umbrella decision-making model specifically tailored for elderly lung cancer patients. Grounded in a multidisciplinary team (MDT) platform, this model deeply integrates oncological indicators with the comprehensive geriatric assessment (CGA) system. By holistically considering multidimensional variables including tumor burden, organ function, frailty index, cognitive status, and social support, the model establishes an operational mechanism characterized by "single entry, precise stratification, and targeted selection". Accordingly, patients can be scientifically triaged into distinct intervention tiers, such as active surveillance, minimally invasive surgery, drug therapy, radiotherapy, and best supportive care, thereby achieving real-time alignment between treatment intensity and patient fitness. This article elaborates on the construction logic and key operational procedures of this novel decision-making framework, aiming to guide clinical practice beyond the limitations of a tumor-centric perspective toward a holistic, dynamic, whole-course management strategy. This transition seeks to ensure optimal quality of life and clinical net benefit for elderly patients alongside survival prolongation.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

To understand the infection status of main intestinal protozoa in BALB/c mice and pro-vide a basis for further control of intestinal protozoa infection.Five hundred and forty BALB/c mice provided by four domestic suppliers of BALB/c mice were detected for intestinal protozoa,in which 140 from supplier A,130 from supplier B,135 from supplier C,and 135 from supplier D,re-spectively.Fresh faecal samples were collected from each mouse separately to extract the genome and amplified by nested PCR based on primers for the 18S rRNA gene sequences of Pent-atrichomonas hominis(P.hominis)and Cryptosporidium tyzzeri(C.tyzzeri),and the 16S-like rRNA gene sequence of Tritrichomonas muris(T.muris)and sequenced.The results showed that the total intestinal protozoan infection rate was 7.1％(10/140)in 140 mice faecal samples provided by supplier A.Among them,the positivity rate of T.muris was 7.1％(10/140),C.tyzzeri was 2.1％(3/140),and P.hominis was 7.1％(10/140),the co-infection rate of two intestinal protozoa was 7.1％(10 mice:T.muris+P.hominis),and three intestinal protozoa was 2.1％(3 mice:T.muris+P.hominis+C.tyzzeri).The total intestinal protozoan infection rate in 135 mice faecal samples provided by supplier C was 7.4％,in which,7.4％(10/135)was positive for T.muris.There are no intestinal protozoa to be detected in 130 mice faecal samples from supplier B and 135 mice faecal samples from supplier D.The homology analysis showed that the homology of ampli-fied sequence of T.muris,P.hominis and C.tyzzeri was 98.52％,98.27％and 99.87％compared with published sequence of GenBank No:AY886846.1,GenBank No:AF156964.1 and GenBank No:KJ000486.1,which was clustered as an independent branch by phylogenetic analysis respec-tively.In conclusion,there are intestinal protozoan infection in BALB/c mice in some animal sup-pliers.The co-infections of more than 3 parasites such as T.muris,P.hominis and C.tyzzeri has been found.It will provide a basis for control of intestinal protozoa infection in BALB/c mice in the future.

Aim To investigate the protective effects of Tilianin on lipopolysaccharide(LPS)-induced septice-mia-induced myocardial injury in rats and to explore the related mechanisms.Methods Animals were ran-domly grouped and a rat septicemia-induced myocardial injury model was constructed.Echocardiography was used to assess the cardiac function of rats,left ventricu-lar internal diameter at end-diastole(LVIDd)and left ventricular internal diameter at end-systole(LVIDs)were measured,and left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)were calculated;the kits were used to detect the serum activity of the relevant cardiac enzymes and the level of inflammatory factors;HE staining was used to observe the morphological changes of myocardium;immunofluorescence staining of cardiac tissues was used to detect the nuclear translocation of NF-κB p65;Western blot was used to detect the expression of TLR4,MyD88,p-NF-κB p65,and NLRP3 proteins in cardiac tissues.Results Compared with the model group,each administration group differently upregulated LVEF,LVFS,and LVIDs,and improved the coordina-tion of LV wall fluctuations in the model group of rats;cardiac enzymes LDH and CK-MB levels increased,and levels of inflammatory factors TNF-α,IL-6,and IL-1 β were reduced,exerting cardioprotective effects;HE staining showed that myocardial tissue cell gap was re-duced,myocardial fiber breakage was reduced,cardio-myocyte arrangement tended to be normal,and inflam-matory cell infiltration was reduced;NF-κB p65 entry into the nucleus was reduced,and phosphorylated NF-κB p65(p-NF-κB p65)expression was reduced;and Western blot results showed that the expression of TLR4,MyD88,and NLRP3 proteins was reduced.Conclusions Tilianin pretreatment reduces serum my-ocardial enzymes and inflammatory factors and im-proves myocardial injury in rats with septicemia-in-duced myocardial injury,which may be related to the Tilianin anti-TLR4/NF-κB/NLRP3 inflammatory signa-ling pathway.

The purpose of this study was to establish a luciferase immunosorbent assay(LISA)using the Crimean-Congo hemorrhagic fever virus(CCHFV)glycoprotein C(Gc),a specific antigen,for the detection of CCHFV IgG antibodies.Three antigenic fragments based on CCHFV glycoprotein C were designed,and three recombinant plasmids were constructed by liga-tion with the NanoLuc luciferase(NLuc)expression vector pNLF1-N through molecular cloning.The accuracy of the sequences in the recombinant plasmids was confirmed through sequencing.The recombinant plasmids were transfected into eukaryotic cells to obtain fusion proteins containing specific antigens and luciferase,and the expression of the fusion proteins was verified by western blotting,thereby facilitating the establishment of the CCHFV-LISA detection technique.The assay's sensitivity,specificity,and stability were evaluated and compared with those of a commercial CCHFV IgG antibody test kit.Three recom-binant antigen fragments of CCHFV Gc—NLuc-Gc-Full,NLuc-Gc-C1,and NLuc-Gc-C2—were expressed,with molecular weights of 80.1 kDa,62.8 kDa,and 53.9 kDa,respectively.The optimal fragment for CCHFV detection was NLuc-Gc-C2.The sensitivity of the CCHFV-LISA was 90.9％,and the specificity was 100％;the findings were highly concordant with those for the commercial CCHFV enzyme-linked immunosorbent assay kit.Repeatability tests indicated no statistically significant differ-ences in inter-and intra-assay variability within the same batch.The LISA was highly specific,sensitive,and user-friendly in detecting IgG antibodies against the CCHFV.Therefore,this method may facilitate serological diagnosis and epidemiological studies in endemic regions,and provide essential technical support for disease surveillance and early warning.

Aim To explore the in vitro anti-human triple-negative breast cancer(TNBC)effect and mech-anism of Austocystin R.Methods MTT assay was used to evaluate the anti-tumor potential of Austocystin R for various human tumor cells and normal cells.Flow cytometry was employed to evaluate the influence on cell cycle progression.mRFP-GFP-LC3 adenovirus transfection was used to evaluate the autophagic flux process.Western blot assay was used to verify the effect of Austocystin R on the expression of related pro-teins.Results The results showed that Austocystin R significantly inhibited the proliferation of multiple tumor cells in a dose-dependent manner,especially for the MDA-MB-231 cells with an IC50 of 1.45μmol·L-1.In addition,Austocystin R increased the protein expression of PTEN,p53,p-p53,p27,p21,and down-regulated the expression of p-PI3K,p-AKT and p-mTOR.Austocystin R can significantly increase the proportion of S-phase MDA-MB-231 cells,inhibit the expression of Cyclin D1,CDK4,CDK6,Rb,Cyclin B1 and CDK1,and promote the expression of Cyclin E1 and CDK2.Austocystin R can promote the autophagic flux process of MDA-MB-231 cells,promote the expres-sion of LC3 Ⅰ/Ⅱ,p-Beclin-1,p-ULK1,HMGB-1 and Atg 14 proteins,and inhibit the expression of Beclin-1,ULK1,p62,ATG 3,ATG 4B,ATG 5,ATG 7,ATG 12,ATG 13 and ATG 16L1 proteins.Conclusion Austo-cystin R can exhibit its anti-TNBC activity by inhibi-ting the PI3K/AKT/mTOR signaling pathway,blocking the cell cycle at the S phase and inducing autophagic cell death.

The purpose of this study was to establish a luciferase immunosorbent assay(LISA)using the Crimean-Congo hemorrhagic fever virus(CCHFV)glycoprotein C(Gc),a specific antigen,for the detection of CCHFV IgG antibodies.Three antigenic fragments based on CCHFV glycoprotein C were designed,and three recombinant plasmids were constructed by liga-tion with the NanoLuc luciferase(NLuc)expression vector pNLF1-N through molecular cloning.The accuracy of the sequences in the recombinant plasmids was confirmed through sequencing.The recombinant plasmids were transfected into eukaryotic cells to obtain fusion proteins containing specific antigens and luciferase,and the expression of the fusion proteins was verified by western blotting,thereby facilitating the establishment of the CCHFV-LISA detection technique.The assay's sensitivity,specificity,and stability were evaluated and compared with those of a commercial CCHFV IgG antibody test kit.Three recom-binant antigen fragments of CCHFV Gc—NLuc-Gc-Full,NLuc-Gc-C1,and NLuc-Gc-C2—were expressed,with molecular weights of 80.1 kDa,62.8 kDa,and 53.9 kDa,respectively.The optimal fragment for CCHFV detection was NLuc-Gc-C2.The sensitivity of the CCHFV-LISA was 90.9％,and the specificity was 100％;the findings were highly concordant with those for the commercial CCHFV enzyme-linked immunosorbent assay kit.Repeatability tests indicated no statistically significant differ-ences in inter-and intra-assay variability within the same batch.The LISA was highly specific,sensitive,and user-friendly in detecting IgG antibodies against the CCHFV.Therefore,this method may facilitate serological diagnosis and epidemiological studies in endemic regions,and provide essential technical support for disease surveillance and early warning.

Objective:To investigate the predictive value of endothelial activation and stress index(EASIX)for the prognosis of patients with mantle cell lymphoma(MCL).Methods:A retrospective analysis was conducted to assess prognosis and compare the clinical features of patients diagnosed with MCL who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to June 2023,had therapeutic indications and received standard treatment.Results:A total of 66 patients were included and divided into high EASIX group and low EASIX group,according to a cutoff value of 0.97 determined by the receiver operating characteristic(ROC)curve.Multivariate Cox regression analysis showed that prealbumin＜0.2 g/L,high EASIX,and ECOG PS score ≥2 were independent risk factors influencing overall survival(OS)in MCL patients.The median OS of patients in the high and low EASIX group was 13.0 and 37.5 months,and the median progression-free survival was 8.8 and 26.0 months,respectively.The proportions of patients with ECOG PS score ≥2 and prealbumin＜0.2 g/L at onset significantly increased in the high EASIX group compared to those in the low EASIX group.Conclusion:At the time of initial diagnosis,EASIX can serve as an independent prognostic indicator impacting OS in patients with MCL.Furthermore,patients in the high EASIX group experience a poorer prognosis and shorter survival duration compared with those in the low EASIX group.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Guided by the concept of quality by design(QbD), this study optimizes the calcination and quenching process of calcined Magnetitum and establishes the XRD characteristic spectra of calcined Magnetitum, providing a scientific basis for the formulation of quality standards. Based on the processing methods and quality requirements of Magnetitum in the Chinese Pharmacopoeia, the critical process parameters(CPPs) identified were calcination temperature, calcination time, particle size, laying thickness, and the number of vinegar quenching cycles. The critical quality attributes(CQAs) included Fe mass fraction, Fe~(2+) dissolution, and surface color. The weight coefficients were determined by combining Analytic Hierarchy Process(AHP) and the criteria importance though intercrieria correlation(CRITIC) method, and the calcination process was optimized using orthogonal experimentation. Surface color was selected as a CQA, and based on the principle of color value, the surface color of calcined Magnetitum was objectively quantified. The vinegar quenching process was then optimized to determine the best processing conditions. X-ray diffraction(XRD) was used to establish the characteristic spectra of calcined Magnetitum, and methods such as similarity evaluation, cluster analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to evaluate the quality of the spectra. The optimized calcined Magnetitum preparation process was found to be calcination at 750 ℃ for 1 h, with a laying thickness of 4 cm, a particle size of 0.4-0.8 cm, and one vinegar quenching cycle(Magnetitum-vinegar ratio 10∶3), which was stable and feasible. The XRD characteristic spectra analysis method, featuring 9 common peaks as fingerprint information, was established. The average correlation coefficient ranged from 0.839 5-0.988 1, and the average angle cosine ranged from 0.914 4 to 0.995 6, indicating good similarity. Cluster analysis results showed that Magnetitum and calcined Magnetitum could be grouped together, with similar compositions. OPLS-DA discriminant analysis identified three key characteristic peaks, with Fe_2O_3 being the distinguishing component between the two. The final optimized processing method is stable and feasible, and the XRD characteristic spectra of calcined Magnetitum was initially established, providing a reference for subsequent quality control and the formulation of quality standards for calcined Magnetitum.
X-Ray Diffraction/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Particle Size