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.

ObjectiveTo investigate the whole genomic characteristics and phylogenetic relationships of clinical isolates of enteroaggregative Escherichia coli (EAEC) in diarrhea outpatients in Pudong New Area, Shanghai. MethodsBased on the diarrheal disease surveillance network in Pudong New Area, Shanghai, whole-genome sequencing was performed on a total of 55 EAEC strains isolated from fecal samples of the diarrhea outpatients from January 2015 to December 2019. The genome analyses based on raw sequencing data encompassed genome size, coding genes, dispersed repeat sequences, genomic islands, and protein coding regions, and pan-genome analyses were conducted simultaneously. Contigs sequences assays were performed to analyze molecular characteristics including serotypes, antibiotic resistance genes, and virulence factors. The phylogenetic clusters and multilocus sequence typing (MLST) were identified, and a phylogenetic tree was constructed. ResultsEAEC exhibited an open pan-genome. The predominant serotype of EAEC in diarrhea outpatients in Pudong New Area was O130:H27, and the carriage rate of β-lactam resistance genes was the highest (67.27%, 37/55). A total of 29 virulence factors and 106 virulence genes were identified, phylogenic group B1 was the predominant group, and clonal group CC31 was the dominant clonal group. The strain distribution was highly heterogeneous. ConclusionThe genomic characteristics of EAEC displayed significant strain polymorphism. It is necessary to develop effective strategies for differential diagnosis and improve detection capabilities for infection with EAEC of different serotypes and genotypes.

Objective To investigate alteration in brain gray matter volume in kidney transplant recipients(KTRs)and its correlation with post-traumatic stress symptoms(PTSS)in KTRs so as to provide neuro-imaging evidence for early detection and intervention of PTSS in KTRs.Methods Forty-six KTRs and 46 age-,sex-,and education-matched heath control(HCs)underwent brain MRI scanning with 3D T1-weighted structural images.Voxel-based morphometry(VBM)was applied to compare the gray matter volume between the two groups.For regions with significant differences in gray matter volume between KTRs and HCs,we analyzed the correlations with the Impact of Event Scale-Revised(IES-R)scores,which assess the severity of PTSS.Results Compared to HCs,KTRs showed significant reductions in gray matter volume in the bilateral precentral gyrus,middle frontal gyrus,supplementary motor area,medial paracingulate gyrus,and bilateral middle temporal gyrus(all P＜0.05,TFCE-FWE correction).The gray matter volume of the left middle frontal gyrus in KTRs was negatively correlated with their IES-R scores(r=-0.235,P=0.022).Conclusion KTRs exhibit abnormal gray matter volume,and the gray matter volume of the left middle frontal gyrus is correlated with the severity of PTSS.

Objective:To analyze the effects of fluorine exposure on calcium ion metabolism and the expression of related calcium-regulating proteins in the kidneys of rats.Methods:Forty-five 5-week-old specific pathogen-free male Wistar rats (weighed 90 - 120 g) were selected and divided into three groups according to the randomized numeric table: 0 (control), 50, and 100 mg/L fluorine exposure groups, with 15 rats in each group. The control group was given deionized water, while the 50 and 100 mg/L fluorine exposure groups were given sodium fluoride solutions containing 50 and 100 mg/L fluorine ions, respectively. After 12 weeks, urine samples were collected, and kidneys and blood were harvested. Urinary fluorine levels were measured using a fluoride ion-selective electrode method. Calcium ion levels in the urine, kidneys, and serum were determinated using the methylthymol blue microplate method. The protein expression levels of transient receptor potential vanilloid receptor 5 (TRPV5), calbindin-D28K (CB-D28K), sodium-calcium exchanger-1 (NCX1), Klotho and plasma membrane calcium ATPase 1b (PMCA1b) in the kidneys were detected by Western blotting and immunohistochemistry.Results:The urinary fluorine levels in the control group and the 50 and 100 mg/L fluorine exposure groups were (0.48 ± 0.09), (20.01 ± 1.68), (37.45 ± 2.45) mg/L, respectively, with statistically significant differences between the groups ( F = 929.58, P < 0.001). Significant differences in calcium ion levels in urine, kidneys, and serum were observed among the three groups ( F = 14.66, 11.09, 10.31, P < 0.05). Compared with the control group, the 100 mg/L fluorine exposure group exhibited higher levels of calcium ion in the urine and kidneys, and lower serum calcium ion levels ( P < 0.05). The results of Western blotting analysis revealed that the protein expression levels of TRPV5 and CB-D28K in the kidneys increased with the increase of fluorine exposure level ( Z = 2.11, 2.11, P = 0.035). The protein expression level of NCX1 in the kidneys showed a decreasing trend with increasing fluorine exposure level ( Z = - 2.11, P = 0.035). Significant differences were also observed in the protein expression levels of Klotho and PMCA1b among the three groups ( F = 8.93, 7.08, P < 0.05). Compared with the control group, the 100 mg/L fluorine exposure group showed higher level of Klotho protein expression and lower level of PMCA1b protein expression in the kidneys ( P < 0.05). Immunohistochemical results indicated significant differences in the protein expression levels of TRPV5, CB-D28K, NCX1, and Klotho in the kidneys of the three groups ( F = 27.56, 24.94, 16.05, 32.72, P < 0.05). Compared with the control group, the protein expression levels of TRPV5, CB-D28K, and Klotho in kidneys of 50 and 100 mg/L fluorine exposure groups were higher, while the protein expression levels of NCX1 were lower ( P < 0.05). Conclusion:Fluorine exposure may cause calcium ion metabolism disorders by regulating the expression levels of Klotho and other calcium-regulating proteins in the kidneys.

Objective:To investigate the influencing factors of adult dental fluorosis in drinking water-borne endemic fluorosis areas of Inner Mongolia Autonomous Region.Methods:A case-control study was conducted in January 2024 to select adult fluorosis patients (case group) and healthy individuals (control group) from the drinking water-borne endemic fluorosis areas in Helinger County, Hohhot City, Inner Mongolia Autonomous Region as the survey subjects. Urine samples were collected to determine urinary fluoride concentration. A questionnaire survey was conducted. SPSS 25.0 software was used for χ 2 test and multivariate logistic regression analysis. Restricted cubic spline (RCS) was used to analyze the association between urinary fluoride concentration and the risk of dental fluorosis in adults. Results:A total of 161 individuals were included in the survey, including 100 in the case group and 61 in the control group. The results of univariate analysis showed that there were statistically significant differences in the distribution of gender, smoking, and urinary fluoride concentration between the case group and the control group (χ 2 = 7.54, 5.02, 9.69, P < 0.05). The results of multivariate logistic regression analysis indicated that gender ( OR = 0.36, 95% CI: 0.18 - 0.73, P = 0.005) and urinary fluoride concentration ( OR = 3.08, 95% CI: 1.46 - 6.67, P = 0.003) were the influencing factors of adult fluorosis. RCS analysis showed a significant linear dose-response relationship between the risk of dental fluorosis and urinary fluoride concentration ( Poverall trend = 0.001, Pnonlinear = 0.071). When the urinary fluoride concentration was greater than 1.57 mg/L, the risk of dental fluorosis increased with the increase of urinary fluoride concentration. Conclusion:Gender and urinary fluoride concentration are the risk factors of dental fluorosis in adults in drinking water-borne endemic fluorosis areas of Inner Mongolia Autonomous Region.

Objective To explore the clinical effect of applying an improved"outside-in"technique in hip arthroscopic surgery.Methods Totally 136 patients undergoing hip arthroscopic surgery between June 2021 and July 2023 were selected and studied retrospectively.According to their different surgi-cal approach,they were divided into a modified approach group(n=75,including 30 males and 45 fe-males,with an average age of 36±14)and a classic approach group(n=61,including 33 males and 28 females,with an average age of 31±11).Before as well as 4 weeks,3 months and 6 months after the surgery,both groups were evaluated using the visual analog scale(VAS)and Harris hip score,and observed their surgical complications.Moreover,the surgical outcomes and time of sur-gical approach establishment were compared between the two groups.Results There was no significant difference between the two groups in general information,preoperative VAS and Harris scores.More-over,no significant difference was found between the two groups in the Harris score after surgery.Compared with the classic approach group,the improved group had significantly less surgical time(49.0±16.9 min vs.66.0±13.3 min,P<0.05),without using the C-arm fluoroscopy during surgery.Moreover,in the modified approach group,the time for establishing the mid-anteriorapproach was sig-nificantly shortened(10.4±5.9 min vs.25.9±15.1 min,P<0.05),along with the traction time during surgery(66.0±13.3 min vs.49.0±16.9 min,P<0.05).Conclusion The modified"outside-in"hip ar-throscopy technique is a safe and effective surgical method,easier to operate,with shorter surgical time.

Objective To explore the clinical effect of applying an improved"outside-in"technique in hip arthroscopic surgery.Methods Totally 136 patients undergoing hip arthroscopic surgery between June 2021 and July 2023 were selected and studied retrospectively.According to their different surgi-cal approach,they were divided into a modified approach group(n=75,including 30 males and 45 fe-males,with an average age of 36±14)and a classic approach group(n=61,including 33 males and 28 females,with an average age of 31±11).Before as well as 4 weeks,3 months and 6 months after the surgery,both groups were evaluated using the visual analog scale(VAS)and Harris hip score,and observed their surgical complications.Moreover,the surgical outcomes and time of sur-gical approach establishment were compared between the two groups.Results There was no significant difference between the two groups in general information,preoperative VAS and Harris scores.More-over,no significant difference was found between the two groups in the Harris score after surgery.Compared with the classic approach group,the improved group had significantly less surgical time(49.0±16.9 min vs.66.0±13.3 min,P<0.05),without using the C-arm fluoroscopy during surgery.Moreover,in the modified approach group,the time for establishing the mid-anteriorapproach was sig-nificantly shortened(10.4±5.9 min vs.25.9±15.1 min,P<0.05),along with the traction time during surgery(66.0±13.3 min vs.49.0±16.9 min,P<0.05).Conclusion The modified"outside-in"hip ar-throscopy technique is a safe and effective surgical method,easier to operate,with shorter surgical time.

Trifluridine-tipiracil(TAS-102),as a novel fluorouracil-based chemotherapeutic agent,effectively overcomes fluorouracil resistance in colorectal cancer(CRC)through its unique pharmacological mechanisms,providing a critical treatment option for advanced CRC patients.Probiotics have shown unique value in CRC prevention and adjuvant therapy by regulating intestinal flora homeostasis and modulating host immune response.It is worth noting that the combination of chemotherapeutic drugs and probiotics not only enhances the anti-tumor activity through synergistic effects,but also reduces the adverse effects caused by chemotherapeutic drugs.Based on this,this paper systematically reviews the pharmacological properties of TAS-102 and describes its synergistic effects in combination with other antitumor drugs.It also summarizes the synergistic effect of fluorouracil drugs combined with probiotics to enhance the effectiveness and reduce the toxicity,and discusses the potential value of the combination of TAS-102 and probiotics,which provides a new research direction for optimizing the precision treatment of CRC and a scientific basis for improving the quality of life of patients.

Objective To explore the biological mechanism of radiation resistance in esophageal squamous cell carcinoma(ESCC)and search for effective sensitization targets.Methods We retrieved 186 signaling pathways and related gene information from the MSigDB database.We also obtained RNA transcriptome data of ESCC patients using the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.We collected clinical pathological characteristics and tissue samples of 97 ESCC patients in our hospital from 2013 to 2020.Gene set variation analysis(GSVA)was made to calculate KEGG signaling pathway score,radiotherapy resistance related signaling pathways were screened through random forest algorithm,key genes in the pathway were screened using DESeq2,and a radiotherapy efficacy prediction model was constructed based on support vector machine-recursive feature elimination(SVM-RFE).The results were validated through experiments such as Western blotting and clonogenic assay.Results Based on the KEGG signaling pathway and GSVA enrichment score,random forest analysis showed that in the TCGA and GSE45670 cohorts,the contribution of tryptophan metabolism pathway enrichment values to radiation resistance in ESCC was significantly better than that of the other pathways.DESeq2 analysis revealed that key molecules in the tryptophan metabolism pathway,namely,IDO1,ALDH1B1,AOC1,INMT,AFMID and ALDH7A1,were significantly differentially expressed in the resistant and sensitive groups of ESCC.Based on the SVM-RFE algorithm,the AUC was 0.77,which could accurately predict the radiotherapy efficacy of ESCC.Western blotting experiments showed that IDO1 was highly expressed in ESCC cells,and IDO1 inhibitor treatment significantly inhibited the survival ability and radiosensitivity of KYSE-410 cells.In the enrolled patients of our hospital,immunohistochemical studies showed that IDO1 was highly expressed in the radiotherapy resistant group of ESCC and was associated with poor radiotherapy prognosis in ESCC patients.In addition,further testing showed that the expression of IDO1 in patient samples from our hospital was positively correlated with its PD-L1 expression,but negatively correlated with the infiltration ratio of CD3/CD8 immune cells.Conclusion Tryptophan catabolism is associated with radiation resistance in ESCC,and the key enzyme IDO1 in tryptophan metabolism can be used as a therapeutic target for radiosensitization in ESCC.

Purpose This study aims to analyze genetic mutations in patients with BCR ∷ABL negative myelopro-liferative neoplasms(MPN)and to explore their relationship with clinical features.Methods We retrospectively ana-lyzed the clinical data of 208 patients diagnosed with BCR ∷ABL negative MPN,which included 34 patients with poly-cythemia vera(PV),33 with essential thrombocytopenia(ET),and 141 with primary myelofibrosis(PMF).Mutations in driver genes were assessed in all patients.A total of 72 patients underwent next-generation sequencing(NGS)with 69-gene panel,and the relationship between gene mutations and clinical features were analyzed.Results Among the 208 MPN patients,at least one driver gene mutation(JAK2,CALR,MPL)was detected in 96.15％(200/208)of the patients.Only 0.48％(1/208)of the patients exhibited both JAK2 and CALR driver mutations.We analyzed the clinical data of 136 patients with only driver gene mutations to compare the relationship between the most common JAK2 mutations(identified in 110 patients)and clinical outcomes.The JAK2 mutation group demonstrated higher white blood cell(WBC)counts and lower platelet(PLT)counts compared to the group without JAK2 mutations.173 muta-tions in 40 genes were detected in 72 patients,per capita carried(2.40±1.40)mutations.TET2,ASXL1,and TP53 are the most prevalent non-driver gene mutations,with 44.4％(32/72)of patients exhibiting at least one mutation in these three genes.In comparison to patients without detected mutations in TET2,ASXL1,and TP53,those with muta-tions in these genes demonstrated lower hemoglobin(HGB)levels,a higher incidence of splenomegaly,and more se-vere bone marrow fibrosis.High-molecular risk category(HMR)mutations were detected in 22.22％(16/72)of the patients,and patients with HMR exhibited lower hemoglobin(HGB)levels,lower PLT counts,a higher likelihood of peripheral blood primitive cell percentage ≥ 1％,a greater incidence of splenomegaly,and more severe myelofibrosis.Mutations in the ASXL1 gene were exclusively observed in patients with PMF.Among the PMF patients with ASXL1 mutations(12 patients),there was a higher likelihood of having a peripheral blood primitive cell percentage of ≥1％,as well as a more severe degree of myelofibrosis.Conclusion Approximately 97％of patients with myeloproliferative neoplasms(MPN)exhibit positivity for driver genes,with a notably high mutation rate of the JAK2 gene.Each sub-group of MPN is characterized by distinct gene mutation patterns.Notably,ASXL1 mutations are exclusive to patients with primary myelofibrosis(PMF).Furthermore,PMF patients harboring ASXL1 mutations tend to demonstrate more pronounced bone marrow fibrosis and a greater proportion of blast cells in peripheral blood.