Objective To investigate the risk factors for postoperative recurrence and metastasis in patients with T1 stageⅢ/Ⅳ clear cell renal cell carcinoma(ccRCC), and to analyze the influence of surgical methods on prognosis, so as to provide prognostic evaluation and treatment guidance for clinical practice. Methods A retrospective analysis was conducted on 398 patients diagnosed with T1 stage Ⅲ/Ⅳ ccRCC who underwent either partial nephrectomy(PN)or radical nephrectomy(RN)at Jiangsu Province Hospital during Jan. 2008 and Sep. 2022. The patients were divided into recurrence group(n=49)and non-recurrence group(n=349)according to whether the tumor recurred during the follow-up period. The general, clinical data and prognosis were compared between the two groups. Univariate and multivariate Cox regression analyses were used to explore the factors influencing disease-free survival(DFS)and overall survival(OS)after surgery. Subgroup analysis using Kaplan-Meier curves was performed for T1a and T1b patients. Results During the median follow-up of 67(42, 98)months, the recurrence group was characterized by older age, larger tumor diameter, higher proportion of T1b stage, and more complex tumor anatomy. Univariate and multivariate Cox regression analyses showed that age ≥55 years and R.E.N.A.L. score ≥7 were independent risk factors for poorer DFS and OS(P＜0.05). Subgroup analysis revealed that PN or RN did not significantly affect DFS or OS in T1a patients and OS in T1b patients, while RN significantly improved DFS in T1b patients(P＜0.05). Conclusion Age ≥55 years and R.E.N.A.L. score ≥7 are independent risk factors for poor DFS and OS in highgrade T1 ccRCC patients. For T1b patients, RN may improve DFS.

Objective To address the bottlenecks in the application of wastewater biological treatment technology under space conditions,an experimental system for the biological treatment of space wastewater was constructed and its biochemical performance examined.The findings of this study will provide technical support for the biological treatment of space wastewater.Methods Based on the Membrane Aerated Biofilm Reactor(MABR)process,a biological treatment experimental system for space wastewater was constructed and conducted the continuous flow test for 77 days to investigate the performance of PVDF and PP membrane modules in the treatment of simulated air condensate.Results The results demonstrated that both membrane modules exhibited an average TOC removal rate of 90%,indicative of their effective organic matter removal capacity.In the air supply mode,the ammonia oxidation capacity was observed to be comparatively lower,whereas in the oxygen source without bubbling mode,the nitrogen oxidation rate and total nitrogen removal rate could be attained above 90%,indicating a notable degree of simultaneous nitrification and denitrification.The results demonstrated that the mode of gas supply had a significant impact on the nitrogen conversion performance.The abundance of nitrogen-converting bacteria in PP membrane module is higher than that in PVDF membrane module,indicating a better nitrogen-converting performance in PP membrane module.Conclusion The constructed wastewater biological treatment system is optimally suited for the treatment of air condensate,thereby offering a novel technical approach for space wastewater treatment.

Objective To investigate the therapeutic mechanism of Thesium chinense Turcz.(TCT)for antibiotic-associated diarrhea(AAD).Methods Network pharmacology,KEGG pathway enrichment analysis and molecular docking were used to identify the shared targets and genes of TCT and AAD,the key signaling pathways and the binding between the active components in TCT and the core protein targets.In a Kunming mouse model of AAD established by intragastric administration of lincomycin hydrochloride,the effects of daily gavage of 1%carboxymethyl cellulose sodium or TCT gel solutions at 1.5 g/kg and 3 g/kg(n=10)on body weight and diarrhea were observed.HE staining,ELISA,16S rRNA sequencing,and Western blotting were used to examine pathologies,expression levels of IL-6 and TNF-α,changes in gut microbiota,and protein expressions of EGFR,p-EGFR,PI3K,p-PI3K,Akt,and p-Akt in the colon tissues of the mice.Results We identified a total of 66 active components of TCT and 68 core targets including EGFR,STAT3 and PIK3CA.KEGG pathway enrichment analysis suggested that the therapeutic effects of TCT was mediated primarily through the PI3K/Akt signaling pathway.Molecular docking showed that EGFR had the highest binding affinity with coniferin,and the EGFR-coniferin complex maintained a stable conformation at 10 ns,whose stability was also confirmed by Gibbs free energy analysis.In the mouse models of AAD,treatment with TCT significantly improved colonic tissue morphology,decreased colonic levels of TNF-α and IL-6,increased gut microbiota diversity,and modulated the relative abundances of the key genera including Lactobacillus and Bacteroides.TCT treatment also markedly reduced protein expressions of p-EGFR,p-PI3K and p-Akt in the colon tissues of the mice.Conclusion TCT can alleviate AAD in mice by modulating gut microbiota composition,regulating the EGFR/PI3K/Akt signaling pathway,and reducing TNF-α and IL-6 expressions.

OBJECTIVE To investigate the impact of vesicular stomatitis virus envelope glycopro-tein-G(VSV-G)modification on the mucosal immune efficacy of antigen-loaded engineered exosome vaccines.METHODS In vitro experiments:Dendritic cells(DCs)were divided into three groups:cell-control(treated with culture medium),receptor binding domain(RBD)(transfected with plasmid RBD),and RBD+VSV-G(co-transfected with plasmids RBD and VSV-G).Expression levels of RBD and VSV-G were assessed using Western blotting,flow cytometry,and immunofluorescence.Exosomes were extracted via ultracentrifugation,whose morphology,size distribution,and marker proteins were analyzed using transmission electron microscopy,nanoparticle tracking analysis,and Western blotting that confirmed the expressions of RBD and VSV-G in the exosomes.In vivo experiments:① Female BALB/c mice were divided into the control group Mock exosomes(Mock-Exo)(derived from the supernatant of cell-control),RBD decorated exosomes(RBD-Exo)(derived from the RBD cell supernatant),and RBD and VSV-G decorated exosomes(RBD+VSV-G-Exo)(derived from RBD+VSV-G cell supernatant).Follow-ing intranasal immunization with the respective vaccines,the nasal retention effects were evaluated using in vivo imaging.Flow cytometry was used to assess the ability to recruit immune cells to the nasal tissue.Serum RBD-specific immunoglobulin G(IgG)and mucosal immunoglobulin A(IgA)(bronchoal-veolar lavage fluid/nasal wash)were quantified at 7 and 21 d post-immunization by enzyme-linked immuno-sorbent assay.Body weight changes were monitored and key serum biochemical parameters along with histopathological damage to major organs were analyzed following immunization.② Female BALB/c mice were divided into the Mock-Exo group(intranasally inoculated with Mock-Exo),RBD+VSV-G-Exo group(intranasally inoculated with RBD+VSV-G-Exo),and RBD+VSV-G-Exo(im)group(intramus-cularly injected with RBD+VSV-G-Exo).RESULTS In vitro experiments:RBD and VSV-G were successfully expressed in cells,with positive rates of RBD+and VSV-G+cells at 64.4%and 31.2%,respectively.The extracted exosomes exhibited regular morphology and qualified purity,with a particle size of approximately 138 nm and successfully loaded RBD and VSV-G proteins.In vivo experiments:Compared to Mock-Exo and RBD-Exo,RBD+VSV-G-Exo prolonged nasal retention time to 96 h and markedly increased the numbers of CD49B+natural killer cells,CD11c+dendritic cells,and F4/80+macrophages in nasal tissues.RBD+VSV-G-Exo induced robust RBD-specific immune responses,with serum IgG titers,BALF IgA titers,and nasal wash IgA titers reaching 1∶5 215,1∶2 560,1∶1 114,respec-tively.In contrast,no RBD-specific IgA antibody titers were detected in the BALF and nasal wash of mice treated with RBD+VSV-G-Exo(im).Mice showed stable body weight gain during 30 d post-immu-nization.Major serum biochemical indices were within normal reference ranges,and no obvious patho-logical changes were observed in major organs or olfactory bulbs 7 d after immunization.CONCLU-SION VSV-G modification extends the retention time of engineered exosome vaccines in nasal tissues,enhance their ability to recruit immune cells,and induce a high-level antigen-specific respiratory mucosal immune response.

Objective:To investigate the effects of Vibrio vulnificus ( Vv) quorum-sensing protein LuxS on the homeostasis of pulmonary innate immune cells in sepsis-induced acute lung injury. Methods:This study constructed luxS knockout and complemented Vv strains. The time required for wild type, luxS knockout, and complemented Vv strains to grow to an absorbance of 600 nm in liquid medium was measured using a spectrophotometer. Iron-overloaded mice were intraperitoneally infected with 1×10 5 CFU of the above three kinds of Vv strains, respectively. Clinical scoring for sepsis-induced dyspnea was used to evaluate the respiratory quality in mice. At 7 h after infection, the pathological changes in lung tissues were observed by HE staining; the bacterial loads in lung tissues were measured; the single-cell suspension of lung tissues was analyzed by flow cytometry. Uniform manifold approximation and projection (UMAP) was used to reduce the dimension of the distribution of CD45 + immune cells in lung tissues of mice in the PBS control group and infection groups with different strains. The frequency and absolute number of innate immune cells in lung tissues were analyzed by multicolor flow cytometry. One-way analysis of variance and t test were used for statistical analysis. Results:There was no significant difference in the growth rate of wild type, luxS knockout, and complemented Vv strains in liquid medium. Compared with the mice infected with the wild type or complemented strain, the mice infected with the luxS knockout strain exhibited overall alleviated respiratory difficulty, decreased inflammatory cell infiltration in lung tissues, and reduced bacterial load in lung tissues ( P<0.05). Besides, there was no significant difference in clinical respiratory scores, inflammatory cell infiltration, or bacterial loads between the mice infected with the complemented strain and wild type strain. UMAP analysis showed that compared with the mice infected with the luxS knockout strain, the mice infected with the wild type or complemented strain showed increased proportions of neutrophils and eosinophils in lung tissues. Results of multicolor flow cytometry analysis further verified that the proportions of neutrophils and eosinophils were significantly lower in the mice infected with the luxS knockout strain than in the mice infected with wild type or complemented strain ( P<0.01, P<0.000 1), while the proportion of alveolar macrophages was significantly higher as compared with that in the mice infected with wild type or complemented strain ( P<0.01). Conclusion:During Vv infection, LuxS may promote acute lung injury by affecting the homeostasis of neutrophils, eosinophils and resident macrophages in lung tissues.

Objective:To construct a nomogram based on preoperative MRI imaging features for the prediction of muscle-invasive upper urinary tract urothelial carcinoma（UTUC）and evaluate its performance.Methods:This retrospective cohort study analyzed the clinical data of 99 UTUC patients treated at the First Affiliated Hospital of Nanjing Medical University from April 2018 to May 2024. Among them，69（69.7%）were male and 30（30.3%）were female，with a median age of 67.0 years. All patients underwent preoperative MRI and radical nephroureterectomy. According to postoperative pathology，tumors staged ≥ T 2 were assigned to the muscle-invasive group，and those staged ≤ T 1 were assigned to the non-muscle-invasive group. Baseline data，pathological information，and imaging characteristics were collected and compared between the two groups. Logistic regression analysis was performed to identify risk factors for muscle-invasive UTUC，and a nomogram was constructed. The diagnostic performance of the model was assessed using receiver operating characteristic（ROC）curves，calibration curves，and decision curve analysis（DCA）. Results:Among the 99 patients，70（70.7%）were diagnosed with muscle-invasive UTUC，and 29（29.3%）with non-muscle-invasive UTUC. The muscle-invasive group had significantly larger tumor size［4.5（2.8，7.0）cm vs. 3.0（2.3，4.5）cm， P = 0.029］，a higher incidence of multifocal tumors［37.1%（26/70）vs. 3.5%（1/29）， P < 0.001］，patchy tumors［30.0%（21/70）vs. 6.9%（2/29）， P = 0.019］，spiculated tumor margins［52.9%（37/70）vs. 17.2%（5/29）， P = 0.001］，tumor compression on renal parenchyma or periureteral/peripelvic fat［68.6%（48/70）vs. 10.3%（3/29）， P < 0.001］，high-grade pathology［92.9%（65/70）vs. 75.9%（22/29）， P = 0.043］，lymph node metastasis［28.6%（20/70）vs. 0， P = 0.001］，and lymphovascular invasion［42.9%（30/70）vs. 10.3%（3/29）， P=0.002］. The apparent diffusion coefficient（ADC）values［0.9（0.8，1.1）× 10 -3 mm2/s vs. 1.1（1.0，1.4）× 10 -3 mm2/s， P < 0.001］and normalized ADC（NADC）values［0.8（0.7，1.0）vs. 0.9（0.8，1.1）， P = 0.002］were significantly lower in the muscle-invasive group. Univariate logistic regression identified multifocality，patchy tumor patterns，spiculated tumor margins，tumor compression on renal parenchyma or periureteral/peripelvic fat，and low NADC values as risk factors for muscle-invasive UTUC（all P < 0.05）. Multivariate analysis revealed multifocality（ OR = 17.903，95% CI 1.650 - 194.253， P = 0.018），tumor compression on renal parenchyma or perirenal / ureteral fat（ OR = 14.690，95% CI 3.069 - 70.323， P < 0.001），and low NADC value（ OR = 0.016，95% CI 0.001 - 0.471， P = 0.017）as independent risk factors. A nomogram was constructed based on these factors. The area under the ROC curve（AUC）of the model was 0.898（95% CI 0.838 - 0.957），with an optimal cutoff value of 0.639. The model showed an accuracy of 83.8%，sensitivity of 81.4%，and specificity of 89.7%. Calibration curves indicated good calibration，and DCA showed that the model provided substantial clinical net benefit. Conclusions:This study constructed a nomogram based on preoperative MRI features，including tumor multifocality，compression on renal parenchyma or periureteral/peripelvic fat and NADC value，which demonstrates good predictive performances for muscle-invasive UTUC.

BACKGROUND:The pathogenesis of patellofemoral pain is complex,and poor movement patterns and incorrect muscle activation patterns have been suggested to increase patellofemoral joint stress and cause injury,but the results of current studies are not uniform.Current biomechanical studies of step-down test in patients with patellofemoral pain have focused on kinematic characteristics,and there is a lack of research on surface electromyographic characteristics.In addition,there are no studies that analyze the differences in biomechanical performance between the healthy and affected sides of patellofemoral pain patients compared with healthy subjects during the downward step test.OBJECTIVE:To investigate the kinematic and surface electromyographic characteristics of patients with patellofemoral pain during bilateral lower extremity step-downs.METHODS:Twenty-one men with patellofemoral pain and 21 healthy men were recruited,and both groups of subjects underwent a step-down test.Kinematic,kinetic and surface electromyographic data were synchronously collected using a three-dimensional dynamic capture system,a force platform and a surface electromyographic tester.RESULTS AND CONCLUSION:(1)Kinematics:Compared with the healthy control group,the affected and healthy sides of the patellofemoral pain group showed a smaller hip flexion angle(P=0.005,P=0.011),a larger hip internal rotation angle(P=0.033,P=0.039),and a larger knee valgus angle(P=0.001,P=0.001),and the affected side of the patellofemoral pain group exhibited a larger hip internal rotation angle(P=0.013),a smaller knee flexion angle(P=0.043),and a smaller ankle dorsiflexion angle(P=0.002);and compared with the healthy side,the affected side exhibited a smaller ankle dorsiflexion angle(P=0.002).(2)Surface electromyography:Compared with the healthy control group,the patellofemoral pain group showed reduced activation of the vastus medialis oblique(P=0.002),reduced activation of the gluteus medius(P=0.015),and a decreased vastus medialis oblique/vastus lateralis ratio(P=0.010)on the affected side;and compared with the healthy side,there was a reduced activation of the gluteus medius on the affected side(P=0.008).(3)The results indicate that patients with patellofemoral pain have abnormal lower limb biomechanical characteristics during step-down test,which are mainly manifested as changes in kinematic and indexes of the lower limb joints in the sagittal and frontal planes as well as changes in activation levels of the medial femoral and gluteus medius muscles.These changes reflect the fact that patients with patellofemoral pain adopt a stifflanding pattern during step-downs and show pronation of other joints of the lower extremity.In addition,abnormal lower extremity biomechanical characteristics are also present in the healthy limbs of patients with patellofemoral pain,and bilateral lower extremity asymmetry exists in such patients.

Objective:To conduct a survey on the influence of personality trait on depres-sive symptom and obesity in patients before bariatric and metabolic surgery.Methods:The retros-pective cross-sectional investigation study was conducted. Patients who underwent bariatric and metabolic surgery in The Third Xiangya Hospital of Central South University and The First Affiliated Hospital of Ji′nan University from January 1 to June 1,2024 were recruited. The survey was conducted in electronic format using the general information survey questionnaire, the patient health question-naire-9 (PHQ-9), and the Chinese big five personality inventory brief version (CBF-PI-B). Observa-tion indicators: (1) results of the questionnaire; (2) general data of patient; (3) personality trait scores for patient with different subtypes of obesity; (4) depression symptom scores for patient with different subtypes of obesity; (5) correlation analysis for patient personality trait, depressive symptom and body mass index (BMI). Comparison of measurement data with normal distribution between groups was conducted using the independent t test, and one-way analysis of variance was used for comparison among multiple groups. LSD test was used for pairwise comparison. Comparison of measurement data with skewed distribution among multiple groups was conducted using the Kruskal-Wallis H test, and Dunn Bonferroni test was used for pairwise comparison. The Spearman correlation analysis and Pearson correlation analysis were used for correlation analysis, and the mediation effect analysis was conducted using the Process 4.0 model and the Bootstrap test. Results:(1)Results of the questionnaire. A total of 146 questionnaires were distributed and collected, including 83 questionnaires from The Third Xiangya Hospital of Central South University and 63 questionnaires from The First Affiliated Hospital of Ji′nan University. Of 146 questionnaires, 137 questionnaires were valid, yielding an effective response rate of 93.836%(137/146). (2)General data of patient. Of the 137 patients who completed valid questionnaires, 52 were male with BMI of (41±5)kg/m 2, 85 were female with BMI of (38±6)kg/m 2, showing a significant difference between them ( t=2.586, P<0.05). There were 40 patients aged ≤25 years, with BMI of (42±5)kg/m 2, 28 patients aged 26-30 years, with BMI of (39±5)kg/m 2, 49 patients aged 31-40 years, with BMI of (38±6)kg/m 2, 14 patients aged 41-50 years, with BMI of (38±7)kg/m 2, 6 patients aged >50 years, with BMI of (37±3)kg/m 2. There were significant differences in BMI of patients of different age groups ( F=2.697, P<0.05). (3)Persona-lity trait scores for patient with different subtypes of obesity. Of the 137 patients who completed valid questionnaires, there were 15 patients of mild obesity, with personality trait neuroticism score of 19.0(14.0,24.0), personality trait strictness score of 32.5±5.2, personality trait extroversion score of 30.0(24.0,40.0), 36 patients of moderate obesity, with personality trait neuro-ticism score of 26.5(22.3,28.8), personality trait strictness score of 32.6±5.9, personality trait extro-version score of 34.0(26.3,39.0), 81 patients of severe obesity, with personality trait neuroticism score of 35.0(29.5,41.0), personality trait strictness score of 26.8±7.4, personality trait extroversion score of 28.0(20.5,35.0), 5 patients of extreme obesity, with personality trait neuroticism score of 28.0(26.5,44.0), personality trait strictness score of 19.6±3.4, personality trait extroversion score of 22.0(18.5,25.0). There were significant differences in personality trait neuroticism, strictness and extroversion among patients of different subtypes of obesity ( H=50.316, F=10.774, H=14.446, P<0.05). (4)Depression symptom scores for patient with different subtypes of obesity. Of the 137 pati-ents who completed valid questionnaires, the depressive symptom score were 4.0(2.0,9.0) for 15 pati-ents of mild obesity, 5.0(3.0,7.0) for 36 patients of moderate obesity, 13.0(8.5,17.0) for 81 patients of severe obesity, and 18.0(9.5,22.0) for 5 patients of extreme obesity, respectively, showing a significant difference among them ( H=50.129, P<0.05). (5) Correlation analysis for patient personality trait, depressive symptom and BMI. Results of Spearman correlation analysis showed that personality trait neuroticism were positively correlated with depressive symptoms and BMI ( r=0.780, 0.557, P<0.05), personality trait strictness was negatively correlated with depressive symptoms ( r=-0.523, P<0.05), personality trait extroversion were negatively correlated with depressive symptoms and BMI ( r=-0.448, -0.323, P<0.05), and depressive symptoms was positively correlated with BMI ( r=0.568, P<0.05). Results of Pearson correlation analysis showed that personality trait strictness was negatively correlated with BMI ( r=-0.489, P<0.05). Conclusion:Preoperative personality trait of patients undergoing bariatric and metabolic surgery can influence their depressive symptom and BMI.

Small cell lung cancer (SCLC) is the thoracic malignant tumor and accounts for about 15% of lung malignancies and transfer often occurs by the time of diagnosis. Extensive stage-small cell lung cancer (ES-SCLC) accounts for about 2/3 of all SCLC. For many years, radiotherapy has occupied an important position in the treatment of SCLC, especially in the treatment of ES-SCLC, because SCLC is more sensitive to radiotherapy. However, in recent years, immune checkpoint inhibitor has shown more excellent antitumor activity in the treatment of ES-SCLC and become the mainstream argument for the treatment of ES-SCLC. However, will radiotherapy be buried by the times among the therapeutic approaches for ES-SCLC? In this article, we will review the clinical progress of radiotherapy, immunotherapy and combination therapy for ES-SCLC.
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Humans ; Small Cell Lung Carcinoma/therapy* ; Lung Neoplasms/therapy* ; Immunotherapy ; Neoplasm Staging ; Radiotherapy/methods* ; Combined Modality Therapy

OBJECTIVES: To investigate the therapeutic mechanism of Thesium chinense Turcz. (TCT) for antibiotic-associated diarrhea (AAD). METHODS: Network pharmacology, KEGG pathway enrichment analysis and molecular docking were used to identify the shared targets and genes of TCT and AAD, the key signaling pathways and the binding between the active components in TCT and the core protein targets. In a Kunming mouse model of AAD established by intragastric administration of lincomycin hydrochloride, the effects of daily gavage of 1% carboxymethyl cellulose sodium or TCT gel solutions at 1.5 g/kg and 3 g/kg (n=10) on body weight and diarrhea were observed. HE staining, ELISA, 16S rRNA sequencing, and Western blotting were used to examine pathologies, expression levels of IL-6 and TNF-α, changes in gut microbiota, and protein expressions of EGFR, p-EGFR, PI3K, p-PI3K, Akt, and p-Akt in the colon tissues of the mice. RESULTS: We identified a total of 66 active components of TCT and 68 core targets including EGFR, STAT3 and PIK3CA. KEGG pathway enrichment analysis suggested that the therapeutic effects of TCT was mediated primarily through the PI3K/Akt signaling pathway. Molecular docking showed that EGFR had the highest binding affinity with coniferin, and the EGFR-coniferin complex maintained a stable conformation at 10 ns, whose stability was also confirmed by Gibbs free energy analysis. In the mouse models of AAD, treatment with TCT significantly improved colonic tissue morphology, decreased colonic levels of TNF-α and IL-6, increased gut microbiota diversity, and modulated the relative abundances of the key genera including Lactobacillus and Bacteroides. TCT treatment also markedly reduced protein expressions of p-EGFR, p-PI3K and p-Akt in the colon tissues of the mice. CONCLUSIONS TCT can alleviate AAD in mice by modulating gut microbiota composition, regulating the EGFR/PI3K/Akt signaling pathway, and reducing TNF‑α and IL-6 expressions.
Animals ; Gastrointestinal Microbiome/drug effects* ; Signal Transduction/drug effects* ; Mice ; ErbB Receptors/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Diarrhea/drug therapy* ; Phosphatidylinositol 3-Kinases/metabolism* ; Anti-Bacterial Agents/adverse effects* ; Drugs, Chinese Herbal/therapeutic use* ; Molecular Docking Simulation