BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

Phages, as obligate bacterial and archaeal parasites, constitute a virus group of paramount ecological significance due to their exceptional abundance and genetic diversity. These biological entities serve as critical regulators in Earth's ecosystems, driving biogeochemical cycles, energy fluxes, and ecosystem services across terrestrial and marine environments. Within soil microbiomes, phages function as microbial "dark matter," maintaining the soil-plant system balance through precise modulation of the microbial community structure and functional dynamics. Despite the growing research interests in soil phages in recent years, the proportion of such studies in environmental virology remains disproportionately low, which is primarily attributed to researchers' limited familiarity with the research methodologies for phage microecology, incomplete technical frameworks, and inherent challenges posed by soil environmental complexity. To address these challenges, this review synthesizes cutting-edge methodologies for soil phage investigation from four aspects: (1) tangential flow filtration (TFF)-based phage enrichment strategies; (2) integrated quantification approaches combining double-layer agar plating, epifluorescence microscopy, and flow cytometry; (3) multi-omics analytical pipelines leveraging metagenomics and viromics datasets; and (4) computational frameworks merging machine learning algorithms with eco-evolutionary theory for deciphering phage-host interaction networks. Through comparative analysis of methodological principles, technical merits, and application scopes, we establish a comprehensive workflow for soil phage research. Future research in this field should prioritize: (1) construction of soil phage resource libraries, (2) exploration of RNA phages based on transcriptomes, (3) functional characterization of unknown genes, and (4) deep integration and interaction validation of multi-omics data. This systematic methodological synthesis provides critical technical references for addressing fundamental challenges in characterizing soil phages regarding the community structure, functional potential, and interaction mechanisms with hosts.
Bacteriophages/physiology* ; Soil Microbiology ; Ecosystem ; Microbiota ; Metagenomics/methods*

Objective:To retrieve, evaluate and integrate the evidence related to the preparation process for initiating extracorporeal cardiopulmonary resuscitation in hospital, so as to provide reference for clinical implementation of extracorporeal cardiopulmonary resuscitation.Methods:According to the evidence-based nursing method and the 6S evidence model, guidelines, clinical decisions, expert consensus, systematic review and other literatures related to the preparation process for initiating extracorporeal cardiopulmonary resuscitation in hospital were searched from National Guideline Clearinghouse, Scottish Intercollegiate Guidelines Network, National Institute for Health and Care Excellence, and other websites, UpToDate, The Cochrane Library, PubMed, Embase, CNKI, Wanfang and other databases. The retrieval date limit was from the establishment of the database to May 20, 2023. Researchers assessed the quality of the included articles, and extracted and summarized the evidence that met the quality standards.Results:A total of 11 articles were included, including 2 guidelines, 6 expert consensuses, 1 systematic review and 2 quasi-experimental studies. A total of 18 pieces of evidences were summarized from 6 aspects, including medical conditions, team building, materials management, operation mechanism, pre-initiating treatment and initiating judgment.Conclusions:This study summarizes the evidence of preparation process for initiating extracorporeal cardiopulmonary resuscitation in hospital, which can provide reference for promoting the implementation of extracorporeal cardiopulmonary resuscitation. Future studies still need to focus on team building, personnel training and assessment, and optimisation of the management system, so as to improve the efficiency and readiness of treatment.

Objective To explore the correlation between hyponatremia at admission and all-cause mortality within one year after discharge in elderly patients with intestinal obstruction.Methods The 331 cases of elderly patients with intestinal obstruction(aged ≥ 60 years)who visited the General Surgery Department of Nanjing Meishan Hospital from January 2017 to December 2020 were selected as the research objects for retrospective cohort study analysis.According to the patient's blood sodium level at admission,they are divided into two groups:the hyponatremia group(Na＜135 mmol/L)and the non hyponatremia group(Na≥135 mmol/L).Divided into death group and survival group based on whether death occurred within one year after discharge.SPSS 25.0 software was used for statistical analysis.Independent sample t test,x2 test,Kaplan Meier method,and multivariate Cox regression analysis were used to observe the correlation between admission hyponatremia and all-cause mortality within one year after discharge in elderly patients with intestinal obstruction.Results A total of 331 patients were enrolled.The incidence of hyponatremia was 32.3％,and 56 deaths occurred within one year,accounting for 16.92％.The one-year mortality rate in the hyponatremia group was 23.4％(25/107),which was higher than 13.8％(31/224)in the non hyponatremia group.The difference was statistically significant(P＜0.05).The survival analysis(Kaplan Meier)results showed that the survival rate of the hyponatremia group was lower than that of the non hyponatremia group(Log Rank P＜0.05).After adjusting for other confounding factors in multivariate Cox regression analysis,hyponatremia(HR=1.88,95％CI:1.07-3.29)was an independent risk factor for one-year all-cause mortality in elderly patients with intestinal obstruction(P＜0.05).Conclusion Hyponatremia at admission is an independent risk factor for all cause mortality in elderly patients with intestinal obstruction within one year after discharge.

Objective:To examine the impact of berberine on polycystic ovary syndrome (PCOS) in mice, and to investigate the effects of berberine on the intestinal flora and the intestinal flora on PCOS.Methods:A mouse model of PCOS was established by administering dehydroepiandrosterone in combination with high fat diet, and the mouse model was given a berberine treatment. The study consisted of a blank control group (C group), a PCOS model group (M group) and a berberine treatment group (T group). During the experiment, the mice were closely monitored through timed body weight measurements and estrous cycle monitoring; intraperitoneal glucose tolerance test and insulin tolerance test were done. Upon completion of the pharmacological intervention, the wet weights of liver, ovary and fat deposits of mice were assessed and subjected to HE staining to confirm the success of PCOS modeling and the efficacy of berberine. Additionally, fecal samples were analyzed for intestinal flora through 16S rRNA analysis.Results:The PCOS model was established successfully, berberine alleviated the disturbance of estrous cycle in mice, and significantly alleviated fat accumulation and metabolic abnormalities of glucose in mice. The cross-sectional area of fat pad cells in T group was (2 858±146) μm2, which was significantly lower than that in M group [(9 518±347) μm2], and the difference was statistically significant ( P<0.001). The blood glucose levels in T group were significantly lower than those in M group ( P<0.05). The composition and structure of intestinal flora in mice of M group with PCOS (compared with C group) and in mice of T group after berberine intervention (compared with M group) were significantly altered. However, alpha diversity did not change significantly among three groups ( P>0.05). Conclusion:Berberine could alleviate PCOS by intervening in the alterations of gut microbiota.

【Objective】 To compare the current standards and explore the influencing factors for hemolysis rate of leukocyte-reduced red blood cells at the end of the preservation period, in order to formulate reasonable internal control indicators. 【Methods】 A retrospective analysis was performed on hemolysis rate of 427 samples of leukocyte-reduced red blood cells at the end of the preservation period in Nanning Blood Center from 2015 to 2022. Compared with the current standard for hemolysis rate at the end of the preservation period (GB 18469-2012 Quality Requirements for Whole Blood and Component Blood), the differences were analyzed, and the factors influncing the hemolysis rate were analyzed in terms of different blood donor groups. 【Results】 1) Among the 427 samples, the hemolysis rate of 418 (97.89%) did not exceed 0.4%, all lower than 0.8%; 2)the hemolysis rate of the male group was higher than that of the female group; 3) the hemolysis rate of the 18-29 years old group was lower than that of the 30-39 year old group and the 40-60 year old group, with statistically significant difference; 4) in terms of occupation, the hemolysis rate of students was the lowest, and the differences between groups were statistically significant; 5) no statistical significance was found in ethnicity and blood type. 【Conclusion】 Statistics indicated that gender, age, blood donation volume and occupation of blood donors were the influencing factors of hemolysis rate. The current standard is obviously higher in the qualified range of blood quality control in Nanning. It is advisable to formulate a reasonable quality control strategy with internal control index of hemolysis rate set <0.4%, which is conducive to making accurate evaluation of internal quality control and ensuring blood safety.

Objective:To investigate the status quo of organizational silence behavior of nurses in Emergency Department, and analyze the influence of working environment and psychological capital on organizational silence.Methods:This study was a cross-sectional study. Using the convenient sampling method, a total of 232 emergency department nurses from 5 ClassⅢ Grade A hospitals in Jiangsu Province were selected as the research objects from April to June 2022. The research objects were surveyed using the general information survey questionnaire, Nurse Organization Silence Assessment Questionnaire, Nurse Work Environment Scale and Nurse Psychological Capital Scale. Pearson correlation was used to analyze the correlations among organizational silence, work environment and psychological capital. The mediation model was modeled using AMOS 24.0 software, and the Bootstrap method was used to verify the mediating effect of psychological capital between work environment and organizational silence. A total of 232 questionnaires were sent out in this study, and 210 were effectively received with effective recovery of 90.5% (210/232) .Results:The organizational silence score of 210 emergency department nurses was (54.70±15.02), The working environment score was (80.72±11.07), and the psychological capital score was (71.59±11.57). Organizational silence was negatively correlated with work environment and psychological capital scores ( r=-0.309, -0.670, respectively; P<0.05) ; Working environment was positively correlated with psychological capital score ( r=0.266, P<0.05). The mediating effect analysis showed that psychological capital had a partial mediating effect between working environment and organizational silence (β=-0.311, P<0.05). The direct effect size of working environment on organizational silence was -0.241 ( P<0.05) . Conclusions:The organizational silence of nurses in emergency department is at a medium high level, and the working environment can indirectly affect the organizational silence through psychological capital. Nursing managers can improve organizational silence by creating a healthy working environment, cultivating nurses' psychological capital and creating more opportunities to communication.

In order to investigate the enzyme production mechanism of yak rumen-derived anaerobic fungus Orpinomyces sp. YF3 under the induction of different carbon sources, anaerobic culture tubes were used for in vitro fermentation. 8 g/L of glucose (Glu), filter paper (Flp) and avicel (Avi) were respectively added to 10 mL of basic culture medium as the sole carbon source. The activity of fiber-degrading enzyme and the concentration of volatile fatty acid in the fermentation liquid were detected, and the enzyme producing mechanism of Orpinomyces sp. YF3 was explored by transcriptomics. It was found that, in glucose-induced fermentation solution, the activities of carboxymethyl cellulase, microcrystalline cellulase, filter paper enzyme, xylanase and the proportion of acetate were significantly increased (P < 0.05), the proportion of propionate, butyrate, isobutyrate were significantly decreased (P < 0.05). The results of transcriptome analysis showed that there were 5 949 differentially expressed genes (DEGs) between the Glu group and the Flp group, 10 970 DEGs between the Glu group and the Avi group, and 6 057 DEGs between the Flp group and the Avi group. It was found that the DEGs associated with fiber degrading enzymes were significantly up-regulated in the Glu group. Gene ontology (GO) function enrichment analysis identified that DEGs were mainly associated with the xylan catabolic process, hemicellulose metabolic process, β-glucan metabolic process, cellulase activity, endo-1,4-β-xylanase activity, cell wall polysaccharide metabolic process, carbohydrate catabolic process, glucan catabolic process and carbohydrate metabolic process. Moreover, the differentially expressed pathways associated with fiber degrading enzymes enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were mainly starch and sucrose metabolic pathways and other glycan degradation pathways. In conclusion, Orpinomyces sp. YF3 with glucose as carbon source substrate significantly increased the activity of cellulose degrading enzyme and the proportion of acetate, decreased the proportion of propionate, butyrate and isobutyrate. Furthermore, the degradation ability and energy utilization efficiency of fungus in the presence of glucose were improved by means of regulating the expression of cellulose degrading enzyme gene and participating in starch and sucrose metabolism pathway, and other glycan degradation pathways, which provides a theoretical basis for the application of Orpinomyces sp. YF3 in practical production and facilitates the application of Orpinomyces sp. YF3 in the future.
Animals ; Cattle ; Neocallimastigales/metabolism* ; Anaerobiosis ; Rumen/microbiology* ; Propionates/metabolism* ; Isobutyrates/metabolism* ; Cellulose/metabolism* ; Fungi ; Starch/metabolism* ; Glucose/metabolism* ; Acetates ; Sucrose/metabolism* ; Cellulases ; Cellulase

BACKGROUND: The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1A1 homozygous mutations, but the impact of UGT1A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear. METHODS: A total of 107 patients with UGT1A1 heterozygous mutation or wild-type, who were treated with CPT-11 from January 2018 to September 2021 in Peking University Third Hospital, were retrospectively enrolled. The adverse reaction spectra of patients with UGT1A1*6 and UGT1A1*28 mutations were analyzed. Adverse reactions were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The genotypes of UGT1A1*6 and UGT1A1*28 were detected by digital fluorescence molecular hybridization. RESULTS: There were 43 patients with UGT1A1*6 heterozygous mutation, 26 patients with UGT1A1*28 heterozygous mutation, 8 patients with UGT1A1*6 and UGT1A1*28 double heterozygous mutations, 61 patients with heterozygous mutation at any gene locus of UGT1A1*6 and UGT1A1*28. Logistic regression analysis showed that the presence or absence of vomiting (P=0.013) and mucositis (P=0.005) was significantly correlated with heterozygous mutation of UGT1A1*28, and the severity of vomiting (P<0.001) and neutropenia (P=0.021) were significantly correlated with heterozygous mutation of UGT1A1*6. In colorectal cancer, UGT1A1*6 was significantly correlated to diarrhea (P=0.005), and the other adverse reactions spectrum was similar to that of the whole patient cohort, and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not. CONCLUSIONS In clinical use, heterozygous mutations of UGT1A1*6 and UGT1A1*28 are related to the risk and severity of vomiting, diarrhea, neutropenia and mucositis in patients with Pan-tumor and colorectal cancer post CPT-11 therpy. In colorectal cancer, UGT1A1*6 is significantly related to diarrhea post CPT-11 use, efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction.
Camptothecin/therapeutic use* ; Glucuronosyltransferase/genetics* ; Humans ; Lung Neoplasms/drug therapy* ; Mutation ; Polymorphism, Genetic ; Retrospective Studies

Objective:To explore the serum cyclic polypeptide biomarkers for ovarian cancer diagnosis.Methods:A total of 54 patients with epithelial ovarian cancer confirmed by pathology in Cancer Hospital, Chinese Academy of Medical Sciences from March 2018 to September 2018 were selected as the study subjects, and 40 healthy women with normal examination results in the cancer screening center were selected as the control. All of the samples were randomly divided into training set and validation set at the ratio of 1∶1 with a random number. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with magnetic bead technology was used for detecting peptide profiling in serum samples to screen significantly differently expressed peptides between ovarian cancer group and control group of the training set (score>5). Receiver operating characteristic (ROC) curve analysis was used to screen differential peptide peaks with area under curve (AUC) ≥0.8, sensitivity and specificity>90% in the training set and validation set. Liquid chromatography-mass spectrometry (LC-MS/MS) was further used to determine the composition of differentially expressed peptides.Results:By comparing the peptide profiles of the two groups, 102 differential peptide peaks were initially detected in the mass-to-charge ratio range of 1 000 to 10 000. ROC curve analysis showed that there were 42 differential peptide peaks with AUC ≥0.8 in both training set and validation set, 19 of which were highly expressed in ovarian cancer group, and 23 were lowly expressed. There were 15 different peptide peaks in highly expressed ovarian cancer group with sensitivity and specificity over 90%. The mass-to-charge ratios were 7 744.27, 5 913.41, 5 329.87, 4 634.21, 4 202.02, 3 879.26, 3 273.35, 3 253.79, 3 234.34, 2 950.33, 2 664.51, 2 018.38, 1 893.37, 1 498.69 and 1 287.55. There were 15 different peptide peaks in lowly expressed ovarian cancer group with sensitivity and specificity over 90%, the mass-to-charge ratios were 9 288.46, 7 759.77, 5 925.24, 4 652.77, 4 210.42, 3 887.02, 3 279.90, 3 240.82, 2 962.15, 2 932.70, 2 022.42, 1 897.16, 1 501.69, 1 337.38 and 1 290.13. No protein composition was identified in 15 different peptide peaks in lowly expressed ovarian cancer group. The two protein compositions identified in 15 different peptide peaks in highly expressed ovarian cancer group were recombinant serglycin (SRGN) and fibinogen alpha chain (FGA), the mass-to-charge ratios of which were 1 498.696 and 5 913.417, respectively. The sensitivity and specificity of the two proteins for ovarian cancer diagnosis were 100%, 100% and 90.9%, 100%, respectively.Conclusion:SRGN and FGA are highly expressed in the serum of ovarian cancer patients, which may be potential diagnostic markers for ovarian cancer.