Lung cancer constitutes the most prevalent and lethal malignant tumor in China. Approximately 85% of lung cancer diagnoses correspond to the non-small cell histological subtype [non-small cell lung cancer (NSCLC)]. Despite surgery being the mainstay for early-stage disease, postoperative recurrence remains high and adjuvant chemotherapy offers limited benefit. In recent years, targeted therapy has demonstrated substantial advantages in driver mutation-positive NSCLC. To this end, the Lung Cancer Medical Education Committee of the Chinese Medical Education Association developed guidelines based on a systematic review of evidence through November 2025, using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach and a modified Delphi method. Focusing on epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and addressing ROS proto-oncogene 1 (ROS1), B-Raf proto-oncogene serine/threonine kinase (BRAF) V600E mutation, and mesenchymal-epithelial transition factor (MET) exon 14 (METex14) skipping, the guideline covers molecular testing, neoadjuvant/adjuvant therapy, perioperative strategies, minimal residual disease monitoring, and postoperative surveillance. It defines testing requirements, specifies stage-directed and subtype-specific treatments, and standardizes minimal residual disease monitoring. These recommendations emphasize precision and feasibility to improve survival and quality of life.

Integrated metabolomic and lipidomic profiling,utilizing liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS),has emerged as a pivotal strategy for biomarker discovery.However,the inherent polarity disparity between metabolites and lipids complicates simultaneous analysis.To address this,a dual-stationary phase polarity-extended liquid chromatography(PELC)system was developed,which surpassed conventional one-dimensional LC(1D-LC)by enabling comprehensive coverage of both polar and non-polar compounds within a single injection.This system enhanced chromatographic resolution,peak capacity,and throughput while minimizing analytical variability.Extracellular vesicles(EVs),lipid bilayer-enclosed nanoparticles ubiquitously present in biofluids,had gained prominence as reservoirs of cancer biomarkers due to their cargo stability and pathophysiological relevance.Herein,the application of PELC-HRMS for concurrent metabolome-lipidome profiling in EVs was pioneered.A total of 193 metabolites were identified using this technique coupled with MS-DIAL software and Human Metabolome Database.Subsequently,this technique was employed to explore potential biomarkers for prostate cancer(PCa).Multivariate analysis identified 17 differentially abundant metabolites in PCa,implicating dysregulated pathways including purine metabolism,starch and sucrose metabolism,galactose metabolism,cysteine and methionine metabolism,and biosynthesis of unsaturated fatty acids.Notably,creatine(AUC=0.92)and DG 42:5(AUC=0.80)demonstrated robust diagnostic efficacy,attributable to their broad polarity ranges and EV-specific enrichment.This study established PELC as a high-fidelity platform for multi-omics integration in complex biospecimens,advancing mechanistic insights into metabolic rewiring and disease pathophysiology.

Objective To analyze the characteristics and risk factors associated with postoperative deep vein thrombosis(DVT)of the lower extremities in patients undergoing surgery for lumbar degenerative diseases.Methods A retrospective analysis was conducted on clinical data from 298 patients who were hospitalized for lumbar degenerative diseases and underwent lumbar spine surgery treatment in the First Affiliated Hospital of Nanchang University from October 1,2022 to April 15,2023.Patients were divided into DVT group(n=71)and non-DVT group(n=227)according to whether DVT of the lower limbs occurred within 1 week postoperatively.The incidence and distribution characteristics of postoperative DVT were analyzed.Univariate and binary logistic regression analyses were performed to identify risk factors for DVT,and receiver operating characteristic(ROC)curves were used to determine cut-off values for relevant risk factors.Results A total of 298 patients were included,among whom 159 were males(53.4%)and 139 were females(46.6%),with an average age of(64.5±9.8)years.DVT occurred in 71 patients,and the incidence of lower extremity DVT was 23.8%.In the DVT group,there were 49 cases(69.0%)of intermuscular vein thrombosis,and 22 cases of other types of thrombosis(7 cases of peroneal vein thrombosis,4 cases of posterior tibial vein thrombosis,3 cases of common femoral vein thrombosis,1 case of anterior tibial vein thrombosis,and 7 cases of multiple thrombosis);58 cases(81.7%)had DVT in one lower extremity,and 13 cases(18.3%)had DVT in both lower extremities.Univariate analysis results showed that age,body mass index(BMI),length of hospital stay,history of hypertension,operative time,and intraoperative blood loss were associated with the occurrence of lower extremity DVT after surgery for lumbar degenerative diseases(P<0.05).Binary logistic regression analysis results indicated that older age(OR=1.079,P<0.01),higher BMI(OR=1.130,P=0.01),history of hypertension(OR=2.992,P<0.01),and larger intraoperative blood loss(OR=1.002,P=0.03)were independent risk factors for the occurrence of lower extremity DVT.ROC curve analysis demonstrated that patients with age>58.5 years,BMI>24.01 kg/m2,history of hypertension,and intraoperative blood loss>550 ml had a significantly increased risk of postoperative lower limb DVT.Conclusions The incidence of lower extremity DVT after surgery for lumbar degenerative disease is high,and intermuscular venous thrombosis is more common.Older age,higher BMI,history of hypertension,and larger intraoperative blood loss are independent risk factors for the occurrence of lower extremity DVT after surgery.

ObjectiveThe study explores the influence of voluntary wheel running on the behavioral abnormalities and the activation state of the hypothalamic-pituitary-adrenal (HPA) axis in autism spectrum disorder (ASD) rats through gut microbiota. MethodsSD female rats were selected and administered either400 mg/kg of valproic acid (VPA) solution or an equivalent volume of saline via intraperitoneal injection on day 12.5 of pregnancy. The resulting offspring were divided into 2 groups: the ASD model group (PASD, n=35) and the normal control group (PCON, n=16). Behavioral assessments, including the three-chamber social test, open field test, and Morris water maze, were conducted on postnatal day 23. After behavioral testing, 8 rats from each group (PCON, PASD) were randomly selected for serum analysis using enzyme-linked immunosorbent assay (ELISA) to measure corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) concentration, to evaluate the functional state of the HPA axis in rats. On postnatal day 28, the remaining 8 rats in the PCON group were designated as the control group (CON, n=8), and the remaining 27 rats in the PASD group were randomly divided into 4 groups: ASD non-intervention group (ASD, n=6), ASD exercise group (ASDE, n=8), ASD fecal microbiota transplantation group (FMT, n=8), and ASD sham fecal microbiota transplantation group (sFMT, n=5). The rats in the ASD group and the CON group were kept under standard conditions, while the rats in the ASDE group performed 6 weeks of voluntary wheel running intervention starting on postnatal day 28. The rats in the FMT group were gavaged daily from postnatal day 42 with 1 ml/100 g fresh fecal suspension from ASDE rats which had undergone exercise for 2 weeks, 5 d per week, continuing for 4 weeks. The sFMT group received an equivalent volume of saline. After the interventions were completed, behavioral assessments and HPA axis markers were measured for all groups. ResultsBefore the intervention, the ASD model group exhibited significantly reduced social ability, social novelty preference, spontaneous activity, and exploratory interest, as well as impaired spatial learning, memory, and navigation abilities compared to the normal control group (P<0.05). Serum concentration of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) in the PASD group were significantly higher than those in the PCON group (P<0.05). Following 6 weeks of voluntary wheel running, the ASDE group showed significant improvements in social ability, social novelty preference, spontaneous activity, exploratory interest, spatial learning, memory, and navigation skills compared to the ASD group (P<0.05), with a significant decrease in serum CORT concentration (P<0.05), and a downward trend in CRH and ACTH concentration. After 4 weeks of fecal microbiota transplantation in the exercise group, the FMT group showed marked improvements in social ability, social novelty preference, spontaneous activity, exploratory interest, as well as spatial learning, memory, and navigation abilities compared to both the ASD and sFMT groups (P<0.05). In addition, serum ACTH and CORT concentration were significantly reduced (P<0.05), and CRH concentration also showed a decreasing trend. ConclusionExercise may improve ASD-related behaviors by suppressing the activation of the HPA axis, with the gut microbiota likely playing a crucial role in this process.

OBJECTIVE: By analyzing the hormone secretion of the adenohypophysis, thyroid glands, gonads, and adrenal cortex in patients with hematological diseases before and after hematopoietic stem cell transplantation (HSCT), this study aims to preliminarily explore the effect of HSCT on patients' hormone secretion and glandular damage. METHODS: The baseline data of 209 hematological disease patients who underwent HSCT in our hospital from January 2019 to December 2023, as well as the data on the levels of hormones secreted by the adenohypophysis, thyroid glands, gonads and adrenal cortex before and after HSCT were collected, and the changes in hormone levels before and after transplantation were analyzed. RESULTS: After allogeneic HSCT, the levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3) and estradiol (E2) decreased, while the levels of luteinizing hormone (LH) and follicle- stimulating hormone (FSH) increased. The T3 level of patients with decreased TSH after transplantation was lower than that of those with increased TSH after transplantation. In female patients, the levels of prolactin (PRL), progesterone (Prog), and testosterone (Testo) decreased after HSCT. Testo and PRL decreased when there was a donor-recipient sex mismatch, and the levels of adrenocorticotropic hormone (ACTH) and cortisol (COR) decreased when the HLA matching was haploidentical. The levels of T3, FT3, and PRL decreased after autologous HSCT. In allogeneic HSCT patients, the levels of TSH, T4, T3, FT3, and ACTH in the group with graft-versus-host disease (GVHD) were significantly lower than those in the group without GVHD. Logistic regression analysis showed the changes in hormone levels after transplantation were not correlated with factors such as the patient's sex, age, or whether the blood types of the donor and the recipient are the same. CONCLUSION HSCT can affect the endocrine function of patients with hematological diseases, mainly affecting target glandular organs such as the thyroid, gonads, and adrenal glands, while the secretory function of the adenohypophysis is less affected.
Humans ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Hematologic Diseases/blood* ; Follicle Stimulating Hormone/blood* ; Triiodothyronine/blood* ; Luteinizing Hormone/blood* ; Thyroid Gland/metabolism* ; Estradiol/blood* ; Thyrotropin/blood* ; Gonads/metabolism* ; Adult ; Middle Aged ; Adrenocorticotropic Hormone/blood* ; Hormones/metabolism* ; Adrenal Cortex/metabolism* ; Prolactin

OBJECTIVE: To investigate the therapeutic potential of pseudolaric acid B (PAB) on non-alcoholic fatty liver disease (NAFLD) and its underlying molecular mechanism in vitro and in vivo. METHODS: Eight-week-old male C57BL/6J mice (n=32) were fed either a normal chow diet (NCD) or a high-fat diet (HFD) for 8 weeks. The HFD mice were divided into 3 groups according to a simple random method, including HFD, PAB low-dose [10 mg/(kg·d), PAB-L], and PAB high-dose [20 mg/(kg·d), PAB-H] groups. After 8 weeks of treatment, glucose metabolism and insulin resistance were assessed by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Biochemical assays were used to measure the serum and cellular levels of total cholesterol (TC), triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). White adipose tissue (WAT), brown adipose tissue (BAT) and liver tissue were subjected to hematoxylin and eosin (H&E) staining or Oil Red O staining to observe the alterations in adipose tissue and liver injury. PharmMapper and DisGeNet were used to predict the NAFLD-related PAB targets. Peroxisome proliferator-activated receptor alpha (PPARα) pathway involvement was suggested by Kyoto Encyclopedia of Genes and Genomes (KEGG) and search tool Retrieval of Interacting Genes (STRING) analyses. Luciferase reporter assay, cellular thermal shift assay (CETSA), and drug affinity responsive target stability assay (DARTS) were conducted to confirm direct binding of PAB with PPARα. Molecular dynamics simulations were applied to further validate target engagement. RT-qPCR and Western blot were performed to assess the downstream genes and proteins expression, and validated by PPARα inhibitor MK886. RESULTS: PAB significantly reduced serum TC, TG, LDL-C, AST, and ALT levels, and increased HDL-C level in HFD mice (P<0.01). Target prediction analysis indicated a significant correlation between PAB and PPARα pathway. PAB direct target binding with PPARα was confirmed through luciferase reporter assay, CETSA, and DARTS (P<0.05 or P<0.01). The target engagement between PAB and PPARα protein was further confirmed by molecular dynamics simulations and the top 3 amino acid residues, LEU321, MET355, and PHE273 showed the most significant changes in mutational energy. Subsequently, PAB upregulated the genes expressions involved in lipid metabolism and mitochondrial biogenesis downstream of PPARα (P<0.05 or P<0.01). Significantly, the PPARα inhibitor MK886 effectively reversed the lipid-lowering and PPARα activation properties of PAB (P<0.05 or P<0.01). CONCLUSION PAB mitigates lipid accumulation, ameliorates liver damage, and improves mitochondrial biogenesis by binding with PPARα, thus presenting a potential candidate for pharmaceutical development in the treatment of NAFLD.
Animals ; PPAR alpha/metabolism* ; Non-alcoholic Fatty Liver Disease/pathology* ; Male ; Mice, Inbred C57BL ; Lipid Metabolism/drug effects* ; Diterpenes/therapeutic use* ; Organelle Biogenesis ; Diet, High-Fat ; Humans ; Mice ; Liver/metabolism* ; Insulin Resistance ; Mitochondria/metabolism* ; Molecular Docking Simulation

Bacillus mycoides JA20-1 was screened and identified as a biocontrol bacterium with a high capacity for producing volatile organic compounds(VOCs) in the laboratory. This strain had significant inhibitory effects on various postharvest disease pathogens in crops, such as Botrytis cinerea, as well as soil-borne disease pathogens in ginseng, such as Sclerotinia ginseng. In order to accelerate its industrialization process, in this study, single-factor experiments and response surface optimization methods were used. The fermentation medium and fermentation conditions in the shake flask of strain JA20-1 were systematically optimized by using cell production volume as the response variable. Meanwhile, the biocontrol effect of JA20-1 on B. cinerea of ginseng during the storage period was evaluated by using the method of fumigation in a dry dish in vitro. The results indicated that the optimal fermentation medium formulation for strain JA20-1 was as follows: 1% yeast paste, 1% soluble starch, 0.25% K_2HPO_4·3H_2O, and 0.2% NaCl. The optimal fermentation conditions in the shake flask were vaccination size of 3%, culture volume of 50 mL in a 250 mL Erlenmeyer flask, pH of 6.2, fermentation temperature of 34 ℃, shaking speed of 180 r·min~(-1), and incubation time of 18 hours. The bacteria count in the fermentation broth under these conditions reached 2.17 × 10~8 CFU·mL~(-1), which was 6.58 times higher than before. The average control efficacy of the fermentation broth on Botrytis cinerea of ginseng under in vitro fumigation reached 61.70% and 84.04% respectively, when 20 mL and 30 mL per dish were used. The research provided theoretical support and technical foundation for the development and utilization of Bacillus mycoides JA20-1 and the biocontrol of soil-borne diseases in ginseng and postharvest diseases in crops.
Botrytis/drug effects* ; Fermentation ; Panax/microbiology* ; Plant Diseases/prevention & control* ; Volatile Organic Compounds/metabolism* ; Bacillus/physiology* ; Pest Control, Biological/methods* ; Biological Control Agents/metabolism* ; Culture Media/chemistry*

Objective To investigate the distribution and antimicrobial resistance of bacterial isolates from blood samples in the hospitals participating in China Antimicrobial Surveillance Network (CHINET) from 2015 to 2021.Methods Bacterial strains isolated from blood samples were collected from 52 medical centers participating in CHINET from 2015 to 2021 for analysis of bacetrial distribution and antimicrobial resistance.Results A total of 153591 isolates were collected,48.8％ of which were gram-positive bacteria and 51.2％ were gram-negative bacteria.The top five bacterial strains were coagulase negative Staphylococcus (28.2％),Escherichia coli (20.7％),Klebsiella (13.7％),Enterococcus (7.2％),and Staphylococcus aureus (6.6％).Compard to female patients,male patients showed lower proportion of E.coli and higher proportions of other bacterial species in all the bacterial isolaets from blood samples.The proportions of Streptococcus pneumoniae and Salmonella in all the bacterial isolaets from blood samples were higher in children compared to adults.Enterobacterales species showed various resistance rates to antimicrobial agents.Overall,≥58.0％,≥36.8％ and ≥56.8％ of E.coli strains were resistant to cefotaxime,gentamicin and levofloxacin respectively over the 7-year period.However,less than 2.5％ of the E.coli strains were resistant to carbapenems.K.pneumoniae showed higher resistance rates to imipenem and meropenem than other Enterobacterales species.During the 7-year period,the prevalence of imipenem-resistant and meropenem-resistant K.pneumoniae increased from 21.4％ and 19.9％ in 2015 to 25.7％ and 26.6％ in 2021,respectively.However,carbapenems still maintained good antibacterial activity against other Enterobacterales,associaetd with lower resistance rates.In the 7-year period,Acinetobacter baumannii showed a dwonward trend in the resistance rates to imipenem and meropenem,but remained 72.9％ and 73.2％ respectively in 2021.The prevalence of imipenem-resistant and meropenem-resistant P.aeruginosa decreased from 26.7％ and 22.9％ in 2015 to 18.5％ and 14.7％ in 2021,respectively.The prevalence of PRSP was 1.5％ in the isolaets from adults and and 0.8％ in the isolates from children.Less than 3.0％ of the Enterococcus faecium and Enterococcus faecalis strains were resistant to vancomycin,teicolanin,or linezolid.The prevalence of methicillin-resistant S.aureus (MRSA) and coagulase negative Staphylococcus (MRCNS) was 32.1％ and 81.0％,respectively.The prevalence of MRSA was relatively stable,28.5％ in 2015 and 28.0％ in 2021.Conclusions Coagulase negative Staphylococcus,E.coli and K.pneumoniae were the main bacterial species isolated from blood samples in the hospitals participaing in the CHINET from 2015 to 2021.Significant sex and age differences were found in the distribution of bcterial isolates from blood samples.The overall resistance rates of the top bacetrial strains from blood samples to antimicrobial agents showed a downward trend.Ongoing surveillance of antimicrobial resistance for the isolates from blood samples is still essential for prescribing rational antimicrobial therapies and curbing bacterial resistance.

Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.