BACKGROUND: Lung cancer is currently the most prevalent malignancy and the leading cause of cancer deaths worldwide. Although the early stage non-small cell lung cancer (NSCLC) presents a relatively good prognosis, a considerable number of lung cancer cases are still detected and diagnosed at locally advanced or late stages. Surgical treatment combined with perioperative multimodality treatment is the mainstay of treatment for locally advanced NSCLC and has been shown to improve patient survival. Following the standard methods of neoadjuvant therapy, perioperative management, postoperative adjuvant therapy, and other therapeutic strategies are important for improving patients' prognosis and quality of life. However, controversies remain over the perioperative management of NSCLC and presently consensus and standardized guidelines are lacking for addressing critical clinical issues in multimodality treatment. METHODS: The working group consisted of 125 multidisciplinary experts from thoracic surgery, medical oncology, radiotherapy, epidemiology, and psychology. This guideline was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The clinical questions were collected and selected based on preliminary open-ended questionnaires and subsequent discussions during the Guideline Working Group meetings. PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNKI) were searched for available evidence. The GRADE system was used to evaluate the quality of evidence and grade the strengths of recommendations. Finally, the recommendations were developed through a structured consensus-building process. RESULTS: The Guideline Development Group initially collected a total of 62 important clinical questions. After a series of consensus-building conferences, 24 clinical questions were identified and corresponding recommendations were ultimately developed, focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assement, and follow-up protocols for NSCLC. CONCLUSIONS This guideline puts forward reasonable recommendations focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assessment, and follow-up protocol of NSCLC. It standardizes perioperative multimodality treatment and provides guidance for clinical practice among thoracic surgeons, medical oncologists, and radiotherapists, aiming to reduce postoperative recurrence, improve patient survival, accelerate recovery, and minimize postoperative complications such as atelectasis.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; Lung Neoplasms/therapy* ; Combined Modality Therapy ; Perioperative Care

Qualitative and quantitative analysis methods for chemical components of different processed products of Corni Fructus were established to systematically characterize and identify these components, and the content of the main differential components was determined. The chemical components of different processed products of Corni Fructus were collected using ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS). Through analysis of self-built databases, literature, and reference standards, a total of 93 components were obtained, including 19 iridoids, 15 flavonoids, 16 organic acids, eight triterpenoids, eight tannins, four amino acids, two polysaccharides, five olefins, and 16 other compounds. Additionally, by using multivariate statistical methods, the differential components between different processed products of Corni Fructus were screened under the conditions of VIP>1.0 and FC<0.5 or FC>2.0 and P<0.05. The PCA and OPLS-DA results showed differences in the chemical components between different processed products of Corni Fructus. A total of 21 differential components were screened, including tartaric acid, morroniside, and rutin. On this basis, ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-QqQ-MS/MS) was used to determine the content of 10 main common differential components, including gallic acid, morroniside, ursolic acid, loganin, swertiamarin, rutin, 5-hydroxymethylfurfural, cornuside Ⅰ, quercetin, and oleanolic acid. The above 10 components showed a good linear relationship within the determined concentration range, with the precision, stability, repeatability, and sample recovery rate all meeting the requirements. Compared with that in Corni Fructus, the content of iridoid glycosides in wine-prepared Corni Fructus and wine-and honey-prepared Corni Fructus decreased, while the content of gallic acid, rutin, quercetin, 5-hydroxymethylfurfural, ursolic acid, and oleanolic acid increased. Compared with wine-prepared Corni Fructus, wine-and honey-prepared Corni Fructus showed varying degrees of increase in all other components, except for a slight decrease in gallic acid content. In summary, this study clarified the influence of different processing methods on the chemical components of Corni Fructus, providing a theoretical basis for the scientific connotation, overall quality evaluation, and clinically rational application of Corni Fructus processing in the future.
Tandem Mass Spectrometry/methods* ; Chromatography, High Pressure Liquid/methods* ; Cornus/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Fruit/chemistry*

Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) can enhance the anti-tumor activity of the anti-programmed cell death-1 (anti-PD-1) antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not performed, and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared with VEGFRi alone, the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and a similar adverse event incidence. Through single-cell and spatial transcriptomic analysis, we determined ten MSS CRC-enriched immune cell types and their spatial distribution, including naive CD4⁺ T, regulatory CD4⁺ T, CD4⁺ Th17, exhausted CD8⁺ T, cytotoxic CD8⁺ T, proliferated CD8⁺ T, natural killer (NK) cells, plasma, and classical and intermediate monocytes. Based on a systemic meta-analysis and ten machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
Humans ; Colorectal Neoplasms/drug therapy* ; Male ; Female ; Immunotherapy ; Middle Aged ; Aged ; Tumor Microenvironment/immunology* ; Retrospective Studies ; Microsatellite Instability ; Transcriptome ; Single-Cell Analysis ; Programmed Cell Death 1 Receptor/immunology* ; Gene Expression Profiling ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*

OBJECTIVE: Acupuncture therapies are known for their effectiveness in treating a variety of gastric diseases, although the mechanisms underlying these effects are not fully understood. This study tested the effectiveness of electroacupuncture (EA) at acupoints Zhongwan (RN12) and Weishu (BL21) for managing gastric motility disorder (GMD) and investigated the underlying mechanisms involved. METHODS: A GMD model was used to evaluate the impact of EA on various aspects of gastric function including the amplitude of gastric motility, electrogastrogram, food intake, and the rate of gastric emptying. Immunofluorescence techniques were used to explore the activation of spinal neurons by EA, specifically examining the presence of cholera toxin B subunit (CTB)-positive neurons and fibers emanating from acupoints RN12 and BL21. The stimulation of γ-aminobutyric acid (GABA)-ergic neurons in the spinal dorsal horn, the inhibition of sympathetic preganglionic neurons in the spinal lateral horn, and their collective effects on the activity of sympathetic nerves were examined. RESULTS: EA at RN12 and BL21 significantly improved gastric motility compromised by GMD. Notably, EA activated spinal neurons, with CTB-positive neurons and fibers from RN12 and BL21 being detectable in both the dorsal root ganglia and the spinal dorsal horn. Further analysis revealed that EA at these acupoints not only stimulated GABAergic neurons in the spinal dorsal horn but also suppressed sympathetic preganglionic neurons in the spinal lateral horn, effectively reducing excessive activity of sympathetic nerves triggered by GMD. CONCLUSION EA treatment at RN12 and BL21 effectively enhances gastric motility in a GMD model. The therapeutic efficacy of this approach is attributed to the activation of spinal neurons and the modulation of the spinal GABAergic-sympathetic pathway, providing a neurobiological foundation for the role of acupuncture in treating gastric disorders. Please cite this article as: Zhang MT, Liang YF, Dai Q, Gao HR, Wang H, Chen L, Huang S, Wang XY, Shen GM. A spinal neural circuit for electroacupuncture that regulates gastric functional disorders. J Integr Med. 2025; 23(1): 56-65.
Electroacupuncture ; Animals ; Male ; Acupuncture Points ; Stomach Diseases/physiopathology* ; Rats, Sprague-Dawley ; Gastrointestinal Motility ; Rats ; Gastric Emptying ; Neurons ; Spinal Cord ; Stomach/physiopathology*

OBJECTIVES: This study investigated the effects of a polycaprolactone (PCL)-polyethylene glycol (PEG) scaffold incorporated with concentrated growth factor (CGF) on the adhesion, proliferation, and osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). METHODS: The PCL-PEG-CGF composite scaffold was fabricated using an immersion and freeze-drying technique. Its microstructure, mechanical properties, and biocompatibility were systematically characterized. The hPDLSCs were isolated through enzymatic digestion, and the hPDLSCs were identified through flow cytometry. Third-passage hPDLSCs were seeded onto the composite scaffolds, and their adhesion, proliferation and osteogenic differentiation were assessed using CCK-8 assays, 4',6-diamidino-2-phenylindole (DAPI) staining, alkaline phosphatase (ALP) staining, alizarin red staining, and Western blot analysis of osteogenesis-related proteins [Runt-related transcription factor 2 (Runx2), ALP, and morphogenetic protein 2 (BMP2)]. RESULTS: Scanning electron microscopy revealed that the PCL-PEG-CGF composite scaffold exhibited a honeycomb-like structure with heterogeneous pore sizes. The composite scaffold exhibited excellent hydrophilicity, as evidenced by a contact angle (θ) approaching 0° within 6 s. Its elastic modulus was measured at (4.590 0±0.149 3) MPa, with comparable hydrophilicity, fracture tensile strength, and fracture elongation to PCL-PEG scaffold. The hPDLSCs exhibited significantly improved adhesion to the PCL-PEG-CGF composite scaffold compared with the PCL-PEG scaffold (P<0.01). Additionally, cell proliferation was markedly improved in all the experimental groups on days 3, 5, and 7 (P<0.01), and statistically significant differences were found between the PCL-PEG-CGF group and other groups (P<0.01). The PCL-PEG-CGF group showed significantly elevated ALP activity (P<0.05), increased mineralization nodule formation, and upregulated expression of osteogenic-related proteins (Runx2, BMP2 and ALP; P<0.05). CONCLUSIONS The PCL-PEG-CGF composite scaffold exhibited excellent mechanical properties and biocompatibility, enhancing the adhesion and proliferation of hPDLSCs and promoting their osteogenic differentiation by upregulating osteogenic-related proteins.
Humans ; Polyesters/chemistry* ; Periodontal Ligament/cytology* ; Polyethylene Glycols/chemistry* ; Stem Cells/cytology* ; Tissue Scaffolds ; Cell Proliferation ; Osteogenesis ; Cell Differentiation ; Cell Adhesion ; Bone Morphogenetic Protein 2/metabolism* ; Cells, Cultured ; Alkaline Phosphatase/metabolism* ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Intercellular Signaling Peptides and Proteins/pharmacology* ; Tissue Engineering/methods*

The ICR(Institute of Cancer Research)mouse infection model was constructed to study the pathogenicity of Sal-monella Telelkebir serotype,and the pathogenic identification of mouse isolates was carried out.Observe the bacterial excretion cycle,evaluate the pathogenicity of Salmonella serotype to mice,and calculate the LD50 by the changes in clinical characteris-tics,histopathology and tissue bacterial load of infected mice;by flight mass spectrometry,biochemical identification,serotype identification,molecular typing and other experiments,compared with human isolates;virulence gene analysis was carried out by PCR experiment and whole genome sequencing.The LD50 of Salmonella Telelkebir is 2.67 × 108 CFU/mL;curling and fluffing may occur 0.5 h after infection;autopsy of dead mice showed that the small intestine was severely congested,with more bubbles and fluid accumulation,cecal necrosis,liver apical degeneration and necrosis,necrotic foci on the surface of the kidney and spleen atrophy;the bacterial load of spleen,kidney,lung,liver and jejunum in mice reached its peak at 3 days after infection,while that of heart at 6 days;the bacterial excretion time of the high-dose group exceeded 100 days;The level of CD3 in tissues increased with increasing dose,with inflammatory cell infiltration,myocardial capillary dilation and hyperemia,large area of vacuoles,degeneration and necrosis of hepatocytes,obvious enlargement of splenic sinus,blurred zoning,thickening of glomerular basement membrane,partial exfoliation of ciliated epithelium,atrophy and exfoliation of jejunal villi;PCR and whole genome sequencing revealed Salmonella-related virulence genes such as cdtB,plt A and pltB.This study was the first to successfully establish the ICR mouse model of Salmonella Telelkebir,demonstrating that this serotype of Salmonella has some pathogenicity.

Objective To investigate the effects of parecoxib sodium injection combined with dexmedetomidine hydrochloride injection on postoperative cognitive function and stress response in patients with osteoporotic compression fractures.Methods The patients with osteoporotic compression fractures were divided into treatment group and control group according to the treatment plan.The control group was given intravenous injection of dexmedetomidine hydrochloride injection 0.2 μg·kg-1load dose,then micro pump injection 0.2 μg·kg-1·min-1 maintenance dose,until 30 min before the end of the operation;patients in the treatment group were intravenously injected with parecoxib sodium injection 20 mg before local anesthesia and 30 min before the end of operation on the basis of the control group.The pain,sedation,hemodynamics[mean arterial pressure(MAP),heart rate(HR)],cognitive function and safety evaluation were compared between the two groups before operation(T0),2 h after operation(T1),6 h after operation(T2),12 h after operation(T3)and 24 h after operation(T4).Results There were 39 cases in the treatment group and 41 cases in the control group.Visual analogue scale(VAS)scores in treatment group and control group were(3.09±0.55)and(3.41±0.62)scores at T1;VAS scores were(3.02±0.57)and(3.35±0.48)scores at T2;VAS scores were(2.64±0.44)and(2.90±0.46)scores at T3;VAS scores were(2.02±0.41)and(2.35±0.47)scores at T4;MMSE scores were(25.28±1.57)and(24.33±1.42)scores at T2;MMSE scores were(28.16±1.01)and(27.25±0.89)scores at T4;MoCA scores were(24.63±1.60)and(23.59±1.25)scores at T2;MoCA scores were(27.20±0.97)and(26.48±0.83)scores at T4.There were statistically significant differences in the above indexes between the treatment group and the control group(all P＜0.05).Adverse drug reactions in the treatment group included bradycardia,hypotension,nausea vomiting and hypokalemia;adverse drug reactions in the control group included bradycardia,hypotension and nausea vomiting.The total incidence rates of adverse drug reactions were 12.82％and 9.76％,without statistically significant difference(P＞0.05).Conclusion Compared with using dexmedetomidine alone,parecoxib sodium combined with dexmedetomidine is beneficial for relieving postoperative pain in patients with osteoporotic compression fractures,improving postoperative cognitive function.

Objective Hand-foot syndrome is a dose-limiting toxicity of capecitabine.At present,there is no unified gold standard for the establishment of hand-foot syndrome model.To induce hand-foot syndrome and provide a reference for the establishment of hand-foot syndrome model by administering capecitabine in ICR mice.Methods 42 male ICR mice were randomly divided into control group(6 mice)and experimental group(36 mice).The experimental group was given capecitabine(275 mg/kg,twice/d)by intragastric administration for two weeks,and the control group was given 0.5%CMC-Na(4 ml/kg,twice/d),to evaluate whether the animal model of hand-foot syndrome was successfully constructed through H&E staining of mouse foot skin samples and observe morphological changes and the characteristic appearance of mouse foot skin.After the experiment,the mice were sacrificed,and plasma was collected to quantify the concentrations of capecitabine and metabolites.Results Control mice did not showed symptoms of hand-foot syndrome.The skin of the feet of 19 mice in the experimental group showed symptoms such as erythema and swelling,and H&E staining results showed that the plantar skin angular epidermis was thickened,and part of the keratin was exfoliated and damaged,which was considered to be hand-foot syndrome.There were no significant differences in the concentrations of capecitabine and its metabolites between mice with and without hand-foot syndrome.Conclusion The model of hand-foot syndrome induced by capecitabine in mice was successfully established.Differences in exposure levels of capecitabine and metabolites may not be the cause of hand-foot syndrome.

The epidemiology and etiology of three suspected cases of imported skin diphtheria infection in Fujian Province were investigated.Secretion samples of patients with skin damage were collected for isolation and culture of Corynebacterium diphtheriae.Biochemical identification and mass spectrum analysis of pure cultures of suspected C.diphtheriae were conduc-ted,the virulence-related genes,including diphtheria toxin reporter(dtxR),toxin A(toxA),and toxin B(toxB)were detec-ted,and multilocus sequence typing(MLST)was performed.All three cases had typical clinical manifestations of cutaneous diphtheria,and C.diphtheriae was isolated from the damaged skin.The virulence genes of two C.diphtheriae strains isolated from two cases were identified as dtxR(+),toxA(-),and toxB(-),and the MLST type was ST-703.The virulence genes of C.diphtheriae isolated from one case were identified as dtxR(+),toxA(+),toxB(+),and the MLST type was ST-248.There is an increased risk of diphtheria in Fujian Province.C.diphtheriae without diphtheria toxin genes can also cause skin diphtheria.

Aim To study the main active components and potential mechanism of selenshenzhi prescription a-gainst esophageal cancer by network pharmacology and in vivo and in vitro experiments.Methods The com-mon target was extracted from TCMSP,OMIM and GeneCards databases,and the PPI network was con-structed using STRING database.DAVID database was used for GO and KEGG enrichment analysis,and a network was constructed based on STRING and DAVID database for in vivo and in vitro experimental verifica-tion.Results Prediction results showed that a total of 100 active ingredients and 749 related targets were ob-tained,and 168 common targets were obtained between selenoshenzhi recipe and esophageal cancer,which were involved in the PI3K-AKT signaling pathway and proteoglycan signaling pathways in cancer.Selenshenz-hi prescription was used to conduct preliminary verifi-cation of related targets for human esophageal cancer EC9706 based on in vitro experiments.The results showed that selenshenzhi prescription could significantly inhibit the proliferation of esophageal cancer cells and induce the apoptosis of EC9706 through the expression of Bax,Bcl-2,caspase-3 and other key apoptotic pro-teins.Lastly,the core target and pathway of selensh-enzhi prescription were preliminically verified based on in vivo animal experiments on nude mice with esopha-geal cancer.The results showed that selenshenzhi pre-scription could significantly inhibit tumor proliferation,promote tumor cell apoptosis,and induce tumor apop-tosis by regulating the expression of key proteins on PI3K/AKT signaling pathway.Conclusions Selensh-enzhi prescription can control the occurrence and de-velopment of esophageal cancer through the synergistic effect of multi-components,multi-targets and multi-pathways,and provide a theoretical basis for further clinical investigation of the mechanism of selenshenzhi prescription in the treatment of esophageal cancer in the future.