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*

This study identified blood-entering components of Anshen Dropping Pills and explored their anti-insomnia effects and mechanisms. The main blood-entering components of Anshen Dropping Pills were detected and identified by UPLC-Q-TOF-MS/MS. The rationality of the formula was assessed by using enrichment analysis based on the relationship between drugs and symptoms, and core targets of its active components were selected as the the potential anti-insomnia targets of Anshen Dropping Pills through network pharmacology analysis. Furthermore, protein-protein interaction(PPI) network, Gene Ontology(GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed on the core targets. An active component-core target network for Anshen Dropping Pills was constructed. Finally, the effects of low-, medium-, and high-dose groups of Anshen Dropping Pills on sleep episodes, sleep duration, and sleep latency in mice were measured by supraliminal and subliminal pentobarbital sodium experiments. Moreover, total scores of the Pittsburgh sleep quality index(PSQI) scale was used to evaluate the changes before and after the treatment with Anshen Dropping Pills in a clinical study. The enrichment analysis based on the relationship between drugs and symptoms verified the rationality of the Anshen Dropping Pills formula, and nine blood-entering components of Anshen Dropping Pills were identified by UPLC-Q-TOF-MS/MS. The network proximity revealed a significant correlation between eight components and insomnia, including magnoflorine, liquiritin, spinosin, quercitrin, jujuboside A, ginsenoside Rb_3, glycyrrhizic acid, and glycyrrhetinic acid. Network pharmacology analysis indicated that the major anti-insomnia pathways of Anshen Dropping Pills involved substance and energy metabolism, neuroprotection, immune system regulation, and endocrine regulation. Seven core genes related to insomnia were identified: APOE, ALB, BDNF, PPARG, INS, TP53, and TNF. In summary, Anshen Dropping Pills could increase sleep episodes, prolong sleep duration, and reduce sleep latency in mice. Clinical study results demonstrated that Anshen Dropping Pills could decrease total scores of PSQI scale. This study reveals the pharmacodynamic basis and potential multi-component, multi-target, and multi-pathway effects of Anshen Dropping Pills, suggesting that its anti-insomnia mechanisms may be associated with the regulation of insomnia-related signaling pathways. These findings offer a theoretical foundation for the clinical application of Anshen Dropping Pills.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Tandem Mass Spectrometry/methods* ; Sleep Initiation and Maintenance Disorders/metabolism* ; Mice ; Network Pharmacology ; Male ; Chromatography, High Pressure Liquid ; Humans ; Protein Interaction Maps/drug effects* ; Sleep/drug effects* ; Female ; Adult

OBJECTIVE: To investigate short-term effectiveness of robot-assisted fracture reduction and fixation combined with arthroscopic exploration for posterolateral depressed tibial plateau fractures. METHODS: Between January 2022 and January 2024, 8 patients with posterolateral depressed tibial plateau fractures (Schatzker type Ⅲ) were treated using robot-assisted fracture reduction and fixation combined with arthroscopic exploration, with simultaneous treatment of concomitant ligament or meniscus tears. There were 3 males and 5 females with an average age of 54.1 years (range, 42-68 years). Injury mechanisms included traffic accidents (3 cases) and falls (5 cases). The time from injury to operation ranged from 2 to 4 days (mean, 3.1 days). Operation time, intraoperative blood loss, hospital stay duration, visual analogue scale (VAS) score for pain, and complications were recorded. Fracture healing and knee Rasmussen scores were assessed radiographically, while knee function was evaluated using range of motion and Hospital for Special Surgery (HSS) scores. RESULTS: All operations were successfully completed. The operation time was 108-129 minutes (mean, 120.1 minutes). The intraoperative blood loss was 10-100 mL (mean, 41.3 mL). The hospital stay duration was 4-7 days (mean, 5.6 days). All incisions healed by first intention without complication such as peroneal nerve injury, vascular damage, or infection. All patients were followed up 32-48 weeks (mean, 40 weeks). Radiographic follow-up confirmed that the knee Rasmussen scores rated as excellent in 8 patients and all fractures healed with the healing time of 12-16 weeks (mean, 13.5 weeks). The VAS score for pain was 2-4 (mean, 2.8) at discharge and improved to 0 at 1 month after operation. The knee range of motion was 80°-110° (mean, 96.1°) at discharge and increased to 135°-140° (mean, 137.9°) at 1 month after operation. At 3 months after operation, the HSS score was 91-94 (mean, 92.8), all graded as excellent. No severe complication, including implant failure, occurred during follow-up. CONCLUSION For posterolateral depressed tibial plateau fractures, the minimally invasive approach combining robot-assisted fracture reduction and fixation with arthroscopic exploration demonstrates multiple advantages, including shorter operation time, reduced intraoperative blood loss, excellent wound healing, fewer complications, and rapid recovery of knee function. This technique achieves satisfactory short-term effectiveness, while its long-term effectiveness requires further evaluation.
Humans ; Male ; Tibial Fractures/surgery* ; Female ; Middle Aged ; Adult ; Arthroscopy/methods* ; Minimally Invasive Surgical Procedures/methods* ; Fracture Fixation, Internal/methods* ; Aged ; Treatment Outcome ; Robotic Surgical Procedures/methods* ; Operative Time ; Range of Motion, Articular ; Fracture Healing ; Length of Stay ; Tibial Plateau Fractures

OBJECTIVE: Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from Astragalus membranaceus (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF. METHODS: The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial-mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations. RESULTS: Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2'-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells. CONCLUSION AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF. Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. J Integr Med. 2025; 23(6):694-705.
Epithelial-Mesenchymal Transition/drug effects* ; Animals ; Saponins/pharmacology* ; Triterpenes/pharmacology* ; Mice ; Peritoneal Fibrosis/pathology* ; Proto-Oncogene Proteins c-akt/metabolism* ; ErbB Receptors/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Signal Transduction/drug effects* ; Male ; Humans ; Molecular Docking Simulation ; Cell Line ; Mice, Inbred C57BL

OBJECTIVE: Several epidemiological observational studies have related particulate matter (PM) exposure to Inflammatory bowel disease (IBD), but many confounding factors make it difficult to draw causal links from observational studies. The objective of this study was to explore the causal association between PM _2.5 exposure, its absorbance, and IBD. METHODS: We assessed the association of PM _2.5 and PM _2.5 absorbance with the two primary forms of IBD (Crohn's disease [CD] and ulcerative colitis [UC]) using Mendelian randomization (MR) to explore the causal relationship. We conducted two-sample MR analyses with aggregated data from the UK Biobank genome-wide association study. Single-nucleotide polymorphisms linked with PM _2.5 concentrations or their absorbance were used as instrumental variables (IVs). We used inverse variance weighting (IVW) as the primary analytical approach and four other standard methods as supplementary analyses for quality control. RESULTS: The results of MR demonstrated that PM _2.5 had an adverse influence on UC risk (odds ratio [ OR] = 1.010; 95% confidence interval [ CI] = 1.001-1.019, P = 0.020). Meanwhile, the results of IVW showed that PM _2.5 absorbance was also causally associated with UC ( OR = 1.012; 95% CI = 1.004-1.019, P = 0.002). We observed no causal relationship between PM _2.5, PM _2.5 absorbance, and CD. The results of sensitivity analysis indicated the absence of heterogeneity or pleiotropy, ensuring the reliability of MR results. CONCLUSION Based on two-sample MR analyses, there are potential positive causal relationships between PM _2.5, PM _2.5 absorbance, and UC.
Humans ; Mendelian Randomization Analysis ; Particulate Matter/analysis* ; Polymorphism, Single Nucleotide ; Inflammatory Bowel Diseases/genetics* ; Air Pollutants/analysis* ; Crohn Disease/genetics* ; Colitis, Ulcerative/genetics* ; Genome-Wide Association Study ; Risk Factors ; Environmental Exposure

OBJECTIVE: Emerging evidence suggests that exposure to ultrafine particulate matter (UPM, aerodynamic diameter < 0.1 µm) is associated with adverse cardiovascular events. Previous studies have found that Shenlian (SL) extract possesses anti-inflammatory and antiapoptotic properties and has a promising protective effect at all stages of the atherosclerotic disease process. In this study, we aimed to investigated whether SL improves UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis. METHODS: We established a mouse model of MI+UPM. Echocardiographic measurement, measurement of myocardialinfarct size, biochemical analysis, enzyme-linked immunosorbent assay (ELISA), histopathological analysis, Transferase dUTP Nick End Labeling (TUNEL), Western blotting (WB), Polymerase Chain Reaction (PCR) and so on were used to explore the anti-inflammatory and anti-apoptotic effects of SL in vivo and in vitro. RESULTS: SL treatment can attenuate UPM-induced cardiac dysfunction by improving left ventricular ejection fraction, fractional shortening, and decreasing cardiac infarction area. SL significantly reduced the levels of myocardial enzymes and attenuated UPM-induced morphological alterations. Moreover, SL significantly reduced expression levels of the inflammatory cytokines IL-6, TNF-α, and MCP-1. UPM further increased the infiltration of macrophages in myocardial tissue, whereas SL intervention reversed this phenomenon. UPM also triggered myocardial apoptosis, which was markedly attenuated by SL treatment. The results of in vitro experiments revealed that SL prevented cell damage caused by exposure to UPM combined with hypoxia by reducing the expression of the inflammatory factor NF-κB and inhibiting apoptosis in H9c2 cells. CONCLUSION Overall, both in vivo and in vitro experiments demonstrated that SL attenuated UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis. The mechanisms were related to the downregulation of macrophages infiltrating heart tissues.
Animals ; Apoptosis/drug effects* ; Particulate Matter/adverse effects* ; Mice ; Male ; Inflammation/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Inbred C57BL ; Myocardial Ischemia/drug therapy* ; Cell Line

OBJECTIVE: Poxviruses are zoonotic pathogens that infect humans, mammals, vertebrates, and arthropods. However, the specific role of ticks in transmission and evolution of these viruses remains unclear. METHODS: Transcriptomic and metatranscriptomic raw data from 329 sampling pools of seven tick species across five continents were mined to assess the diversity and abundance of poxviruses. Chordopoxviral sequences were assembled and subjected to phylogenetic analysis to trace the origins of the unblasted fragments within these sequences. RESULTS: Fifty-eight poxvirus species, representing two subfamilies and 20 genera, were identified, with 212 poxviral sequences assembled. A substantial proportion of AT-rich fragments were detected in the assembled poxviral genomes. These genomic sequences contained fragments originating from rodents, archaea, and arthropods. CONCLUSION Our findings indicate that ticks play a significant role in the transmission and evolution of poxviruses. These viruses demonstrate the capacity to modulate virulence and adaptability through horizontal gene transfer, gene recombination, and gene mutations, thereby promoting co-existence and co-evolution with their hosts. This study advances understanding of the ecological dynamics of poxvirus transmission and evolution and highlights the potential role of ticks as vectors and vessels in these processes.
Animals ; Poxviridae/physiology* ; Ticks/virology* ; Phylogeny ; Transcriptome ; Evolution, Molecular ; Poxviridae Infections/virology* ; Genome, Viral

AIM: To explore the clinical features, diagnosis and treatment experience and the distribution characteristics of pathogenic microorganisms of primary canaliculitis, and provide reference for its diagnosis and treatment. METHODS: Retrospective clinical study. A total of 119 cases(120 eyes)diagnosed as primary canaliculitis in the department of ophthalmology of Wuxi No.2 People's Hospital from June 2019 to February 2023 were included. The treatment methods were mainly divided into conservative treatment(removing canaliculus stones through lacrimal punctum combined with injecting antibiotic eye ointment into the tube)and surgical treatment. The inspection methods of pathogenic microorganisms included secretion smear microscopy and microbial culture.RESULTS: Primary canaliculitis was more common in middle-aged and older female, mainly manifested by long-term red eye and increased secretion; however, the majority was not accompanied by tearing. Totally, 118 cases(99.2%)had monocular disease, while 63 cases(63 eyes; 52.5%)had inferior lacrimal canaliculus disease. Laboratory examination: Among 119 cases(120 eyes), 4 cases(4 eyes)did not undergo laboratory examination, and the other 115 cases(116 eyes)were as follows: Gram staining microscopy of secretion smear showed that Actinomyces were detected in 102 cases(103 eyes; 88.8%), while no fungus was detected; Microbial culture: 85 cases(86 eyes; 74.1%)were positive for bacterial culture. A total of 111 bacterial strains were cultured, which contained 26 types of bacteria. Among them, 32 strains were aerobic(28.8%); 26 strains were anaerobic(23.4%); and 53 strains were facultative anaerobic(47.7%). The most common bacteria were streptococcus(20 strains), staphylococcus(13 strains), Propionibacterium(10 strains), and capnocytophaga(10 strains). Only 4 cases(4 eyes; 3.4%)of microbial cultures were positive for Actinomyces. Fungus was negative in all microbial cultures. Treatment: Of the 119 cases(120 eyes), 114 cases(115 eyes; 95.8%)were cured by conservative treatment of removing lacrimal canaliculus stones through lacrimal punctum and intracanalicular ointment infiltration(IOI), while 5 cases(5 eyes)were not effective in conservative treatment; however, all of them were cured after surgical treatment, and the cure rate for primary canaliculitis was 100.0%.CONCLUSION: The incidence of primary canaliculitis is low, and it is prevalent in middle-aged and older female. Single lacrimal canaliculus is more common, which could be missed and misdiagnosed in clinic. Actinomyces is the major pathogen observed mostly in mixed infections, with heterogeneous strains, mainly anaerobic or facultative anaerobic bacteria. Streptococcus and Staphylococcus are the most common whereas fungal canaliculitis is rare. The cure rate of primary canaliculitis is high after diagnosis, and IOI method is recommended as the initial treatment of canaliculitis.

Objective: human cysteine protease inhibitor S; helicobacter pylori antibody typing; human epidermal growth factor receptor 2 ; gastric cancer; pathological stage; gastric cancer lymph node metastasis Methods: A total of 150 gastric cancer patients admitted to Chaohu Hospital Affiliated to Anhui Medical University for surgery from December 2021 to December 2023 were selected as the study objects. Serum CST4 and HP antibody typing were performed before surgery, and HER2 expression levels in gastric cancer tissues were detected by immunohistochemistry after surgery. The clinicopathological data of gastric cancer patients with different serum CST4, HP antibody types and HER2 expression were compared and the correlation was analyzed. ROC curve was used to compare the predictive value of single and combined detection of serum CST4, HP antibody typing and HER2 expression in lymph node metastasis and TNM staging of gastric cancer. Results: Patients with CST4, HPI and HER2-positive expression had deeper tumor invasion and were more likely to develop distant lymph node metastasis, and TNM stages were more likely to occur in Ⅲ and Ⅳ stages(P<0.05). Meanwhile, patients with CST4 positive expression were more likely to have vascular and nerve invasion(P<0.05). In patients with HPI positive expression, tumors were more likely to occur in the cardia and the bottom of the stomach, and the tumor diameter was larger and vascular invasion was more likely(P<0.05), while HER2 was negatively correlated with the degree of tumor differentiation, and the tumors were more likely to occur in high and secondary differentiation(P<0.05). ROC curve analysis showed that the AUC of single and combined detection of serum CST4, HPI and HER2 expression to predict lymph node metastasis of gastric cancer were 0.780, 0.676, 0.611 and 0.872, respectively(P<0.05). The AUC for TNM stage diagnosis of gastric cancer were 0.762, 0.635, 0.613 and 0.801(P<0.05), respectively. The diagnostic efficiency of combined detection was higher than that of single detection. Conclusion The expression of CST4, HPI and HER2 in serum is closely related to the depth of tumor invasion, lymph node metastasis and TNM stage. The expression of CST4, HPI and HER2 in serum can be used as an important predictor of lymph node metastasis and TNM stage in gastric cancer patients, providing a new idea for clinical diagnosis.

Objective:To understand the current status of gastroscopy in diagnosing gastric lesions in general population, and to recommend the optimal age for the first gastroscopy and intervals for repeated gastroscopy.Methods:The gastroscopy records of residents aged 18-80 years in Yinzhou District of Ningbo, Zhejiang Province, between April 2010 and December 2021 were analyzed retrospectively. The detections of gastric lesions across different years, age and genders were described. Goodness of fit tests were applied to compare the differences in detection rates of different lesions in first-time endoscopy in different age groups and different populations. Generalized additive models were used to fit the trend of age specific gastric lesion detection rate explore the optimal age for gastroscopy. The appropriate gastroscopy intervals were determined according to the progress of the gastric lesions detected in repeated gastroscopy.Results:A total of 237 751 participants with 344 398 gastroscopy records were included in analyses. A total of 5 597 cases of chronic atrophic gastritis (CAG), 9 796 cases of intestinal metaplasia (IM), 165 cases of low-grade intraepithelial neoplasia (LGIN), 52 cases of high-grade intraepithelial neoplasia (HGIN) and 435 cases of gastric cancer were detected by the first gastroscopy. The overall detection rate of gastric lesions increased significantly in age group 45-70 years, and remained stable after 70 years old, with LGIN and HGIN showing notable increases at 50 and 55 years old, respectively. Repeated gastroscopy detected CAG, IM, LGIN, and HGIN at a higher rate compared with the first gastroscopy. Normal/superficial gastritis progressed in 3-5 years, whereas CAG or more severe lesions progressed in 1-6 years.Conclusion:Gastroscopy is recommended for general population aged 45 years and above. Furthermore, gastroscopy can be performed every 3-5 years for individuals with normal endoscopy results and once a year for patients with CAG or more severe gastric lesions.