Immunobiological signatures and the emerging role of SPP1 in predicting tumor heterogeneity, malignancy, and clinical outcomes in stomach adenocarcinoma.

BACKGROUND: Immunotherapy, as a form of immunobiological therapy, represents a promising approach for enhancing patients' immune responses. This work aims to present innovative ideas and insights for prognostic assessment and clinical treatment of stomach adenocarcinoma (STAD) by leveraging immunobiological signatures. METHODS: We employed weighted gene co-expression network analysis (WGCNA) and unsupervised clustering analysis to identify hub genes. These hub genes were utilized to construct a prognostic risk model, and their impact on the tumor microenvironment (TME) and DNA variations was assessed using large-scale STAD patient cohorts. Additionally, we conducted transfection experiments with plasmids to investigate the influence of SPP1 on the malignancy of HGC27 and NCI-N87 cells. RESULTS: Unsupervised clustering of 12 immune-related genes (IRGs) revealed three distinct alteration patterns with unique molecular phenotypes, clinicopathological characteristics, prognosis, and TME features. Using LASSO and multivariate Cox regression analyses, we identified three hub genes (MMP12, SPP1, PLAU) from the IRGs to establish a risk signature. This IRG-related risk model significantly stratified the prognosis risk among STAD patients in the training (n = 522), testing (n = 521), and validation (n = 300) cohorts. Notably, there were discernible differences in therapy responses and TME characteristics, such as tumor purity and lymphocyte infiltration, between the risk model groups. Subsequently, a nomogram that incorporates the IRG signature and clinicopathological factors demonstrated superior sensitivity and specificity in predicting outcomes for STAD patients. Furthermore, down-regulation of SPP1, as observed after siRNA transfection, significantly inhibited the proliferation and migration abilities of HGC27 and NCI-N87 cells. CONCLUSIONS: In summary, this study highlights the critical role of immune-related signatures in STAD and offers novel insights into prognosis indicators and immunotherapeutic targets for this condition. SPP1 emerges as an independent prognostic factor for STAD and appears to regulate STAD progression by influencing the immune microenvironment.

Epidemiological study of capillary malformation among 7299 infants under 1 year of age in China.

BACKGROUND: Capillary malformation (CM) is the most common vascular malformation. Large scale studies on its incidence and risk factors are limited in China. OBJECTIVE: Our study aimed to investigate the incidence of CM in Chinese infants and to evaluate its potential risk factors. METHODS: A cross-sectional study, including 7299 infants (aged < 1 year) were collected by a self-administered questionnaire. Independent-samples T tests or χ2 tests and multivariable logistic models were used to examine the potential risk factors for CM. RESULTS: The incidences of salmon patches and port-wine stains (PWSs) were 9.10% and 0.80%, respectively. In analyses, male sex (OR: 1.32, 95% CI: 1.12-1.55) and birth hypoxia (OR: 5.61, 95% CI: 4.39-7.16) were risk factors for salmon patches. Birth hypoxia (OR: 12.58, 95% CI: 7.26-21.79) and pregnancy-induced hypertension syndrome (PIH; OR: 3.66, 95% CI: 1.49-8.99) were associated with a higher risk of PWSs. CONCLUSION: This epidemiological study had the largest sample size of infants with CM in the world thus far, which updated its incidence in Chinese infants and found the potential risk factors for CM.

CCL5 as a Prognostic Marker for Survival and an Indicator for Immune Checkpoint Therapies in Small Cell Lung Cancer.

The standard treatment for small cell lung cancer (SCLC) has not changed in decades. Recently, important advances have been made in immunotherapy. However, analysis of these trials suggests that only a small proportion of patients benefit from immune checkpoint blockade (ICB). Identifying these patients is a clinical challenge. In this study, we applied the ESTIMATE calculation to calculate immune scores in 159 cases of SCLC from two published cohorts. COX regression analysis was used to analyze the differentially expressed genes (DEGs) with high and low immune score. We found that CCL5 expression was positively correlated with survival in SCLC patients. In addition, we verified the effect of CCL5 on survival and response to treatment in another cohort that received immunotherapy. Meanwhile, Gene set enrichment analysis (GSEA) showed that genes with high expression of CCL5 were mainly enriched in immune-related activities. The result of Tumor Immune Dysfunction and Exclusion (TIDE) demonstrated that CCL5 was a potential biomarker to predict response to ICB for SCLC, which is correspondent with the result in verified cohort. These results suggest that CCL5 may be the reason for TME to maintain its immune dominance, making it a favorable factor for ICB. Therefore, CCL5 levels may help to outline the prognosis of patients with SCLC.

MGA Mutation as a Novel Biomarker for Immune Checkpoint Therapies in Non-Squamous Non-Small Cell Lung Cancer.

Background: Immune checkpoint inhibitors have changed the treatment landscape for advanced non-small cell lung cancer. However, only a small proportion of patients experience clinical benefit from ICIs. Thus, the discovery of predictive biomarkers is urgently warranted. Evidence have shown that genetic aberrations in cancer cells can modulate the tumor immune milieu. We therefore explored the association between oncogenic mutations and efficacy to ICIs in non-squamous NSCLC. Methods: We curated genomic and clinical data of 314 non-squamous NSCLC patients receiving ICIs from four independent studies for the discovery cohort. For external validation, 305 patients from an ICI-treated cohort and 1,027 patients from two non-ICI-treated cohorts were used. Relations between oncogenic mutations and outcomes of immunotherapy were examined. Multivariate Cox regression models were applied to adjust confounding factors. Further investigation on tumor antigenicity and antitumor immunity was performed in The Cancer Genome Atlas lung adenocarcinoma cohort. Results: A total of 82 oncogenes/tumor suppressor genes according to the Oncology Knowledge base database with a frequency greater than 3% were identified and investigated in the discovery cohort. Within these genes, MGA mutations were enriched in patients with durable clinical benefit (p = 0.001, false discovery rate q < 0.05). The objective response rate was also significantly higher in patients with MGA mutation (2.63-fold, p < 0.001, FDR q < 0.05). Longer progression-free survival was found in MGA-mutated patients (HR, 0.41; 95% CI, 0.23-0.73; p = 0.003), and the association remained significant after controlling for tumor mutational burden (TMB), programmed cell death ligand-1 expression, and treatment regimens. In the validation cohort, significant improvement in overall survival was found in patients harboring MGA mutation (HR, 0.39; 95% CI, 0.17-0.88; p = 0.02). Furthermore, the survival difference was not detected in non-ICI-treated cohorts. We also demonstrated that MGA mutation correlate with higher TMB, elevated neoantigen load and DNA damage repair deficiency. Gene set enrichment analysis revealed that gene sets regarding activated immune responses were enriched in MGA-mutated tumors. Conclusion: Our work provides evidence that MGA mutation can be used as a novel predictive biomarker for ICI response in non-squamous NSCLC and merits further clinical and preclinical validation.

Gut Microbiota and Lung Injury.

Gut microbiota are known to impact multiple organs including the lung. The cross talk between gut microbes and lungs, termed as the "gut-lung axis," is vital for immune response and homeostasis in the airways. In this chapter, we summarized the coordinated development of microorganisms in the gut and lung, exogenous and endogenous factors related to the cross talk, the mechanisms of the gut-lung axis and their dysbiosis in lung diseases. Although the current understanding of the gut-lung axis is in its infancy, several gut microbiota-associated strategies have been designed to treat and prevent lung diseases.

Low-Cost Haptic Simulation Using Material Fracture.

Medical simulation training is widely used to effectively train for invasive medical procedures such as peripheral nerve blocks. Traditionally, accurate haptic training relies on expensive cadavers, manikins, or advanced haptic robots. Proposed herein is a novel concept for haptic training called the low-cost haptic force needle insertion simulator (LCNIS), which uses material fracture inside disposable cartridges to accurately replicate the force of inserting a needle into tissue. Cadaver and material fracture experiments were performed to develop and determine the accuracy of the LCNIS. The material testing showed that polycarbonate had the highest maximum needle puncture force of the materials tested, 9.85 N, and that fluorinated ethylene propylene had the lowest maximum puncture force, 0.84 N. The cadaver results showed that the error between the three peak forces in a cadaver and a cadaver mimicking cartridge was 1.00 N, 0.01 N, and 1.54 N. The standard deviation of these peaks was 0.60 N, 0.55 N, and 0.41 N. This novel method of haptic simulation can easily be adapted to recreate any type of force and, therefore, could be utilized to train for a wide variety of medical procedures.

Prophylactic air-extraction strategy after thoracoscopic wedge resection.

BACKGROUND: Since the conception of enhanced recovery after surgery protocols, tubeless strategies have become popular. Herein, we introduce a previously unreported alternative air-extraction strategy for patients who have undergone thoracoscopic wedge resection and explore its feasibility and safety. METHODS: Between January 2015 and June 2017, 264 consecutive patients underwent thoracoscopic wedge resection with different drainage strategies. Patients were divided according to the postoperative drainage strategies used: routine chest tube drainage (RT group), complete omission of chest tube drainage (OT group), and prophylactic air-extraction catheter insertion procedure (PC group). Using the propensity score matching method, clinical parameters and objective operative qualities were compared among the three groups. RESULTS: Optimal 1:1 matching was used to form pairs of RT (n =36) and PC (n =36) groups and balance baseline characteristics among the three groups. The incidence rates of pneumothorax were 5.6% (2/36), 9.8% (5/51), and 19.4% (7/36) in the RT, OT, and PC groups, respectively (P = 0.07). Chest tube reinsertion incidence for postoperative pneumothorax was 19.4% (1/7) in the PC group and 60% (3/5) in the OT group. Other postoperative complications were comparable among these groups. CONCLUSIONS: The prophylactic air-extraction strategy may be an alternative procedure for selected patients. Remedial air extraction may reduce the occurrence of chest tube reinsertion for pneumothorax patients, but further investigation is required.

Effects and mechanisms of auricular electroacupuncture on visceral pain induced by colorectal distension in conscious rats.

OBJECTIVE: To investigate the effects and mechanisms of action of auricular electroacupuncture (AEA) on visceral pain induced by colorectal distension (CRD). METHODS: Twenty-nine female Sprague-Dawley rats were randomly divided into four groups: control; untreated CRD; CRD+AEA; and CRD+sham electroacupuncture (SEA). An electromyogram (EMG) was recorded for 120 min in the conscious state. After a 30 min baseline recording, CRD was performed in untreated CRD, AEA and SEA groups and lasted for 90 min. AEA and SEA were started at 30 min and lasted for 30 min. The EMG was recorded and analysed to evaluate the severity of visceral pain, indicated by the magnitude of the vasomotor response (VMR). mRNA expression of the 5-hydroxytryptamine 1a (5-HT1a) receptor was measured separately in the colon and raphe nuclei using real-time fluorescent quantitative PCR. RESULTS: No differences were seen in the baseline EMG among the four groups (p>0.05). During pre-stimulation, VMR magnitude in the CRD, AEA and SEA groups increased compared with that in the control group (p<0.05). During stimulation, the VMR magnitude was significantly decreased in AEA but not SEA groups relative to the (untreated) CRD group. Similarly, mRNA expression of the 5-HT1a receptor in both the colon and raphe nuclei was lower in AEA but not SEA groups compared with the CRD group (p<0.05). CONCLUSIONS: AEA can ameliorate CRD-induced visceral pain in rats, and increase mRNA expression of the 5-HT1a receptor peripherally (in the colon) and centrally (in the raphe nuclei), suggesting a serotonergic mechanism of action.

[Exploration on the origin and development of pressing moxibustion].

Through arranging of ancient books and literatures related pressing moxibustion, the history along with origin and development of pressing moxibustion is systematically investigated and analyzed, which provided theoretical basis for the clinical practice of pressing moxibustion. It is found that after 600 years of development and innovation, pressing moxibustion already has complete theoretical system which is reflected in the unitarity of formulating prescription, the diversity of the manipulation the universality of indications. What's more, the functional characteristics and mechanism of pressing moxibustion are initially discussed and its present research status and prospect in the field of modern moxibustion are revealed.