Construction and Validation of a Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Gastric Cancer.

BACKGROUND: Increasing evidence indicated that the tumor microenvironment (TME) plays a critical role in tumor progression. This study aimed to identify and evaluate mRNA signature involved in lymph node metastasis (LNM) in TME for gastric cancer (GC). METHODS: Gene expression and clinical data were downloaded from The Cancer Genome Atlas (TCGA). The ESTIMATE algorithm was used to evaluate the TME of GC. The heatmap and Venn plots were applied for visualizing and screening out intersect differentially expressed genes (DEGs) involved in LNM in TME. Functional enrichment analysis, gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) network were also conducted. Furthermore, binary logistic regression analysis were employed to develop a 4-mRNAs signature for the LNM prediction. ROC curves were applied to validate the LNM predictive ability of the riskscore. Nomogram was constructed and calibration curve was plotted to verify the predictive power of nomogram. RESULTS: A total of 88 LNM related DEGs were identified. Functional enrichment analysis and GSEA implied that those genes were associated with some biological processes, such as ion transportation, lipid metabolism and thiolester hydrolase activity. After univariate and multivariate logistic regression analysis, 4 mRNAs (RASSF2, MS4A2, ANKRD33B and ADH1B) were eventually screened out to develop a predictive model. ROC curves manifested the good performance of the 4-mRNAs signature. The proportion of patients with LNM in high-risk group was significantly higher than that in low-risk group. The C-index of nomogram from training and test cohorts were 0.865 and 0.765, and the nomogram was well calibrated. CONCLUSIONS: In general, we identified a 4-mRNAs signature that effectively predicted LNM in GC patients. Moreover, the 4-mRNAs signature and nomogram provide a guidance for the preoperative evaluation and postoperative treatment of GC patients.

Lever-elevating vs. liquid-isolating maneuvers during microwave ablation of high-risk benign thyroid nodules: a prospective single-center study.

Aim: To compare the effects of the liquid-isolating maneuver and the lever-elevating maneuver in protecting cervical structures during microwave ablation for treating high-risk benign thyroid nodules.Methods: This prospectively study was approved by the Medical Ethics Committee of Panzhihua Central Hospital. A total of 174 patients were enrolled and randomly assigned to a liquid-isolating maneuver group (LIM, n = 87) or a lever-elevating maneuver group (LEM, n = 87). Operation time, postoperative voice change, time to recovery of baseline voice, peri-thyroid hematoma, neck tension, and intraoperative vasovagal reaction were assessed.Results: Operation time was greater in the LIM group than in the LEM group (44.75 ± 13.14 vs. 32.87 ± 10.84 min; p = .017).Voice changes were observed in 6 patients in the LIM group and 2 in the LEM group (6.9% vs. 2.3%, p = .278). The time to recovery of baseline voice was significantly greater in the LIM group compared with the LEM group (36.15 ± 10.24 vs. 24.48 ± 11.53 days, p = .014). The incidences of peri-thyroid hematoma and neck tension were higher in the LIM than in the LEM group (11.5% vs. 3.4%, 10.3% vs. 2.3%, p = .044 and p = .029). One patient (1.1%) in the LEM group and none of the patients in the LIM group experienced a vasovagal response (p = 1.000).Conclusion: The lever-elevating method is feasible and effective for the microwave ablation of benign thyroid nodules, with better protection of neck structures than observed with the liquid-isolating method.

Silk Nanofiber Carriers for Both Hydrophilic and Hydrophobic Drugs to Achieve Improved Combination Chemotherapy.

Combination chemotherapy is considered an effective strategy to inhibit tumor growth. Here, beta-sheet-rich silk nanofibers are co-loaded with hydrophilic doxorubicin (DOX) and hydrophobic paclitaxel (PTX) through a sequential physical blending-centrifugation-blending process. The ratio and amount of DOX and PTX on the nanofibers are regulated independently to optimize cooperative interaction. Both PTX and DOX are immobilized on the same nanofibers to avoid burst release problems. Besides the water-insoluble PTX, more than half of the DOX remained fixed on the nanofibers for more than 28 days, which facilitated the co-internalization of both DOX and PTX by tumor cells in vitro. Changing the ratio of co-loaded DOX and PTX achieved optimal combination therapy in vitro. The DOX-PTX co-loaded nanofibers are assembled into injectable hydrogels to facilitate in situ injection around tumor tissues in vivo. Long-term inhibition is achieved for tumors treated with DOX-PTX co-loaded hydrogels, superior to those treated with free DOX and PTX, and hydrogels loaded with only DOX or PTX. Considering the mild and controllable physical loading process and superior loading capacity for both hydrophilic and hydrophobic ingredients, these injectable silk nanofiber hydrogels are promising carriers to deliver multiple drug types simultaneously in situ, enhancing combination chemotherapies towards clinical applications.

Nanosized Silk-Magnesium Complexes for Promotion of Angiogenic and Osteogenic Activities.

Injectable hydrogels with osteogenic and angiogenetic properties are of interest in bone tissue engineering. Since the bioactivity of ions is concentration-dependent, nanosized silk-magnesium (Mg) complexes were previously developed and assembled into hydrogels with angiogenic capabilities but failed to control both osteogenic and angiogenetic activities effectively. Here, nanosized silk particles with different sizes were obtained by using ultrasonic treatment to control silk-Mg coordination and particle formation, resulting in silk-Mg hydrogels with different types of bioactivity. Fourier transform infrared and X-ray diffraction results revealed that different coordination intensities were present in the different complexes as a basis for the differences in activities. Slow Mg ion release was controlled by these nanosized silk-Mg complexes through degradation. With the same amount of Mg ions, the different silk-Mg complexes exhibited different angiogenic and osteogenic capacities. Complexes with both angiogenic and osteogenic capacities were developed by optimizing the sizes of the silk particles, resulting in faster and improved quality of bone formed in vivo than complexes with the same composition of silk and Mg but only angiogenic or osteogenic capacities. The biological selectivity of silk-Mg complexes should facilitate applications in tissue regeneration.

Post-synthesis of Sn-beta zeolite by aerosol method.

Sn-beta zeolite is a Lewis acid catalyst which can activate the C-O and C[double bond, length as m-dash]O bonds of many organic compounds. In this paper, a simple aerosol method has been firstly applied to the post-synthesis of Sn-beta zeolite. The aqueous solution containing SnCl2 and dealuminated beta zeolite was rapidly dried using an aerosol generator to obtain the Sn-beta zeolites with different Sn contents. The physicochemical properties of the Sn-beta zeolites were further characterized by XRD, nitrogen adsorption-desorption, FT-IR and Py-FT-IR techniques. The catalysts exhibited good catalytic performances in the Baeyer-Villiger oxidation reaction of cyclohexanone.

Role of Hydrogen Sulfide and Hypoxia in Hepatic Angiogenesis of Portal Hypertension.

The pathogenesis of portal hypertension remains unclear, and is believed to involve dysfunction of liver sinusoidal endothelial cells (LSEC), activation of hepatic stellate cells (HSC), dysregulation of endogenous hydrogen sulfide (H2S) synthesis, and hypoxia-induced angiogenic responses. H2S, a novel gas transmitter, plays an important role in various pathophysiological processes, especially in hepatic angiogenesis. Inhibition of endogenous H2S synthase by pharmaceutical agents or gene silencing may enhance the angiogenic response of endothelial cells. Hypoxia-inducible factor-1 (HIF-1) is the main transcription factor of hypoxia, which induces hepatic angiogenesis through up-regulation of vascular endothelial growth factor (VEGF) in HSC and LSEC. H2S has also been shown to be involved in the regulation of VEGF-mediated angiogenesis. Therefore, H2S and HIF-1 may be potential therapeutic targets for portal hypertension. The effects of H2S donors or prodrugs on the hemodynamics of portal hypertension and the mechanism of H2S-induced angiogenesis are promising areas for future research.

Evaluation of voice function after BABA robotic thyroid lobectomy: A comparative analysis with endoscopic thyroid lobectomy.

The purpose of this study was to compare the effect of robotic thyroid lobectomy via Bilateral Axlio-Breast Approach (BABA) and endoscopic thyroid lobectomy on the voice function. A total of 125 patients with thyroid cancer from March 2021 to July 2022 were divided into the robotic thyroid lobectomy group and the endoscopic thyroid lobectomy group. Acoustic index and voice handicap index (VHI-10) were compared between the 2 groups before and after (1 week, 1 month, 3 month) the surgery. In the robotic group, VHI-10 score was not significantly different before and after the surgery. In the endoscopic group, VHI-10 score after the surgery was significantly higher than that before the surgery. In the endoscopic group, the fundamental frequency (F0) declined significantly 1 week and 1 month after the surgery compared with that before the surgery. One week after surgery, F0 in the endoscopic group was (197.91 ±â€…24.15) Hz, which was significantly lower than that (206.77 ±â€…20.13) Hz in the robotic group. In the robotic group, there was no obvious decline in F0 and MPT in each follow-up period after surgery compared with those before surgery. In the endoscopic group, MPT declined significantly 1 week after the surgery compared with that before surgery. One week after surgery, MPT in the endoscopic group was (13.02 ±â€…9.28) s, which was significantly lower than that (17.55 ±â€…9.25) s in the robotic groups. There were no significant differences in Shimmer, Jitter, DSI and NHR during all postoperative follow-up periods compared with those before surgery in both groups. The voice function of robotic thyroid lobectomy via BABA is superior to endoscopic thyroid lobectomy.

High expression of regulator of G-protein signalling 1 is associated with the poor differentiation and prognosis of gastric cancer.

Emerging evidence has highlighted that immune and stromal cells form the majority of the tumour microenvironment (TME), which plays important roles in tumour progression. The present study aimed to screen vital prognostic genes associated with the TME in gastric cancer (GC). The ESTIMATE algorithm was applied to calculate TME-related scores, and the relationship between clinicopathological variables and these scores was analysed. Heatmaps and Venn plots were then used to visualize and screen differentially expressed genes. Furthermore, functional enrichment analysis was performed, and a protein-protein interaction network was constructed. Kaplan-Meier curves were generated to evaluate survival differences for each hub gene. Reverse transcription quantitative PCR was employed to evaluate the expression of the three hub genes in the validation cohort. The association between gene expression, clinicopathological variables and survival was also evaluated. Higher stromal scores were associated with worse outcomes in patients with GC. In addition, higher scores were significantly associated with a higher tumour grade, American Joint Committee on Cancer stage and T stage with regard to immune scores, stromal scores and ESTIMATE scores, respectively. In total, 644 upregulated intersecting genes and 126 downregulated genes were identified. Moreover, 71 TME-associated hub genes were identified. Batch survival analysis revealed that higher expression of CXCR4, PTGFR and RGS1 was significantly associated with worse outcome. Subsequently, the relationship between high expression of RGS1 and poor prognosis was verified, and high expression of RGS1 was associated with poor differentiation. In conclusion, it was found that compared with immune cells, stromal cells may play a more important role in the prognosis of patients with GC. In addition, the influence of RGS1 expression on survival in GC patients was identified and verified, and high expression of RGS1 was found to be associated with a low differentiation degree of GC.

Novel Prognostic Nomogram for Recurrence-Free Survival of Patients With Primary Gastrointestinal Stromal Tumors After Surgical Resection: Combination of Prognostic Nutritional Index and Basic Variables.

BACKGROUND: Gastrointestinal stromal tumor (GIST) is the most common type of mesenchymal tumors in the digestive tract, often recrudescing even after R0 resection. Adjuvant tyrosine kinase inhibitor therapy prolonged recurrence-free survival (RFS). This study aimed to develop a novel nomogram for predicting the RFS of patients following surgical resection of GISTs. METHODS: Clinicopathologic data of patients with GISTs at Tianjin Medical University General Hospital (Tianjin, China) from January 2000 to October 2019 were retrospectively reviewed. Univariate and multivariate Cox regression analyses were used to select the suitable variables from the training cohort to construct a nomogram for 2- and 5-year RFS. The 1,000 bootstrap samples and calibration curves were used to validate the discrimination of the nomogram. The receiver operating characteristic analysis(ROC) was used to compare the predictive ability of the nomogram and present four commonly used risk stratification systems: National Institutes of Health (NIH)-Fletcher staging system; NIH-Miettinen criteria; Modified NIH criteria; and Air Forces Institute of Pathology risk criteria (AFIP). RESULTS: Univariate and multivariate analyses showed that the tumor site, tumor size, mitotic index, tumor rupture, and prognostic nutritional index were significant factors associated with RFS. These variables were selected to create the nomogram for 2- and 5-year RFS (all P<0.05). The 2- and 5-year the ROC of the nomogram were 0.821 (95% confidence interval [CI]: 0.740-0.903) and 0.798 (95% CI: 0.739-0.903); NIH-Fletcher criteria were 0.757 (95% CI: 0.667-0.846) and 0.683 (95% CI: 0.613-0.753); NIH-Miettinen criteria were 0.762 (95% CI: 0.678-0.845) and 0.718 (95% CI: 0.653-0.783); Modified NIH criteria were 0.750 (95% CI: 0.661-0.838) and 0.689 (95% CI: 0.619-0.760); and AFIP were 0.777 (95% CI: 0.685-0.869) and 0.708 (95% CI: 0.636-0.780). Hence, the predictive probabilities of our nomogram are better than those of other GIST risk stratification systems. CONCLUSION: This nomogram, combining tumor site, tumor size, mitotic index, tumor rupture, and prognostic nutritional index, may assist physicians in providing individualized treatment and surveillance protocols for patients with GISTs following surgical resection.