Epidemiology and Clinical Characteristics of Pediatric Sepsis in PICUs in Southwest China: A Prospective Multicenter Study.

OBJECTIVES: To describe the epidemiological characteristics of pediatric sepsis in Southwest China PICUs. DESIGN: A prospective, multicenter, and observational study. SETTING: Twelve PICUs in Southwest China. PATIENTS: The patients admitted to the PICU from April 1, 2022, to March 31, 2023. The age ranged from 28 days to 18 years. All patients met the criteria of severe sepsis or septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 31 PICUs invited to participate, 12 PICUs (capacity of 292 beds) enrolled patients in the study. During the study period, 11,238 children were admitted to the participating PICUs, 367 (3.3%) of whom met the diagnosis of severe sepsis or septic shock. The most prevalent sites of infection were the respiratory system (55%) and the digestive system (15%). The primary treatments administered to these patients included antibiotics (100%), albumin (61.3%), invasive mechanical ventilation (58.7%), glucocorticoids (55.6%), blood products (51%), gammaglobulin (51%), and vasoactive medications (46.6%). Sepsis-related mortality in the PICU was 11.2% (41/367). Nearly half of the sepsis deaths occurred within the first 3 days of PICU admission (22/41, 53.7%). The mortality rate of septic shock (32/167, 19.2%) was significantly higher than that of severe sepsis (9/200, 4.5%; p < 0.001). The outcomes of a multivariate logistic regression analysis suggested that a higher pediatric Sequential Organ Failure Assessment score, and the use of invasive mechanical ventilation and vasoactive medications were independently associated with PICU mortality in children with sepsis. CONCLUSIONS: This report updates the epidemiological data of pediatric sepsis in PICUs in Southwest China. Sepsis is still a life-threatening disease in children.

Circ-LARP1B knockdown restrains the tumorigenicity and enhances radiosensitivity by regulating miR-578/IGF1R axis in hepatocellular carcinoma.

INTRODUCTION AND OBJECTIVES: Circular RNA La Ribonucleoprotein 1B (circ-LARP1B) was reported to serve as an oncogene in many types of cancers. Radiotherapy (RT) is an important element of the multimodal treatment concept in malignancies. Here, this work aimed to investigate the role of circ-LARP1B in the tumorigenesis and radiosensitivity of hepatocellular carcinoma (HCC). PATIENTS OR MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression of genes and proteins. In vitro experiments were conducted using cell counting Kit-8 (CCK-8), colony formation, EDU, transwell, and tube formation assays, respectively. Dual-luciferase reporter assay was employed to identify the target relationship between miR-578 and circ-LARP1B or IGF1R (insulin-like growth factor 1 receptor). In vivo assay was performed using murine xenograft model. RESULTS: Circ-LARP1B was highly expressed in HCC tissues and cells, and high expression of circ-LARP1B was closely associated with poor prognosis. Functional experiments demonstrated that circ-LARP1B silencing impaired cell proliferation, invasion, angiogenesis and reduced radioresistance in vitro. Mechanistically, circ-LARP1B could competitively bind with miR-578 to relieve the repression of miR-578 on the expression of its target gene IGF1R. Further rescue assay confirmed that miR-578 inhibition reversed the inhibitory effects of circ-LARP1B knockdown on HCC cell malignant phenotypes and radioresistance. Moreover, miR-578 overexpression restrained tumorigenicity and enhanced radiosensitivity in HCC cells, which were attenuated by IGF1R up-regulation. Besides that, circ-LARP1B knockdown impeded tumor growth and enhanced irradiation sensitivity in HCC in vivo. CONCLUSIONS: Circ-LARP1B knockdown restrained HCC tumorigenicity and enhanced radiosensitivity by regulating miR-578/IGF1R axis, providing a new target for the treatment of HCC.

Plasmon coupling nanorice trimer for ultrahigh enhancement of hyper-Raman scattering.

A new tactic that using Ag nanorice trimer as surface-enhanced hyper Raman scattering substrate is proposed for realizing maximum signal enhancement. In this paper, we numerically simulate and theoretically analyze the optical properties of the nanorice trimer consisting of two short nanorices and a long nanorice. The Ag nanorice trimer can excite Fano resonance at optical frequencies based on the strong interaction between the bright and the dark mode. The bright mode is attributed to the first longitudinal resonance of the short nanorice pair, while the dark mode originates from the third longitudinal mode resonance of the long nanorice. The electric field distributions demonstrate that the two resonances with the largest field strength correspond to the first-order resonance of the long nanorice and the Fano resonance of the trimer, respectively. Two plasmon resonances with maximum electromagnetic field enhancements and same spatial hot spot regions can match spectrally with the pump and second-order Stokes beams of hyper Raman scattering, respectively, through reasonable design of the trimer structure parameters. The estimated enhancement factor of surface-enhanced hyper Raman scattering can achieve as high as 5.32 × 1013.

miR-483-5p promotes esophageal cancer progression by targeting KCNQ1.

OBJECTIVES: miR-483-5p has been reported to be an oncogene of various cancers, but its functional and regulatory mechanisms in esophageal cancer (EC) remain unclear. This study aimed to investigate the functional and molecular mechanisms of miR-483-5p in EC so as to provide a theoretical basis for exploring the therapeutic target for EC. METHODS: miRNA expression profiles were downloaded from the TCGA-ESCA dataset to screen the target miRNA. Real-time quantitative PCR was performed to detect the transcriptional levels of miR-483-5p and KCNQ1 in EC cells. Western blot was conducted to determine the protein expression of KCNQ1. Cell Counting Kit-8 assay was carried out to assess cell proliferation. Transwell assay was performed to evaluate cell migration and invasion. Dual-luciferase reporter assay was conducted to verify the targeting relationship between miR-483-5p and KCNQ1. RESULTS: miR-483-5p was up-regulated in EC cells and could bind to the 3'-untranslational region of KCNQ1. Over-expressing miR-483-5p suppressed KCNQ1 expression. Besides, miR-483-5p over-expression facilitated EC cell proliferation, migration and invasion, while its down-regulation triggered opposite result. Over-expressing miR-483-5p and KCNQ1 simultaneously could weaken the promoting effect of miR-483-5p over-expression on EC cell proliferation, migration and invasion. CONCLUSION: miR-483-5p as an oncogene facilitated EC cell proliferation, migration and invasion by targeted silencing KCNQ1, which is likely to provide a basis for further exploring the molecular mechanism of EC progression.

Theoretical investigation of a plasmonic substrate with multi-resonance for surface enhanced hyper-Raman scattering.

Because of the unique selection rule, hyper-Raman scattering (HRS) can provide spectral information that linear Raman and infrared spectroscopy cannot obtain. However, the weak signal is the key bottleneck that restricts the application of HRS technique in study of the molecular structure, surface or interface behavior. Here, we theoretically design and investigate a kind of plasmonic substrate consisting of Ag nanorices for enhancing the HRS signal based on the electromagnetic enhancement mechanism. The Ag nanorice can excite multiple resonances at optical and near-infrared frequencies. By properly designing the structure parameters of Ag nanorice, multi- plasmon resonances with large electromagnetic field enhancements can be excited, when the "hot spots" locate on the same spatial positions and the resonance wavelengths match with the pump and the second-order Stokes beams, respectively. Assisted by the field enhancements resulting from the first- and second-longitudinal plasmon resonance of Ag nanorice, the enhancement factor of surface enhanced hyper-Raman scattering can reach as high as 5.08 × 109, meaning 9 orders of magnitude enhancement over the conventional HRS without the plasmonic substrate.

Neoadjuvant chemoradiotherapy or chemotherapy followed by surgery is superior to that followed by definitive chemoradiation or radiotherapy in stage IIIA (N2) nonsmall-cell lung cancer: a meta-analysis and system review.

BACKGROUND: Approximately 30% of all cases of nonsmall-cell lung cancer (NSCLC) are of a locally advanced (IIIA or IIIB) stage. However, surgical therapy for patients with stage IIIA (N2) NSCLC is associated with a disappointing 5-year survival rate. The optimal treatment for stage IIIA (N2) NSCLC is still in dispute. METHODS: A literature search was performed in the PubMed, Embase, and MEDLINE databases (last search updated in March 2015), and a meta-analysis of the available data was conducted. Two authors independently extracted data from each eligible study. RESULTS: A total of nine studies, including five randomized controlled trials and four retrospective studies, were enrolled in this meta-analysis. Significant homogeneity (χ (2)=49.62, P=0.000, I (2)=81.9%) was detected between four of the studies, including a total of 11,948 selected cases. Among the nine studies that investigated overall survival, the pooled hazard ratio (HR) was 0.70 (95% confidence interval (CI): 0.56-0.87; P=0.000). Subgroup analyses were performed according to the study design and the extent of resection. We observed a statistically significant better outcome after lobectomy (pooled HR: 0.52; 95% CI: 0.47-0.58; P=0.000) than after pneumonectomy (pooled HR: 0.82; 95% CI: 0.69-0.98; P=0.028). Unfortunately, there was no significant difference between the randomized controlled studies, as the pooled HR was 0.94 (95% CI: 0.81-1.09; P=0.440). CONCLUSION: Neoadjuvant chemoradiotherapy or chemotherapy followed by surgery (particularly lobectomy) is superior to following these therapies with definitive chemoradiation or radiotherapy, particularly in patients undergoing lobectomy.

Near-field engineering of Fano resonances in a plasmonic assembly for maximizing CARS enhancements.

Surface enhanced coherent anti-Stokes Raman scattering (SECARS) is a sensitive tool and promising for single molecular detection and chemical selective imaging. However, the enhancement factors (EF) were only 10~100 for colloidal silver and gold nanoparticles usually used as SECARS substrates. In this paper, we present a design of SECARS substrate consisting of three asymmetric gold disks and strategies for maximizing the EF by engineering near-field properties of the plasmonic Fano nanoassembly. It is found that the E-field "hot spots" corresponding to three different frequencies involved in SECARS process can be brought to the same spatial locations by tuning incident orientations, giving rise to highly confined SECARS "hot spots" with the EF reaching single-molecule sensitivity. Besides, an even higher EF of SECARS is achieved by introducing double Fano resonances in this plasmonic nanoassembly via further enlarging the sizes of the constituent disks. These findings put an important step forward to the plasmonic substrate design for SECARS as well as for other nonlinear optical processes.

A monolayer of hierarchical silver hemi-mesoparticles with tunable surface topographies for highly sensitive surface-enhanced Raman spectroscopy.

We proposed a facile green synthesis system to synthesize large-scale Ag hemi-mesoparticles monolayer on Cu foil. Ag hemi-mesoparticles have different surface morphologies on their surfaces, including ridge-like, meatball-like, and fluffy-like shapes. In the reaction, silver nitrate was reduced by copper at room temperature in dimethyl sulfoxide via the galvanic displacement reaction. The different surface morphologies of the Ag hemi-mesoparticles were adjusted by changing the reaction time, and the hemi-mesoparticle surface formed fluffy-spherical nanoprotrusions at longer reaction time. At the same time, we explored the growth mechanism of silver hemi-mesoparticles with different surface morphologies. With 4-mercaptobenzoic acid as Raman probe molecules, the fluffy-like silver hemi-mesoparticles monolayer with the best activity of surface enhanced Raman scattering (SERS), the enhancement factor is up to 7.33 × 10(7) and the detection limit can reach 10(-10)M. SERS measurements demonstrate that these Ag hemi-mesoparticles can serve as sensitive SERS substrates. At the same time, using finite element method, the distribution of the localized electromagnetic field near the particle surface was simulated to verify the enhanced mechanism. This study helps us to understand the relationship between morphology Ag hemi-mesoparicles and the properties of SERS.

Expression levels of HER2 and MRP1 are not prognostic factors of long-term survival in 829 patients with esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the eighth most frequent neoplasm in China. However, the expression levels of human epidermal growth factor receptor 2 (HER2) and multidrug resistance protein 1 (MRP1) in patients with ESCC remain to be determined. In the present study, 829 ESCC cases were evaluated using immunohistochemistry. The association between the expression levels of HER2 and MRP1 and the patient's clinicopathological factors was analyzed using Fisher's exact test or χ2 test. Univariate analysis was performed via Kaplan-Meier survival curves, while the Cox proportional hazard model was used for multivariate analysis. A significant correlation was observed between the expression levels of HER2 and the patient's gender (P<0.050), tumor size (P=0.013) and venous/lymphatic invasion (P=0.039). However, no significant correlation was identified between the expression levels of MRP1 and the clinicopathological factors of the patients. In univariate analysis, gender, differentiation, depth of invasion, clinical stage, adjuvant radiotherapy or chemotherapy and lymph node metastasis were significantly correlated with progression-free survival (PFS) and overall survival (OS) in patients with ESCC (P<0.050). The graphical representation of the Kaplan-Meier estimate curves suggested that the expression levels of HER2 or MRP1 did not exert any influence on prognosis (log-rank test, P>0.050). In multivariate analysis, tumor location, gender, clinical stage, differentiation and lymph node metastasis were identified as independent factors of prognosis in patients with ESCC (P<0.050). However, the expression levels of HER2 or MRP1 were not independently associated with PFS or OS in these patients. In conclusion, the present large-scale study demonstrates that the protein expression levels of HER2 and MRP1 does not exert any influence on the prognosis of ESCC.

The Prognostic Impact of Lymph Node Involvement in Large Scale Operable Node-Positive Esophageal Squamous Cell Carcinoma Patients: A 10-Year Experience.

BACKGROUND: Lymph node (LN)-related factors including the number of LN regions involved, the LN ratio (LNR), and the number of metastatic LNs are strong prognostic indicators for esophageal squamous cell carcinoma (ESCC) patients. Accurately staging LN involvement may improve the stratification of patients and guide the management of patients. METHODS: A total of 688 potentially resectable patients who had regional LN metastases were enrolled in this retrospective study. RESULTS: ESCC involving a single region was associated with better outcomes than that involving multiple regions (P < 0.001 for both PFS and OS). An increased number of metastatic LNs was significantly associated with reduced PFS and OS based on univariate analysis (P < 0.001). PFS and OS were significantly higher in patients with a lower cancer-involved LNR, with 5-year OS rates of 9.7% and 31.4% for patients with a lower and higher cancer-involved LNR, respectively. Based on multivariate analysis, patients with N1 LN involvement experienced longer survival than patients with N2 LN involvement (HR: 1.37; 95% CI: 1.12-1.68) or N3 LN involvement (HR: 1.96; 95% CI: 1.52-2.53). Higher LNR resulted in longer OS than lower LNR based on multivariate analysis (HR: 1.45; 95% CI: 1.15-1.84; P = 0.002). CONCLUSIONS: Our study has shown that not only the number of metastatic LNs but also the number of involved LN regions predicts outcomes after definitive surgery among Chinese patients with N-positive ESCC. LNR might serve as a powerful indicator that should be included in TNM staging for EC patients.

Impact of alcohol dehydrogenase gene 4 polymorphisms on esophageal squamous cell carcinoma risk in a Chinese population.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is very common in China and is also one of the most common cancers worldwide. The purpose of this study was to examine the associations between genetic variants of various cancer-related genes and the risk of ESCC. METHODS: In this study, we first examined the association between 18 potentially disruptive genetic variants of 17 genes, including alcohol dehydrogenase 4 (ADH4) and checkpoint kinase 2 (CHEK2), and ESCC risk in a Hangzhou population of 617 patients matched with 534 controls. Among the 18 single nucleotide polymorphisms (SNPs), two were validated in a Jinan population of 540 patients matched with 550 controls. RESULTS: Sixteen SNPs in 15 genes, including CHEK2, did not have significantly different allele frequency distributions between ESCC patients and control subjects. A significantly increased risk of developing ESCC was revealed in subjects with the AA genotype of rs3805322 (ADH4) compared with those with the AG or GG genotype by unconditional univariate logistic regression analysis. Using a dominant model, the CC genotype of rs4822983 (CHEK2) had a marginally significant protective effect compared to the CT and TT genotypes. The association of ESCC risk with these two SNPs (rs3805322 and rs4822983) was further validated in a Jinan case-control set. Individuals with the ADH4 rs3805322 AA or AG genotype had ORs of 1.10 (95% CI = 0.81-1.49, P < 0.001) or 1.86 (95% CI = 1.33-2.59, P = 0.559), respectively, for developing ESCC compared with individuals with the GG genotype. CHEK2 rs4822983 CC carriers showed a marginally significantly decreased ESCC risk compared with those carrying the CT and TT genotypes in the validation set (95% CI = 0.61-1.01, P = 0.064). However, no evidence of interaction existed between the two SNPs and smoking or drinking in the Jinan case-control set. CONCLUSIONS: In conclusion, this current study provides substantial evidence that genetic polymorphisms of rs3805322 in the ADH4 gene may be associated with an increased risk of developing ESCC in two Chinese Han populations. Future studies to address the biological function of this polymorphism in the development of ESCC are warranted.

Prognostic role of apoptosis-related gene functional variants in advanced non-small-cell lung cancer patients treated with first-line platinum-based chemotherapy.

BACKGROUND: Single-nucleotide polymorphisms in apoptosis-related genes have been shown to play a role in the efficacy of platinum-based chemotherapy and may influence clinical outcomes. Our study aimed to evaluate the correlations of four functional single-nucleotide polymorphisms - FAS -670 A>G, FAS ligand -844 T>C, survivin -31 G>C, and survivin 9386 C>T - with drug response and clinical outcomes in advanced non-small-cell lung cancer patients who received platinum-based chemotherapy. MATERIALS AND METHODS: Polymorphisms were evaluated using the polymerase chain reaction-based restriction fragment-length polymorphism technique. RESULTS: Patients with the CC genotype of FAS -670 A>G had worse overall survival (OS) than those with the CT or TT genotype (P=0.044), with median OS values of 20.1 months, 22.8 months, and 26.0 months, respectively. Furthermore, progression-free survival was associated with the FAS -670 A>G polymorphism (P=0.032). In addition, patients with the TC and CC genotypes of survivin 9386 C>T experienced improved survival compared with patients with the TT genotype (median OS 31.4 months and 22.8 months, respectively). CONCLUSION: The functional FAS -670 A>G and survivin 9386 C>T polymorphisms are potential independent prognostic factors in advanced non-small-cell lung cancer patients treated with platinum-based chemotherapy.

Realization of high sensitive SERS substrates with one-pot fabrication of Ag-Fe3O4 nanocomposites.

Ag-Fe3O4 nanocomposites were synthesized by the redox reaction between Ag2O and Fe(OH)2 in the absence of additional reductant at moderate temperature and atmospheric condition. The as-synthesized Ag-Fe3O4 nanocomposites are assembled into an orderly arrayed SERS substrate holding clean and reproducible properties with an applied external magnetic field. 4-mercaptobenzoic acid (4-MBA) is chosen as the probe molecule to test the enhancement factors (EF), uniformity and reproducibility of the SERS substrate. Experimental results indicate that the EF of 4-MBA on our proposed SERS substrate is up to 5.2×10(6) and the detection limit is down to ∼10(-10) M. The SERS spectra of 4-MBA molecules ranging from 200 cm(-1) to 2000 cm(-1) were randomly collected from a number of positions on the substrate and six Ag-Fe3O4 nanocomposites substrates are measured with the same procedure. It is shown that the SERS substrate have the good uniformity and reproducibility with low standard deviation, indicating our proposed Ag-Fe3O4 nanocomposites with external magnetic field control abilities have potential applications in the fields of magnetic separation and SERS techniques.

Topo2A as a prognostic biomarker for patients with resectable esophageal squamous cell carcinomas.

Topoisomerase 2α (Topo2A) is a key enzyme in replication. It functions as a cell proliferation and cell cycle-specific marker and it is identified mainly in the interphase nuclei of proliferating cells. Many studies have shown that Topo2A protein expression is up-regulated in various cancers including esophageal cancer. However, to date, no studies have adequately addressed the prognostic value of Topo2A in patients with resectable esophageal squamous cell carcinoma (ESCC). Therefore, we conducted a large-scale retrospective study investigating the expression of Topo2A and the clinicopathological characteristics or prognosis of ESCC patients. Eight hundred and twenty-nine specimens of ESCC from patients who underwent complete esophageal cancer resection were evaluated using an immunohistochemical assay. Among them, 404 (48.7 %) cases with a score >2 were determined to be positive for Topo2A expression. Topo2A overexpression was significantly associated with poorer differentiation (P = 0.007) and perineural invasion (P = 0.046). The median progression-free survival (PFS) of 319 patients with Topo2A-positive expression and 336 patients with Topo2A-negative expression was 19.5 and 26.5 months, respectively (P = 0.000). The overall survival (OS) in patients with and without Topo2A expression was 34.0 and 44.5 months, respectively (P = 0.002). In the multivariate analysis, Topo2A overexpression was identified as an independent prognostic factor for PFS (P = 0.001) and OS (P = 0.009). We determined that Topo2A overexpression was not only associated with poorer differentiation and perineural invasion, but it could also act as an independent risk factor for ESCC.

p53 is an independent prognostic factor in operable esophageal squamous cell carcinoma: a large-scale study with a long follow-up.

The p53 protein is involved in many biological functions in cancer, such as cell cycle arrest, DNA repair, apoptosis, senescence, DNA metabolism, angiogenesis, and cellular differentiation. However, the association between p53 expression and clinicopathological findings or prognosis in esophageal squamous cell carcinoma (ESCC) is controversial. We designed a large-scale study of 830 operable ESCC patients with a long follow-up to investigate the relationship between p53 expression and the clinicopathological characteristics and prognosis of patients. Immunohistochemistry was used to detect p53 protein expression. When the patients were divided into two groups, a positive expression group and a negative expression group, p53-positive expression positively correlated with a poorer differentiation level (P = 0.044). The overexpression of p53 was associated with a more advanced clinical stage (P = 0.015). A total of 775 patients were available for survival analysis. The median OS of 160 patients who had p53-positive expression and 486 patients who had p53-negative expression were 58.8 and 46.3 months, respectively (P = 0.021); the median PFS of the two groups were 39.6 and 27.5 months, respectively (P = 0.015). Lymph node metastasis, gender, differentiation, depth of invasion, and p53 protein expression were proven to have an influence on both OS and PFS in a univariate analysis. In the multivariate analysis, p53-positive expression maintained its independent prognostic impact on OS (P = 0.048) and PFS (P = 0.039), as did lymph node metastasis, differentiation, and depth of invasion. We identified that p53 protein-positive expression can serve as an independent, unfavorable prognosis biomarker in ESCC.