Immune checkpoint inhibitor combined with chemotherapy versus chemotherapy alone in the first-line treatment for recurrent or metastatic nasopharyngeal carcinoma: a meta-analysis of random controlled trials.

PURPOSE: Immune checkpoint inhibitor (ICI) monotherapy and chemotherapy (CT) have been used to treat recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC), with demonstrated survival benefits and good safety. However, whether combination therapy is superior to CT alone remains unclear. We summarized the existing evidence comparing the effectiveness and toxicities of ICI combined with CT versus CT alone. METHODS: Online databases was conducted for eligible randomized controlled trials (RCTs) published up to November 1, 2023. Progression-free survival (PFS) and overall survival (OS) were the primary endpoint. Objective response rates (ORRs) and adverse events (AEs) were the secondary endpoint. RESULTS: Three randomized controlled trials (Capture-1st, JUPITER-02, and RATIONALE-309) were included. First-line ICI therapy combined with CT showed significant improvement in PFS (hazard ratio[HR], 0.53; 95% confidence interval[CI]: 0.44-0.64), OS (HR, 0.63;95%CI: 0.49-0.81) and ORRs (odds ratio[OR], 1.79;95%CI: 1.30-2.46), when compared with CT alone. AEs ≥ grade 3 during treatment and treatment-related deaths were not significantly different between the two groups. CONCLUSIONS: In patients with R/M-NPC, ICI therapy combined with CT showed improved ORRs, PFS, and OS, with similar safety as CT alone.

Causal analysis of gastroesophageal reflux disease and esophageal cancer.

Patients with gastroesophageal reflux disease (GERD) are more likely to develop esophageal cancer (EC). However, a causal relationship between the 2 has been difficult to determine. Therefore, this study aimed to evaluate the impact of GERD on EC using the Mendelian randomization (MR) method. The causal association between GERD and EC was analyzed based on 2 publicly available genetic summary datasets for the GERD cohort (129,080 cases vs 473,524 controls) and the EC cohort (740 cases vs 372,016 controls). The causal inference was mainly evaluated by the inverse variance weighted MR. The MR-Egger regression, MR Pleiotropy Residual Sum and Outlier test, and leave-one-out test were used to confirm the sensitivity of the MR results. Possible interfering factors were excluded by multivariate MR (MVMR) analysis. We used 73 single nucleotide polymorphisms as instrumental variables. GERD was associated with increasing EC risk (odds ratio [OR], 1.001; 95% confidence interval, 1.001-1.002; P < .001), which was identified using the inverse variance weighted method. The sensitivity analysis also demonstrated similar results with the causal explanation, and major bias in genetic pleiotropy was not identified (intercept, 0.001; standard error, 0.001; P = .418). The multivariate MR analysis demonstrated the effect of GERD on EC even after excluding possible mediating factors (OR, 1.003; 95% confidence interval, 1.001-1.005; P = .012). This study confirmed that GERD has a causal effect on EC. Therefore, interventional measures are recommended to prevent EC.

Quantitative parameter analysis of pretreatment dual-energy computed tomography in nasopharyngeal carcinoma cervical lymph node characteristics and prediction of radiotherapy sensitivity.

BACKGROUND: Treatment efficacy may differ among patients with nasopharyngeal carcinoma (NPC) at similar tumor-node-metastasis stages. Moreover, end-of-treatment tumor regression is a reliable indicator of treatment sensitivity. This study aimed to investigate whether quantitative dual-energy computed tomography (DECT) parameters could predict sensitivity to neck-lymph node radiotherapy in patients with NPC. METHODS: Overall, 388 lymph nodes were collected from 98 patients with NPC who underwent pretreatment DECT. The patients were divided into complete response (CR) and partial response (PR) groups. Clinical characteristics and quantitative DECT parameters were compared between the groups, and the optimal predictive ability of each parameter was determined using receiver operating characteristic (ROC) analysis. A nomogram prediction model was constructed and validated using univariate and binary logistic regression. RESULTS: DECT parameters were higher in the CR group than in the PR group. The iodine concentration (IC), normalized IC, Mix-0.6, spectral Hounsfield unit curve slope, effective atomic number, and virtual monoenergetic images were significantly different between the groups. The area under the ROC curve of the DECT parameters was 0.73-0.77. Based on the binary logistic regression, a column chart was constructed using 10 predictive factors, including age, sex, N stage, maximum lymph node diameter, arterial phase NIC, venous phase NIC, λHU and spectral Hounsfield units at 70 keV. The area under the ROC curve value of the constructed model was 0.813, with a sensitivity and specificity of 85.6% and 81.3%, respectively. CONCLUSION: Quantitative DECT parameters could effectively predict the sensitivity of NPC to radiotherapy. Therefore, DECT parameters and NPC clinical features can be combined to construct a nomogram with high predictive power and used as a clinical analytical tool.

The feasibility of level Ib-sparing intensity-modulated radiation therapy in patients with nasopharyngeal carcinoma and high-risk factors classified based on the International Guideline.

BACKGROUND AND PURPOSE: To examine the feasibility of level Ib-sparing intensity-modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma (NPC) who had high-risk factors classified based on the International Guideline (IG). MATERIALS AND METHODS: We evaluated 961 non-metastatic NPC cases based on IG recommendations for prophylactic Ib irradiation. Four high-risk factors were used to categorise patients into three cohorts: A, B, and C. Propensity score matching was used to balance baseline characteristics in Cohort C, resulting in a matched Cohort C. Recurrence rates at level Ib and regional relapse-free survival (RRFS) rates were evaluated. RESULTS: Among patients with negative Ib lymph nodes (LNs), 18, 54, 420, and 444 exhibited involvement of structures that drain to level Ib as the first echelon (FES), involvement of the submandibular gland (SMG), level II LNs with radiologic extranodal extension (rENE), and level II nodes with a maximal axial diameter (MAD) ≥ 2 cm, respectively. The recurrence rate was highest in Cohort A (11.1 %). Cohort B had no level Ib recurrence. In matched Cohort C, recurrence rates were low in both groups (Ib-sparing group: 0.6 % vs. Ib-covering group: 0.6 %, P > 0.999). No significant differences were observed in 5-year RRFS rates between the two groups in cohort A (p = 0.208), cohort B (p = 0.905), and matched cohort C (p = 0.423). CONCLUSIONS: Level Ib-sparing IMRT could be performed safely for NPC patients with level II LNs who had rENE and/or MAD ≥ 2 cm. Further research should determine the necessity of level Ib prophylactic irradiation for patients with FES or SMG involvement.

Study on the Fractal Characteristics and Seepage Properties of Channels Filled by Coal Particles.

Studying the seepage process in fracture channels (where coal particles are deposited) is of great significance for improving the performance of both on-site coal seam water injection and dust reduction technology. Through a self-developed simulation experiment of water-borne coal particle migration and accumulation and computer graphics, we investigated the influencing factors of particle accumulation in water injection and their influence law on seepage, discussed the interaction relationship between the fractal structure of coal and the characteristics of accumulated coal particles, and established a new fractal model of fracture permeability based on different particle accumulation states. The results show that the seepage velocity and the particle size jointly affect the migration and accumulation process of water-borne coal particles. When the coal particle size is constant and the seepage velocity increases, then the output of the coal powder increases, the deposition decreases, and the structure fractal dimension D3 of fractures decreases. At the same seepage velocity, with the increase of the coal particle size, the output of coal powder decreases, the deposition increases, and the structure fractal dimension D3 of fractures increases. In addition, the amount of coal powder produced in the intermittent water injection process is smaller than that produced in the continuous water injection process, more easily leading to accumulation. The variation law of the theoretical permeability with porosity remains consistent for different particle accumulation states: with the increase of porosity, the structure fractal dimension D3 of fractures decreases, while the theoretical permeability increases. The above research results can provide a theoretical basis for reducing the seepage damage of coal under the particle blocking effect.

Hydrazine Hydrate Intercalated 1T-Dominant MoS2 with Superior Ambient Stability for Highly Efficient Electrocatalytic Applications.

Metallic 1T-phase MoS2 exhibits superior hydrogen evolution reaction (HER) performance than natural 2H-phase MoS2 owing to its higher electrical conductivity and abundance of active sites. However, the reported 1T-MoS2 catalysts usually suffer from extreme instability, which results in quick phase transformation at ambient conditions. Herein, we present a facile approach to engineer the phase of MoS2 by introducing intercalated hydrazine. Interestingly, the as-synthesized 1T-dominant MoS2 sample demonstrates excellent ambient stability without noticeable degradation for 3 months. Additionally, the 1T-dominant MoS2 exhibits superior electrical conductivity (∼700 times higher than that of 2H-MoS2) and improved electrochemical catalytic performance (current density ∼12 times larger than that of 2H-MoS2 at an overpotential of 300 mV vs the reversible hydrogen electrode, RHE). Through experimental characterizations and density functional theory (DFT) calculation, we conclude that the stabilization of the metallic phase could be attributed to the electron donation from hydrazine molecules to the adjacent Mo atoms. The phase control strategy in this work provides a guideline to develop other highly efficient and stable two-dimensional (2D) electrocatalysts.

The Pseudomonas aeruginosa PAAR2 cluster encodes a putative VRR-NUC domain-containing effector.

The bacterial type VI secretion system (T6SS) secretes many toxic effectors to gain advantage in inter-bacterial competition and for eukaryotic host infection. The cognate immunity proteins of these effectors protect bacteria from the virulence of their own effectors. The T6SS injects its inner-needle Hcp tube, the sharpening tip complex -consisting of VgrG and proline-alanine-alanine-arginine repeats (PAAR) proteins- and toxic effectors into neighboring cells. Its functions are largely determined by the activities of its delivered effectors. Five PAAR proteins were found in the Pseudomonas aeruginosa PAO1 genome with three of them shown to facilitate the delivery of various effectors. Here, we report a putative virus-type replication-repair nuclease domain-containing effector TseV encoded by the least investigated P. aeruginosa PAAR2 cluster. The crystal structure of its putative cognate effector TsiV is presented at 1.6 Å resolution. Through structure and sequence comparisons, we propose TseV-TsiV to be a putative novel effector-immunity (E-I) pair and we discuss the roles of other PAAR2 cluster encoded proteins.

Growth of High-Quality Monolayer Transition Metal Dichalcogenide Nanocrystals by Chemical Vapor Deposition and Their Photoluminescence and Electrocatalytic Properties.

Two-dimensional transition metal dichalcogenide (TMDC) nanocrystals (NCs) exhibit unique optical and electrocatalytic properties. However, the growth of uniform and high-quality NCs of monolayer TMDC remains a challenge. Until now, most of them are synthesized via a solution-based hydrothermal process or ultrasonic exfoliation method, in which the capping ligands introduced from organic solution often quench the optical and electrocatalytic properties of TMDC NCs. Moreover, it is difficult to homogeneously disperse the solution-based TMDC NCs on a substrate for device fabrication, since the dispersed NCs can easily aggregate. Here, we put forward a novel CVD method to grow closely spaced MoS2 NCs around 5 nm in lateral size. TEM and AFM characterizations demonstrate the monolayer and high-crystalline nature of MoS2 NCs. An obvious blue-shift with 130 meV in photoluminescence signals can be observed. The MoS2 NCs also show an outstanding surface-enhanced Raman scattering for organic molecules due to their localized surface plasmon and abundant edge sites and exhibit excellent electrocatalytic properties for the hydrogen-evolution reaction with a very low onset potential of ∼50 mV and Tafel slope of ∼57 mV/decade. Finally, we further demonstrate this kind of CVD method as a versatile platform for the growth of other TMDC NCs, such as WSe2 and MoSe2 NCs.

TEM and STEM Studies on the Cross-sectional Morphologies of Dual-/Tri-layer Broadband SiO2 Antireflective Films.

Dual-layer and tri-layer broadband antireflective (AR) films with excellent transmittance were successfully fabricated using base-/acid-catalyzed mixed sols and propylene oxide (PO) modified silica sols. The sols and films were characterized by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), transmission electron microscope (TEM), and scanning transmission electron microscope (STEM). FTIR and TEM results suggest that the PO molecules were covalently bonded to the silica particles and the bridge structure existing in PO modified silica sol is responsible for the low density of the top layer. The density ratio between different layers was measured by cross-sectional STEM, and the results are 1.69:1 and 2.1:1.7:1 from bottom-layer to top-layer for dual-layer and tri-layer films, respectively. The dual-layer film demonstrates good stability with 99.8% at the central wavelength of 351 nm and nearly 99.5% at the central wavelength of 1053 nm in laser system, and for the tri-layer AR film, the maximum transmittance reached nearly 100% at both the central wavelengths of 527 and 1053 nm.

Surface acoustic wave ammonia sensor based on ZnO/SiO2 composite film.

A surface acoustic wave (SAW) resonator with ZnO/SiO2 (ZS) composite film was used as an ammonia sensor in this study. ZS composite films were deposited on the surface of SAW devices using the sol-gel method, and were characterized using SEM, AFM, and XRD. The performance of the sensors under ammonia gas was optimized by adjusting the molar ratio of ZnO:SiO2 to 1:1, 1:2 and 1:3, and the sensor with the ratio of ZnO to SiO2 equaling to 1:2 was found to have the best performance. The response of sensor was 1.132 kHz under 10 ppm NH3, which was much higher than that of the sensor based on a pristine ZnO film. Moreover, the sensor has good selectivity, reversibility and stability at room temperature. These can be attributed to the enhanced absorption of ammonia and unique surface reaction on composite films due to the existence of silica.