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Abstract Objective There is a lack of standard salvage treatment options for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) that has failed platinum-containing regimens. Breakthroughs in immunotherapy have opened up new options for these patients. However, the efficacy and safety of immunotherapy have not been clarified. This study aimed to summarize and assess the efficacy and safety of PD-1 inhibitors in patients with RM-NPC who failed platinum-containing chemotherapy. Methods Up to August 25, 2022, clinical trials of PD-1 inhibitors in RM-NPC patients who failed platinum-containing regimens were searched in the PubMed, Embase, Cochrane, and Web of Science databases. Retrieval subject terms included “nasopharyngeal carcinoma”, “metastatic”, “recurrence”, “PD-1”, and “PD-L1”. The clinical trials eligible for inclusion were systematically reviewed and meta-analyzed. Results A total of 9 studies including 842 patients with RM-NPC were included in this meta-analysis. The results showed that PD-1 inhibitors had promising efficacy in patients with RM-NPC who failed platinum-containing regimens: objective response rate (ORR) was 24% (95% confidence interval [CI] 21–26%), disease control rate (DCR) was 52% (95% CI 45–58%), 1-year progression-free survival (PFS) rate was 25% (95% CI 18–32%), and 1-year overall survival (OS) rate was 53% (95% CI 37–68%). In terms of treatment-related adverse events (AEs), the incidence of grade ≥ 3 treatment-related AEs was 19% (95% CI 13–24%). In addition, we found that PD-1 inhibitors were more effective in patients with PD-L1 positive than in patients with PD-L1 negative nasopharyngeal carcinoma who had failed platinum-containing regimens (ORR 31% (95%CI 26–35%) vs. 21% (95% CI 17–25%)). Conclusion PD-1 inhibitors may provide a survival benefit for patients with RM-NPC who have failed platinum-containing regimens and have the advantage of a good safety profile, making them a promising treatment option.

BackgroundClaustrophobia is a psychological disease. It is estimated to occur in 2.1–14.3% of all magnetic resonance imaging (MRI) examinations. Mindfulness decompression is an effective means to treat and reduce fear and anxiety. There is a rare report on the application of mindfulness-based stress reduction therapy in the magnetic resonance examinations of patients with claustrophobia to date.PurposeThe purpose of this study is to explore the intervention effect of mindfulness respiratory decompression therapy on the MRI inspection of patients with claustrophobia.MethodsA total of 86 patients with claustrophobia requiring MRI in our hospital from January 2018 to December 2020 were divided into two groups. The control group was given routine psychological nursing, and the observation group was given a mindfulness breathing technique on the basis of the control group. Before and after the intervention, we compared the intervention effect, satisfaction with nurses’ psychological intervention technique, severe autonomic nervous symptoms during the examination, self-rating anxiety scale (SAS) scores, and profile of mood states revised (POMS-R) scores.ResultsThe total effective rate of intervention in the observation group was 90.90%, which was significantly higher (χ2 = 6.857, p = 0.00004) than that in the control group (26.19%). Severe autonomic nervous symptoms in the observation group were significantly lower than those in the control group (p

Despite improvements in modern medical therapies, inflammatory diseases, such as atherosclerosis, diabetes, non-alcoholic fatty liver, chronic kidney diseases, and autoimmune diseases have high incidence rates, still threaten human health, and represent a huge financial burden. N6-methyladenosine (m6A) modification of RNA contributes to the pathogenesis of various diseases. As the most widely discussed m6A methyltransferase, the pathogenic role of METTL3 in inflammatory diseases has become a research hotspot, but there has been no comprehensive review of the topic. Here, we summarize the expression changes, modified target genes, and pathogenesis related to METTL3 in cardiovascular, metabolic, degenerative, immune, and infectious diseases, as well as tumors. In addition to epithelial cells, endothelial cells, and fibroblasts, METTL3 also regulates the function of inflammation-related immune cells, including macrophages, neutrophils, dendritic cells, Th17 cells, and NK cells. Regarding therapeutic applications, METTL3 serves as a target for the treatment of inflammatory diseases with natural plant drug components, such as emodin, cinnamaldehyde, total flavonoids of Abelmoschus manihot, and resveratrol. This review focuses on recent advances in the initiation, development, and therapeutic application of METTL3 in inflammatory diseases. Knowledge of the specific regulatory mechanisms involving METTL3 can help to deepen understanding of inflammatory diseases and lay the foundation for the development of precisely targeted drugs to address inflammatory processes.

A method for the determination of 14 pesticide residues in tea was developed by QuEChERS (Quick, Easy, Cheap, Effective, Rugged, Safe) pretreatment combined with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The tea samples were extracted with acetonitrile (with 1% acetic acid), purified using QuEChERS purification columns and then analyzed by UPLC-MS/MS. The effects of four purification columns on tea extracts and the recoveries of pesticide residues were compared. The column with better purification effect and recovery was selected to further investigate the matrix effect, linear relationship, and recovery of the method. The results showed that the detection limit of the method was 0.001~2.000 μg/L, and the limit of quantification was 0.003~5.000 μg/L. Reliable linear relationship within the corresponding concentration range were observed for 14 pesticides, with coefficient of determination between 0.9926 and 0.9989. The average recoveries were 71.2%~117.4% at the spiking levels of 100, 500, and 800 μg/kg with RSDs at the range of 1.1%~14.2%. This method showed its advantages of simple and fast operation, sensitivity and recovery rate, meeting the requirements for determination of multi pesticide residues in tea.

Abstract This study aimed to investigate the prognostic factors related to overall survival (OS) and cancer-specific survival (CSS) in patients with de novo metastatic nasopharyngeal carcinoma (NPC) aged ≥ 65 years in nonendemic areas. The Surveillance, Epidemiology, and End Results database was queried for elderly patients with M1 stage NPC at initial diagnosis between 2004 and 2016. This study examined 100 patients and evaluated the relationship of sex, age, race, pathological grade, T stage, N stage, sequence number, site of metastasis, number of metastatic organs, and other related factors with OS and CSS. The median survival and follow-up time were 10 and 48 months, respectively. The survival curves for race, bone metastasis, radiation, and chemotherapy significantly affected OS on the log-rank test. Advanced N stage and liver metastasis may be associated with poor survival. Race, bone metastasis, and chemotherapy were independent prognostic factors of OS. Bone metastasis was associated with poor survival. The survival curves for CSS were significantly different between races, N stage, sequence number, and bone metastasis. In Cox regression multivariate analysis, only sequence number had an independent effect on prognosis. This study revealed that chemotherapy prolonged survival in elderly patients with metastatic NPC, whereas bone metastasis shortened survival.

Background: Numerous lncRNAs have been shown to affect colon cancer (CC) progression, and tumor necroptosis is regulated by several of them. However, the prognostic value of necroptosis-related lncRNA in CC has rarely been reported. In this study, a necroptosis-related lncRNA prognostic model was constructed, which can provide a reference for clinical diagnosis and treatment.Methods: The Cancer Genome Atlas (TCGA) database provided gene expression and lncRNA sequencing data for CC patients, and GSEA provided necroptosis gene data. Differentially expressed necroptosis-related lncRNAs related to prognosis were identified by differential expression analysis, Pearson correlation analysis, and least absolute shrinkage and selection operator (LASSO) regression. Based on the results of the multivariate COX regression analysis, a risk scoring model was constructed, A Kaplan-Meier analysis was performed to compare overall survival (OS) between low-risk and high-risk groups. A nomogram was then developed and validated based on the clinical data and risk scores of CC patients. In addition, Gene Set Enrichment Analysis (GSEA) and immune correlation analysis were conducted to explore the possible pathways and immune regulatory effects of these necroptosis-related lncRNAs.Results: In total, we identified 326 differentially expressed necroptosis-related lncRNAs in the TCGA database. Survival analysis showed that the OS of patients in the low-risk group was significantly better than that in the high-risk group (p < 0.05). Finally, 10 prognostic necroptosis-related lncRNAs were used to construct the nomogram. The composite nomogram prediction model evaluated and validated with good prediction performance (3-year AUC = 0.85, 5-years AUC = 0.82, C-index = 0.78). The GSEA and immune correlation analyses indicated that these lncRNAs may participate in multiple pathways involved in CC pathogenesis and progression.Conclusion: We established a novel necroptosis-related lncRNA CC prognosis prediction model, which can provide a reference for clinicians to formulate personalized treatment and review plans for CC patients. In addition, we also found that these necroptosis-related lncRNAs may affect the pathogenesis and progression of colon cancer through multiple pathways, including altering the activity of various immune cells.

Abstract To investigate the efficacy of 125I seed implantation in the treatment regimen of pelvic recurrence after early cervical cancer surgery and to analyse prognostic factors. To evaluate efficacy and analyse prognostic factors of 125I seed implantation for pelvic recurrence after early cervical cancer surgery. A prospective study was conducted on 62 patients who experienced pelvic recurrence after early cervical cancer surgery between August 2005 and September 2015. The 62 patients were treated and assessed in 2 groups (n = 30). All 62 patients were randomized into two groups that received two different treatment regimens: the treatment group (n = 30), which received 125I particle implantation therapy, and the control group (n = 32), which received whole-pelvic irradiation using the anteroposterior/posteroanterior field and cisplatin-based concurrent chemoradiation therapy. The efficacy/efficiency of 125I seed implantation and prognostic factors were analysed by logistic regression. Overall survival was determined by Kaplan–Meier analysis. Multivariate analysis results were obtained by the Cox proportional hazards regression model. The effective control rates at 1, 3, 6 and 12 months were 76.7%, 80.0%, 83.3%, and 86.7% in the 125I particle implantation group. The total effective control rates at 1, 3, 6 and 12 months were 65.6%, 65.5%, 62.5%, and 71.9% in the chemoradiotherapy group. Significant differences were observed between the two groups. The overall survival rates at 1, 2, 3, 4, and 5 years and the median overall were 96.7%, 93.3%, 86.7%, 71.9%, 65.6% and 4.34 years, respectively, in the 125I seed implantation group and 81.3%, 71.9%, 62.5%, 56.3%, 53.1% and 3.59 years, respectively, in the control group. There were statistically significant differences in survival rates depending on the diameter of the largest recurrent pelvic tumour (χ2 = 6.611, P = 0.010). The multivariate analysis showed that the survival rates were related to the diameter of the largest recurrent pelvic tumour (χ2 = 4.538, P = 0.033). 125I implantation is an effective, safe, and promising method for the treatment of pelvic recurrence after early cervical cancer surgery. The diameter of the recurrent pelvic tumour was identified as a significant independent prognostic factor in patients who received 125I implantation.

Benzodiazepines (BZDs) produce versatile pharmacological actions through positive modulation of GABAA receptors (GABAARs). A previous study has demonstrated that high concentrations of diazepam potentiate GABA currents on the α1β2γ2 and α1β2 GABAARs in a flumazenil-insensitive manner. In this study, the high-concentration effects of BZDs and their sensitivity to flumazenil were determined on synaptic (α1β2γ2, α2β2γ2, α5β2γ2) and extra-synaptic (α4β2δ) GABAARs using the voltage-clamp electrophysiology technique. The in vivo evaluation of flumazenil-insensitive BZD effects was conducted in mice via the loss of righting reflex (LORR) test. Diazepam induced biphasic potentiation on the α1β2γ2, α2β2γ2 and α5β2γ2 GABAARs, but did not affect the α4β2δ receptor. In contrast to the nanomolar component of potentiation, the second potentiation elicited by micromolar diazepam was insensitive to flumazenil. Midazolam, clonazepam, and lorazepam at 200 µM exhibited similar flumazenil-insensitive effects on the α1β2γ2, α2β2γ2 and α5β2γ2 receptors, whereas the potentiation induced by 200 µM zolpidem or triazolam was abolished by flumazenil. Both the GABAAR antagonist pentylenetetrazol and Fa173, a proposed transmembrane site antagonist, abolished the potentiation induced by 200 µM diazepam. Consistent with the in vitro results, flumazenil antagonized the zolpidem-induced LORR, but not that induced by diazepam or midazolam. Pentylenetetrazol and Fa173 antagonized the diazepam-induced LORR. These findings support the existence of non-classical BZD binding sites on certain GABAAR subtypes and indicate that the flumazenil-insensitive effects depend on the chemical structures of BZD ligands.

Carbonate rocks are deposited in the Ordovician, Cambrian, and Sinian of eastern Tarim Basin with a cumulative maximum thickness exceeding 2000 m. They are the main carriers of oil and gas, and a great deal of natural gas has been found there in the past five years. Based on lithofacies and reservoir differences, natural gas exploration domains of eastern Tarim Basin can be classified into five types: Ordovician platform limestone; Ordovician platform dolomite; Cambrian platform margin mound shoal; Cambrian slope gravity flow deposits, and; Sinian dolomite. Carbonate reservoir characteristics of all the types were synthetically analyzed through observation on drilling core and thin sections, porosity and permeability measurement, and logging data of over 10 drilling wells. We find distribution of part of good fracture and cave reservoir in carbonate platform limestone of Ordovician. In the Ordovician, platform facies dolomite is better than limestone, and in the Cambrian, platform margin mound shoal dolomite has large stacking thickness. Good quality and significantly thick carbonate gravity deposit flow can be found in the Cambrian slope, and effective reservoir has also been found in Sinian dolomite. Commercial gas has been found in the limestone and dolomite of Ordovician in Shunnan and Gucheng areas. Exploration experiences from these two areas are instructive, enabling a deeper understanding of this scene.

This study used ethnographic methods to examine the efficacy of the Interfaith Encounter Association (IEA) in promoting peace in the middle of the Israeli-Palestinian conflict. The IEA is an apolitical organization based in Jerusalem that strives to build bridges between the Jewish and Arab people in the Holy Land through interfaith activities. Through participant observation of thirteen encounters and semistructured interviews with ten participants, this study explores the effects of interfaith discourse on perceptions, emotions, and reconciliation attempts in the Holy Land. This paper argues that interfaith encounters do not negate or ignore the complexities inherent in the power dynamics between the Jewish and Arab people, the tensions upon initial interaction, or linguistic barriers; rather, these challenges remind participants of the political background and the hostility among people that this organization seeks to overcome. While scholarly debates still exist on the impact of dialogues that do not explicitly address political themes, the IEA’s endeavors in peacemaking demonstrate the efficacy of religion in establishing a common ground for peaceful interactions between Jewish and Arab communities. [ABSTRACT FROM AUTHOR]