Prospective observational study of surgery alone for locally advanced oral squamous cell carcinoma: a real-world study.

INTRODUCTION: A prospective observational study was modified to assess the efficacy of surgery alone for the treatment of locally advanced oral squamous cell carcinoma. (LA-OSCC) MATERIALS AND METHODS: This prospective, single-institution, single-arm study involved 174 patients who underwent major surgery for LA-OSCC. Participating patients did not receive postoperative radiation. After initial curative treatment, patients were routinely monitored via clinical examination and imaging. The follow-up period was 3-70 months. Tumour recurrence and death were considered as the Clinical End Point in Research. RESULTS: The 5-year overall survival (OS), disease-free survival (DFS), and locoregional control rates for 174 patients were 66.7% (95% confidence interval [CI], 59.8 to 73.6), 66.1% (95% CI, 59.2 to 73.0), and 82.4% (95% CI, 76.5 to 88.3), respectively. CONCLUSION: A study of patients with LA-OSCC treated with surgery alone may have the optimal therapeutic impact for LA-OSCC, as evidenced by solid data for our next RCT trial. This conclusion still needs to be validated in higher-level RCTs.

DEAD-box RNA helicase 6 regulates drought and abscisic acid stress responses in rapeseed (Brassica napus).

DEAD-box RNA helicase is a major subfamily of RNA helicases with vital roles played in plant growth, development, and plant-environment interactions. RNA helicase 6 in rapeseed (Brassica napus) (BnRH6) is a member of DEAD-box RNA helicase. While previous research has demonstrated the role of BnRH6 in salt stress regulation, the involvement of BnRH6 in drought stress adaptation remains unknown. This report described a function of BnRH6 in drought stress response. BnRH6 was sufficiently induced by osmotic stress. Transgenic Brassica napus and Arabidopsis thaliana (Arabidopsis) overexpressing BnRH6 (OE) showed a drought tolerance phenotype, characterized by improved plant growth, increased survival rates, reduced water loss, leaf chlorosis and oxidative stress. Furthermore, BnRH6 was also induced by exogenous abscisic acid (ABA). BnRH6 overexpression plants exhibited ABA hypersensitivity with lagging seed germination, growth stunt and diminished stomatal opening in the presence of ABA, suggesting the involvement of ABA signal. Assessment of several well-identified drought stress responsive genes such as Calcium-dependent Protein Kinase 14 (BnCDPK14), Enhanced Response to ABA1 (BnERA1) and ABA Insensitive 1 (BnABI1) revealed that their expressions were accordingly changed in BnOE plants, possibly with interplays between BnRH6 and those genes. Our data highlighted the functional role of BnRH6, which plays a positive role in active regulation of drought stress response likely through an ABA-dependent manner in rapeseed plants.

[Effect of Biogas Slurry Return to Field on Heavy Metal Accumulation in Soil-crop System: A Meta-analysis].

To investigate the effects of biogas slurry return-to-field methods, the duration of biogas slurry return to field and the amount of heavy metals brought in from biogas slurry on the accumulation of heavy metals in soil-crop systems, and the importance of factors influencing heavy metal accumulation, 41 papers and 1972 pairs of data were integrated and analyzed. The results showed that the application of biogas slurry alone significantly increased the accumulation of As, Cd, Cr, Cu, and Zn in soil and As and Cr in crops by 20.5%, 15.2%, 25.6%, 18.7%, and 26.3% and 14.6% and 39.5%, respectively, and it had no significant effect on the accumulation of other heavy metals in crops. The combined application of biogas slurry and chemical fertilizers significantly increased the accumulation of soil Cr and Zn by 8.05% and 4.70% and decreased the accumulation of As by crops. Correlation analysis showed that the accumulation rates of soil As, Cd, and Cr were highly significantly and positively correlated (P<0.01) with the duration of biogas slurry return to field and soil organic matter (SOM) content, with correlation coefficients of 0.30, 0.15, and 0.13 and 0.22, 0.27, and 0.22, respectively; they were highly significantly and negatively correlated (P<0.01) with soil pH, with correlation coefficients of 0.16, 0.13, and 0.11, respectively. The heavy metals brought in by biogas slurry return to field promoted the accumulation of As, Cd, and Cr in soil and As, Cd, Cr, and Zn in crops, whereas the accumulation of Cd, Cu, and Zn in soil promoted the accumulation of Cd, Cu, and Zn in crops, with correlation coefficients of 0.45, 0.58, and 0.42, respectively. The main factors of heavy metal accumulation in the soil-crop systems were the duration of biogas slurry return to field, SOM, and soil pH.

Anti-apoptotic effect of adrenomedullin gene delivery on Leydig cells by suppressing TGF-ß1 via the Hippo signaling pathway.

This study aims to establish whether adrenomedullin (ADM) is capable to restore the steroidogenic functions of Leydig cells by suppressing transforming growth factor-ß1 (TGF-ß1) through Hippo signaling. Primary Leydig cells were treated with lipopolysaccharide (LPS), an adeno-associated virus vector that expressed ADM (Ad-ADM) or sh-RNA of TGF-ß1 (Ad-sh-TGF-ß1). The cell viability and medium concentrations of testosterone were detected. Gene expression and protein levels were determined for steroidogenic enzymes, TGF-ß1, RhoA, YAP, TAZ and TEAD1. The role of Ad-ADM in the regulation of TGF-ß1 promoter was confirmed by ChIP and Co-IP. Similar to Ad-sh-TGF-ß1, Ad-ADM mitigated the decline in the number of Leydig cells and plasma concentrations of testosterone by restoring the gene and protein levels of SF-1, LRH1, NUR77, StAR, P450scc, 3ß-HSD, CYP17 and 17ß-HSD. Similar to Ad-sh-TGF-ß1, Ad-ADM not only inhibited the LPS-induced cytotoxicity and cell apoptosis but also restored the gene and protein levels of SF-1, LRH1, NUR77, StAR, P450scc, 3ß-HSD, CYP17 and 17ß-HSD, along with the medium concentrations of testosterone in LPS-induced Leydig cells. Like Ad-sh-TGF-ß1, Ad-ADM improved LPS-induced TGF-ß1 expression. In addition, Ad-ADM suppressed RhoA activation, enhanced the phosphorylation of YAP and TAZ, reduced the expression of TEAD1 which interacted with HDAC5 and then bound to TGF-ß1 gene promoter in LPS-exposed Leydig cells. It is thus suspected that ADM can exert anti-apoptotic effect to restore the steroidogenic functions of Leydig cells by suppressing TGF-ß1 through Hippo signaling.

Regulatory considerations for paediatric drug evaluation in China.

The regulatory guidelines for the research and development of paediatric drugs are still evolving in China. The formulation of the guidelines started from learning and borrowing existing experience, and gradually changed to the exploration and improvement of local guidelines, which was not only in line with international standards but also had breakthroughs, innovations and Chinese characteristics. In this paper, the current setting of paediatric drug research and development in China and corresponding technical guidelines have been introduced from regulatory perspectives, and the accessibility of further improvement in regulatory strategies has also been discussed.

Evolution of the CBL and CIPK gene families in Medicago: genome-wide characterization, pervasive duplication, and expression pattern under salt and drought stress.

BACKGROUND: Calcineurin B-like proteins (CBLs) are ubiquitous Ca2+ sensors that mediate plant responses to various stress and developmental processes by interacting with CBL-interacting protein kinases (CIPKs). CBLs and CIPKs play essential roles in acclimatization of crop plants. However, evolution of these two gene families in the genus Medicago is poorly understood. RESULTS: A total of 68 CBL and 135 CIPK genes have been identified in five genomes from Medicago. Among these genomes, the gene number of CBLs and CIPKs shows no significant difference at the haploid genome level. Phylogenetic and comprehensive characteristic analyses reveal that CBLs and CIPKs are classified into four clades respectively, which is validated by distribution of conserved motifs. The synteny analysis indicates that the whole genome duplication events (WGDs) have contributed to the expansion of both families. Expression analysis demonstrates that two MsCBLs and three MsCIPKs are specifically expressed in roots, mature leaves, developing flowers and nitrogen fixing nodules of Medicago sativa spp. sativa, the widely grown tetraploid species. In particular, the expression of these five genes was highly up-regulated in roots when exposed to salt and drought stress, indicating crucial roles in stress responses. CONCLUSIONS: Our study leads to a comprehensive understanding of evolution of CBL and CIPK gene families in Medicago, but also provides a rich resource to further address the functions of CBL-CIPK complexes in cultivated species and their closely related wild relatives.

Local adrenomedullin gene delivery inhibits Leydig cell dysfunction by rescuing steroidogenic enzymes in vivo.

Adrenomedullin (ADM) has beneficial effects on Leydig cells under pathological conditions, including lipopolysaccharide (LPS)-induced orchitis. Our previous studies demonstrated that ADM exerts a restorative effect on steroidogenesis in LPS-treated primary rat Leydig cells by attenuating oxidative stress, inflammation and apoptosis. In this study, we aim to investigate whether ADM inhibits Leydig cell dysfunction by rescuing steroidogenic enzymes in vivo. Rats were administered with LPS and injected with Ad-ADM, an adeno-associated virus vector that expressed ADM. Then, rat testes were collected for 3ß-hydroxysteroid dehydrogenase (3ß-HSD) immunofluorescence staining. Steroidogenic enzymes or steroidogenic regulatory factors or protein, including steroidogenic factor-1 (SF-1), liver receptor homologue-1 (LRH1), Nur77, steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side chain cleavage enzyme (P450scc), 3ß-HSD, cytochrome P450 17α-hydroxylase/17, 20 lyase (CYP17) and 17ß-hydroxysteroid dehydrogenase (17ß-HSD), were detected via gene expression profiling and western blot analysis. Plasma testosterone concentrations were measured. Results showed that ADM may inhibit Leydig cell dysfunction by rescuing steroidogenic enzymes and steroidogenic regulatory factors in vivo. The reduction in the number of Leydig cells after LPS exposure was reversed by ADM. ADM rescued the gene or protein levels of SF-1, LRH1, Nur77, StAR, P450scc, 3ß-HSD, CYP17 and 17ß-HSD and plasma testosterone concentrations. To summarize ADM could rescue some important steroidogenic enzymes, steroidogenic regulatory factors and testosterone production in Leydig cells in vivo.

A metal chaperone OsHIPP16 detoxifies cadmium by repressing its accumulation in rice crops.

Cadmium (Cd) is an environmentally polluted toxic heavy metal and seriously risks food safety and human health through food chain. Mining genetic potentials of plants is a crucial step for limiting Cd accumulation in rice crops and improving environmental quality. This study characterized a novel locus in rice genome encoding a Cd-binding protein named OsHIPP16, which resides in the nucleus and near plasma membrane. OsHIPP16 was strongly induced by Cd stress. Histochemical analysis with pHIPP16::GUS reveals that OsHIPP16 is primarily expressed in root and leaf vascular tissues. Expression of OsHIPP16 in the yeast mutant strain ycf1 sensitive to Cd conferred cellular tolerance. Transgenic rice overexpressing OsHIPP16 (OE) improved rice growth with increased plant height, biomass, and chlorophyll content but with a lower degree of oxidative injury and Cd accumulation, whereas knocking out OsHIPP16 by CRISPR-Cas9 compromised the growth and physiological response. A lifelong trial with Cd-polluted soil shows that the OE plants accumulated much less Cd, particularly in brown rice where the Cd concentrations declined by 11.76-34.64%. Conversely, the knockout oshipp16 mutants had higher levels of Cd with the concentration in leaves being increased by 26.36-35.23% over the wild-type. These results suggest that adequate expression of OsHIPP16 would profoundly contribute to Cd detoxification by regulating Cd accumulation in rice, suggesting that both OE and oshipp16 mutant plants have great potentials for restricting Cd acquisition in the rice crop and phytoremediation of Cd-contaminated wetland soils.

Predictive Role of NEK6 in Prognosis and Immune Infiltration in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC), as one of the common malignant tumors, seriously threatens human health. NEK6 (Never in Mitosis A (NIMA) related kinases 6), as a cyclin, promotes cancer cell proliferation and cancer progression. However, the prognostic value of NEK6 and its correlation with immune cell infiltration in HNSCC remain unclear. In this study, we comprehensively elucidated the prognostic role and potential function of NEK6 expression in HNSCC. The expression of NEK6 was significantly up-regulated by immunohistochemistry in HNSCC. Upregulation of NEK6 expression in gene expression studies predicts poor prognosis in HNSCC patients. The results of Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene set variation analysis indicated that NEK6 is mainly involved in extracellular matrix metabolism and EMT processes. The expression of NEK6 increased with the level of immune cell infiltration and the expression of various immune checkpoints. In conclusion, NEK6 may serve as a candidate prognostic predictor and may predict the response of HNSCC patients to immunotherapy.

[Spatial Characterization of Stable Isotope Composition of Organic Carbon from Farmland Soils in Chongqing].

Soil was sampled from 182 profiles in typical farmlands of Chongqing and analyzed for the stable carbon isotope composition of organic matter (δ13CSOC). The results showed that the values of δ13CSOC for each soil profile were gradually increasing with increasing soil depth, and the mean values were (-23.63±1.53)‰, (-22.43±1.59)‰, and (-21.42±1.90)‰ for surface, middle, and bottom layers, respectively. The δ13CSOC values in the northeastern region of Chongqing tended to be more negative, whereas those in central Chongqing were less negative. Paddy fields showed the most negative values of δ13CSOC, followed by rice-upland rotating fields and upland fields, with the average being (-25.32±0.93)‰, (-23.17±1.37)‰, and (-24.75±1.28)‰ for the surface layers, respectively. For different soil types, the δ13C values in the surface layers were in the order of paddy soil

Postoperative radiotherapy may not be necessary for locally advanced head and neck squamous cell carcinoma: a case-match multicentre study.

BACKGROUND: Some head and neck cancer surgeons found that many patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) without postoperative radiotherapy (PORT) also have a good prognosis. The purpose of this study was to determine the effect of PORT on survival in patients with LA-HNSCC. METHODS: A case-match cohort analysis was performed at two institutions on patients with LA-HNSCC. Patients who received surgery alone were case-matched 1: 1 with patients treated by surgery plus PORT based on pT, pN, tumor subsite etc. RESULTS: 114 patients were matched into 57 pairs, with a median follow-up period of 40.2 months. No difference in overall survival (OS, HR 0.88; 95% CI 0.50-1.58; P = 0.79) or disease-specific survival (DFS, 0.86; 95% CI 0.50-1.50; P = 0.76) was observed with no PORT. CONCLUSIONS: PORT isn't necessary for patients with LA-HNSCC who are treated for the first time as long as the head and neck cancer surgeon adhere to appropriate surgical concepts. The indications of PORT for patients with LA-HNSCC need to be further discussed.

OsZIP11 is a trans-Golgi-residing transporter required for rice iron accumulation and development.

Iron (Fe) is a mineral nutrient necessary for plant growth and development. Whether the rice ZRT/IRT-like protein family metal transporter OsZIP11 is involved in Fe transport has not been functionally defined. The objective of the study is to figure out the essential role of the uncharacterized OsZIP11 played in rice growth, development, and iron accumulation, particularly in seeds. Transient subcellular location assays show that OsZIP11 was targeted to the trans-Golgi network. OsZIP11 was preferentially expressed in the rice tissues (or organs) at later flowering and seed development stages. Transcripts of OsZIP11 were significantly induced under Fe but not under zinc (Zn), copper (Cu) or manganese (Mn) deficiency. Yeast (Saccharomyces cerevisiae) transformed with OsZIP11 sequences displayed an active iron input which turned out that excessive iron accumulated in the cells. Knocking out OsZIP11 by CRISPR-Cas9 approach led to the attenuated rice growth and physiological phenotypes, depicting shorter plant height, reduced biomass, chlorosis (a symptom of lower chlorophyll concentration), and over-accumulation of malondialdehyde (complex representing the peroxidation of membrane lipids) in rice plantlets. The field trials demonstrated that OsZIP11 mutation impaired the capacity of seed development, with shortened panicle and seed length, compromised spikelet fertility, and reduced grain per plant or 1000-grain weight. Knocking out OsZIP11 also lowered the accumulation of iron in the brown rice by 48-51% compared to the wild-type. Our work pointed out that OsZIP11 is required for iron acquisition for rice growth and development.

Metallochaperones: A critical regulator of metal homeostasis and beyond.

Metallochaperones are a class of unique protein families that was originally found to interact with cellular metal ions by metal delivery to specific target proteins such as metal enzymes. Recently, some members of metallochaperones receive much attention owning to their multi-biological functions in mediating plant growth, development and biotic or abiotic stress responses, particularly in the aspects of metal transport and accumulation in plants. For example, some non-essential toxic heavy metals (e.g. cadmium and mercury) accumulating in farmland due to the industrial and agronomic activities, are a constant threat to crop production, food safety and human health. Digging genetic resources and functional genes like metallochaperones is critical for understanding the metal detoxification in plants, and may help develop cleaner crops with minimal toxic metals in leafy vegetables and grains, or plants for metal-polluted soil phytoremediation. In this review, we highlight the current advancement of the research on functions of metallochaperones in metal accumulation, detoxification and homeostasis. We also summarize the recent progress of the research on the critical roles of the metal-binding proteins in regulating plant responses to some other biological processes including plant growth, development, pathogen stresses, and abiotic stresses such salt, drought, cold and light. Finally, an additional capacity of some members of metallochaperones involved in the resistance to the pathogen attack and possibly regulatory roles was reviewed.

Identification of a DEAD-box RNA Helicase BnRH6 Reveals Its Involvement in Salt Stress Response in Rapeseed (Brassica napus).

Rapeseed (Brassica napus) is one of the most important vegetable oil crops worldwide. Abiotic stresses such as salinity are great challenges for its growth and productivity. DEAD-box RNA helicase 6 (RH6) is a subfamily member of superfamily 2 (SF2), which plays crucial roles in plant growth and development. However, no report is available on RH6 in regulating plant abiotic stress response. This study investigated the function and regulatory mechanism for BnRH6. BnRH6 was targeted to the nucleus and cytoplasmic processing body (P-body), constitutively expressed throughout the lifespan, and induced by salt stress. Transgenic overexpressing BnRH6 in Brassica and Arabidopsis displayed salt hypersensitivity, manifested by lagging seed germination (decreased to 55−85% of wild-type), growth stunt, leaf chlorosis, oxidative stress, and over-accumulation of Na ions with the K+/Na+ ratio being decreased by 18.3−28.6%. Given the undesirable quality of knockout Brassica plants, we utilized an Arabidopsis T-DNA insertion mutant rh6-1 to investigate downstream genes by transcriptomics. We constructed four libraries with three biological replicates to investigate global downstream genes by RNA sequencing. Genome-wide analysis of differentially expressed genes (DEGs) (2-fold, p < 0.05) showed that 41 genes were upregulated and 66 genes were downregulated in rh6-1 relative to wild-type under salt stress. Most of them are well-identified and involved in transcription factors, ABA-responsive genes, and detoxified components or antioxidants. Our research suggests that BnRH6 can regulate a group of salt-tolerance genes to negatively promote Brassica adaptation to salt stress.

The F-box E3 ubiquitin ligase AtSDR is involved in salt and drought stress responses in Arabidopsis.

F-box protein genes have been shown to play vital roles in plant development and stress respones. In Arabidopsis, there are more than 600 F-box proteins, and most of their functions are unclear. The present study shows that the F-box (SKP1-Cullin/CDC53-F-box) gene At5g15710 (Salt and Drought Responsiveness, SDR) is involved in abiotic stress responses in Arabidopsis. SDR is expressed in all tissues of Arabidopsis and is upregulated by salt and heat stresses and ABA treatment but downregulated by drought stress. Subcellular localization analysis shows that the SDR protein colocalizes with the nucleus. 35S:AntiSDR plants are hypersensitive to salt stress, but 35S:SDR plants display a salt-tolerant phenotype. Furthermore, 35S:SDR plants are hypersensitive to drought stress, while 35S:AntiSDR plants are significantly more drought tolerant. Overall, our results suggest that SDR is involved in salt and drought stress responses in Arabidopsis.

Identification of a rice metallochaperone for cadmium tolerance by an epigenetic mechanism and potential use for clean up in wetland.

Cadmium (Cd) is a toxic heavy metal that initiates diverse chronic diseases through food chains. Developing a biotechnology for manipulating Cd uptake in plants is beneficial to reduce environmental and health risks. Here, we identified a novel epigenetic mechanism underlying Cd accumulation regulated by an uncharacterized metallochaperone namely Heavy Metal Responsive Protein (HMP) in rice plants. OsHMP resides in cytoplasm and nucleus, dominantly induced by Cd stress and binds directly to Cd ions. OsHMP overexpression enhanced the rice growth under Cd stress but accumulated more Cd, whereas knockout or knockdown of OsHMP showed a contrasting effect. The enhanced Cd accumulation in the transgenic lines was confirmed by a long-term experiment with rice growing at the environmentally realistic Cd concentration in soil. The bisulfite sequencing and chromatin immunoprecipitation assessments revealed that Cd stress reduced significantly the DNA methylation at CpG (Cytosine-Guanine) and histone H3K9me2 marks in the upstream of OsHMP. By identifying a couple of mutants defective in DNA methylation and histone modification (H3K9me2) such as Osmet1 (methylatransfease1) and Ossdg714 (kryptonite), we found that the Cd-induced epigenetic hypomethylation at the region was associated with OsHMP overexpression, which consequently led to Cd detoxification in rice. The causal relationship was confirmed by the GUS reporter gene coupled with OsHMP and OsMET1 whereby OsMET1 repressed directly the OsHMP expression. Our work signifies that expression of OsHMP is required for Cd detoxification in rice plants, and the Cd-induced hypomethylation in the specific region is responsible for the enhanced OsHMP expression. In summary, this study gained an insight into the epigenetic mechanism for additional OsHMP expression which consequently ensures rice adaptation to the Cd-contaminated environment.

Exploration of modified progression-free survival as a novel surrogate endpoint for overall survival in immuno-oncology trials.

BACKGROUND: Progression-free survival (PFS) exhibits suboptimal performance as the surrogate endpoint for overall survival (OS) in trials studying immune checkpoint inhibitors (ICIs). Here we propose a novel surrogate endpoint, modified PFS (mPFS), which omits the events of disease progression (but not deaths) within 3 months after randomization. METHODS: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for randomized trials studying ICIs in advanced solid tumors with available PFS and OS data up to May 2020. Individual patient-level data (IPD) for PFS and OS were reconstructed for eligible trials. A simulation-based algorithm was used to match the reconstructed, disconnected PFS and OS IPD, and 1000 independent simulated datasets of matched PFS-OS IPD were generated for each trial. mPFS durations and statuses were then measured for each of the matched PFS-OS IPD. Trial-level correlation between Cox HRs for PFS or mPFS and HRs for OS was assessed using Pearson correlation coefficient (rp) weighted by trial size; patient-level correlation between PFS or mPFS and OS was assessed using Spearman's rank correlation coefficient (rs). Findings were further validated using the original IPD from two randomized ICI trials. RESULTS: Fifty-seven ICI trials totaling 29,429 participants were included. PFS HR showed moderate correlation with OS HR (rp=0.60), and PFS was moderately correlated with OS at the patient level (median rs=0.66; range, 0.65-0.68 among the 1000 simulations). In contrast, mPFS HR achieved stronger correlation with OS HR (median rp=0.81; range, 0.77-0.84), and mPFS was more strongly correlated with OS at the patient level (median rs=0.79; range, 0.78-0.80). The superiority of mPFS over PFS remained consistent in subgroup analyses by cancer type, therapeutic regimen, and treatment setting. In both trials with the original IPD where experimental treatment significantly improved OS, mPFS successfully captured such clinical benefits whereas PFS did not. CONCLUSIONS: mPFS outperformed PFS as the surrogate endpoint for OS in ICI trials. mPFS is worthy of further investigation as a secondary endpoint in future ICI trials.

Coupling ITO3dE model and GIS for spatiotemporal evolution analysis of agricultural non-point source pollution risks in Chongqing in China.

To determine the risk state distribution, risk level, and risk evolution situation of agricultural non-point source pollution (AGNPS), we built an 'Input-Translate-Output' three-dimensional evaluation (ITO3dE) model that involved 12 factors under the support of GIS and analyzed the spatiotemporal evolution characteristics of AGNPS risks from 2005 to 2015 in Chongqing by using GIS space matrix, kernel density analysis, and Getis-Ord Gi* analysis. Land use changes during the 10 years had a certain influence on the AGNPS risk. The risk values in 2005, 2010, and 2015 were in the ranges of 0.40-2.28, 0.41-2.57, and 0.41-2.28, respectively, with the main distribution regions being the western regions of Chongqing (Dazu, Jiangjin, etc.) and other counties such as Dianjiang, Liangping, Kaizhou, Wanzhou, and Zhongxian. The spatiotemporal transition matrix could well exhibit the risk transition situation, and the risks generally showed no changes over time. The proportions of 'no-risk no-change', 'low-risk no-change', and 'medium-risk no-change' were 10.86%, 33.42%, and 17.25%, respectively, accounting for 61.53% of the coverage area of Chongqing. The proportions of risk increase, risk decline, and risk fluctuation were 13.45%, 17.66%, and 7.36%, respectively. Kernel density analysis was suitable to explore high-risk gathering areas. The peak values of kernel density in the three periods were around 1110, suggesting that the maximum gathering degree of medium-risk pattern spots basically showed no changes, but the spatial positions of high-risk gathering areas somehow changed. Getis-Ord Gi* analysis was suitable to explore the relationships between hot and cold spots. Counties with high pollution risks were Yongchuan, Shapingba, Dianjiang, Liangping, northwestern Fengdu, and Zhongxian, while counties with low risks were Chengkou, Wuxi, Wushan, Pengshui, and Rongchang. High-value hot spot zones gradually dominated in the northeast of Chongqing, while low-value cold spot zones gradually dominated in the Midwest. Our results provide a scientific base for the development of strategies to prevent and control AGNPS in Chongqing.

Radioactive seeds insertion with chemotherapy for advanced non-small-cell lung cancer: A meta-analysis.

BACKGROUND: Non-small-cell lung cancers (NSCLCs) are only eligible to undergo curative surgical resection in <20% of patients. In patients with inoperable NSCLC, computed tomography (CT)-guided radioactive seed insertion (RSI) is a common treatment practice. OBJECTIVES: To assess the relative efficacy of chemotherapy alone versus chemotherapy in combination with CT-guided RSI in patients with advanced NSCLC. METHODS: We searched the Pubmed, Embase, and Cochrane Library databases for relevant articles published as of July 2020. Complete and total response rates (CR and TR, respectively) served as the primary endpoints for this meta-analysis, with disease control (DC) rate, myelosuppression rate, progression-free survival (PFS), overall survival (OS), and CT-guided RSI-related pneumothorax serving as secondary endpoints. RESULTS: In total, eight studies incorporating 281 patients that underwent combination treatment and 297 patients that underwent chemotherapy along were included in this meta-analysis. The CR (21.5% vs. 4.0%, P < 0.00001), TR (73.8% vs. 42.6%, P < 0.00001), and DC (94.1% vs. 78.2%, P < 0.00001) rates were significantly higher for patients in the combined treatment group relative to patients in the chemotherapy only group. Furthermore, pooled PFS (P < 0.00001) and OS (P = 0.0006) were significantly longer for patients in the combined treatment group, whereas no differences in pooled myelosuppression rates were observed between groups (34.3% vs. 30.7%, P = 0.47). The pooled rate of CT-guided RSI-related pneumothorax was 15%. CONCLUSIONS: Combination chemotherapy and CT-guided RSI can significantly improve clinical response and prolong survival in advanced-stage NSCLC patients without inducing other significant toxic side effects.

Radioactive Stent for Malignant Esophageal Obstruction: A Meta-Analysis of Randomized Controlled Trials.

Purpose: To compare the relative clinical efficacies of radioactive and normal stent insertion methods as a means of treating patients suffering from malignant esophageal obstruction (MEO). Materials and Methods: The Pubmed, Embase, and Cochrane Library databases were searched for relevant randomized controlled trials (RCTs) from the date of inception through to July 2020. RevMan v5.3 was used for all data analyses. Results: This meta-analysis included six RCTs that included a total of 194 patients who had undergone radioactive stent insertion and 209 who had normal stent insertion. There were no significant differences in pooled improvement of dysphagia scores (P = .40), rates of stent restenosis (24.7% versus 28.7%, P = .35), stent migration (3.3% versus 4.4%, P = .61), severe chest pain (22.8% versus 20.3%, P = .61), hemorrhage (11.0% versus 9.8%, P = .80), or fistula formation (6.1% versus 4.2%, P = .55) between two groups. The pooled time to restenosis (P < .00001) and survival (P < .00001) were significant longer in the radioactive stent group. Significant heterogeneity was detected in the endpoint of improvement of dysphagia score (I2 = 89%; P = .0002). Funnel plot analyses did not detect any evidence of publication bias pertaining to the selected study endpoints. Conclusions: Our meta-analysis demonstrated that radioactive stent insertion can prolong stent patency and survival for patients with MEO compared with normal stent insertion.