Enhancement of cadmium uptake in Sedum alfredii through interactions between salicylic acid/jasmonic acid and rhizosphere microbial communities.

The focus on phytoremediation in soil cadmium (Cd) remediation is driven by its cost-effectiveness and eco-friendliness. Selecting suitable hyperaccumulators and optimizing their growth conditions are key to enhance the efficiency of heavy metal absorption and accumulation. Our research has concentrated on the role of salicylic acid (SA) and jasmonic acid (JA) in facilitating Cd phytoextraction by "Sedum alfredii (S. alfredii)" through improved soil-microbe interactions. Results showed that SA or JA significantly boosted the growth, stress resistance, and Cd extraction efficiency in S. alfredii. Moreover, these phytohormones enhanced the chemical and biochemical attributes of the rhizosphere soil, such as pH and enzyme activity, affecting soil-root interactions. High-throughput sequencing analysis has shown that Patescibacteria and Umbelopsis enhanced S. alfredii's growth and Cd extraction by modifying the bioavailability and the chemical conditions of Cd in soil. Structural Equation Model analysis further verified that phytohormones significantly enhanced the interaction between S. alfredii, soil, and microbes, leading to a marked increase in Cd accumulation in the plant. These discoveries emphasized the pivotal role of phytohormones in modulating the hyperaccumulators' response to environmental stress and offered significant scientific support for further enhancing the potential of hyperaccumulators in ecological restoration technologies using phytohormones.

Analysis of the sodium pump subunit ATP1A3 in glioma patients: Potential value in prognostic prediction and immunotherapy.

The ATP1A3 gene is associated with the development and progression of neurological diseases. However, the pathological function and therapeutic value of ATP1A3 in glioblastoma (GBM) remains unknown. In this study, we tried to explore the correlation between the ATP1A3 gene expression and immune features in GBM samples. We found that ATP1A3 gene expression levels showed significant negative correlation with immune checkpoints such as PD-L1, CTLA-4 and IDO1. Next, ATP1A3 gene expression levels showed significant negative correlation with the anti-cancer immune cell process, the immune score and stromal score. By grouping ATP1A3 expression levels, we found that that immunomodulator-related genes and tumor-associated immune cell effector gene expression levels were associated with lower ATP1A3 expression. In addition, immunotherapy prediction pathway activity and a majority of the anti-cancer immune cell process activity levels were also showed to be correlated with lower ATP1A3 gene expression. Further, nine prognostic factors were identified by prognostic analysis, and a GBM prognostic model (risk score) was established. We applied the model to the TCGA GBM training set sample and the GSE4412 validation set sample and found that patients in the high risk score subgroup had significantly shorter survival time, demonstrating the prognostic value and prognostic efficacy of the risk score. Furthermore, ATP1A3 overexpression has also been found to sensitize cancer cells to anti-PD-1 therapy. In conclusion, we showed that ATP1A3 is a highly promising treatment target in GBM and the risk score is an independent prognostic factor for cancer and can be used to help guide the prediction of survival time in patients with GBM.

NAD+ supplementation prevents STING-induced senescence in CD8+ T cells by improving mitochondrial homeostasis.

Understanding the connection between senescence phenotypes and mitochondrial dysfunction is crucial in aging and premature aging diseases. Loss of mitochondrial function leads to a decline in T cell function, which plays a significant role in this process. However, more research is required to determine if improving mitochondrial homeostasis alleviates senescence phenotypes. Our research has shown an association between NAD+ and senescent T cells through the cGAS-STING pathway, which can lead to an inflammatory phenotype. Further research is needed to fully understand the role of NAD+ in T-cell aging and how it can be utilized to improve mitochondrial homeostasis and alleviate senescence phenotypes. We demonstrate here that mitochondrial dysfunction and cellular senescence with a senescence-associated secretory phenotype (SASP) occur in senescent T cells and tumor-bearing mice. Senescence is mediated by a stimulator of interferon genes (STING) and involves ectopic cytoplasmic DNA. We further show that boosting intracellular NAD+ levels with nicotinamide mononucleotide (NMN) prevents senescence and SASP by promoting mitophagy. NMN treatment also suppresses senescence and neuroinflammation and improves the survival cycle of mice. Encouraging mitophagy may be a useful strategy to prevent CD8+ T cells from senescence due to mitochondrial dysfunction. Additionally, supplementing with NMN to increase NAD+ levels could enhance survival rates in mice while also reducing senescence and inflammation, and enhancing mitophagy as a potential therapeutic intervention.

LncRNA MIR210HG promotes the proliferation, migration, and invasion of lung cancer cells by inhibiting the transcription of SH3GL3.

Lung cancer (LCa), the most frequent malignancy worldwide, causes millions of mortalities each year. Overexpression of the long noncoding RNA MIR210HG in LCa has been established; however, a more comprehensive investigation into its biological role within LCa is imperative. This study aimed to validate the MIR210H levels in LCa tissues and cells. The expression of indicated genes was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR) and/or Western blotting. The viability, proliferation, migration, and invasion of LCa cells were measured using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), colony formation, wound healing, and transwell assays, respectively. The methylation levels of LCa cells were determined via methylation-specific PCR; additionally, chromatin immunoprecipitation or RNA immunoprecipitation assays were performed to determine the targeting relationship between DNA methyltransferase 1 (DNMT1) and the SH3-domain containing CRB2 like 3 (SH3GL3) promoters and the interaction between DNMT1 and MIR210HG, respectively. Our findings revealed the upregulation of MIR210HG, coupled with a diminished expression of SH3GL3 in LCa tissues and cells. Knockdown of MIR210HG or overexpression of SH3GL3 suppressed the proliferative, migratory, and invasive capacities of the cells. DNMT1 bound to the SH3GL3 promoter region, and MIR210HG inhibited the transcription of SH3GL3 by recruiting DNMT1. These findings indicate that MIR210HG facilitates LCa cell growth and metastasis by repressing SH3GL3 transcription via the recruitment of DNMT1 to the SH3GL3 promoter region.

Progress in cancer neuroscience.

Cancer of the central nervous system (CNS) can crosstalk systemically and locally in the tumor microenvironment and has become a topic of attention for tumor initiation and advancement. Recently studied neuronal and cancer interaction fundamentally altered the knowledge about glioma and metastases, indicating how cancers invade complex neuronal networks. This review systematically discussed the interactions between neurons and cancers and elucidates new therapeutic avenues. We have overviewed the current understanding of direct or indirect communications of neuronal cells with cancer and the mechanisms associated with cancer invasion. Besides, tumor-associated neuronal dysfunction and the influence of cancer therapies on the CNS are highlighted. Furthermore, interactions between peripheral nervous system and various cancers have also been discussed separately. Intriguingly and importantly, it cannot be ignored that exosomes could mediate the "wireless communications" between nervous system and cancer. Finally, promising future strategies targeting neuronal-brain tumor interactions were reviewed. A great deal of work remains to be done to elucidate the neuroscience of cancer, and future more research should be directed toward clarifying the precise mechanisms of cancer neuroscience, which hold enormous promise to improve outcomes for a wide range of malignancies.

Impact of enhanced recovery after surgery program for hungry bone syndrome in patients on maintenance hemodialysis undergoing parathyroidectomy for secondary hyperparathyroidism.

Purpose: Hungry bone syndrome after parathyroidectomy is an important clinical problem in patients on maintenance hemodialysis. We examined the effect of an enhanced recovery after surgery (ERAS) program on the incidence of hungry bone syndrome after parathyroidectomy in this population. Methods: This single-institution, retrospective study analyzed 108 patients on hemodialysis who underwent parathyroidectomy for secondary hyperparathyroidism. Patients were classified into the pre-ERAS (n = 52) and post-ERAS (n = 56) groups. The ERAS program identified high-risk patients and enforced aggressive measures to normalize calcium levels following parathyroidectomy. Results: There was no significant difference in age, sex, body weight, presenting symptoms, preoperative calcium and alkaline phosphatase levels, postoperative intact parathyroid levels, postoperative calcium levels at 1 and 24 hours after parathyroidectomy, and 30-day readmission rates between the groups. The post-ERAS group had significantly higher levels of postoperative calcium at 48 and 72 hours after parathyroidectomy, but a lower incidence of hungry bone syndrome and shorter postoperative length of stay. Patients with hungry bone syndrome had higher preoperative levels of alkaline phosphatase and intact parathyroid, longer postoperative length of stay, and were less likely to have been part of the ERAS program. High preoperative alkaline phosphatase levels and absence of the ERAS program were independent risk factors for hungry bone syndrome after parathyroidectomy. Conclusion: The ERAS program reduced the incidence of hungry bone syndrome and shortened the postoperative length of stay in patients on maintenance hemodialysis who underwent parathyroidectomy for secondary hyperparathyroidism.

Identification of the prognostic and immunological roles of aquaporin 4: A potential target for survival and immunotherapy in glioma patients.

Recent studies have revealed the critical role of AQP4 in the occurrence and development of gliomas. However, the role of AQP4 in immune regulation has not yet been reported. Many recent reports have identified the lymphatic system's occurrence within the central nervous system (CNS) and the vital role of immune regulation in treating brain tumors. Therefore, the present study aimed to explore the role of AQP4 in the immune regulation of glioma. We used bioinformatics analysis to investigate the immunoregulatory function of AQP4, including its correlation with immunity, anti-tumor immune processes, immunotherapy, immune infiltration, tumor mutational burden (TMB), stemness, mutation, and pan-cancer. The results revealed that AQP4 was significantly associated with the expression of multiple immune checkpoints, immune cells, as well as multiple immune cell effector genes, and antigen presentation and processing abilities. Although no significant correlation was found between the AQP4 gene and IDH mutation and MGMT, AQP4 demonstrated substantial expression differences in different immunophenotypes and molecular types. Using the TTD database, we discovered that EGFR, ABAT, and PDGFRA are strongly associated with AQP4 expression in the glioblastoma (GBM) classification, and these factors could be the potential AQP4-related immunotherapy targets. Afterward, we screened the differential genes in the high and low AQP4 gene expression group, the high and low immune score group, and the high and low matrix score group and took the intersection as the candidate factor. Finally, univariate Cox analysis was used to find eight prognostic variables with significant differences across the candidate genes. After lasso dimensionality reduction, three genes built the model (RARRES1, SOCS3, and TTYH1). The scoring model generated by the three genes was eventually obtained after the multi-factor screening of the three genes. Finally, combined with clinical information and cox regression analysis, it was further confirmed that the model score could be used as an independent prognostic factor.

BML-111 alleviates inflammatory response of alveolar epithelial cells via miR-494/Slit2/Robo4 signalling axis to improve acute lung injury.

Acute lung injury (ALI) is a common, variously induced lung cell injury with high mortality. It is also an early stage of acute respiratory distress syndrome. BML-111 is a lipoxin A4 receptor agonist that plays an important role in inflammation. However, its function on ALI remains unclear. To explore whether BML-111 is involved in ALI and its regulatory molecular mechanism, we constructed an in vitro ALI model by stimulating primary mouse alveolar epithelial cells (AECs) with lipopolysaccharide (LPS). The downstream target of microRNA (miR)-494 was predicted by Targetscan. The apoptosis and expression of inflammatory cytokines were analysed by RT-qPCR, Western blot, and ELISA. BML-111 treatment alleviated LPS-induced apoptosis and the production of inflammatory cytokines, such as tumour necrosis factor α, interleukin (IL)-6, IL-1ß, in primary mouse AECs via downregulating miR-494. MiR-494 targeted and downregulated slit guidance ligand 2 (Slit2) in primary mouse AECs. BML-111 activated the Slit2/roundabout guidance receptor 4 (Robo4) axis via downregulating miR-494 to reduce LPS-induced damage in AECs. This study elucidated that miR-494 on BML-111 alleviated LPS-induced ALI in primary mouse AECs via downregulating miR-494 and subsequently activating the Slit2/Robo4 axis. These findings provided a new idea for the prevention and treatment of ALI and respiratory distress syndrome.

Flavonoid and chromone-rich extract from Euscaphis Konishii Hayata leaf attenuated alcoholic liver injury in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Euscaphis konishii Hayata is a traditional medicinal plant in China, and its leaves are usually used to make dishes for hepatic or gastrointestinal issues by Chinese She nationality. Pharmacological analysis showed that E. konishii leaves contain high levels of flavonoids and chromones with favorable anti-hepatoma effect. AIM OF THE STUDY: The extract from E. konishii leaves was detected to evaluate its chemical composition, and the alcoholic liver injury mice model was adopted to elucidate its hepatoprotective effects. MATERIALS AND METHODS: The total leaf extract from E. konishii was separated by polyamide column to get the flavonoid and chromone-rich extract (FCE). Single compounds from FCE was purified by gel and Sephadex LH-20 chromatography and analyzed by nuclear magnetic resonance (NMR). The chemical component of FCE was confirmed and quantified by HPLC-MS. The OH·, O2-, DPPH and ABTS + free radical assays were adopted to estimate the antioxidant activity of FCE in vitro. The alcohol-fed model mice were established to assess the hepatoprotective capacity of FCE in vivo, through biochemical determination, histopathological analysis, mitochondrial function measurement, quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) detection and Western blot determination. RESULTS: 8 flavonoids and 2 chromones were recognized in the FCEextract by both NMR and HPLC-MS. FCE represented strong free radicals scavenging activity in vitro. With oral administration, FCE (50, 100 and 200 mg/kg) dose-dependently decreased the serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP) and aspartate aminotransferase (AST) in alcohol-fed mice. FCE gradually reduced the malondialdehyde (MDA) content, increased the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the alcohol-treated liver tissues. FCE also alleviated the hepatic inflammation, inhibited the hepatocyte apoptosis and lessened the alcohol-induced histological alteration and lipid accumulation in the liver tissues. FCE administration inhibited the overexpression of endoplasmic reticulum (ER) chaperones signaling and unfolded protein response (UPR) pathways to defense the ER-induced apoptosis. Pretreatment with FCE also restored the mitochondrial membrane potentials andadenosine triphosphate (ATP) levels, which in turn suppressed the Cytochrome C release and mitochondria-induced apoptosis. CONCLUSIONS: FCE conferred great protection against alcoholic liver injury, which might be associated with its viability through suppressing reactive oxygen species (ROS) stress and hepatocyte apoptosis.

Preoperative Concurrent Chemoradiotherapy Versus Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer: Phase II Randomized Study.

Objective: We evaluated and compared the efficacy and safety of neoadjuvant chemoradiotherapy (NACRT) versus neoadjuvant chemotherapy (NACT) for locally advanced gastric cancer (LAGC) in a single-center randomized phase II trial. Methods: Patients with LAGC were enrolled and received either NACT or NACRT, followed by gastrectomy and adjuvant chemotherapy. The primary endpoint was an R0 resection rate. Results: We enrolled 75 patients: 75.7% (NACT, 28/37 patients) and 76.3% (NACRT, 29/38 patients) underwent surgery; R0 resection rates were 73.0% (27/37) and 73.7% (28/38), respectively. The NACRT group had significantly better major pathological response than the NACT group (37.9% vs 17.9%, p = 0.019). Between-group postoperative complications were not significantly different. The median follow-up was 59.6 months; 5-year overall survival (OS) rate was 50.1% (NACT) and 61.9% (NACRT); neither group reached the median OS; median progression-free survival was 37.3 and 63.4 months, respectively. Conclusions: S-1-based NACRT did not improve the R0 resection rate, although it presented better tumor regression with similar safety to NACT. Trial registration: ClinicalTrial.gov NCT02301481.

Multicenter, Randomized, Phase III Trial of Short-Term Radiotherapy Plus Chemotherapy Versus Long-Term Chemoradiotherapy in Locally Advanced Rectal Cancer (STELLAR).

PURPOSE: To ascertain if preoperative short-term radiotherapy followed by chemotherapy is not inferior to a standard schedule of long-term chemoradiotherapy in patients with locally advanced rectal cancer. MATERIALS AND METHODS: Patients with distal or middle-third, clinical primary tumor stage 3-4 and/or regional lymph node-positive rectal cancer were randomly assigned (1:1) to short-term radiotherapy (25 Gy in five fractions over 1 week) followed by four cycles of chemotherapy (total neoadjuvant therapy [TNT]) or chemoradiotherapy (50 Gy in 25 fractions over 5 weeks, concurrently with capecitabine [chemoradiotherapy; CRT]). Total mesorectal excision was undertaken 6-8 weeks after preoperative treatment, with two additional cycles of CAPOX (intravenous oxaliplatin [130 mg/m2, once a day] on day 1 and capecitabine [1,000 mg/m2, twice a day] from days 1 to 14) in the TNT group and six cycles of CAPOX in the CRT group. The primary end point was 3-year disease-free survival (DFS). RESULTS: Between August 2015 and August 2018, a total of 599 patients were randomly assigned to receive TNT (n = 302) or CRT (n = 297). At a median follow-up of 35.0 months, 3-year DFS was 64.5% and 62.3% in TNT and CRT groups, respectively (hazard ratio, 0.883; one-sided 95% CI, not applicable to 1.11; P < .001 for noninferiority). There was no significant difference in metastasis-free survival or locoregional recurrence, but the TNT group had better 3-year overall survival than the CRT group (86.5% v 75.1%; P = .033). Treatment effects on DFS and overall survival were similar regardless of prognostic factors. The prevalence of acute grade III-V toxicities during preoperative treatment was 26.5% in the TNT group versus 12.6% in the CRT group (P < .001). CONCLUSION: Short-term radiotherapy with preoperative chemotherapy followed by surgery was efficacious with acceptable toxicity and could be used as an alternative to CRT for locally advanced rectal cancer.

Classification and genetic counselling for a novel splicing mutation of the MLH1 intron associated with Lynch syndrome in colorectal cancer.

BACKGROUND: Lynch-syndrome-associated cancer is caused by germline pathogenic mutations in mismatch repair genes. The major challenge to Lynch-syndrome screening is the interpretation of variants found by diagnostic testing. This study aimed to classify the MLH1 c.1989 + 5G>A mutation, which was previously reported as a variant of uncertain significance, to describe its clinical phenotypes and characteristics, to enable detailed genetic counselling. METHODS: We reviewed the database of patients with Lynch-syndrome gene detection in our hospital. A novel variant of MLH1 c.1989 + 5G>A identified by next-generation sequencing was further investigated in this study. Immunohistochemical staining was carried out to assess the expression of MLH1 and PMS2 protein in tumour tissue. In silico analysis by Alamut software was used to predict the MLH1 c.1989 + 5G>A variant function. Reverse transcription-polymerase chain reaction and sequencing of RNA from whole blood were used to analyse the functional significance of this mutation. RESULTS: Among affected family members in the suspected Lynch-syndrome pedigree, the patient suffered from late-stage colorectal cancer but had a good prognosis. We found the MLH1 c.1989 + 5G>A variant, which led to aberrant splicing and loss of MLH1 and PMS2 protein in the nuclei of tumour cells. An aberrant transcript was detectable and skipping of MLH1 exon 17 in carriers of MLH1 c.1989 + 5G>A was confirmed. CONCLUSIONS: MLH1 c.1989 + 5G>A was detected in a cancer family pedigree and identified as a pathological variant in patients with Lynch syndrome. The mutation spectrum of Lynch syndrome was enriched through enhanced genetic testing and close surveillance might help future patients who are suspected of having Lynch syndrome to obtain a definitive early diagnosis.

The Euscaphis japonica genome and the evolution of malvids.

Malvids is one of the largest clades of rosids, includes 58 families and exhibits remarkable morphological and ecological diversity. Here, we report a high-quality chromosome-level genome assembly for Euscaphis japonica, an early-diverging species within malvids. Genome-based phylogenetic analysis suggests that the unstable phylogenetic position of E. japonica may result from incomplete lineage sorting and hybridization event during the diversification of the ancestral population of malvids. Euscaphis japonica experienced two polyploidization events: the ancient whole genome triplication event shared with most eudicots (commonly known as the γ event) and a more recent whole genome duplication event, unique to E. japonica. By resequencing 101 samples from 11 populations, we speculate that the temperature has led to the differentiation of the evergreen and deciduous of E. japonica and the completely different population histories of these two groups. In total, 1012 candidate positively selected genes in the evergreen were detected, some of which are involved in flower and fruit development. We found that reddening and dehiscence of the E. japonica pericarp and long fruit-hanging time promoted the reproduction of E. japonica populations, and revealed the expression patterns of genes related to fruit reddening, dehiscence and abscission. The key genes involved in pentacyclic triterpene synthesis in E. japonica were identified, and different expression patterns of these genes may contribute to pentacyclic triterpene diversification. Our work sheds light on the evolution of E. japonica and malvids, particularly on the diversification of E. japonica and the genetic basis for their fruit dehiscence and abscission.

Wolfberry genomes and the evolution of Lycium (Solanaceae).

Wolfberry Lycium, an economically important genus of the Solanaceae family, contains approximately 80 species and shows a fragmented distribution pattern among the Northern and Southern Hemispheres. Although several herbaceous species of Solanaceae have been subjected to genome sequencing, thus far, no genome sequences of woody representatives have been available. Here, we sequenced the genomes of 13 perennial woody species of Lycium, with a focus on Lycium barbarum. Integration with other genomes provides clear evidence supporting a whole-genome triplication (WGT) event shared by all hitherto sequenced solanaceous plants, which occurred shortly after the divergence of Solanaceae and Convolvulaceae. We identified new gene families and gene family expansions and contractions that first appeared in Solanaceae. Based on the identification of self-incompatibility related-gene families, we inferred that hybridization hotspots are enriched for genes that might be functioning in gametophytic self-incompatibility pathways in wolfberry. Extremely low expression of LOCULE NUBER (LC) and COLORLESS NON-RIPENING (CNR) orthologous genes during Lycium fruit development and ripening processes suggests functional diversification of these two genes between Lycium and tomato. The existence of additional flowering locus C-like MADS-box genes might correlate with the perennial flowering cycle of Lycium. Differential gene expression involved in the lignin biosynthetic pathway between Lycium and tomato likely illustrates woody and herbaceous differentiation. We also provide evidence that Lycium migrated from Africa into Asia, and subsequently from Asia into North America. Our results provide functional insights into Solanaceae origins, evolution and diversification.

A Bioinformatics Analysis of the Potential Roles of Aquaporin 4 in Human Brain Tumors: An Immune-Related Process.

Aquaporin 4 (AQP4) is an ubiquitously expressed membrane protein channel found in the central nervous system and mainly on astrocytes. Recent studies on AQP4 has implicated it in tumorigenesis. It is of interest to determine the potential value of AQP4 in identifying, guiding treatment and prognosticating various types of CNS cancers. This investigation systematically investigated the oncogenic role of AQP4 across 33 CNS tumors found in GEO and TCGA datasets. We found that CNS tumors strongly expressed AQP4. There appeared to be a strong link between the prognosis of patients with a CNS malignancy and degree of AQP4 expression. AQP4 expression influences the degree of CD8+ T-cell infiltration level as well as cancer-associated fibroblast infiltration in CNS tumors. Moreover, synaptic vesicle cycle and phosphatidylinositol signaling system-associated functions were also found to be related to AQP4 functional mechanisms. Furthermore, potential AQP4 inhibitors have also been explored by using Specs data base and virtual screening technique. This study contributes toward current knowledge regarding the role of AQP4 in CNS tumors.

[A new lignan from Euscaphis konishii].

The chemical constituents from the extract of the twigs of Euscaphis konishii with anti-hepatoma activity were investigated, twelve compounds by repeated chromatography with silica gel, Sephadex LH-20 and preparative-HPLC. The structures of the chemical components were elucidated by spectroscopy methods, as konilignan(1),(7R, 8S)-dihydrodehydrodico-niferylalcohol-9-O-ß-D-glucopyranoside(2),illiciumlignan B(3),threo-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-1,3-panediol(4),erythro-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-1,3-panediol(5), matairesinol(6), wikstromol(7), isolariciresinol(8),(+)-lyoniresinol(9), 4-ketopinoresinol(10), syringaresin(11), and vladinol D(12). Among them, compound 1 is a new lignan. Compounds 10 and 12 had moderate inhibitory activity on HepG2 cells, with IC_(50) values of 107.12 µmol·L~(-1) and 183.56 µmol·L~(-1), respectively.

Clinical characteristics, medical service utilization, and expenditure for colorectal cancer in China, 2005 to 2014: Overall design and results from a multicenter retrospective epidemiologic survey.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in China, however, publicly available, descriptive information on the clinical epidemiology of CRC is limited. METHODS: Patients diagnosed with primary CRC during 2005 through 2014 were sampled from 13 tertiary hospitals in 9 provinces across China. Data related to sociodemographic characteristics, the use of diagnostic technology, treatment adoption, and expenditure were extracted from individual medical records. RESULTS: In the full cohort of 8465 patients, the mean ± SD age at diagnosis was 59.3 ± 12.8 years, 57.2% were men, and 58.7% had rectal cancer. On average, 14.4% of patients were diagnosed with stage IV disease, and this proportion increased from 13.5% in 2005 to 20.5% in 2014 (P value for trend < .05). For diagnostic techniques, along with less use of x-rays (average, 81.6%; decreased from 90.0% to 65.7%), there were increases in the use of computed tomography (average, 70.4%; increased from 4.5% to 90.5%) and magnetic resonance imaging (average, 8.8%; increased from 0.1% to 20.4%) over the study period from 2005 to 2014. With regard to treatment, surgery alone was the most common (average, 50.1%), but its use decreased from 51.3% to 39.8% during 2005 through 2014; and the use of other treatments increased simultaneously, such as chemotherapy alone (average, 4.1%; increased from 4.1% to 11.9%). The average medical expenditure per patient was 66,291 Chinese Yuan (2014 value) and increased from 47,259 to 86,709 Chinese Yuan. CONCLUSIONS: The increasing proportion of late-stage diagnoses presents a challenge for CRC control in China. Changes in diagnostic and treatment options and increased expenditures are clearly illustrated in this study. Coupled with the recent introduction of screening initiatives, these data provide an understanding of changes over time and may form a benchmark for future related evaluations of CRC interventions in China.

Alantolactone suppresses the metastatic phenotype and induces the apoptosis of glioblastoma cells by targeting LIMK kinase activity and activating the cofilin/G­actin signaling cascade.

Glioblastoma (GBM) is the most common aggressive brain tumor and is associated with an extremely poor prognosis, as the current standard of care treatments have limited efficacy. Natural compounds have attracted increasing attention as potential anticancer drugs. Alantolactone (ATL) is a natural small molecule inhibitor, that has antitumor properties. In the present study, U87MG and U251 cells were treated ATL and changes in actin/G­actin/F­actin/cofilin pathway were detected in whole cells, in the cytoplasm and mitochondria by western blot analysis. Immunofluorescence and immunoprecipitation analysis identified changes in the expression levels of target proteins and interactions, respectively. A LIMK enzyme inhibitor was also applied to assess the effects of ATL on the migration and invasion of GBM cells. Flow cytometry was used to detect the levels of apoptosis of GBM cells. The expression of matrix metalloproteinase (MMP)­2/MMP­9, caspase­3/caspase­9/poly(ADP­ribose) polymerase (PARP)/cytochrome c, were determined by western blot analysis to assess the effects of targeting LIMK. The in vitro findings were verified in vivo by characterizing changes in the expression of cofilin/LIMK in xenograft tumors in immunodeficient mice. It was found that ATL activated cofilin through the targeted inhibition of LIMK enzyme activity and it thus upregulated the ratio of G/F actin, and inhibited GBM cell migration and invasion. Conversely, the activation of cofilin and G­actin could be co­transferred to the mitochondria to initiate the mitochondrial­cytochrome c pathway to induce apoptosis. On the whole, the findings of the present study further illustrate the molecular mechanisms through which ATL inhibits the metastatic phenotype of GBM cells and induces apoptosis. Given previous findings, it can be deduced that ATL can function through multiple pathways and has multiple targets in GBM models, highlighting its potential for use in clinical applications.

The role of cytology in endobronchial ultrasound-guided transbronchial needle aspiration: A study of 813 cases focusing on diagnostic yield, an analysis of misdiagnosed cases and diagnostic accordance rate of cytological subtyping.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive technique for cytological and histological diagnosis. The objective of this study was to explore the role of cytological diagnosis in EBUS-TBNAs. METHODS: Eight hundred and thirteen consecutive cases performed EBUS-TBNA with both cytological and histological diagnoses were retrospectively reviewed. All patients were followed up for clinical data. RESULTS: Before immunohistochemical examination, the cytological sensitivity, specificity, and diagnostic accuracy of EBUS-TBNAs were 92.9% (421/453), 98.9% (348/352), 95.5% (769/805), respectively. After immunohistochemical examination, the sensitivity, specificity, and diagnostic accuracy were 93.0% (423/455), 99.4% (348/350), 95.8% (771/805), respectively. The majority of false-negative were cases whose cytological diagnosis was "atypical" or the cytological diagnosis suggested "inadequate." "Neoplastic" were also prone to false-negative cytology. The diagnostic accordance rate of cytological subtyping was 90.3% for squamous-cell carcinoma, 99.2% for adenocarcinoma, and 98.1% for small-cell carcinoma before immunohistochemical examination, and became 85.9%, 98.5%, and 98.2% after immunohistochemical examination, respectively. CONCLUSION: Cytological diagnosis in EBUS-TBNAs had a good sensitivity and high specificity. The sensitivity and specificity of cytological diagnosis were proved to be higher after the immunohistochemical examination. At the same time, cytology had high accordance rate in subtype diagnosis. False-negative results occurred more commonly in cases whose cytological diagnosis was "atypical" or the cytological diagnosis suggested "inadequate" or the corresponding histological diagnosis was "Neoplastic."

Submucosal Enhancing Stripe as a Contrast Material-enhanced MRI-based Imaging Feature for the Differentiation of Stage T0-T1 from Early T2 Rectal Cancers.

Background Accurate differentiation of stage T0-T1 rectal tumors from stage T2 rectal tumors facilitates the selection of appropriate surgical treatment. MRI is a recommended technique for local staging, but its ability to distinguish T1 from T2 tumors is poor. Purpose To explore the value of a submucosal enhancing stripe (SES), an uninterrupted enhancing band between the rectal tumor and the muscular layer on contrast material-enhanced T1-weighted images, as a potential imaging feature to differentiate T0-T1 from T2 rectal tumors. Materials and Methods This retrospective study included patients with pT0-T1 and pT2 rectal tumors who underwent pretreatment MRI and rectal tumor resection between January 2012 and November 2019. Two radiologists independently evaluated tumor characteristics (SES; status of muscularis propria [SMP]; and tumor shape, location, and size) at MRI. The associations of clinical and imaging characteristics with stage T0-T1 or T2 tumors were assessed, ß values were calculated, and predictive models were built. The diagnostic accuracies for the differentiation of T0-T1 tumors from T2 tumors with SES and SMP were compared. Results Data from 431 patients (mean age, 60 years ± 10 [standard deviation]; 261 men) were evaluated. SES (ß = 3.9; 95% CI: 3.1, 4.7; P < .001), SMP (ß = 1.3; 95% CI: 0.7, 1.9; P < .001), and carpetlike shape (ß = 1.6; 95% CI: 0.5, 2.8; P = .01) were independent factors distinguishing T0-T1 tumors from T2 tumors. The diagnostic accuracy was 87% (95% CI: 84, 90; 376 of 431) for SES and 67% (95% CI: 63, 72; 290 of 431) for SMP (P < .001). Conclusion Submucosal enhancing stripe (SES) at contrasted-enhanced MRI, status of muscularis propria (SMP) on T2-weighted images, and tumor shape can serve as independent imaging features to differentiate stage T0-T1 rectal tumors from stage T2 rectal tumors. Moreover, SES is a more accurate feature than is SMP. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Turkbey in this issue.