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Highly diversified astigmatic mites comprise many medically important human household pests such as house dust mites causing roughly 1–2% of the allergic diseases globally; however, their evolutionary origin, diverse lifestyles including reversible parasitism and quick adaptation to rather new human household environments have not been illustrated at genomic level, which hamper the allergy prevention and our exploration of these household pests. Using six high-quality assembled and annotated genomes, this comparative genomics study not only refuted the monophyly of mites and ticks, but also thoroughly explored the divergence of Acariformes and the divergent evolution of astigmatic mites. In the monophyletic Acariformes, Prostigmata known as notorious plant pests first evolved, then rapidly evolving Astigmata diverged from soil oribatid mites. Within astigmatic mites, a wide range of gene families rapidly expanded via tandem gene duplications, including ionotropic glutamate receptors, triacylglycerol lipases, serine proteases and UDP glucuronosyltransferases (UGTs), which enriched their capacities of adapting to rapidly changing household environments. The gene diversification after tandem duplications provided plenty of genetic resources for their adaptations of sensing environmental signals, digestion, and detoxification. Whilst many gene decay events only occurred in the skin-burrowing parasitic mite Sarcoptes scabiei. Throughout the evolution of Acariformes, massive horizontal gene transfer events occurred in gene families such as UGTs and several important fungal cell wall lytic enzymes, which enable the detoxification and associated digestive functions and provide perfect drug targets for pest control. Our comparative study sheds light on the rapid divergent evolution of astigmatic mites from the divergence of Acariformes to their diversification and provides novel insights into the genetic adaptations and even control of human household pests.

Background Whether hypokalemia can affect the short-term outcomes of CRC patients after radical surgery remains unclear. The purpose of this study was to investigate the impact of preoperative hypokalemia on the short-term outcomes for colorectal cancer (CRC) patients who underwent radical CRC surgery using propensity score matching (PSM). Methods We retrospectively enrolled consecutive CRC patients from Jan 2011 to Dec 2021 in a single-center hospital. Hypokalemia was defined as a serum potassium concentration Results A total of 6183 CRC patients who underwent radical surgery were included in this study, of whom 390 (6.3%) patients were diagnosed with hypokalemia before surgery. After 1:1 ratio PSM, there were 390 patients in the hypokalemia group and in the normal potassium group. No significant difference was found between the two groups after PSM in terms of baseline information (p > 0.05). Regarding short-term outcomes, the hypokalemia group had a longer hospital stay (p = 0.028), a higher proportion of overall complications (p = 0.048) and a higher incidence of postoperative pneumonia (p = 0.008) after PSM. Moreover, hypokalemia (p = 0.036, OR = 1.291, 95% CI = 1.017–1.639) was an independent risk factor for overall complications. Conclusion Preoperative hypokalemia could increase complications after CRC surgery and prolong the hospital stay. Moreover, preoperative hypokalemia was an independent risk factor for overall complications.

Hydrogen sulfide (H2S) has been highlighted as an important gasotransmitter in mammals. A growing number of studies have indicated that H2S plays a key role in the pathophysiology of vascular diseases and physiological vascular homeostasis. Alteration in H2S biogenesis has been reported in a variety of vascular diseases and H2S supplementation exerts effects of vasodilation. Accumulating evidence has shown vascular potassium channels activation is involved in H2S-induced vasodilation. This review aimed to summarize and discuss the role of H2S in the regulation of vascular tone, especially by interaction with different vascular potassium channels and the underlying mechanisms.

Previous studies reported hypertension remission after gastrectomy for gastric cancer patients, and the remission rate was 11.1%-93.8%. We have reported the factors of hypertension remission previously, however, the follow-up time was six months. It is necessary to identify risk factors for hypertension for a relatively longer follow-up time.To analyze the predictive factors for hypertension remission one year after gastrectomy of gastric cancer patients and to construct a risk model for hypertension remission.We retrospectively collected the medical information of patients with concurrent gastric cancer and hypertension in a single clinical center from January 2013 to December 2020. Univariate and multivariate logistic regression of hypertension remission were conducted, and a nomogram model was established.A total of 209 patients with concurrent gastric cancer and hypertension were included in the current study. There were 108 patients in the remission group and 101 patients in the non-remission group. The hypertension remission rate was 51.7% one year after gastrectomy. The remission group had younger aged patients (Younger age, higher weight loss and total gastrectomy were independent predictors for hypertension remission after gastrectomy for gastric cancer patients. The nomogram could visually display these results.

With the rising demand for fast-charging technology in electric vehicles and portable devices, significant efforts have been devoted to the development of the high-rate batteries. Among numerous candidates, rechargeable aqueous zinc-ion batteries (ZIBs) are a promising option due to its high theoretical capacity, low redox potential of zinc metal anode and inherent high ionic conductivity of aqueous electrolyte. As the strong electrostatic interaction between Zn2+ and host generally leads to sluggish electrode kinetics, many strategies have been proposed to enhance fast (dis)charging performance. Herein, we review the state-of-the-art ultrafast aqueous ZIBs and focus on the rational electrode-designing strategies, such as crystal structure engineering, nanostructuring and morphology controlling, conductive materials introducing and organic molecule designing. Recent research directions and future perspectives are also proposed in this review.

BACKGROUND Hemophilic pseudotumor (HP) is a rare complication in patients with hemophilia. The lesion most frequently occurs in the long bones, pelvis, small bones of the hands and feet, or rarely in the maxillofacial region. Postoperative changes in HP are seldom arrested, whereas angiogenesis characterized by disturbed wound healing in HP may cause vascular malformations. CASE SUMMARY We report the case of an 11-year-old boy who was affected by maxillary intraosseous venous malformation. Enucleation of an HP without factor replacement was performed initially on the right side of the maxilla 3 years ago. The patient was referred to us because of painless swelling in the same location. Factor replacement and subtotal maxillectomy were performed. Pathological examinations revealed intraosseous venous malformation. CONCLUSION This study is the first to document the development of intraosseous venous malformation after enucleation of an HP in the maxillofacial region. Angiogenesis characterized by disturbed wound healing in patients with hemophilia may be pivotal in the pathogenesis of this condition.

Liver disease is associated with increased bleeding risk. The efficacy and safety of direct oral anticoagulants (DOACs) is a subject of contention in atrial fibrillation (AF) patients with liver disease. Electronic databases (PubMed, Embase, and Cochrane Library) were searched to retrieve studies on the efficacy and safety of DOACs versus warfarin in AF patients with liver disease from January 1980 to April 2020. A meta-analysis was conducted using a random-effects model. Six studies involving 41,859 patients were included. Compared with warfarin, DOACs demonstrated significant reduction in ischemic stroke (HR, 0.68; 95% CI (0.54–0.86)), major bleeding (0.74 (0.59–0.92)), and intracranial hemorrhage (ICH) (0.48 (0.40–0.58)), with no significant effect on gastrointestinal bleeding (P = 0.893) in AF patients with liver disease. Similar results were observed in regular-dose, reduced-dose, and active liver disease subgroups, albeit Asian patients had a slight reduction in major bleeding (P = 0.055). Furthermore, the pooled estimates of individual DOAC subgroups indicated that dabigatran and apixaban led to greater safety in major bleeding (P

Gastroparesis is a common symptom in Parkinson's disease (PD) and whether any change occurs in gastric smooth muscle cells (SMCs) of PD patients is unclear. We previously reported that rats with bilateral substantia nigra lesions induced by 6-hydroxydopamine (6-OHDA), referred to as 6-OHDA rats, manifest typical gastroparesis. In the present study, we further investigate the underlying mechanism. By means of an organ bath system and an implantable radiotelemetry system, both a weakened contractile force of gastric circular smooth muscle and gastric myoelectric activity were detected in the 6-OHDA rats and phasic and tonic contractions elicited by carbachol or high concentration of potassium were significantly reduced in gastric circular muscle strips. A thickened smooth muscle layer was observed under a light microscope and an ultrastructure of hypertrophic SMCs, with increased caveolae and decreased dense bodies, was observed under transmission electron microscope. Furthermore, the mRNA and protein expression levels of contractile markers (myosin light chain 20, myosin heavy chain 11 and α-smooth muscle actin) and the transcription factor serum response factor (SRF) were significantly decreased, while the TNFα and IL-1β content was increased in the 6-OHDA rats. These results suggest that the decreased contractile force in 6-OHDA rats may be associated with the phenotypic abnormality observed in SMCs, which is due to downregulated contractile proteins induced by decreased SRF expression in the inflammatory muscular microenvironment.

The Gaokao, a mandatory postsecondary entrance examination for all Chinese students, is often associated with psychological stress among Chinese students in their final year of high school. This project was conducted in summer 2017 in urban Beijing and rural Xi’an, China. The purpose is to explore the perspectives of urban and rural secondary school graduates after they have completed the examination, using in-depth clinical interviews. The study draws on Self-Determination Theory and research on moral reasoning to examine several themes surrounding Chinese adolescents’ perceptions of the Gaokao, including general perceptions of the purpose of education, intrinsic and extrinsic motivation, sources of support and pressure during study for the Gaokao, and issues of fairness and social inequality. The major findings are that students from all backgrounds reported psychological conflict regarding their general views of the aims of education and the extrinsic pressure deriving from the high-stakes Gaokao examination. Inequality was seen as further exacerbated by family background, resources, and quality of teaching. Urban parents tended to provide more support, both academic and interpersonal. Rural students rated their mental health as significantly lower than urban students during their senior year of high school.

Purpose Hepatocellular carcinoma (HCC) is a common malignant cancer and the third leading cause of death worldwide. The molecular mechanism of HCC remains unclear. Recent studies have demonstrated that the ubiquitin‐proteasome system (UPS) is associated with HCC. Ubqln2, a member of the UPS, is abnormally expressed in HCC. However, whether Ubqln2 is associated with HCC prognosis remains unknown. Patients and Methods We analyzed the associations between overall survival and various risk factors in 355 HCC tissue samples obtained from the Cancer Genomic Atlas (TCGA) database at the mRNA level and in 166 HCC tissue samples from Southwest Hospital at the protein level. qRCR was used to determinate Ubqln2 expression in cancer and noncancerous tissues. The association between Ubqln2 and Ki‐67 was analyzed by immunohistochemistry. The association between Ubqln2 expression and survival was analyzed using Kaplan‐Meier curve and Cox proportional hazards models. A nomogram was used to predict the impact of Ubqln2 on prognosis. Mutated genes were analyzed to determine the potential mechanism. Results Ubqln2 highly expressed in HCC tissues. The Ubqln2 mRNA level had significant relations with UICC tumor stage (P = .022), UICC stage (P = .034) and resection potential (P = .017). Concordantly, the Ubqln2 protein was closely associated with tumor size (P = .005), UICC stage (P = .012), and recurrence (P = .009). Ubqln2 was highly expressed in HCC and positively associated with poor survival. The nomogram precisely predicted the prognosis of HCC patients with high or low Ubqln2 expression. A genomic waterfall plot suggested that Ubqln2 expression was closely associated with mutated CTNNB1. Conclusion Our findings reveal that Ubqln2, an independent risk factor for HCC, is a potential prognostic marker in HCC patients. Ubqln2 expression is positively associated with mutated CTNNB1., Ubqln2 is abnormally expressed in HCC but its role remains unknown. Here, we reported that Ubqln2, an independent risk factor for HCC, is a potential prognostic marker in HCC patients. Ubqln2 expression is positively associated with mutated CTNNB1.

An asymmetric synthetic approach to the octahydrofuro[3,4-b]pyridine framework of marine natural product zamamiphidin A has been described. The key steps include an asymmetric Michael addition of (R)-N-tert-butanesulfinyl imidate with enamidomalonate to install the C10 stereocenter, an intramolecular alkoxide exchange/Michael addition/hydrogenation sequence to construct the bicyclic ring system.

A practical synthesis of immucillins BCX-1777 and BCX-4430 is disclosed. Highlights of the synthesis include the addition of lithiated 9-deazapurine derivative 10 to the stable tri-O-benzyl cyclic nitrone 13 to form the imino-C-nucleoside skeleton, and an efficient copper-catalysed Ullmann-type amination to install the amino group on the heterocyclic moiety of BCX-4430.

Purpose. The purpose of this study is to analyze the effect of preoperative waiting time on the short-term outcomes and prognosis in colorectal cancer (CRC) patients. Methods. We retrospectively analyzed 3744 CRC patients who underwent primary CRC surgery at a single clinical medical center from Jan 2011 to Jan 2020. The baseline information, short-term outcomes, overall survival (OS), and disease-free survival (DFS) were compared among the short-waiting group, the intermediate-waiting group, and the long-waiting group. Results. A total of 3744 eligible CRC patients were enrolled for analysis. There were no significant differences in all of the baseline information and short-term outcomes among the three groups. In multivariate analysis, older age (OS: p = 0.000 , HR = 1.947, 95% CI = 1.631–2.324; DFS: p = 0.000 , HR = 1.693, 95% CI = 1.445–1.983), advanced clinical stage (OS: p = 0.000 , HR = 1.301, 95% CI = 1.161–1.457; DFS: p = 0.000 , HR = 1.262, 95% CI = 1.139–1.400), overall complications (OS: p = 0.000 , HR = 1.613, 95% CI = 1.303–1.895; DFS: p = 0.000 , HR = 1.560, 95% CI = 1.312–1.855), and major complications (OS: p = 0.001 , HR = 1.812, 95% CI = 1.338–2.945; DFS: p = 0.006 , HR = 1.647, 95% CI = 1.153–2.352) were independent factors of OS and DFS. In addition, no significant difference was found in all stages (OS, p = 0.203 ; DFS, p = 0.108 ), stage I (OS, p = 0.419 ; DFS, p = 0.579 ), stage II (OS, p = 0.465 ; DFS, p = 0.385 ), or stage III (OS, p = 0.539 ; DFS, p = 0.259 ) in terms of OS and DFS among the three groups. Conclusion. Preoperative waiting time did not affect the short-term outcomes or prognosis in CRC patients.

The diterpenoid alkaloids are a family of extremely important natural products that have long been a research hotspot due to their myriad of intricate structures and diverse biological properties. This chapter systematically summarizes the past 11 years (2009-2019) of studies on the diterpenoid alkaloids, including the "so-called" atypical ones, covering the classification and biogenetic relationships, phytochemistry together with 444 new alkaloids covering 32 novel skeletons and the corrected structures, chemical reactions including conversion toward toxoids, synthetic studies, as well as biological activities. It should be noted that the synthetic studies, especially the total syntheses of various diterpenoid alkaloids, are for the first time reviewed in this treatise. This chapter, in combination with our four previous reviews in volumes 42, 59, 67, and 69, will present to the readers a more completed and updated profile of the diterpenoid alkaloids.

The purpose of this study was to evaluate the effect of colorectal cancer surgery on hypertension. Patients who underwent colorectal cancer surgery were retrospectively enrolled. Hypertension before and 1 year after colorectal cancer surgery was recorded. As a result, eighty patients had remission of hypertension, 307 patients had no remission 1 year after colorectal cancer surgery, and the remission rate was 20.7%. In conclusion, patients with concurrent colorectal cancer and hypertension had a 20.7% remission rate 1 year after colorectal cancer surgery. Age, but not the type of surgery, was a predictive factor for the remission of hypertension.

PurposeThe current study aims to explore the outcomes of type 2 diabetes mellitus (T2DM) on gastric cancer patients following gastrectomy through propensity score matching (PSM) analysis.MethodsA retrospective study of gastric cancer patients following gastrectomy was conducted in a single clinical center from January 2014 to December 2019. The short-term outcomes, overall survival (OS) and disease-free survival (DFS) were analyzed between T2DM group and Non-T2DM group.ResultsA total of 703 patients were enrolled in this study. After 1:1 PSM, 84 patients in T2DM group and 84 patients in Non-T2DM were matched for final analysis. No significant difference was found in terms of operation time, intra-operative blood loss, retrieved lymph nodes, postoperative stay, blood transfusion and complications between T2DM group and Non-T2DM group (p > 0.05). The Kaplan-Meier curve implied that T2DM had no impact on OS or DFS. Cox regression was conducted to identify predictive factors for prognosis. Body mass index (BMI) (p = 0.039 < 0.05, HR = 0.725, 95% CI = 0.534–0.983), pre-operative lymphocyte (p = 0.017 < 0.05, HR = 0.678, 95% CI = 0.493–0.932), pathological tumor node metastasis (pTNM) stage (p = 0.000 < 0.05, HR = 2.619, 95% CI = 2.048–3.349) and complications (p = 0.006 < 0.05, HR = 1.528, 95% CI = 1.132–2.061) were predictive factors for OS, and BMI (p = 0.013 < 0.05, HR = 0.524, 95% CI = 0.315–0.872), pTNM stage (p = 0.000 < 0.05, HR = 2.619, 95% CI = 2.048–3.349) and complications (p = 0.008 < 0.05, HR = 1.892, 95% CI = 1.179–3.036) were independent predictive factors for DFS.ConclusionT2DM did not have an impact on gastric cancer patients following gastrectomy in terms of short-term outcomes and prognosis.

Nicotinamide adenine dinucleotide (NADH) has been reported to regulate synaptic plasticity recently, while its role in this process remains unclear. To explore the contribution and the underlying mechanisms of NADH regulating synaptic plasticity, here, we examined NADH's effect on immediate-early response genes (IEGs) expressions, including C-Fos and Arc in primary cultured cortical neurons and the frontal cortex of mouse brain. Our results showed that NADH promoted IEGs expression and that the C-Fos and Arc levels are increased in primary cultured cortical neurons, which is almost completely blocked by N-methyl-D-aspartate receptor (NMDAR) inhibitor, MK-801. Moreover, NADH significantly increased intracellular Ca

Two new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperbeanins P-Q (

Purpose. The purpose of the current study is to analyze whether preoperative hyponatremia affected the short-term outcomes of colorectal cancer (CRC) surgery. Methods. This retrospective study was conducted in a single clinical center where we enrolled patients who underwent primary CRC surgery from January 2011 to December 2021. The short-term outcomes were compared between the hyponatremia group and the normal sodium group using propensity score matching (PSM) analysis. Results. A total of 6730 cases of patients who received CRC surgery were finally included in this study. There were 184 patients in the hyponatremia group and 6546 patients in the normal sodium group. After 1 : 1 ratio PSM, 184 patients in the normal sodium group were matched to 184 patients in the hyponatremia group. No significant difference was found in baseline information after PSM ( P > 0.05 ). After PSM, the hyponatremia group had higher patients with overall complications ( P = 0.013 ). Univariate and multivariate logistic regression analysis were conducted to find predictors of complications, and we found that older age ( P = 0.032 , OR = 1.023 , 95 % CI = 1.002 − 1.044 ), open surgery (P =0.001, OR = 2.300 , 95 % CI = 1.420 − 3.727 ), blood loss ( P = 0.015 , OR = 1.002 , 95 % CI = 1.000 − 1.003 ), and hyponatremia ( P = 0.012 , OR = 1.856 , 95 % CI = 1.148 − 3.001 ) were independent predictors of patients with overall complications. Conclusion. Hyponatremia was an independent predictor of patients with overall complications after CRC surgery, therefore, the adequate preparation of the patients for surgery remained fundamental.

Background. Gubitong Recipe (GBT) is a prescription based on the Traditional Chinese Medicine (TCM) theory of tonifying the kidney yang and strengthening the bone. A previous multicentral randomized clinical trial has shown that GBT can effectively relieve joint pain and improve quality of life with a high safety in treating osteoarthritis (OA). This study is aimed at elucidating the active compounds, potential targets, and mechanisms of GBT for treating OA. Method. The network pharmacology method was used to predict the key active compounds, targets, and mechanisms of GBT in treating OA. An OA rat model was established with Hulth surgery, and the pathological changes of articular cartilage were observed to evaluate the effects of GBT. Chondrocytes were stimulated with LPS to establish in vitro models, and key targets and mechanisms predicted by network pharmacology were verified via qRT-PCR, ELISA, western blot, and immunofluorescence. The Contribution Index Model and molecular docking were used to determine the key active compounds of GBT and the major nodes affecting predicted pathways. Result. A total of 500 compounds were acquired from related databases, where 87 active compounds and their 254 corresponding targets were identified. 2979 OA-related genes were collected from three databases, 150 of which were GBT-regulating OA genes. The compound-target network weight analysis and PPI results showed that IL-6 and PGE2 are key targets of GBT in treating OA. KEGG results showed that PI3K/AKT, Toll-like receptor, NFκB, TNF, and HIF-1 are the key signaling pathways. An in vivo experiment showed that GBT could effectively suppress cartilage degradation of OA rats. In vitro experiments demonstrated that GBT can inhibit the key targets of KEGG-related pathways. Molecular-docking results suggested that luteolin, licochalcone A, and β-carotene were key targets of GBT, and the mechanisms may be associated with the NFκB signaling pathway. Blockage experiments showed that the NFκB pathway is the key pathway of GBT in treating OA. Conclusion. This study verified that GBT can effectively protect articular cartilage through multitarget and multipathway, and its inhibitory effect on the NFκB pathway is the most key mechanism in treating OA.

BACKGROUND: Sepsis-induced liver injury is a fatal complication of sepsis. Trichostatin A (TSA) regulates inflammation and autophagy in some human diseases, and forkhead box O3a (FoxO3a) has been shown to regulate autophagy. The present study aims to investigate whether TSA exerts its effects on septic liver injury through the FoxO3a/autophagy signaling pathway. METHODS: A sepsis mouse model was constructed by the cecal ligation and puncture (CLP) method, and AML12 cells were pretreated with lipopolysaccharide (LPS) (1 μg/mL) to establish a sepsis cell model. Forty mice were divided into four groups, namely control group, TSA group, CLP group, and CLP+TSA group, with 10 mice in each group. Cells were divided into control group, TSA group, LPS group, and LPS+TSA group. Hematoxylin-eosin (H&E) staining and biochemical methods were used to evaluate liver tissue injury. Enzyme-linked immunosorbent assay (ELISA) was applied to detect the expression of proinflammatory cytokines, and Western blotting and immunofluorescence were used to measure autophagy-related protein expression. RESULTS: Compared with the CLP group (mice), the proinflammatory cytokines (interleukin-β [IL-β] 2,665.27±324.90 pg/mL to 2,080.26±373.66 pg/mL; interleukin-6 [IL-6] 399.01±60.98 pg/mL to 221.90±46.89 pg/mL) and the hepatocyte injury markers (aspartate transaminase [AST] from 198.18±27.07 U/L to 128.42±20.55 U/L; alanine aminotransferase [ALT] from 634.98±74.10 U/L to 478.60±32.56 U/L) were notably decreased after TSA intervention. Moreover, LC3 II and FoxO3a showed an obvious increase and P62 showed an obvious decrease in the CLP+TSA group. Cell experiment results showed the similar trend. After FoxO3a gene was knocked down in AML12 cells, the promotion of autophagy and the improvement of liver enzyme index and inflammation by TSA were weakened. CONCLUSION: TSA may improve the inflammatory response and liver injury in septic mice through FoxO3a/autophagy.

BackgroundIn several countries, thyroid dyshormonogenesis is more common than thyroid dysgenesis in patients with congenital hypothyroidism (CH). However, known pathogenic genes are limited to those directly involved in hormone biosynthesis. The aetiology and pathogenesis of thyroid dyshormonogenesis remain unknown in many patients.MethodsTo identify additional candidate pathogenetic genes, we performed next-generation sequencing in 538 patients with CH and then confirmed the functions of the identified genes in vitro using HEK293T and Nthy-ori 3.1 cells, and in vivo using zebrafish and mouse model organisms.ResultsWe identified one pathogenicMAML2variant and two pathogenicMAMLD1variants that downregulated canonical Notch signalling in three patients with CH. Zebrafish and mice treated with N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butylester, a γ-secretase inhibitor exhibited clinical manifestations of hypothyroidism and thyroid dyshormonogenesis. Through organoid culture of primary mouse thyroid cells and transcriptome sequencing, we demonstrated that Notch signalling within thyroid cells directly affects thyroid hormone biosynthesis rather than follicular formation. Additionally, these three variants blocked the expression of genes associated with thyroid hormone biosynthesis, which was restored byHES1expression. TheMAML2variant exerted a dominant-negative effect on both the canonical pathway and thyroid hormone biosynthesis.MAMLD1also regulated hormone biosynthesis through the expression ofHES3, the target gene of the non-canonical pathway.ConclusionsThis study identified three mastermind-like family gene variants in CH and revealed that both canonical and non-canonical Notch signalling affected thyroid hormone biosynthesis.

Purpose The purpose of this study was to investigate the short-term outcomes and prognosis of elderly and very elderly colorectal cancer (CRC) patients after primary CRC surgery using propensity score matching (PSM). Methods This study retrospectively collected the medical records of CRC patients ≥ 65 years old undergoing primary CRC surgery from Jan 2011 to Jan 2020. Short-term outcomes, overall survival (OS) and disease-free survival (DFS) were compared between very elderly CRC patients (≥ 80 years old) and elderly CRC patients (65–79 years old). Results A total of 2084 patients were enrolled for analysis. After PSM, 331 very elderly patients were matched to 331 elderly patients. In terms of short-term outcomes, the very elderly patients had longer postoperative hospital stays (p = 0.007) after PSM. In terms of OS, it was found that age (p Conclusion Very elderly patients had a poorer prognosis than elderly patients after primary CRC surgery. Surgeons should be cautious when treating very elderly CRC patients.

Background: YTHDF1 is highly expressed in multiple tumors and affects tumor progression. However, there are only a few comprehensive studies on the analysis of YTHDF1 in esophageal cancer.Methods: We analyzed YTHDF1 expression in pan-cancer by comparing both the GEPIA and TCGA cohorts, and further verified the differences in YTHDF1 expression between the ESCA and normal groups by the GEO ESCA cohort and in vitro experiments. The correlation of YTHDF1 expression and the clinical characteristics of ESCA patients was analyzed using the TCGA ESCA clinical data. The GO and KEGG enrichment analyses of the YTHDF1 coexpressed genes were completed by bioinformatics analysis, and the GGI and PPI were constructed for the YTHDF1, respectively. The relationship between YTHDF1 expression and the infiltration of ESCA immune cells was analyzed by using the TIMER database and the TCGA ESCA cohort. The relationships between YTHDF1 expression levels and glycolysis and ferroptosis-related genes were analyzed using the TCGA and GEPIA ESCA cohorts. Finally, the ceRNA network that may be involved in YTHDF1 in ESCA was predicted and constructed through a variety of databases.Results: YTHDF1 was overexpressed in various cancers, and in vitro experiments confirmed that YTHDF1 expression was higher in ESCA samples than in normal samples. The expression of YTHDF1 has some accuracy in predicting the tumor outcome. Expression of YTHDF1 was significantly associated with multiple clinical features in ESCA patients. GO and KEGG enrichment analyses indicated that YTHDF1 coexpressed genes involved multiple biological functions. There is a potential association between YTHDF1 expression and multiple immune cell infiltration, glycolysis, and ferroptosis-related genes in ESCA. YTHDF1 may be involved in multiple ceRNA regulatory networks in ESCA, including PAXIP1-AS1/hsa-miR-376c-3p/YTHDF1 axis, THUMPD3-AS1/hsa-miR-655-3p/YTHDF1 axis, and SNHG20/hsa-miR-655-3p/YTHDF1 axis, respectively.Conclusion: YTHDF1 can serve as a biomarker of ESCA, related to the immune cell infiltration of ESCA, regulation of glycolysis and ferroptosis, and the ceRNA regulatory network.

Background Emerging evidence has indicated the critical role of TRPV4 in diverse human cancers. However, the underlying molecular mechanism of TRPV4 in colon cancer invasiveness is still unknown. Methods Immunohistochemistry staining was used to analyze the expression of TRPV4 and ZEB1 in clinical tissues; Wound healing and transwell assays were applied to determine the cell invasiveness; Western blot was used to explore the relation between TRPV4 and ZEB1. Results Colon cancer cells were transfected with siRNA against TRPV4 or HC067047 (a selective TRPV4 antagonist), TRPV4 full-length plasmid or siRNA against ZEB1, or both, in order to measure cell migration and invasion. And we found that TRPV4 silencing or inhibition exhibited an inhibitory role in colon cancer cell migration and invasion, coupled with compromised EMT process, and suppressed AKT activity. TRPV4 stimulated expression of ZEB1 and consequently contributed to EMT process and invasiveness. It was also revealed that overexpression of TRPV4 and ZEB1 in clinical patients with local metastasis, and positive correlation between TRPV4 and ZEB1. Conclusions Our results uncovered the role of TRPV4 in tumor metastasis and highlighted the potential mechanism of TRPV4-ZEB1 axis in indicating EMT.

Purpose The purpose of the current study was to compare the postoperative complications, overall survival and disease-free survival in young and old gastric cancer patients after gastrectomy using propensity score matching (PSM). Methods Adult patients (aged ≥ 18 years) who underwent gastrectomy for gastric cancer in a single clinical center from January 2013 to December 2017 were enrolled continuously for retrospective analysis. To minimize the selection bias between the young and old groups, the PSM was conducted in this study. Results A total of 558 patients were included in this study, with 51 patients in the young group (aged ≤ 45 years) and 507 patients in the old group (aged > 45 years). After 1:1 matching according to PSM, 51 patients in the young group were matched to 51 patients in the old group. After PSM, there was no difference in the baseline information. In terms of short-term outcomes, no difference was found in operation time (P = 0.190), intraoperative blood loss (P = 0.336), retrieved lymph nodes (P = 0.948), blood transfusion (P = 0.339), postoperative hospital stay (P = 0.194), or postoperative complications (P = 0.477) between the two groups. For overall survival, no statistically significant difference was found in all stages (P = 0.383), stage I (P = 0.431), stage II (P = 0.875) or stage III (P = 0.446) gastric cancer. Furthermore, regarding disease-free survival, no differences were found between the two groups in all stages (P = 0.378), stage I (P = 0.431), stage II (P = 0.879) or stage III (P = 0.510) gastric cancer. Conclusion Age might not be an independent prognostic factor for short-term outcomes, OS, or DFS in gastric cancer patients who underwent gastrectomy. The pTNM stage of GC might be an independent prognostic factor for OS and DFS.

The sodium pump α3 subunit is associated with colorectal liver metastasis. However, the underlying mechanism involved in this effect is not yet known. In this study, we found that the expression levels of the sodium pump α3 subunit were positively associated with metastasis in colorectal cancer (CRC). Knockdown of the α3 subunit or inhibition of the sodium pump could significantly inhibit the migration of colorectal cancer cells, whereas overexpression of the α3 subunit promoted colorectal cancer cell migration. Mechanistically, the α3 subunit decreased p53 expression, which subsequently downregulated PTEN/IGFBP3 and activated mTOR, leading to the promotion of colorectal cancer cell metastasis. Reciprocally, knockdown of the α3 subunit or inhibition of the sodium pump dramatically blocked this effect in vitro and in vivo via the downregulation of mTOR activity. Furthermore, a positive correlation between α3 subunit expression and mTOR activity was observed in an aggressive CRC subtype. Conclusions: Elevated expression of the sodium pump α3 subunit promotes CRC liver metastasis via the PTEN/IGFBP3-mediated mTOR pathway, suggesting that sodium pump α3 could represent a critical prognostic marker and/or therapeutic target for this disease.

BackgroundSolute carrier family 17 member 9 (SLC17A9) encodes a member of a family of transmembrane proteins that are involved in the transport of small molecules. SLC17A9 is involved in the occurrence and development of various cancers, but its biological role in liver hepatocellular carcinoma (LIHC) is unclear.MethodsThe expression level of SLC17A9 was assessed using The Cancer Genome Atlas (TCGA) database and immunohistochemistry of tumor tissues and adjacent normal liver tissues. The receiver operating characteristic (ROC) and R software package performed diagnosis and prognosis. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes functional enrichment and co-expression of SLC17A9, gene–gene interaction (GGI), and protein–protein interaction (PPI) networks were performed using R, GeneMANIA, and STRING. Western blot, real-time quantitative PCR (RT-qPCR), immunofluorescence, colony formation, wound scratch assay, ATP production assays, and high connotation were applied to determine the effect of SLC17A9 knockdown on HEPG2 (hepatocellular liver carcinoma) cells. TIMER, GEPIA, and TCGA analyzed the relationship between SLC17A9 expression and immune cells, m6A modification, and ferroptosis.ResultsSLC17A9 expression in LIHC tissues was higher than in normal liver tissues (p < 0.001), and SLC17A9 was related to sex, DSS (disease-specific survival), and PFI (progression-free interval) (p = 0.015, 0.006, and 0.023). SLC17A9 expression has diagnostic (AUC: 0.812; CI: 0.770–0.854) and prognostic potential (p = 0.015) in LIHC. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) functional enrichment analysis showed that SLC17A9 was closely related to neuronal cell body, presynapse, axonogenesis, PI3K/Akt signaling pathway. GGI showed that SLC17A9 was closely related to MYO5A. PPI showed that SLC17A9 was closely related to SLC18A3. SLC17A9 silencing inhibited HepG2 cells proliferation, migration, colony formation, and reduced their ATP level. SLC17A9 expression level was related to immune cells: B cells (r = 0.094, P = 8.06E-02), CD4+ T cells (r = 0.184, P = 5.95E-04), and macrophages (r = 0.137, P = 1.15E-02); m6A modification: HNRNPC (r = 0.220, p < 0.001), METTL3 (r = 0.180, p < 0.001), and WTAP (r = 0.130, p = 0.009); and ferroptosis: HSPA5 (r = 0.240, p < 0.001), SLC7A11 (r = 0.180, p < 0.001), and FANCD2 (r = 0.280, p < 0.001).ConclusionOur data show that SLC17A9 may influence LIHC progression. SLC17A9 expression correlates with tumor immune infiltration, m6A modification, and ferroptosis in LIHC and may have diagnostic and prognostic value in LIHC.

Diutina catenulata (Candida catenulata) is an ascomycete yeast species widely used in environmental and industrial research and capable of causing infections in humans and animals. At present, there are only a few studies on D. catenulata, and further research is required for its more in-depth characterization and analysis. Eleven strains of D. catenulata collected from China Hospital Invasive Fungal Surveillance Net (CHIF-NET) and the CHIF-NET North China Program were identified using matrix-assisted laser desorption ionization–time of flight mass spectrometry and internal transcribed spacer sequencing. The antifungal susceptibility of the Diutina catenulata strains was tested using the Clinical and Laboratory Standards Institute broth microdilution method and Sensititre YeastOne™. Furthermore, ERG11 and FKS1 were sequenced to determine any mutations related to azole and echinocandin resistance in D. catenulata. All isolates exhibited low minimum inhibitory concentration (MIC) values for itraconazole (0.06–0.12 μg/ml), posaconazole (0.06–0.12 μg/ml), amphotericin B (0.25–1 μg/ml), and 5-flucytosine (range, ERG11 mutations, namely, F126L/K143R. In addition, L139R mutations may be linked to high MICs of fluconazole. Two amino acid alterations reported to correspond to high MIC values of echinocandin, namely, F621I (F641) and S625L (S645), were found in the hot spot 1 region of FKS1. In addition, one new amino acid alteration, I1348S (I1368), was found outside of the FKS1 hot spot 2 region, and its contribution to echinocandin resistance requires future investigation. Diutina catenulata mainly infects patients with a weak immune system, and the high MIC values for various antifungals exhibited by these isolates may represent a challenge to clinical treatment.

Background: The purpose of this study was to explore the effect of abdominal shape on the short-term surgical outcomes.Methods: This was a retrospective study that included 425 patients undergoing laparoscopic distal gastrectomy plus D2 lymph node dissection (LADG) from January 2013 to January 2021. The abdominal parameters, including the shortest distance of the pancreas from the anterior abdominal skin (PAAD), the lower sternum angle (LSA), the thickness of the subcutaneous fat at the navel level (SFT), the anteroposterior diameters (APD) and the left-right diameters (LRD) at the navel level, the distance from the xiphoid process to the navel (XND) and the distance from the xiphoid process to the pubis (XBD), were calculated by preoperative abdominal computed tomography (CT) imaging. The parameters and short-term surgical outcomes were analyzed.Results: In males, the number of retrieved lymph nodes was significantly higher in patients with a lower APD group (p = 0.031). The operation time was significantly shorter in the lower body mass index (BMI) (p = 0.007), lower LSA (p = 0.035), lower PAAD (p = 0.000), lower SFT (p = 0.004), lower APD (p = 0.000) and lower LRD (p = 0.014) groups. The estimated blood loss was significantly less in the lower BMI (p = 0.035), lower LSA (p = 0.001), lower PAAD (p = 0.012), lower SFT (p = 0.003), lower APD (p = 0.000) and lower LRD (p = 0.005) groups. The complications were fewer in the lower LSA (p = 0.012), lower APD (p = 0.043) and lower LRD (p = 0.023) groups. In females, the postoperative hospital stay was shorter in the lower PAAD (p = 0.027) and lower SFT (p = 0.004) groups, and the lower SFT group had fewer complications (p = 0.020). Furthermore, in multivariate analysis, higher PAAD (p = 0.037, odds ratio = 1.030, 95% CI = 1.002–1.059) was an independent factor for predicting postoperative complications in males.Conclusion: Various abdominal shapes can affect the difficulty of LADG. Higher PAAD is a simple independent index for predicting postoperative complications in males.

Marine aerosol samples of total suspended particulates (TSP) were collected in winter (2017) and spring and summer (2018) over the Yellow Sea and Bohai Sea. These samples were analyzed for total arsenic (As), As(Ⅴ) and As(Ⅲ), and water soluble ions to investigate the distribution and seasonal variation of As in atmospheric aerosols, as well as the dry deposition flux. Results showed that As concentrations in winter, spring, and summer were 6.6, 5.5, and 4.4 ng·m

PurposeThe purpose of the current meta-analysis is to analyze whether extended intraoperative peritoneal lavage (EIPL) can bring benefit on short-term outcomes or survival for patients undergoing curative gastrectomy for gastric cancer.MethodsThe PubMed, Embase, and Cochrane Library databases were searched from inception to May 3, 2021, to find eligible studies. Postoperative complications, overall survival (OS), disease-free survival (DFS), and peritoneal recurrence–free survival (PRFS) were compared between EIPL group and No EIPL group.ResultsA total of five randomized controlled trials with 1,790 patients were included in the current meta-analysis. No difference was found in baseline information (p > 0.05). After pooling up the data of overall postoperative complications, no significant difference was found between EIPL group and No EIPL group (OR = 0.88, 95% CI = 0.51 to 1.53, P = 0.65). Furthermore, there was no significant difference between EIPL group and No EIPL group in terms of OS (HR = 0.77, 95% CI = 0.36 to 1.64, P = 0.49), DFS (HR = 0.97, 95% CI = 0.71 to 1.33, P = 0.87), and PRFS (HR = 1.03, 95% CI = 0.74 to 1.43, P = 0.86). In terms of subgroup analysis of OS, no significant difference was found as well (HR = 1.05, 95% CI = 0.82 to 1.34, P = 0.69).ConclusionsEIPL did not bring benefit in terms of short-term outcomes or survival. Therefore, EIPL is not recommended for patients undergoing curative gastrectomy for gastric cancer.

Fibroblast growth factors (FGFs) include a large family of growth factors that play a critical role in maintaining bone homeostasis, but the specific role of its members such as FGF7 does not well understand. Osteoblasts are a kind of major cells essential for bone formation. Osteoblasts interact with one another to create the unique structure of osteons. The well-connected osteons constitute the cortical bone. As an early osteocyte marker that triggers actin cytoskeleton dynamics, E11 is essential for osteoblasts' dendrites formation. However, the upstream which regulates E11 is mainly unknown. The purpose of this study was to examine the influence of FGF7 on the expression and the distribution of E11 in osteoblasts, which mediated osteoblasts' processes formation and gap junctional intercellular communication (GJIC) partly through connexin43 (Cx43). We first demonstrated that FGF7 increased the expression of E11 in osteoblasts. We then showed that FGF7 promoted osteoblasts' dendrites elongation and functional gap junctions formation. Furthermore, E11 interacted directly with Cx43 in primary osteoblasts. MAPK pathway and PI3K-AKT pathway were involved in the effect of FGF7. Our results shed light on the unique role of FGF7 on osteoblasts, which may indicate that FGF7 plays a more significant role in the later stages of bone development and homeostasis.

PurposeThe purpose of the current study was to evaluate the impact of colorectal cancer (CRC) surgery on type 2 diabetes mellitus (T2DM) and to analyze the change in T2DM on overall survival after CRC surgery.MethodsPatients who underwent CRC surgery were retrospectively enrolled from January 2013 to December 2019. The status of T2DM pre- and 1-year after CRC surgery was recorded, and predictive factors for T2DM remission and overall survival were analyzed.ResultsA total of 296 patients were included in this study. Thirty-eight patients experienced remission of T2DM 1 year after CRC surgery, and the remission rate was 12.8%. Weight loss was significantly higher in the T2DM remission group (p = 0.038), and the T2DM duration was significantly shorter in the T2DM remission group (p = 0.015). In the multivariate logistic regression analysis, higher weight loss (p = 0.046, odds ratio = 1.060, 95% CI = 1.001–1.122) and shorter T2DM duration (p = 0.019, odds ratio = 1007, 95% CI = 1.001–1.014) were predictive factors for remission of T2DM. Furthermore, in multivariate Cox regression analysis, lower TNM stage (p = 0.000, odds ratio = 2.147, 95% CI = 1.474–3.128) and T2DM remission (p = 0.033, odds ratio = 2.999, 95% CI = 1.091–8.243) were the predictive factors for better overall survival.ConclusionPatients with concurrent CRC and T2DM had a 12.8% remission 1 year after CRC surgery. Higher weight loss and shorter T2DM duration contributed to T2DM remission, and patients with T2DM remission could improve in terms of their overall survival.

BackgroundOverexpression of NPM1 can promote the growth and proliferation of various tumor cells. However, there are few studies on the comprehensive analysis of NPM1 in lung adenocarcinoma (LUAD).MethodsTCGA and GEO data sets were used to analyze the expression of NPM1 in LUAD and clinicopathological analysis. The GO/KEGG enrichment analysis of NPM1 co-expression and gene set enrichment analysis (GSEA) were performed using R software package. The relationship between NPM1 expression and LUAD immune infiltration was analyzed using TIMER, GEPIA database and TCGA data sets, and the relationship between NPM1 expression level and LUAD m6A modification and glycolysis was analyzed using TCGA and GEO data sets.ResultsNPM1 was overexpressed in a variety of tumors including LUAD, and the ROC curve showed that NPM1 had a certain accuracy in predicting the outcome of tumors and normal samples. The expression level of NPM1 in LUAD is significantly related to tumor stage and prognosis. The GO/KEGG enrichment analysis indicated that NPM1 was closely related to translational initiation, ribosome, structural constituent of ribosome, ribosome, Parkinson disease, and RNA transport. GSEA showed that the main enrichment pathway of NPM1-related differential genes was mainly related to mTORC1 mediated signaling, p53 hypoxia pathway, signaling by EGFR in cancer, antigen activates B cell receptor BCR leading to generation of second messengers, aerobic glycolysis and methylation pathways. The analysis of TIMER, GEPIA database and TCGA data sets showed that the expression level of NPM1 was negatively correlated with B cells and NK cells. The TCGA and GEO data sets analysis indicated that the NPM1 expression was significantly correlated with one m6A modifier related gene (HNRNPC) and five glycolysis related genes (ENO1, HK2, LDHA, LDHB and SLC2A1).ConclusionNPM1 is a prognostic biomarker involved in immune infiltration of LUAD and associated with m6A modification and glycolysis. NPM1 can be used as an effective target for diagnosis and treatment of LUAD.