Peripheral inflammation as a potential mechanism and preventive strategy for perioperative neurocognitive disorder under general anesthesia and surgery.

General anesthesia, as a commonly used medical intervention, has been widely applied during surgical procedures to ensure rapid loss of consciousness and pain relief for patients. However, recent research suggests that general anesthesia may be associated with the occurrence of perioperative neurocognitive disorder (PND). PND is characterized by a decline in cognitive function after surgery, including impairments in attention, memory, learning, and executive functions. With the increasing trend of population aging, the burden of PND on patients and society's health and economy is becoming more evident. Currently, the clinical consensus tends to believe that peripheral inflammation is involved in the pathogenesis of PND, providing strong support for further investigating the mechanisms and prevention of PND.

Decreased ß-catenin Protein in Lungs From Human Congenital Diaphragmatic Hernia Archival Pathology Specimens: A Case-control Study.

BACKGROUND: Lung hypoplasia contributes to congenital diaphragmatic hernia (CDH) associated morbidity and mortality. Changes in lung wingless-type MMTV integration site family member (Wnt)-signalling and its downstream effector beta-catenin (CTNNB1), which acts as a transcription coactivator, exist in animal CDH models but are not well characterized in humans. We aim to identify changes to Wnt-signalling gene expression in human CDH lungs and hypothesize that pathway expression will be lower than controls. METHODS: We identified 51 CDH cases and 10 non-CDH controls with archival formalin-fixed paraffin-embedded (FFPE) autopsy lung tissue from 2012 to 2022. 11 liveborn CDH cases and an additional two anterior diaphragmatic hernias were excluded from the study, leaving 38 CDH cases. Messenger ribonucleic acid (mRNA) expression of Wnt-signalling effectors WNT2B and CTNNB1 was determined for 19 CDH cases and 9 controls. A subset of CDH cases and controls lung sections were immunostained for ß-catenin. Clinical variables were obtained from autopsy reports. RESULTS: Median gestational age was 21 weeks. 81% (n = 31) of hernias were left-sided. 47% (n = 18) were posterolateral. Liver position was up in 81% (n = 31) of cases. Defect size was Type C or D in 58% (n = 22) of cases based on autopsy photos, and indeterminable in 42% (n = 16) of cases. WNT2B and CTNNB1 mRNA expression did not differ between CDH and non-CDH lungs. CDH lungs had fewer interstitial cells expressing ß-catenin protein than non-CDH lungs (13.2% vs 42.4%; p = 0.006). CONCLUSION: There appear to be differences in the abundance and/or localization of ß-catenin proteins between CDH and non-CDH lungs. LEVEL OF EVIDENCE: Level III. TYPE OF STUDY: Case-Control Study.

Network pharmacology and molecular docking-based analyses to predict the potential mechanism of Huangqin decoction in treating colorectal cancer.

BACKGROUND: To analyze the potential action mechanism of Huangqin decoction (HQD) in colorectal cancer (CRC) treatment on the basis of network pharmacology and molecular docking. AIM: To investigate the molecular mechanisms of HQD for CRC treatment by using network pharmacology and molecular docking. METHODS: All HQD active ingredients were searched using the Systematic Pharmacology and Traditional Chinese Medicine Systems Pharmacology databases and the Bioinformatics Analysis Tool for Molecular Mechanisms in traditional Chinese medicine. Then, the targets of the active ingredients were screened. The abbreviations of protein targets were obtained from the UniProt database. A "drug-compound-target" network was constructed to screen for some main active ingredients. Some targets related to the therapeutic effect of CRC were obtained from the GeneCards, DisGeNET, Therapeutic Target Database, and Online Mendelian Inheritance in Man databases. The intersection of targets of Chinese herbs and CRC was taken. A Venn diagram was drawn to construct the intersection target interactions network by referring to the STRING database. Topological analysis of the protein interaction network was performed using Cytoscape 3.7.2 software to screen the core HQD targets for CRC. The core targets were imported into the DAVID 6.8 analysis website for gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses and visualization. Finally, molecular docking was performed using AutoDockTool and PyMOL for validation. RESULTS: In total, 280 potential drug-active ingredients were present in HQD, including 1474 targets of the drug-active ingredients. The main active ingredients identified were betulin, tetrahydropalmatine, and quercetin. In total, 10249 CRC-related targets and 1014 drug-disease intersecting targets were identified, including 28 core targets of action such as Jun proto-oncogene, AP-1 transcription factor subunit, signal transducer and activator of transcription 3, tumor protein p53, vascular endothelial growth factor, and AKT serine/threonine kinase 1. The gene ontology enrichment functional analysis yielded 503 enrichment results, including 406 biological processes that were mainly related to the positive regulation of both gene expression and transcription and cellular response to hypoxia, etc. In total, 38 cellular components were primarily related to polymer complexes, transcription factor complexes, and platelet alpha granule lumen. Then, 59 molecular functions were closely related to the binding of enzymes, homologous proteins, and transcription factors. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis yielded 139 enrichment results, involving epidermal growth factor receptor tyrosine kinase inhibitor resistance and HIF-1 and mitogen-activated protein kinase signaling pathways. CONCLUSION: HQD can play a role in CRC treatment through the "multi-component-target-pathway". The active ingredients betulin, tetrahydropalmatine, and quercetin may act on targets such as Jun proto-oncogene, AP-1 transcription factor subunit, signal transducer and activator of transcription 3, tumor protein p53, vascular endothelial growth factor, and AKT serine/threonine kinase 1, which in turn regulate HIF-1 and mitogen-activated protein kinase signaling pathways in CRC treatment. The molecular docking junction clarified that all four key target proteins could bind strongly to the main HQD active ingredients. This indicates that HQD could slow down CRC progression by modulating multiple targets and signaling pathways.

Efficacy and safety of preoperative immunotherapy in patients with mismatch repair-deficient or microsatellite instability-high gastrointestinal malignancies.

BACKGROUND: Programmed death protein (PD)-1 blockade immunotherapy significantly prolongs survival in patients with metastatic mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastrointestinal malignancies such gastric and colorectal cancer. However, the data on preoperative immunotherapy are limited. AIM: To evaluate the short-term efficacy and toxicity of preoperative PD-1 blockade immunotherapy. METHODS: In this retrospective study, we enrolled 36 patients with dMMR/MSI-H gastrointestinal malignancies. All the patients received PD-1 blockade with or without chemotherapy of CapOx regime preoperatively. PD1 blockade 200 mg was given intravenously over 30 min on day 1 of each 21-d cycle. RESULTS: Three patients with locally advanced gastric cancer achieved pathological complete response (pCR). Three patients with locally advanced duodenal carcinoma achieved clinical complete response (cCR), followed by watch and wait. Eight of 16 patients with locally advanced colon cancer achieved pCR. All four patients with liver metastasis from colon cancer reached CR, including three with pCR and one with cCR. pCR was achieved in two of five patients with non-liver metastatic colorectal cancer. CR was achieved in four of five patients with low rectal cancer, including three with cCR and one with pCR. cCR was achieved in seven of 36 cases, among which, six were selected for watch and wait strategy. No cCR was observed in gastric or colon cancer. CONCLUSION: Preoperative PD-1 blockade immunotherapy in dMMR/MSI-H gastrointestinal malignancies can achieve a high CR, especially in patients with duodenal or low rectal cancer, and can achieve high organ function protection.

Single-cell profiling reveals differences between human classical adenocarcinoma and mucinous adenocarcinoma.

Colorectal cancer is a highly heterogeneous disease. Most colorectal cancers are classical adenocarcinoma, and mucinous adenocarcinoma is a unique histological subtype that is known to respond poorly to chemoradiotherapy. The difference in prognosis between mucinous adenocarcinoma and classical adenocarcinoma is controversial. Here, to gain insight into the differences between classical adenocarcinoma and mucinous adenocarcinoma, we analyse 7 surgical tumour samples from 4 classical adenocarcinoma and 3 mucinous adenocarcinoma patients by single-cell RNA sequencing. Our results indicate that mucinous adenocarcinoma cancer cells have goblet cell-like properties, and express high levels of goblet cell markers (REG4, SPINK4, FCGBP and MUC2) compared to classical adenocarcinoma cancer cells. TFF3 is essential for the transcriptional regulation of these molecules, and may cooperate with RPS4X to eventually lead to the mucinous adenocarcinoma mucus phenotype. The observed molecular characteristics may be critical in the specific biological behavior of mucinous adenocarcinoma.

Advances in Medical Treatment of Primary Aldosteronism.

Primary aldosteronism (PA) is the most common form of secondary hypertension, with its main manifestations including hypertension and hypokalemia. Early identification of PA is extremely important as PA patients can easily develop cardiovascular complications such as atrial fibrillation, stroke, and myocardial infarction. The past decade has witnessed the rapid advances in the genetics of PA, which has shed new light on PA treatment. While surgery is the first choice for unilateral diseases, bilateral lesions can be treated with mineralocorticoid receptor antagonists (MRAs). The next-generation non-steroidal MRAs are under investigations. New medications including calcium channel blockers, macrophage antibiotics, and aldosterone synthase inhibitors have provided a new perspective for the medical treatment of PA.

Purinergic signaling: a potential therapeutic target for ischemic stroke.

Pathogenesis of ischemic stroke is mainly characterized by thrombosis and neuroinflammation. Purinergic signaling pathway constitutes adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine (ADO). ATP is hydrolyzed to ADP and then to AMP by extracellular nucleotidase CD39; AMP is subsequently converted to adenosine by CD73. All these nucleotides and nucleosides act on purinergic receptors protecting against thrombosis and inhibit inflammation. In addition, many physical methods have been found to play a neuroprotective role through purinergic signaling. This review mainly introduces the role and potential mechanism of purinergic signalings in the treatment of ischemic stroke, so as to provide reference for seeking new treatment methods for stroke.

Ornithinimicrobium laminariae sp. nov., isolated from the kelp Laminaria japonica.

A Gram-stain-positive, aerobic, non-sporulating, yellow-pigmented and rod or cocci-shaped bacterium, designated Arc0846-15T, was isolated from the kelp Laminaria japonica. Strain Arc0846-15T was found to grow at 16-35 °C (optimum, 28 °C), at pH 6.0-9.5 (optimum, 7.0) and in the presence of 0-6 % (w/v) NaCl (optimum, 2 %). Cells were positive for catalase and negative for oxidase activity. Phylogenetic analyses, based on 16S rRNA gene sequence comparisons, revealed that the nearest phylogenetic neighbour strains of strain Arc0846-15T were Ornithinimicrobium murale 01 Gi-040T (96.2 %), Ornithinimicrobium kibberense K22-20T (96.1 %) and Ornithinimicrobium humiphilum HKI 0124T (95.2 %). Based on phylogenomic analysis, the average nucleotide identity values between strain Arc0846-15T and the neighbour strains were 69.8, 69.7 and 69.8 %, respectively; the digital DNA-DNA hybridization values between strain Arc0846-15T and its three closest neighbour strains were 18.8, 19.1 and 19.3 %, respectively. The predominant menaquinone was MK-8 (H4). The dominant cellular fatty acids were C17 : 1 ω8c, iso-C15 : 0, iso-C16 : 0 and C17 : 0. The polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, glycolipid, one unidentified aminolipid and four unidentified lipids. The DNA G+C content of strain Arc0846-15T was 61.6 mol% based on the whole genome sequence. Based on the phylogenetic and phenotypic characteristics, strain Arc0846-15T is considered to represent a novel species of the genus Ornithinimicrobium, for which the name Ornithinimicrobium laminariae sp. nov. is proposed, with Arc0846-15T (=KCTC 49655T=MCCC 1K06093T) as the type strain.

Shewanella nanhaiensis sp. nov., a marine bacterium isolated from sediment of South China Sea, and emended descriptions of Shewanella woodyi, Shewanella hanedai and Shewanella canadensis.

A Gram-stain-negative, motile, facultative anaerobic and rod-shaped bacterium, designated strain NR704-98T, was isolated from marine sediment of the northern South China Sea. Cells were positive for oxidase and catalase activity. Growth was observed at 4-30 °C (optimum 20-25 °C), at pH 6-9 (pH 7) and with 0.5-7 % NaCl (2 %). The 16S rRNA gene-based phylogenetic analysis revealed that the nearest phylogenetic neighbours of strain NR704-98T were Shewanella woodyi MS32T (97.9 %), Shewanella hanedai 281T (97.1 %), Shewanella sediminis HAW-EB3T (96.8 %) and Shewanella canadensis HAW-EB2T (96.7 %). Based on the results of phylogenomic analysis, the average nucleotide identity and the digital DNA-DNA hybridization values between strain NR704-98T and the previously mentioned type strains of species of the genus Shewanella were in the range of 74.9-93.1 % and 20.6-51.4 %, respectively. The respiratory quinones were Q-7 and Q-8. The predominant fatty acids (>10 %) of strain NR704-98T were C16 : 0, summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) and iso-C15 : 0. Phosphatidylethanolamine, phosphatidylglycerol, two unidentified aminophospholipids and five unidentified lipids were detected in strain NR704-98T. Based on the phylogenetic and phenotypic characteristics, strain NR704-98T is considered to represent a novel species of the genus Shewanella, for which the name Shewanella nanhaiensis sp. nov. is proposed. The type strain is NR704-98T (=KCTC 82799T=MCCC 1K06091T).

Laparoscopy-assisted transanal total mesorectal excision for lower rectal cancer: A feasible and innovative technique.

BACKGROUND: Transanal total mesorectal excision (taTME) is a new technique with many potential technical advantages. Laparoscopy-assisted taTME is a combination of transabdominal taTME and transluminal endoscopic surgery taTME. Laparoscopy-assisted taTME is a combination of techniques such as minimally invasive surgery, intersphincter-assisted resection, natural orifice extraction, ta minimally invasive surgery, and ultralow-level preservation of the anus. AIM: To verify the feasibility and safety of an innovative technique of taTME for treatment of cancer located in the lower rectum. METHODS: From January 2016 to March 2018, we attempted to perform laparoscopy-assisted taTME surgery in 24 patients with lower rectal cancer. RESULTS: The new technique of laparoscopy-assisted taTME was successfully performed in all 24 patients. Mean operating time was 310.0 min and mean intraoperative blood loss was 69.1 mL. The mean time to passing of first flatus was 3.1 d, and mean postoperative hospital stay was 9.2 d. Two patients were given postoperative analgesics due to anal pain. Twenty-three patients were able to walk in first 2 d, and five patients had postoperative complications. CONCLUSION: Laparoscopy-assisted taTME is suitable for selected patients with lower rectal cancer, and this technique is worthy of further recommendation.

Discovery of a novel EGFR ligand DPBA that degrades EGFR and suppresses EGFR-positive NSCLC growth.

Epidermal growth factor receptor (EGFR) activation plays a pivotal role in EGFR-driven non-small cell lung cancer (NSCLC) and is considered as a key target of molecular targeted therapy. EGFR tyrosine kinase inhibitors (TKIs) have been canonically used in NSCLC treatment. However, prevalent innate and acquired resistances and EGFR kinase-independent pro-survival properties limit the clinical efficacy of EGFR TKIs. Therefore, the discovery of novel EGFR degraders is a promising approach towards improving therapeutic efficacy and overcoming drug resistance. Here, we identified a 23-hydroxybetulinic acid derivative, namely DPBA, as a novel EGFR small-molecule ligand. It exerted potent in vitro and in vivo anticancer activity in both EGFR wild type and mutant NSCLC by degrading EGFR. Mechanistic studies disclosed that DPBA binds to the EGFR extracellular domain at sites differing from those of EGF and EGFR. DPBA did not induce EGFR dimerization, phosphorylation, and ubiquitination, but it significantly promoted EGFR degradation and repressed downstream survival pathways. Further analyses showed that DPBA induced clathrin-independent EGFR endocytosis mediated by flotillin-dependent lipid rafts and unaffected by EGFR TKIs. Activation of the early and late endosome markers rab5 and rab7 but not the recycling endosome marker rab11 was involved in DPBA-induced EGFR lysosomal degradation. The present study offers a new EGFR ligand for EGFR pharmacological degradation and proposes it as a potential treatment for EGFR-positive NSCLC, particularly NSCLC with innate or acquired EGFR TKI resistance. DPBA can also serve as a chemical probe in the studies on EGFR trafficking and degradation.

Inhibition of glycolysis by targeting lactate dehydrogenase A facilitates hyaluronan synthase 2 synthesis in synovial fibroblasts of temporomandibular joint osteoarthritis.

OBJECTIVE: Although associations between dysregulated glucose metabolism and human rheumatoid arthritis have been reported, the disturbance and influence of glycolytic metabolism on temporomandibular joint osteoarthritis remains unclear. This study aimed to investigate the expression level and metabolite profile of the critical glycolytic enzyme, lactate dehydrogenase A (LDHA) in synovial fibroblasts (SFs) of TMJOA, assess the effect of glycolytic inhibition on synthesis of hyaluronan synthase 2 (HAS2) and inflammation progression in these cells. METHODS: Immunohistochemistry and western blotting were performed to detect the expression of LDHA in the lining and sub-lining layers of synovial tissue and SFs. MTT and EdU assays were used to measure the cell proliferation. The cell apoptosis were demonstrated by TUNEL staining and Annexin V/PI double staining. A potent and specific inhibitor of LDHA, GSK2837808A, was administrated to suppress the activity of LDHA and detect the potential efficacy on HAS2. RESULTS: LDHA expression was dramatically higher in the synovial tissue and SFs from TMJOA patients compared to control groups. LDHA inhibition impaired active LDHA performance, suppressed the glucose uptake and decreased lactate concentration. Furthermore, GSK2837808A reversed the occurrence of low ratio of ATP/AMP, high level of Adenosine Monophosphate-activated Protein Kinase (AMPK) activation, disturbed HAS2 synthesis and hyaluronic acid (HA) production by inhibiting LDHA. The cellular viability and cell cycle were not affected by GSK2837808A at the working concentration. CONCLUSIONS: Targeting LDHA using its specific suppressant GSK2837808A impeded lactate secretion and contributed to HAS2 and HA synthesis in TMJOA SFs, providing the vital role of LDHA associated with TMJOA pathogenesis and a novel therapeutic approach for TMJOA.

Salinimicrobium nanhaiense sp. nov. and Salinimicrobium oceani sp. nov., two novel species of the family Flavobacteriaceae isolated from the South China Sea.

Strains J15B81-2T and J15B91T were isolated from a sediment sample collected from the South China Sea. Cells of both strains were observed to be rod-shaped, non-gliding, Gram-stain-negative, yellow-pigmented, facultatively anaerobic, catalase-positive, oxidase-negative and showing optimum growth at 30 °C. Strains J15B81-2T and J15B91T could tolerate up to 9 and 10  % (w/v) NaCl concentration and grow at pH 6.5-9.5 and 6.0-9.0, respectively. The strains shared 97.4 % 16S rRNA gene sequence similarity to each other but were identified as two distinct species based on 81.1-85.8 % ANIb and 31.5 % dDDH values calculated using whole genome sequences. Strains J15B81-2T and J15B91T shared highest 16S rRNA gene sequence similarity to Salinimicrobium xinjiangense CGMCC 1.12522T (98.4 %) and Salinimicrobium sediminis CGMCC 1.12641T (98.0 %), respectively. Among species with validly published names, S. sediminis CGMCC 1.12641T shared close genetic relatedness with strains J15B81-2T [85.1-85.3% average nucleotide identity based on blastBlast+ (ANIb) and 30.6 % digital DNA-DNA hybridization (dDDH)] and J15B91T (76.6-79.1 % ANIb and 21.5 % dDDH). The major fatty acid of strains J15B81-2T and J15B91T were identified as iso-C15 : 0 and iso-C16 : 0, respectively, and the major polar lipids of the two strains consisted of phosphatidylethanolamine, one unidentified phospholipid, one unidentified aminolipid and one unidentified lipid. The strains contained MK-6 as their predominant menaquinone. The genomic G+C contents of strains J15B81-2T and J15B91T were determined to be 41.7 and 41.8 mol %, respectively. Both strains are considered to represent two novel species of the genus Salinimicrobium and the names Salinimicrobium nanhaiense sp. nov. and Salinimicrobium oceani sp. nov. are proposed for strains J15B81-2T (=KCTC 72867T=MCCC 1H00410T) and J15B91T (=KCTC 72869T=MCCC 1H00411T), respectively.

[Clinical features of catch-up growth after kidney transplantation in children].

OBJECTIVE: To study the clinical features of catch-up growth of body height after kidney transplantation in children and related influencing factors. METHODS: A retrospective analysis was performed from the chart review data of 15 children who underwent kidney transplantation in Guangzhou Women and Children's Medical Center from July 2017 to November 2019. According to whether the increase in height standard deviation score (ΔHtSDS) in the first year after kidney transplantation reached ≥0.5, the children were divided into a catch-up group with 8 children and a non-catch-up group with 7 children. According to whether final HtSDS was ≥-2, the children were divided into a standard group with 6 children and a non-standard group with 9 children. The features of catch-up growth of body height and related influencing factors were compared between groups. RESULTS: The data showed that median ΔHtSDS was 0.8 in the first year after transplantation, which suggested catch-up growth of body height. There was a significant difference in HtSDS between the non-catch-up and catch-up groups (P<0.05). Baseline HtSDS before transplantation was positively correlated with HtSDS at the end of follow-up (r=0.622, P<0.05) and was negatively correlated with ∆HtSDS in the first year after transplantation (r=-0.705, P<0.05). Age of transplantation and mean dose of glucocorticoid (GC) per kg body weight were risk factors for catch-up growth after kidney transplantation (OR=1.23 and 1.74 respectively; P<0.05), while baseline HtSDS and use of antihypertensive drugs were independent protective factors for catch-up growth (OR=0.08 and 0.18 respectively; P<0.05); baseline HtSDS and ΔHtSDS in the first year after kidney transplantation were influencing factors for final HtSDS (ß=0.984 and 1.271 respectively; P<0.05). CONCLUSIONS: Kidney transplantation should be performed for children as early as possible, growth retardation before transplantation should be improved as far as possible, and multiple treatment methods (including the use of GC and antihypertensive drugs) should be optimized after surgery, in order to help these children achieve an ideal body height.

Formosa maritima sp. nov., isolated from coastal sediment.

A Gram-stain-negative, strictly aerobic, gliding-motile, rod-shaped and orange-pigmented bacterium, designated 1494T, was isolated from marine sediment collected off the coast of Weihai, PR China. Strain 1494T was found to grow at 4-37 °C (optimum, 30 °C), at pH 6.0-9.0 (pH 7.0) and in the presence of 0-8 % (w/v) NaCl (2 %). Cells were positive for oxidase and catalase activity. The results of 16S rRNA gene based phylogenetic analysis revealed that strain 1494T belonged to the genus Formosa and exhibited the highest sequence similarity to Formosa spongicola KCTC 22662 T (98.4 %). Menaquinone-6 (MK-6) was detected as the major respiratory quinone. The dominant cellular fatty acids were iso-C15 : 1 G and iso-C15 : 0. The DNA G+C content of strain 1494T was 31.1 mol%. The major polar lipids included phosphatidylethanolamine, one unidentified phospholipid and one unidentified lipid. Based on its phylogenetic and phenotypic characteristics, strain 1494T is considered to represent a novel species from the genus Formosa, for which the name Formosa maritima sp. nov. is proposed. The type strain is 1494T (=KCTC 72531T=MCCC 1H00385T).

Prognostic value of preoperative carcinoembryonic antigen/tumor size in rectal cancer.

BACKGROUND: Carcinoembryonic antigen (CEA) is a commonly used biomarker in colorectal cancer. However, controversy exists regarding the insufficient prognostic value of preoperative serum CEA alone in rectal cancer. Here, we combined preoperative serum CEA and the maximum tumor diameter to correct the CEA level, which may better reflect the malignancy of rectal cancer. AIM: To assess the prognostic impact of preoperative CEA/tumor size in rectal cancer. METHODS: We retrospectively reviewed 696 stage I to III rectal cancer patients who underwent curative tumor resection from 2007 to 2012. These patients were randomly divided into two cohorts for cross-validation: training cohort and validation cohort. The training cohort was used to generate an optimal cutoff point and the validation cohort was used to further validate the model. Maximally selected rank statistics were used to identify the optimum cutoff for CEA/tumor size. The Kaplan-Meier method and log-rank test were used to plot the survival curve and to compare the survival data. Univariate and multivariate Cox regression analyses were used to determine the prognostic value of CEA/tumor size. The primary and secondary outcomes were overall survival (OS) and disease-free survival (DFS), respectively. RESULTS: In all, 556 patients who satisfied both the inclusion and exclusion criteria were included and randomly divided into the training cohort (2/3 of 556, n = 371) and the validation cohort (1/3 of 556, n = 185). The cutoff was 2.429 ng/mL per cm. Comparison of the baseline data showed that high CEA/tumor size was correlated with older age, high TNM stage, the presence of perineural invasion, high CEA, and high carbohydrate antigen 19-9 (CA 19-9). Kaplan-Meier curves showed a manifest reduction in 5-year OS (training cohort: 56.7% vs 81.1%, P < 0.001; validation cohort: 58.8% vs 85.6%, P < 0.001) and DFS (training cohort: 52.5% vs 71.9%, P = 0.02; validation cohort: 50.3% vs 79.3%, P = 0.002) in the high CEA/tumor size group compared with the low CEA/tumor size group. Univariate and multivariate analyses identified CEA/tumor size as an independent prognostic factor for OS (training cohort: hazard ratio (HR) = 2.18, 95% confidence interval (CI): 1.28-3.73, P = 0.004; validation cohort: HR = 4.83, 95%CI: 2.21-10.52, P < 0.001) as well as DFS (training cohort: HR = 1.47, 95%CI: 0.93-2.33, P = 0.096; validation cohort: HR = 2.61, 95%CI: 1.38-4.95, P = 0.003). CONCLUSION: Preoperative CEA/tumor size is an independent prognostic factor for patients with stage I-III rectal cancer. Higher CEA/tumor size is associated with worse OS and DFS.

Effects of bariatric surgery on obese polycystic ovary syndrome: a systematic review and meta-analysis.

BACKGROUND: Bariatric surgery has been widely used for the treatment of obesity and its related metabolic diseases, such as type 2 diabetes (T2D), hypertension, and sleep apnea syndrome. Polycystic ovary syndrome (PCOS) is a common reproductive endocrine metabolic disease; however, little attention has been paid to the efficacy of bariatric surgery on PCOS. OBJECTIVE: To evaluate the efficacy of bariatric surgery on obese PCOS patients. SETTING: A systematic review and meta-analysis at a university hospital. METHODS: Online databases were searched for all studies reporting the efficacy of bariatric surgery for obese patients with PCOS up to October 2018. RESULTS: A total of 9 studies with 234 obese PCOS patients were included in this article. The results of meta-analysis showed that after bariatric surgery, there was a significant reduction of the incidence of abnormal menstruation (relative risk [RR] .23; 95% confidence interval [CI] .13-.43; P < .00001) and hirsutism (RR .47; 95% CI .28-.79; P = .004). Bariatric surgery can also cause a decrease in the serum total testosterone level (mean difference [MD] = -25.82; 95% CI -30.06 to -21.58; P < .00001), serum free testosterone level (MD = -4.10; 95% CI -6.97 to -1.23; P = .005), and body mass index (MD = -14.51; 95% CI -17.88 to -11.14; P < .00001). It also showed a significant effect on T2D (RR .09; 95% CI .03-.32; P = .0002) and hypertension (RR .21; 95% CI .05-.98; P = .05) in obese patients with PCOS. CONCLUSIONS: Bariatric surgery can reduce the incidence of abnormal menstruation, improve hyperandrogenism and its clinical manifestations, and decrease the body mass index, prevalence of T2D, and hypertension in obese patients with PCOS.

Cloud-Point Extraction Combined with Thermal Degradation for Nanoplastic Analysis Using Pyrolysis Gas Chromatography-Mass Spectrometry.

The contamination of micro- and nanoplastics in marine systems and freshwater is a global issue. Determination of micro- and nanoplastics in the aqueous environment is of high priority to fully assess the risk that plastic particles will pose. Although microplastics have been detected in a variety of aquatic ecosystems, the analysis of nanoplastics remains an unsolved challenge. Herein, for the first time, a Triton X-45 (TX-45)-based cloud-point extraction (CPE) was proposed to preconcentrate trace nanoplastics in environmental waters. Under the optimum extraction conditions, an enrichment factor of 500 was obtained for two types of nanoplastics with different compositions, polystyrene (PS) and poly(methyl methacrylate) (PMMA), without disturbing their original morphology and sizes. Additionally, following thermal treatment at 190 °C for 3 h, the CPE-obtained extract could be submitted to pyrolysis gas chromatography-mass spectrometry (Py-GC/MS) analysis for mass quantification of nanoplastics. Taking 66.2 nm PS nanoplastics and 86.2 nm PMMA nanoplastics as examples, the proposed method showed excellent reproducibility, and high sensitivity with respective detection limits of 11.5 and 2.5 fM. Feasibility of the proposed approach was verified by application of the optimized procedure to four real water samples. Recoveries of 84.6-96.6% at a spiked level of 88.6 fM for PS nanoplastics and 76.5-96.6% at a spiked level of 50.4 fM for PMMA nanoplastics were obtained. Consequently, this work provides an efficient approach for nanoplastic analysis in environmental waters.

Capn4 promotes esophageal squamous cell carcinoma metastasis by regulating ZEB1 through the Wnt/ß-catenin signaling pathway.

BACKGROUND: Capn4 and ZEB1 play important roles in the metastasis of several types of cancer. However, the roles and relationship of Capn4 and ZEB1 in esophageal squamous cell carcinoma (ESCC) remain unclear. METHODS: ESCC tumor tissues and corresponding normal esophageal epithelial tissues were obtained from 86 patients undergoing resection surgery at the Department of General Surgery, First Affiliated Hospital of Chinese PLA General Hospital from 2012 to 2017. Cell migration and invasion were examined via quantitative real-time PCR and Western blot assay. RESULTS: Our results indicate that both Capn4 and ZEB1 are significantly upregulated in ESCC tissues compared to corresponding adjacent tissues, and a positive correlation between expression and associated malignant characteristics was found. Silencing of Capn4 expression markedly inhibited ESCC invasion and metastasis in vitro and in vivo, and was accompanied by decreased ZEB1 expression. Furthermore, the anti-metastasis role of Capn4 silencing was reversed by ZEB1 overexpression, whereas knockdown of ZEB1 decreased ESCC metastasis driven by the upregulation of Capn4. Mechanistically, Capn4 regulated ZEB1 expression via activation of the Wnt/ß-catenin signaling pathway in ESCC cells. CONCLUSION: Overall, our results show that enhanced Capn4 expression activates the Wnt/ß-catenin signaling pathway, resulting in increased ZEB1 expression and the promotion of ESCC cell metastasis.

Influence of miR-520e-mediated MAPK signalling pathway on HBV replication and regulation of hepatocellular carcinoma cells via targeting EphA2.

We determined the role of miR-520e in the replication of hepatitis B virus (HBV) and the growth of hepatocellular carcinoma (HCC) cells. MiR-520e and EPH receptor A2 (EphA2) in HBV-positive HCC tissues and cells were detected, and we studied the impact of miR-520e and the EphA2 receptor in cellular and murine HBV replication models. We find that MiR-520e was upregulated and EphA2 was downregulated in HBV-positive HCC tissues and cells. MiR-520e was decreased in Huh7-X and HepG2-X cells in which HBx was stably expressed, but was dose-dependently elevated after interfering with HBx. Additionally, miR-520e mimic and si-EphA2 groups were reduced in association with increases in HBV DNA content, HBsAg and HBeAg levels, cell proliferation and were enhanced in the expressions of EphA2, p-p38MAPK/p38MAPK, phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2)/ERK1/2 and cell apoptosis. Furthermore, si-EphA2 reversed the promotion effect of miR-520e inhibitor on HBV replication and tumour cell growth. Upregulating miR-520e in rAAV8-1.3HBV-infected mouse resulted in reduced EphA2 in liver tissues and HBV DNA content in serum. We find that MiR-520e was decreased in HBV-positive HCC, while overexpression of miR-520e blocked p38MAPK and ERK1/2 signalling pathways by an inhibitory effect on EphA2 and ultimately reduced HBV replication and inhibited tumour cell growth. These data indicate a role for miR-520e in the regulation of HBV replication.