Risk factors for positive resection margins after endoscopic resection for gastrointestinal neuroendocrine tumors.

BACKGROUND: In recent years, the incidence of gastrointestinal neuroendocrine tumors (GI-NETs) has remarkably increased due to the widespread use of screening gastrointestinal endoscopy. Currently, the most common treatments are surgery and endoscopic resection. Compared to surgery, endoscopic resection possesses a higher risk of resection margin residues for the treatment of GI-NETs. METHODS: A total of 315 patients who underwent surgery or endoscopic resection for GI-NETs were included. We analyzed their resection modality (surgery, ESD, EMR), margin status, Preoperative marking and Prognosis. RESULTS: Among 315 patients included, 175 cases underwent endoscopic resection and 140 cases underwent surgical treatment. A total of 43 (43/175, 24.57%) and 10 (10/140, 7.14%) patients exhibited positive resection margins after endoscopic resection and surgery, respectively. Multivariate regression analysis suggested that no preoperative marking and endoscopic treatment methods were risk factors for resection margin residues. Among the patients with positive margin residues after endoscopic resection, 5 patients underwent the radical surgical resection and 1 patient underwent additional ESD resection. The remaining 37 patients had no recurrence during a median follow-up of 36 months. CONCLUSIONS: Compared with surgery, endoscopic therapy has a higher margin residual rate. During endoscopic resection, preoperative marking may reduce the rate of lateral margin residues, and endoscopic submucosal dissection may be preferred than endoscopic mucosal resection. Periodical follow-up may be an alternative method for patients with positive margin residues after endoscopic resection.

Association Between Glycemic Variability and Persistent Acute Kidney Injury After Noncardiac Major Surgery: A Multicenter Retrospective Cohort Study.

BACKGROUND: While the relationship between glycemic variability (GV) and acute kidney injury (AKI) has been a subject of interest, the specific association of GV with persistent AKI beyond 48 hours postoperative after noncardiac surgery is not well-established. METHODS: This retrospective cohort study aimed to describe the patterns of different GV metrics in the immediate 48 hours after noncardiac surgery, evaluate the association between GV indices and persistent AKI within the 7-day postoperative window, and compare the risk identification capabilities of various GV for persistent AKI. A total of 10,937 patients who underwent major noncardiac surgery across 3 medical centers in eastern China between January 2015 and September 2023 were enrolled. GV was characterized using the coefficient of variations (CV), mean amplitude of glycemic excursions (MAGE), and the blood glucose risk index (BGRI). Multivariable logistic regression was used to examine the relationship between GV and AKI. Optimal cutoff values for GV metrics were calculated through the risk identification models, and an independent cohort from the INformative Surgical Patient dataset for Innovative Research Environment (INSPIRE) database with 7714 eligible cases served to externally validate the risk identification capability. RESULTS: Overall, 274 (2.5%) of the 10,937 patients undergoing major noncardiac surgery met the criteria of persistent AKI. Higher GV was associated with an increased risk of persistent AKI (CV: odds ratio [OR] = 1.26, 95% confidence interval [CI], 1.08-1.46; MAGE: OR = 1.31, 95% CI, 1.15-1.49; BGRI: OR = 1.18, 95% CI, 1.08-1.29). Compared to models that did not consider glycemic factors, MAGE and BGRI independently contributed to predicting persistent AKI (MAGE: areas under the curve [AUC] = 0.768, P = .011; BGRI: AUC = 0.764, P = .014), with cutoff points of 3.78 for MAGE, and 3.02 for BGRI. The classification of both the internal and external validation cohorts using cutoffs demonstrated good performance, achieving the best AUC values of 0.768 for MAGE in the internal cohort and 0.777 for MAGE in the external cohort. CONCLUSIONS: GV measured within 48 hours postoperative period is an independent risk factor for persistent AKI in patients undergoing noncardiac surgery. Specific cutoff points can be used to stratify at-risk patients. These findings indicate that stabilizing GV may potentially mitigate adverse kidney outcomes after noncardiac surgery, highlighting the importance of glycemic control in the perioperative period.

Ultrasound-guided superior laryngeal nerve block: a randomized comparison between parasagittal and transverse approach.

BACKGROUND: Different approach ultrasound-guided superior laryngeal nerve block was used to aid awake intubation, but little is known which approach was superior. We aimed to compare the parasagittal and transverse approaches for ultrasound-guided superior laryngeal nerve block in adult patients undergoing awake intubation. METHODS: Fifty patients with awake orotracheal intubation were randomized to receive either a parasagittal or transverse ultrasound-guided superior laryngeal nerve block. The primary outcome was patient's quality of airway anesthesia grade during insertion of the tube into the trachea. The patients' tube tolerance score after intubation, total procedure time, mean arterial pressure, heart rate, Ramsay sedation score at each time point, incidence of sore throat both 1 h and 24 h after extubation, and hoarseness before intubation, 1 h and 24 h after extubation were documented. RESULTS: Patients' quality of airway anesthesia was significantly better in the parasagittal group than in the transverse group (median grade[IQR], 0 [0-1] vs. 1 [0-1], P = 0.036). Patients in the parasagittal approach group had better tube tolerance scores (median score [IQR],1[1-1] vs. 1 [1-1.5], P = 0.042) and shorter total procedure time (median time [IQR], 113 s [98.5-125.5] vs. 188 s [149.5-260], P < 0.001) than those in the transverse approach group. The incidence of sore throat 24 h after extubation was lower in the parasagittal group (8% vs. 36%, P = 0.041). Hoarseness occurred in more than half of the patients in parasagittal group before intubation (72% vs. 40%, P = 0.023). CONCLUSIONS: Compared to the transverse approach, the ultrasound-guided parasagittal approach showed improved efficacy in terms of the quality of airway topical anesthesia and shorter total procedure time for superior laryngeal nerve block. TRIAL REGISTRATION: This prospective, randomized controlled trial was approved by the Ethics Committee of Nanjing First Hospital (KY20220425-014) and registered in the Chinese Clinical Trial Registry (19/6/2022, ChiCTR2200061287) prior to patient enrollment. Written informed consent was obtained from all participants in this trial.

The Causal Relationship Between Skin Microbiota and Facial Aging: A Mendelian Randomization Study.

BACKGROUND: Facial aging is a complex process influenced by environmental factors, genetics, and lifestyle. The contribution of the skin microbiota to this process remains poorly understood. METHODS: This two-sample Mendelian randomization (MR) study was performed using genome-wide genotype data from the UK Biobank and previously published studies on skin microbiota. The primary approach for MR analyses included inverse-variance weighting (IVW), MR-Egger regression, simple mode, weighted median, and weighted mode methods. Sensitivity analyses were performed to assess heterogeneity and pleiotropy, and reverse-direction MR analyses were performed to evaluate potential reverse causation. RESULTS: The MR analysis identified ten skin microbiotas with potential causal relationships with facial aging. Protective skin microbiotas included Genus Finegoldia, ASV011 [Staphylococcus (unc.)], ASV008 [Staphylococcus (unc.)], phylum Firmicutes, Family Rhodobacteraceae, and ASV021 [Micrococcus (unc.)], which were negatively associated with facial aging. Conversely, Order Pseudomonadales, Family Moraxellaceae, ASV039 [Acinetobacter (unc.)], and phylum Bacteroidetes were positively associated with facial aging, indicating a risk factor for accelerated aging. Sensitivity analyses confirmed the robustness of these findings, and reverse-direction MR analyses did not suggest any reverse causation. CONCLUSION: This study identified specific skin microbial that may influence facial aging and offered new insights into the rejuvenation strategies. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Integration of Transcriptomics and Metabolomics Reveals the Antitumor Mechanism of Protopanaxadiol Triphenylphosphate Derivative in Non-Small-Cell Lung Cancer.

The objective of this study was to enhance the membrane permeability and anticancer effectiveness of (20S)-protopanaxadiol (PPD) by introducing triphenylphosphonium into the OH group at the C-3 site. This study shows that the anti-proliferation activity of CTPPPPD, with an IC50 value of 1.65 ± 0.10 µmol/L, was 33-times better than that of PPD (with an IC50 value of 54.56 ± 4.56 µmol/L) and superior to that of cisplatin (with an IC50 value of 1.82 ± 0.25 µmol/L) against A549 cells. Biological examinations suggested that CTPPPPD treatment reduced the growth rate of A549 cells, increased the permeability of cell membranes, and changed the structure of chromosomal DNA in a concentration-dependent manner. Annexin V/PI assay and flow cytometry were employed to detect the effect of CTPPPPD on the apoptosis of A549 cells. The results showed that CTPPPPD could induce the apoptosis of A549 cells, and the apoptosis rate of A549 cells treated with 0, 1.0, 2.0, and 4.0 µM of CTPPPPD for 24 h was 0%, 4.9%, 12.7%, and 31.0%, respectively. The integration of transcriptomics and metabolomics provided a systematic and detailed perspective on the induced antitumor mechanisms. A combined analysis of DEGs and DAMs suggested that they were primarily involved in the central carbon metabolism pathway in cancer, as well as the metabolism of aminoacyl-tRNA biosynthesis, alanine, aspartate, and glutamate. Central carbon metabolism in cancer-related genes, i.e., SLC16A3, FGFR3, LDHA, PGAM1, and SLC2A1, significantly reduced after treatment with CTPPPPD. In particular, the dominant mechanism responsible for total antitumor activity may be attributed to perturbations in the PI3K-AKT, MAPK, and P53 pathways. The findings derived from transcriptomics and metabolomics were empirically confirmed through q-PCR and molecular docking. Further analyses revealed that CTPPPPD could be a promising lead for the development of protopanaxadiol for non-small-cell lung cancer (NSCLC) drugs.

Characterisation of kapok fibre's biochar for arsenate adsorption removal from aqueous solution.

Al-KBC was produced through the simple pyrolysis of Al-modified kapok fibres at high temperatures. Using the N2 adsorption Brunauer Emmett Teller (BET) process, Fourier transforms infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), the energy-dispersive X-ray spectroscopy (EDS) spectroscopy, and X-ray photoelectron spectroscopy (XPS), the sorbent changes and characteristics were analysed. As a result of Al's addition to the fibre's surface, Al-KBC exhibited superior As(V) adsorption performance compared to KBC due to better pore structures. Experiments on the kinetics of As(V) adsorption revealed that the adsorption followed the pseudo-second-order model and that intradiffusion was not the only factor governing the adsorption. Experiments with isotherms indicated that the adsorption mechanism corresponded to the Langmuir model, and the adsorption capacity Qm of Al-KBC at 25 °C was 483 µg/g. The thermodynamic experiments suggested that the adsorption reactions were spontaneous endothermic with a random approach at the adsorption interface. 25 mg/L of coexisting ions such as sulphate and phosphate reduced the sorbent As(V) removal ability to 65% and 39%. After seven cycles of adsorption/desorption, Al-KBC demonstrated satisfactory performance in terms of reusability, adsorbing 53% of 100 µg/L As(V) from the water. This novel BC can probably be used as a filter to purify groundwater with high As(V) concentration in the rural zone.

The relationship between longer leukocyte telomeres and dNCR in non-cardiac surgery patients: a retrospective analysis.

BACKGROUND: Cognitive decline following surgery is a common concern among elderly individuals. Leukocyte telomere length (LTL) can be assessed as a biological clock connected to an individual lifespan. However, the mechanisms causing this inference are still not fully understood. As a result of this, LTL has the potential to be useful as an aging-related biomarker for assessing delayed neurocognitive recovery (dNCR) and related diseases. METHODS: For this study, 196 individuals over 60 who were scheduled due to major non-cardiac surgical operations attended neuropsychological testing before surgery, followed by additional testing one week later. The finding of dNCR was based on a measured Z-score ≤ -1.96 on two or more separate tests. The frequency of dNCR was presented as the primary outcome of the study. Secondly, we evaluated the association between dNCR and preoperative LTL. RESULTS: Overall, 20.4% [40/196; 95% confidence interval (CI), 14.7-26.1%] of patients exhibited dNCR 1-week post-surgery. Longer LTL was identified as a predictor for the onset of early cognitive impairment resulting in postoperative cognitive decline [odds ratio (OR), 14.82; 95% CI, 4.01-54.84; P < 0.001], following adjustment of age (OR, 12.33; 95% CI, 3.29-46.24; P < 0.001). The dNCR incidence based on LTL values of these patients, the area under the receiver operating characteristic (ROC) curve was 0.79 (95% CI, 0.722-0.859; P < 0.001). At an optimal cut-off value of 0.959, LTL values offered respective specificity and sensitivity values of 64.7% and 87.5%. CONCLUSIONS: In summary, the current study revealed that the incidence of dNCR was strongly associated with prolonged LTL. Furthermore, this biomarker could help identify high-risk patients and offer insight into the pathophysiology of dNCR.

Appraising the quality of guidelines for peripheral arterial catheters care: A systematic review of reviews.

INTRODUCTION: Catheter-related bloodstream infections are among the most critical adverse events in critical patients with peripheral arterial catheters (ACs). Adherence to evidence-based guidelines can prevent and reduce arterial bloodstream infections. OBJECTIVE: The objectives of this study were to assess clinical practice guidelines for AC care and analyse methodological factors related to their development for effective dissemination and implementation in clinical practice. REVIEW METHOD USED: This was a systematic review of guidelines. DATA SOURCES: We searched PubMed, CINAHL, EMBASE, CNKI, and WANFANG databases from inception until September 2021 and evaluated websites of organisations that complied or produced guidelines. REVIEW METHODS: A comprehensive list of guidelines for ACs care was included. We excluded incomplete guidelines, guidelines translated in other languages, duplicate publications, and summaries of multiple guidelines. Two reviewers independently extracted and collected the data, and three authors conducted quality assessments independently using the Appraisal of Guidelines for Research and Evaluation, Second Edition (AGREE II) tool. The intraclass correlation coefficient (two-way random) with a 95% confidence interval was used to evaluate the concordance between reviewers. RESULTS: Of the 738 total publications screened, seven were selected for evaluation. The concordance between observers was substantial (intraclass correlation coefficient >0.9, P < 0.001). Most guidelines (4/6) were developed in the United States and the United Kingdom. The median scores for the six domains were 89.0%, 65.5%, 58.0%, 86.0%, 65.0%, and 86.0%. The domains of stakeholder involvement, rigour of development, and applicability had the lowest scores. Guidelines by the United Kingdom's National Institute for Health and Care Excellence showed the highest quality. CONCLUSIONS: The guidelines we included scored poorly on crucial domains (rigour of development, applicability, and stakeholder involvement). Most of the current recommendations on ACs were included in the guidelines for vascular catheter-related bloodstream infections. Therefore, targeted guidelines created specifically for ACs are warranted to reduce the incidence of catheter-related complications and ensure patient safety.

Pseudo-sapogenin DQ 3-Maleate Derivative Induces Ovarian Carcinoma Cell Apoptosis via Mitochondrial Pathway.

In the present study, four novel ginsenosides fatty acid and aromatic acid derivatives were designed and synthesized, and their cytotoxic effects on human ovarian carcinoma cells (SKOV3) were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The results demonstrated that all derivatives inhibited SKOV3 cell growth, and Compound 3 showed the most outstanding anti-proliferative effect on SKOV3 cells. The IC50 value of Compound 3 was 33.8 ± 2.21 µM, less than half of that of cis-platinum (70.1 ± 7.64 µM). Subsequent analysis revealed that Compound 3 could promote SKOV3 cell apoptosis, and the percentage of apoptotic cell population increased with increasing Compound 3 concentrations. In addition, the expression ratios of Bax/Bcl-2, cleaved-Caspase-3/Caspase-3 and cleaved-Caspase-9/Caspase-9 were gradually elevated in Compound 3-treated SKOV3 cells compared with control cells. Furthermore, translocation of Bax to mitochondria was associated with the release of Cytochrome C. Molecular docking analysis revealed three hydrogen-bonds existed in Compound 3 with poly(ADP-ribose)polymerase (PARP) receptor (PDB code: 5DSY), which may be the target of the anti-ovarian cancer effect of Compound 3. Altogether, our study indicates that Compound 3 induces SKOV3 cell apoptosis via reactive oxygen species (ROS)-dependent mitochondrial pathway, and can serve as an anti-cancer agent for treating ovarian carcinoma.

Gender differences in prevalence and clinical correlates of anxiety symptoms in first-episode and drug-naïve patients with major depressive disorder.

AIM: Gender differences in major depressive disorder (MDD) are commonly reported; however, gender differences in first-episode and drug-naïve (FEDN) patients with major depressive disorder remain unclear. This study aimed to examine potential gender differences in the prevalence and clinical correlates of comorbid anxiety in FEDN patients with MDD. METHODS: A cross-sectional study was conducted with1718 FEDN patients with MDD. Patients' demographic and clinical data were collected and analyzed using standardized clinical evaluation forms. The Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and Positive and Negative Syndrome Scale (PANSS) were used to evaluate depression, anxiety and psychotic symptoms, respectively. RESULTS: There were no gender-based differences in the comorbidity rates of MDD and anxiety disorders (male: 10.2% vs. female:12.7%, P = 0.123). The prevalence of MDD with severe anxiety symptoms in male patients was similar to that of female patients (80.8%vs. 80.1%, P = 0.749). Male MDD patients were younger, had earlier age of onset, and were less likely to be married. In both the male and female groups, HAMD scores, HAMA scores, suicide attempts, and psychotic symptoms in patients with severe anxiety symptoms were higher than those patients without severe anxiety symptoms (all p ≤ 0.001). Furthermore, binary logistic regression analysis showed that psychotic symptoms and suicide attempts significantly predicted severe anxiety symptoms in both male and female patients with MDD, while body mass index(BMI)significantly predicted severe anxiety symptoms in MDD females only. CONCLUSION: Our study showed that there were no gender differences in the prevalence of comorbid anxiety in FEDN patients with MDD. Suicide attempts and psychiatric symptoms were associated with severe anxiety symptoms in both men and women with MDD, whereas BMI was only correlated with severe anxiety symptoms in women.

A redox-responsive dihydroartemisinin dimeric nanoprodrug for enhanced antitumor activity.

Redox-responsive drug delivery system emerges as a hopeful platform for tumor treatment. Dihydroartemisinin (DHA) has been investigated as an innovative tumor therapeutic agent. Herein, a DHA dimeric prodrug bridged with disulfide bond as linker (DHA2-SS) has been designed and synthesized. The prepared prodrugs could self-assemble into nanoparticles (SS NPs) with high DHA content (> 90%) and robust stability. These SS NPs display sensitive redox responsive capability and can release DHA under the tumor heterogeneity microenvironment. SS NPs possess preferable antitumor therapeutic activity in contrast with free DHA. Moreover, the possible anti-cancer mechanism of SS NPs was investigated through RNA-seq analysis, bioinformatics and molecular biological method. SS NPs could induce apoptosis via mitochondrial apoptosis pathway, as well as glycolysis inhibition associate with the regulation of PI3K/AKT/HIF-1α signal path, which may offer an underlying therapeutic target for liver cancer. Our study highlights the potential of using redox responsive prodrug nanoparticles to treat cancer, meanwhile provides insights into the anti-cancer mechanism of DHA prodrug.

Enhanced recovery after surgery protocols in total knee arthroplasty via midvastus approach: a randomized controlled trial.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols were rapidly adopted in many surgeries such as fast-track arthroplasty. The study aimed to investigate the impact of ERAS protocols on the clinical effect of total knee arthroplasty (TKA) via the midvastus approach. METHODS: A total of 69 patients who underwent primary unilateral TKA via the midvastus approach from October 2018 to June 2019 were enrolled and randomly divided into two groups: ERAS group and Control group. The ERAS protocols were adopted for the ERAS group and consisted of pure juice drinking 2 h before the surgery, optimization of the preoperative anesthesia plan, phased use of tourniquets, and the use of tranexamic acid as well as a drug cocktail. The operative time, first postoperative walking time, first straight leg elevation time, postoperative hospitalization time, visual analogue scale score (VAS score), Hospital for Special Surgery score (HSS score), conventional Knee Society score (KSS), and knee range of motion (ROM) were used to assess the clinical effects in the two groups. All the included patients were followed up for 12 months. RESULTS: There were no significant differences in the basic demographic information and operation time between the ERAS and Control groups (P > 0.05). The first postoperative walking time (2.11 ± 0.11 h) and first postoperative straight leg elevation time (6.14 ± 1.73 h) in the ERAS group were significantly earlier than those in the Control group (P < 0.001) and the postoperative hospitalization time was significantly shorter (3.11 ± 0.32 days). The postoperative mean VAS scores in both groups were significantly reduced compared with those before surgery (P < 0.001). The VAS scores for the ERAS group were significantly lower than those for the Control group at 1, 2, and 7 days after surgery (P < 0.001). The mean HSS scores, KSS, and knee ROM were significantly increased in both the ERAS and Control groups at 1, 3, 6, and 12 months after surgery (P < 0.001). In addition, the HSS scores, KSS, and knee ROM in the ERAS group were significantly higher than those in the Control group at 1 month after surgery (P < 0.001). CONCLUSIONS: ERAS protocols improved the clinical effects of TKA via the midvastus approach, facilitating early out-of-bed activity and comfortable postoperative rehabilitation exercise, and further increasing patient satisfaction. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04873544 .

miR-26a promotes hepatocellular carcinoma invasion and metastasis by inhibiting PTEN and inhibits cell growth by repressing EZH2.

A previous study revealed that therapeutic miR-26a delivery suppresses tumorigenesis in a murine liver cancer model, whereas we found that forced miR-26a expression increased hepatocellular carcinoma (HCC) cell migration and invasion, which prompted us to characterize the causes and mechanisms underlying enhanced invasion due to ectopic miR-26a expression. Gain-of-function and loss-of-function experiments demonstrated that miR-26a promoted migration and invasion of BEL-7402 and HepG2 cells in vitro and positively modulated matrix metalloproteinase (MMP)-1, MMP-2, MMP-9, and MMP-10 expression. In addition, exogenous miR-26a expression significantly enhanced the metastatic ability of HepG2 cells in vivo. miR-26a negatively regulated in vitro proliferation of HCC cells, and miR-26a overexpression suppressed HepG2 cell tumor growth in nude mice. Further studies revealed that miR-26a inhibited cell growth by repressing the methyltransferase EZH2 and promoted cell migration and invasion by inhibiting the phosphatase PTEN. Furthermore, PTEN expression negatively correlated with miR-26a expression in HCC specimens from patients with and without metastasis. Thus, our findings suggest for the first time that miR-26a promotes invasion/metastasis by inhibiting PTEN and inhibits cell proliferation by repressing EZH2 in HCC. More importantly, our data also suggest caution if miR-26a is used as a target for cancer therapy in the future.

Extracellular vesicles in the tumor microenvironment: old stories, but new tales.

Mammalian cells synthesize and release heterogeneous extracellular vesicles (EVs) which can be generally recognized as subclasses including exosomes, microvesicles (MVs), and apoptotic bodies (ABs), each differing in their biogenesis, composition and biological functions from others. EVs can originate from normal or cancer cells, transfer bioactive cargoes to both adjacent and distant sites, and orchestrate multiple key pathophysiological events such as carcinogenesis and malignant progression. Emerging as key messengers that mediate intercellular communications, EVs are being paid substantial attention in various disciplines including but not limited to cancer biology and immunology. Increasing lines of research advances have revealed the critical role of EVs in the establishment and maintenance of the tumor microenvironment (TME), including sustaining cell proliferation, evading growth suppression, resisting cell death, acquiring genomic instability and reprogramming stromal cell lineages, together contributing to the generation of a functionally remodeled TME. In this article, we present updates on major topics that document how EVs are implicated in proliferative expansion of cancer cells, promotion of drug resistance, reprogramming of metabolic activity, enhancement of metastatic potential, induction of angiogenesis, and escape from immune surveillance. Appropriate and insightful understanding of EVs and their contribution to cancer progression can lead to new avenues in the prevention, diagnosis and treatment of human malignancies in future medicine.

Preoperative Salivary Cortisol AM/PM Ratio Predicts Early Postoperative Cognitive Dysfunction After Noncardiac Surgery in Elderly Patients.

BACKGROUND: The diagnosis of postoperative cognitive dysfunction (POCD) requires complicated neuropsychological testing and is often delayed. Possible biomarkers for early detection or prediction are essential for the prevention and treatment of POCD. Preoperative screening of salivary cortisol levels may help to identify patients at elevated risk for POCD. METHODS: One hundred twenty patients >60 years of age and undergoing major noncardiac surgery underwent neuropsychological testing 1 day before and 1 week after surgery. Saliva samples were collected in the morning and the evening 1 day before surgery. POCD was defined as a Z-score of ≤-1.96 on at least 2 different tests. The primary outcome was the presence of POCD. The primary objective of this study was to assess the relationship between the ratio of AM (morning) to PM (evening) salivary cortisol levels and the presence of POCD. The secondary objective was to assess the relationship between POCD and salivary cortisol absolute values in the morning or in the evening. RESULTS: POCD was observed in 17.02% (16 of 94; 95% confidence interval [CI], 9.28%-24.76%) of patients 1 week after the operation. A higher preoperative AM/PM salivary cortisol ratio predicted early POCD onset (odds ratio [OR], 1.56; 95% CI, 1.20-2.02; P = .001), even after adjusting for the Mini-Mental Sate Examination score (odds ratio, 1.55; 95% CI, 1.19-2.02; P = .001). The area under the receiver operating characteristic curve for the salivary cortisol AM/PM ratio in individuals with POCD was 0.72 (95% CI, 0.56-0.88; P = .006). The optimal cutoff value was 5.69, with a sensitivity of 50% and specificity of 91%. CONCLUSIONS: The preoperative salivary cortisol AM/PM ratio was significantly associated with the presence of early POCD. This biomarker may have potential utility for screening patients for an increased risk and also for further elucidating the etiology of POCD.

DMBT1 suppresses progression of gallbladder carcinoma through PI3K/AKT signaling pathway by targeting PTEN.

Gallbladder carcinoma (GBC) is a highly lethal malignancy of the gastrointestinal tract. Despite extensive research, the underlying molecular mechanism of GBC remains largely unclear. Deleted in malignant brain tumors 1 (DMBT1) is low-expression during cancer progression and as a potential tumor-suppressor gene in various types of cancer. However, its role in Gallbladder cancer remains poorly understood. Here, we found that DMBT1 was significantly low-expression and deletion of copy number in GBC tissues by qRT-PCR and Western blot. Overexpression of DMBT1 impaired survival, promoted apoptosis in GBC cells in vitro, and inhibited tumor progression in vivo. Further study of underlying mechanisms demonstrated that DMBT1 combined with PTEN which could stabilize PTEN protein, resulting in inhibiting the activation of PI3K/AKT signaling pathway. Our study revealed a new sight of DMBT1 as a tumor-suppressor gene on the PI3K/AKT pathway in GBC, which may be a potential therapeutic target for improving treatment.

Reliability assessment of an optical current sensor based on accelerated aging tests.

The operational reliability directly affects the practical application of optical current transformers (OCTs) in smart substations. As the key component of the OCT, the reliability of the optical current sensor (OCS) largely determines the reliability level of the OCT. This paper proposes a reliability assessment method of the OCS based on accelerated aging tests. The failure modes and failure mechanisms of the OCS are analyzed, and the concept of OCS insertion loss variation is proposed. An allowable range of insertion loss variation is selected as the failure criterion of the OCS. From the viewpoint of the OCS measurement error generated by the quantization error of the analog-to-digital converter, the allowable range of insertion loss variation is obtained. By selecting a high temperature as the accelerated thermal stress, we design the accelerated aging test scheme of the OCS and analyze the sample test data to obtain the activation energy of the OCS insertion loss failure. Based on this activation energy, the median time to failure and instantaneous failure rate curve of the OCS at normal temperature are obtained. The results indicate that the designed OCS has an expected service life of 50 years and a low instantaneous failure rate at normal temperature. This paper provides basic critical reliability analysis data for the system reliability assessment of OCTs.

Risk factors for early postoperative cognitive dysfunction after colorectal surgery.

BACKGROUND: It has been reported that postoperative cognitive dysfunction (POCD) is correlated with the degeneration of the central nervous system, oxidative stress, inflammation, and endocrine and immune dysfunction. Increased age, predisposed comorbidity, long surgery time, and prolonged stay in the intensive care unit have been reported to be risk factors for developing POCD for cardiac surgery. In the present study, the risk factors of early POCD after colorectal surgery were investigated. METHODS: Eighty patients, who provided informed consents for their participation in this study, were enrolled and received colorectal surgery under general anesthesia. Neuropsychological tests were performed preoperatively and on postoperative day seven. The risk factors for POCD were analyzed using a multivariate logistic regression model. RESULTS: Nineteen patients were diagnosed with POCD (24.7%). Diabetes history (OR = 8.391 [2.208-31.882], P = 0.012), fasting over 3 days after surgery (OR = 5.236 [1.998-13.721], P = 0.001) and an SIRS score of > 3 on the second day after surgery (OR = 6.995 [1.948-25.111], P = 0.003) were risk factors for early POCD in colorectal cancer patients. CONCLUSION: The risk factors for early POCD after colorectal surgery included diabetes history, fasting over 3 days, and an SIRS score of > 3 on the second day.

[Propofol protects human cardiac AC16 cells from CoCl2-induced hypoxic injury].

OBJECTIVE: To explore the effect of propofol on human cardiac AC16 cells under CoCl2-induced hypoxic injury and the possible mechanisms.
 Methods: Human AC16 cardiomyocytes were treated with cobalt chloride (CoCl2) to mimic hypoxic condition in cultured cardiomyocytes. The AC16 cells were divided into 3 groups: a control group, a CoCl2 hypoxia group (CoCl2 group), and a propofol+CoCl2 group (propofol+ CoCl2 group). The cell viability was assessed by cell counting kit-8 (CCK-8). Cell apoptosis ratio (AR) and the mitochondrial membrane potential (Δψm) were detected by flow cytometry. The reactive oxygen species (ROS) production in AC16 cells were determined with the ROS-sensitive fluorescent probe. Meanwhile, total intracellular levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in AC16 cells were detected with commercially available kits. Western blot was used to evaluate the activation of c-Jun N-terminal kinase (JNK) and p38 signaling pathways.
 Results: 1) Compared with the control group, AC16 cell viability was decreased significantly in the CoCl2 group following the treatment with 500 µmol/L CoCl2 (P<0.01); 2) Compared with the control group, AR value in AC16 cells was increased significantly in the CoCl2 group, while Δψm was decreased significantly (all P<0.01). Compared with the CoCl2 group, AR value in AC16 cells was decreased significantly in the propofol+CoCl2 group, while Δψm was increased significantly (both P<0.05); 3) Compared with the control group, the levels of ROS and MDA were increased significantly, and the level of SOD was significantly decreased in the CoCl2 group (all P<0.01). Compared with the CoCl2 group, the ROS and MDA levels in the propofol+CoCl2 group were increased significantly and the SOD levels were decreased significantly (all P<0.05); 4) Compared with the control group, the phosphorylation levels of JNK and p38 were increased significantly (both P<0.05) in the CoCl2 group. Compared with the CoCl2 group, the phosphorylation levels of JNK and p38 were decreased significantly in the propofol+CoCl2 group (both P<0.05).
 Conclusion: The pretreatment with propofol may protect human cardiac AC16 cells from the chemical hypoxia-induced injury through regulation of JNK and p38 signaling pathways.

Comparison of a loading dose of dexmedetomidine combined with propofol or sevoflurane for hemodynamic changes during anesthesia maintenance: a prospective, randomized, double-blind, controlled clinical trial.

BACKGROUND: There may be great individual variability in the hemodynamic effects of this dexmedetomidine. For this reason, the dose must be carefully adjusted to achieve the desired clinical effect. Whether a loading dose of dexmedetomidine produces hemodynamic side effects during the anesthesia maintenance is unknown. The aim of this study was to compare the effects of a loading dose of dexmedetomidine combined with propofol or sevoflurane on hemodynamics during anesthesia maintenance. METHODS: Eighty-four patients who were scheduled for general surgery under balanced general anesthesia were randomly allocated into 4 groups (n = 21): the propofol and dexmedetomidine group, the sevoflurane and dexmedetomidine group, the propofol and normal saline group, or the sevoflurane and normal saline group. The hemodynamic indexes at the time of just before, 5 min after and the end of study drug infusion (dexmedetomidine or normal saline) were recorded. The incidence rates of increasing blood pressure at the end of study drug infusion (greater than 20% compared to baseline or before study drug infusion) were evaluated. RESULTS: Mean arterial pressure increased significantly (P < 0.01) only in the propofol and dexmedetomidine group after intravenous dexmedetomidine compared administration. 80% of cases with propofol and dexmedetomidine had increased mean arterial blood pressure compared to only 5% of cases in the sevoflurane and dexmedetomidine group (P < 0.05). Heart rates in the propofol and dexmedetomidine and the sevoflurane and dexmedetomidine groups decreased significantly after dexmedetomidine infusion (P < 0.01). CONCLUSIONS: Intraoperative administration of a loading dose of dexmedetomidine combined with propofol in anesthesia maintenance proceeded a significant increase in blood pressure. In contrast, it combines with sevoflurane didn't produce increased blood pressure. Meanwhile it is not unexpected that dexmedetomidine combined with propofol or sevofurance decreased heart rate, due to the known side effects of DEX. Therefore, dexmedetomidine should be used cautiously during the entire intravenous anesthesia maintenance period, especially during maintenance with propofol. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IOR-17010423 , registered on 13 January 2017.