Associations of sleep disorders with all-cause and cause-specific mortality in cancer survivors: a cross-sectional analysis of the NHANES 2005-2016.

BACKGROUND: The circadian clock and endoplasmic reticulum stress signaling play important roles in oncogenesis and development of cancer. Sleep disorders have been linked to an elevated risk of mortality in general populations. Nonetheless, the evidence for the sleep disorders-mortality association among cancer patients is limited. We aimed to prospectively investigate the association of sleep disorders with all-cause, cancer, and cardiovascular disease (CVD) mortality among cancer individuals. METHODS: We assessed 3187 participants with cancer from the National Health and Nutrition Examination Survey 2005-2016 cohorts with a median follow-up time of 83.0 months. Multivariable Cox proportional hazards models estimated the adjusted hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Multivariable Cox proportional hazards models showed that sleep disorders were associated with a higher risk of all-cause mortality (HR 1.23, 95%CI: 1.06,1.42), cancer mortality (HR 1.30, 95%CI: 1.02, 1.66), and cardiovascular disease mortality (HR 1.35, 95%CI: 1.02, 1.80). After the total group was stratified by gender, the high HRs were observed in men (P < 0.05), not in women. The correlation between sleep disorders and higher long-term mortality was also significant after individuals who died within 2 years of follow-up were excluded, with HR 1.24 (95%CI: 1.07, 1.45) in model I, HR 1.20 (95%CI: 1.02, 1.42) in model II for long-term all-cause mortality, HR (95%CI: 1.00, 1.74) in model I for long-term cancer mortality, and HR 1.5 (95%CI:1.12, 2.02) in model I, HR 1.45 (95%CI: 1.06, 1.99) in model II for long-term CVD mortality. CONCLUSIONS: Sleep disorders were associated with a higher risk of all-cause mortality, cancer mortality, and CVD mortality, as well as long-term mortality in cancer patients. Our finding underlies the importance of screening for sleep disorders for all cancer survivors and the urge to integrate sleep health as an important part of cancer care more effectively. Male individuals may be particularly vulnerable and could benefit from more frequent screening.

Dexmedetomidine prolongs the duration of local anesthetics when used as an adjuvant through both perineural and systemic mechanisms: a prospective randomized double-blinded trial.

BACKGROUND: To study the respective peripheral and systemic mechanisms of action of dexmedetomidine, as adjuvant to regional anesthesia, we compared dexmedetomidine added to ropivacaine for mid-forearm nerve blocks, to either systemic-only dexmedetomidine, and to a control with no dexmedetomidine. METHODS: Sixty patients undergoing hand surgery were randomly divided into three groups (n = 20 per group). Each group underwent a triple-nerve (median, radial and ulnar) mid-forearm blocks with 0.75% ropivacaine. In the DexP group, 60 µg of dexmedetomidine were added to the anesthetic mixture, while in the DexIV group, they were intravenously infused. Normal saline as a placebo was used, either as adjuvant, or intravenously. All patients underwent also a supraclavicular block with 1.5% lidocaine for tourniquet pain. The main outcomes were the duration of analgesia and the duration of sensory blockade separately for each nerve termination of the upper limb, and the duration of motor blockade of the upper limb. Tolerance was assessed by blood pressure and heart rate, and the report of adverse events. RESULTS: Duration of analgesia was longer in the DexP group, in comparison to the two other groups (P < 0.001), while it was similar in the DexIV and the control group. For cutaneous territories targeted by the three mid-forearm blocks, the between-group differences behaved similarly. For the other cutaneous territories (musculocutaneous and posterior brachial cutaneous nerves), duration of sensory blockade was shorter in the control group than in the two dexmedetomidine groups. For duration of motor blockade, the between-group differences behaved similarly. Both blood pressure and heart rate were reduced in the DexP and the DexIV groups, compared to the control. CONCLUSIONS: Dexmedetomidine used as an adjuvant to regional anesthesia may act mostly though a perineural mechanism, especially for the sensory aspects of anesthesia. A systemic action might however explain other clinical effects. TRIAL REGISTRATION: ChiCTR-IOR-17011149 , date of registration: 16/04/2017.

p53 controls the switch between autophagy and apoptosis through regulation of PLSCR1 in sodium selenite-treated leukemia cells.

Coordinated regulation of autophagy and apoptosis helps to enhance the antitumor effects of sodium selenite. However, the potential molecules that act as switch nodes in the crosstalk between autophagy and apoptosis is still elusive. Phospholipid scramblase 1 (PLSCR1) has been shown to regulate leukocyte differentiation, while its role in autophagy/apoptosis toggle switch remains unexplored. In this study, we showed that sodium selenite switched protective autophagy to apoptosis in p53-wild type NB4 cells without obvious caspase-8/apoptosis-inducing factor (AIF) axis activation, while induced autophagy-dependent caspase-8/AIF axis activation in p53-mutant Jurkat cells. Additionally, p53 was demonstrated as a positive regulator of PLSCR1. p53-dependent up-regulation of PLSCR1 accounted for the differential regulation of autophagy and apoptosis induced by sodium selenite. Furthermore, sodium selenite induced the release of AIF from mitochondria to cytosol with the facilitation of caspase-8 in Jurkat cells, while not in NB4 cells. The released AIF further enhanced autophagy flux through interacting with PLSCR1, which hereby resulting in the disassociation of PLSCR1 from Atg5-Atg12 complex. Our results indicate that PLSCR1 plays a critical role in p53-dependent regulation of autophagy and apoptosis in sodium selenite-treated leukemia cells. Manipulation of p53-PLSCR1 cascade might be beneficial to enhance the anti-tumor effects of sodium selenite.

Apelin-13 Reverses Bupivacaine-Induced Cardiotoxicity via the Adenosine Monophosphate-Activated Protein Kinase Pathway.

BACKGROUND: Cardiotoxicity can be induced by the commonly used amide local anesthetic, bupivacaine. Bupivacaine can inhibit protein kinase B (AKT) phosphorylation and activated adenosine monophosphate-activated protein kinase alpha (AMPKα). It can decouple mitochondrial oxidative phosphorylation and enhance reactive oxygen species (ROS) production. Apelin enhances the phosphatidylinositol 3-kinase (PI3K)/AKT and AMPK/acetyl-CoA carboxylase (ACC) pathways, promotes the complete fatty acid oxidation in the heart, and reduces the release of ROS. In this study, we examined whether exogenous (Pyr1) apelin-13 could reverse bupivacaine-induced cardiotoxicity. METHODS: We used the bupivacaine-induced inhibition model in adult male Sprague Dawley (SD) rats (n = 48) and H9c2 cardiomyocyte cell cultures to explore the role of apelin-13 in the reversal of bupivacaine cardiotoxicity, and its possible mechanism of action. AMPKα, ACC, carnitine palmitoyl transferase (CPT), PI3K, AKT, superoxide dismutase 1 (SOD1), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p47-phox) were quantified. Changes in mitochondrial ultrastructure were examined, and mitochondrial DNA, cell viability, ROS release, oxygen consumption rate (OCR) were determined. RESULTS: Apelin-13 reduced bupivacaine-induced mitochondrial DNA lesions in SD rats (P < .001), while increasing the expression of AMPKα (P = .007) and PI3K (P = .002). Furthermore, apelin-13 blocked bupivacaine-induced depolarization of the mitochondrial membrane potential (P = .019) and the bupivacaine-induced increases in ROS (P = .001). Also, the AMPK pathway was activated by bupivacaine as well as apelin-13 (P = .002) in H9c2 cardiomyocytes. Additionally, the reduction in the PI3K expression by bupivacaine was mitigated by apelin-13 in H9c2 cardiomyocytes (P = .001). While the aforementioned changes induced by bupivacaine were not abated by apelin-13 after pretreatment with AMPK inhibitor compound C; the bupivacaine-induced changes were still mitigated by apelin-13, even when pretreated with PI3K inhibitor-LY294002. CONCLUSIONS: Apelin-13 treatment reduced bupivacaine-induced oxidative stress, attenuated mitochondrial morphological changes and mitochondrial DNA damage, enhanced mitochondrial energy metabolism, and ultimately reversed bupivacaine-induced cardiotoxicity. Our results suggest a role for the AMPK in apelin-13 reversal of bupivacaine-induced cardiotoxicity.

Comparative Regimens of Lipid Rescue From Bupivacaine-Induced Asystole in a Rat Model.

BACKGROUND: It is currently unknown whether bupivacaine-induced asystole is better resuscitated with lipid emulsion (LE) administered peripherally or centrally, and whether different LE regimens administered peripherally demonstrated similar effects. In this study, we compared the effects of various regimens of lipid administration in a rat model of bupivacaine-induced asystole. METHODS: Forty-five adult male Sprague-Dawley rats were subjected to bupivacaine-induced asystole and randomly divided into 3 lipid regimens groups: (1) 20% LE was administered continuously via the internal jugular vein (CV-infusion group); (2) 20% LE was administered continuously via the tail vein (PV-infusion group); and (3) 20% LE was administered as divided boluses via the tail vein (PV-bolus group). The maximum dose of LE did not exceed 10 mL·kg(-1). External chest compressions were administered until the return of spontaneous circulation (ROSC) or the end of a 40-minute resuscitation period. RESULTS: The survival rate, rate of ROSC, systolic blood pressure, heart rate, heart rate-blood pressure product, and coronary perfusion pressure during 2-40 minutes in the CV-infusion and PV-bolus groups were significantly higher than those in the PV-infusion group (P < .01), and the plasma total bupivacaine concentration and myocardial bupivacaine content were significantly lower (P < .05). Time to heartbeat return and time to ROSC in the CV-infusion and PV-bolus groups were significantly shorter than those in the PV-infusion group (P < .05). CONCLUSIONS: In the rat model of bupivacaine-induced asystole, a divided LE bolus regimen administered peripherally provided a better resuscitation outcome than that of a continuous LE infusion regimen peripherally, and performed in a similar fashion as the continuous LE infusion regimen administered centrally.

Levosimendan is superior to epinephrine on coronary flow for lipid-base resuscitation of bupivacaine-induced asystole in the isolated rat heart.

BACKGROUND: Successful resuscitation from asystole induced by bupivacaine requires the reestablishment of a sufficient coronary flow (CF) quickly. This study was designed to test whether levosimendan was superior to epinephrine in the reestablishment of crucial coronary flows after bupivacaine-induced asystole. METHODS: The isolated, perfused, nonrecirculating, Langendorff rat heart preparation was used. Bupivacaine 100 µmol/L was perfused into rat hearts to induce asystole, and then for 3 min thereafter. Three experimental groups were assessed after asystole with infusions as follow: (1) a mixture of 2% lipid emulsion and 40 µmol/L bupivacaine (control group), (2) a mixture of 0.15 µg/mL epinephrine combined with 2% lipid emulsion and 40 µmol/L bupivacaine (epinephrine group), and (3) a mixture of 5 µmol/L levosimendan combined with a 2% lipid emulsion and 40 µmol/L bupivacaine mixture (levosimendan group). Coronary flow (CF), the time to recovery (Trecovery), the number of ventricular arrhythmias, and cardiac function parameters were recorded for 40 min after heartbeat recovery. RESULTS: All hearts in the control, epinephrine and levosimendan groups had heartbeat recovery. The rank order of the mean CF from highest to lowest was the levosimendan group > the epinepgrine group > the control group (P < 0.05). The rank order of Trecovery from shortest to longest was the levosimendan group < the epinephrine group < the control group (P < 0.01). During the recovery phase, isolated rat hearts developed more ventricular arrhythmias in the epinephrine group than in the levosimendan group (P = 0.01). CONCLUSION: Levosimendan is superior to epinephrine in producing higher CFs and faster recovery when reversing bupivacaine-induced asystole in the isolated rat hearts.

The Effect of Lipid Emulsion on Pharmacokinetics of Bupivacaine in Rats: Long-Chain Triglyceride Versus Long- and Medium-Chain Triglyceride.

BACKGROUND: Lipid infusions have been proposed to treat local anesthetic-induced cardiac toxicity. This study compared the effects of long-chain triglyceride (LCT) emulsions with those of long- and medium-chain triglyceride (LCT/MCT) emulsions on the pharmacokinetics of bupivacaine in a rat model. METHODS: After administration of intravenous infusion of bupivacaine at 2 mg·kg·min for 5 minutes in Sprague-Dawley (SD) rats, either Intralipid 20%, an LCT emulsion (LCT group, n = 6), or Lipovenoes 20%, an LCT/MCT emulsion (LCT/MCT group, n = 6), was infused at 2mg·kg·min for 5 minutes. The concentrations of total plasma bupivacaine and bupivacaine that were not bound by lipid (lipid unbound) were measured by a liquid chromatography-tandem mass spectrometric method. A 2-compartmental analysis was performed to calculate the lipid-bound percentage of bupivacaine and its pharmacokinetics. RESULTS: In the LCT group, the clearance (15 ± 2 vs 10 ± 1 mL·min·kg, P = .003) was higher; the volume of distribution (0.57 ± 0.10 vs 0.36 ± 0.11 L·kg, P = .007) and K21 (0.0100 ± 0.0018 vs 0.0070 ± 0.0020 min, P = .021, P' = .032) were larger; and the area under the blood concentration-time curve 0 - t; (605 ± 82 vs 867 ± 110 mgL·min, P =.001) and the area under the blood concentration-time curve (0 - ∞) (697 ± 111 vs 991 ± 121 mgL·min, P =.001) were less, when compared with the LCT/MCT group. CONCLUSIONS: LCT emulsions are more effective than LCT/MCT emulsions in the metabolism of bupivacaine through demonstration of a superior pharmacokinetic profile.

Flurbiprofen Axetil Enhances Analgesic Effects of Sufentanil and Attenuates Postoperative Emergence Agitation and Systemic Proinflammation in Patients Undergoing Tangential Excision Surgery.

OBJECTIVE: Our present study tested whether flurbiprofen axetil could reduce perioperative sufentanil consumption and provide postoperative analgesia with decrease in emergency agitation and systemic proinflammatory cytokines release. METHODS: Ninety patients undergoing tangential excision surgery were randomly assigned to three groups: (1) preoperative dose of 100 mg flurbiprofen axetil and a postoperative dose of 2 µg/kg sufentanil and 10 mL placebo by patient-controlled analgesia (PCA) pump, (2) preoperative dose of 100 mg flurbiprofen axetil and a postoperative dose of 2 µg/kg sufentanil and 100 mg flurbiprofen axetil by PCA pump, and (3) 10 mL placebo and a postoperative dose of 2 µg/kg sufentanil and 10 mL placebo by PCA pump. RESULTS: Preoperative administration of flurbiprofen axetil decreased postoperative tramadol consumption and the visual analog scale at 4, 6, 12, and 24 h after surgery, which were further decreased by postoperative administration of flurbiprofen axetil. Furthermore, flurbiprofen axetil attenuated emergency agitation score and Ramsay score at 0, 5, and 10 min after extubation and reduced the TNF-α and interleukin- (IL-) 6 levels at 24 and 48 h after the operation. CONCLUSION: Flurbiprofen axetil enhances analgesic effects of sufentanil and attenuates emergence agitation and systemic proinflammation in patients undergoing tangential excision surgery.

Predictive value of systemic immune-inflammation index in the high-grade subtypes components of small-sized lung adenocarcinoma.

BACKGROUND: Identification of micropapillary and solid subtypes components in small-sized (≤ 2 cm) lung adenocarcinoma plays a crucial role in determining optimal surgical procedures. This study aims to propose a straightforward prediction method utilizing preoperative available indicators. METHODS: From January 2019 to July 2022, 341 consecutive patients with small-sized lung adenocarcinoma who underwent curative resection in thoracic surgery department of Xuanwu Hospital, Capital Medical University were retrospectively analyzed. The patients were divided into two groups based on whether solid or micropapillary components ≥ 5% or not (S/MP5+ and S/MP5-). Univariate analysis and multivariate logistic regression analysis were utilized to identify independent predictors of S/MP5+. Then a nomogram was constructed to intuitively show the results. Finally, the calibration curve with a 1000 bootstrap resampling and the receiver operating characteristic (ROC) curve were depicted to evaluate its performance. RESULTS: According to postoperative pathological results, 79 (23.2%) patients were confirmed as S/MP5+ while 262 (76.8%) patients were S/MP5-. Based on multivariate analysis, maximum diameter (p = 0.010), consolidation tumor ratio (CTR) (p < 0.001) and systemic immune-inflammation index (SII) (p < 0.001) were identified as three independent risk factors and incorporated into the nomogram. The calibration curve showed good concordance between the predicted and actual probability of S/MP5+. Besides, the model showed certain discrimination, with an area under ROC curve of 0.893. CONCLUSIONS: The model constructed based on SII is a practical tool to predict high-grade subtypes components of small-sized lung adenocarcinoma preoperatively and contribute to determine the optimal surgical approach.

Prognostic predictive modeling of non-small cell lung cancer associated with cadmium-related pathogenic genes.

Persistent exposure to low-dose of cadmium is strongly linked to both the development and prognosis of non-small cell lung cancer (NSCLC), yet the precise molecular mechanism behind this relationship remains uncertain. In this study, cadmium-related pathogenic genes (CRPGs) in NSCLC were identified via differential expression analysis. NSCLC patient clusters related to CRPGs were constructed through univariate Cox and K-means clustering algorithms. Multivariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were employed to determine the prognosis. Sixteen CRPGs showed a significant association with NSCLC. We found biological and prognostic differences between patients in clusters A and B. A predictive prognostic risk model for NSCLC revealed that FAM83H, MSMO1, and SNAI1 are central. Hence, the 3 hub genes were named. To further elucidate the role of CRPGs in NSCLC, A549 cells were exposed to CdCl2. The mRNA and protein expression levels of the 3 hub genes and cell invasion were detected. Moreover, 10 µM CdCl2 may increase the protein expression of 3 hub genes and enhance the invasive ability of A549 cells. This risk model may have established a theoretical foundation for investigating the mechanisms, treatment, and prognosis of NSCLC.

The effect of lipid emulsion on pharmacokinetics and tissue distribution of bupivacaine in rats.

BACKGROUND: While lipid emulsion may reverse the systemic toxicity of bupivacaine, the pharmacokinetics and tissue distribution of bupivacaine after lipid emulsion infusion are not clear. In this study, we assessed the influence of lipid emulsion administration on the pharmacokinetics and tissue distribution of bupivacaine. METHODS: Rats in the lipid group were administered IV bupivacaine at the rate of 2 mg·kg(-1)·min(-1) for 4 minutes, and then were treated with an infusion of 30% lipid emulsion at the rate of 3 mL·kg(-1)·min(-1) for 5 minutes; saline was substituted in the control group (n = 6 for pharmacokinetics). We then randomly assigned 100 rats into the lipid group and control group (n = 50 for distribution). The toxicity model and treatment were the same as the pharmacokinetic portion. Plasma and tissues including brain, heart, liver, spleen, lung, kidney, omentum, and muscle were collected. The plasma concentration and tissue content of bupivacaine were measured by a liquid chromatography-tandem mass spectrometric method. A 2-compartmental analysis was performed to calculate the pharmacokinetics of bupivacaine. RESULTS: All data are shown as mean ± SD. After treatment with the lipid emulsion, t1/2ß of bupivacaine in the lipid group was significantly shorter (110 ± 25 minutes vs 199 ± 38 minutes, P = 0.001), the clearance was higher (14 ± 4 mL·mg(-1)·kg(-1) vs 9 ± 4 mL·mg(-1)·kg(-1), P = 0.038), and the t1/2α was longer than that of the control group (4 ± 1 minutes vs 2 ± 1 minutes, P = 0.014); the K12 in the lipid group was less than that of the control group (0.13 ± 0.04 vs 0.32 ± 0.13, P = 0.011). In the lipid group, the bupivacaine content in heart, brain, lung, kidney, and spleen was lower than that in the control group, but higher in the liver at 20, 30, and 45 minutes. CONCLUSION: The lipid sink phenomenon was observed in this study. The use of a lipid emulsion accelerated the elimination of bupivacaine.

Ultrasound-guided anterior quadratus lumborum block at the L2 level for postsurgical analgesia in patients undergoing laparoscopic gynaecological surgery: a single-centre, randomised, double-blinded trial at a university-affiliated hospital in China.

OBJECTIVE: This study aimed to investigate the analgesic effect of an ultrasound-guided anterior quadratus lumborum block (QLB) at the L2 level on postoperative pain after laparoscopic gynaecological surgery. DESIGN: Prospective single-centre randomised double-blind trial. SETTING: University-affiliated hospital. PARTICIPANTS: Sixty patients aged between 18 and 65 years scheduled for laparoscopic gynaecological surgery. INTERVENTIONS: Before surgery, bilateral anterior QLB was performed with 20 mL of 0.375% ropivacaine injected on each side in the QLB group, whereas equal amount of saline was administered in the placebo group. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was the cumulative morphine dose in the first 24 hours, and the secondary endpoints were morphine consumption at each time interval, area under the curve (AUC) of the numeric rating scale (NRS) for pain, maximum pain intensity, incidence of moderate-to-severe pain (NRS>3), sedation score, adverse events, and time to home-readiness. RESULTS: Cumulative morphine consumption in the first 24 hours after surgery was significantly lower in the QLB group than in the placebo group (mean difference, 14.2; 95% CI 6.3 to 22.1; p<0.001). The AUCs of NRS pain intensity scores, including visceral and incisional pain at rest and on movement, were significantly lower in the QLB group than in the placebo group (all p<0.001). The time to home-readiness was significantly shorter in the QLB group than in the placebo group (p<0.05). CONCLUSION: Ultrasound-guided anterior QLB at the L2 level significantly reduced morphine consumption and relieved visceral and incision pain intensity after laparoscopic gynaecological surgery, which was beneficial for enhanced recovery. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR-IOR-17011960).

Cytosolic JNK-dependent microtubule reassembly protects Jurkat leukemia cells from selenite-induced apoptosis.

BACKGROUND: Selenite at high dosage exhibits great potential in curing tumors. It has been shown that selenite inhibits tumor growth through regulation of microtubule dynamics, however, the exact underlying mechanisms remained to be fully elucidated. METHODS & RESULTS: Western blots were carried out to evaluate expression level of different molecules. Our current study discovered that selenite induced microtubule disassembly, cell cycle arrest and finally resulted in apoptosis in Jurkat leukemia cells, while during this process disassembled tubulins were re-organized after long-term exposure to selenite. Furthermore, JNK was activated in the cytoplasm of selenite-treated Jurkat cells, and inhibition of JNK activity successfully prevented the process of microtubule re-assembly. Moreover, inactivation of JNK further enhanced selenite-induced cell cycle arrest and apoptosis. According to the results from cell counting-8 assay, blockage of microtubule re-assembly by colchicine further inhibited Jurkat cell viability after exposure to selenite. Experiments in a xenograft model also proved that selenite could alter JNK activity, destroy microtubule structure and inhibit cell division in vivo. Moreover, TP53, MAPT and YWHAZ were identified to be three most confident interactors that link JNK to microtubule assembly using PPIs analysis. CONCLUSION: Our study indicated that cytosolic JNK-dependent microtubule re-organization took a protective function during selenite-induced apoptosis, while inhibition of this process would finally enhance the anti-tumor effect of selenite.

Efficacy of ultrasound-guided bilateral costal margin block in laparoscopy-assisted gastrectomy: A double-blind randomized trial.

BACKGROUND: Ultrasound-guided costal margin block (CMB) is a superficial and easily applicable technique. The current study aims to investigate its analgesic efficacy in patients undergoing laparoscopy-assisted gastrectomy and describe its feasibility. METHODS: Forty-two patients undergoing laparoscopy-assisted gastrectomy were enrolled in this prospective, double-blind, randomized clinical trial. Patients were randomized to receive standard general anesthesia with (block group, n = 21) or without (control group, n = 21) ultrasound-guided bilateral CMB. The primary outcome was 24-h intravenous morphine equivalents after surgery. Secondary outcomes included consumption of titrated morphine, 24-48 h morphine equivalents, consumption of intraoperative remifentanil, numerical pain rating scale scores, time to first opioid dose, patient satisfaction, adverse effects, and recovery events. RESULTS: The postoperative 24-h morphine equivalents in the block group were significantly reduced compared to the control group (14.4 ± 7.4 mg vs. 29.9 ± 9.8 mg, p < 0.001). Both the titrated morphine consumption in the post-anesthesia care unit (PACU) and intraoperative remifentanil consumption were lower in the block group than in the control group. Patients in the block group had relatively lower average pain scores in PACU and reported more satisfaction with pain relief. Adverse effects and hospital length of stay after surgery were comparable between the two groups (p > 0.05). CONCLUSION: As a novel and easily-performed technique, ultrasound-guided bilateral CMB can reduce opioid consumption in patients undergoing laparoscopy-assisted gastrectomy.

Bibliometric Analysis Reveals the Progress of PM2.5 in Health Research, Especially in Cancer Research.

PM2.5 has an aerodynamic diameter of less than or equal to 2.5 microns due to its inherent physical and chemical properties so that it can enter the alveoli through the respiratory tract for blood gas exchange. Numerous studies have shown that PM2.5 is a serious air pollutant that poses a wide range of health risks, especially for cancer. Bibliometric methods were employed to have comprehensively analyzed the research of PM2.5 in cancer for about a decade in Web of Science to identify hotspots and trends using VOSviewer, CiteSpace, and R. The field has undergone overall growth in the past decade. As research on PM2.5 in health deepens, cancer related to it expanded beyond the respiratory system to the digestive system, urinary system, female gonadal axis, breast cancer and other cancers. Another observation is that research on PM2.5 in cancer has progressed in the mechanisms of deterioration, such as the role of matrix metalloproteinases in cancer. In addition, research on the risks of PM2.5 in combination with polycyclic aromatic hydrocarbons and heavy metals has also emerged. Results showed that there are relatively more studies on PM2.5 in high-latitude countries, which may be due to different national conditions, such as climate and coal combustion. Our research has combed through the progress of PM2.5 in cancer research and provided a supplement for developing pollution prevention ideas with different national conditions in this field.

[Mechanisms of moxibustion preconditioning underlying improving learning-memory ability by regulating polarization of microglia via TLR4/NF-κB signaling pathway in AD rats].

OBJECTIVE: To observe the effect of moxibustion preconditioning on learning-memory ability, Toll like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) signal pathway related proteins and microglia in rats with Alzheimer's disease (AD), so as to explore its possible mechanisms underlying improvement of AD. METHODS: Male SD rats were randomly divided into normal, sham operation, AD model and pre-moxibustion groups, with 9 rats in each group. Moxibustion was applied to "Baihui"(GV20), "Shenshu"(BL23) and "Zusanli"(ST36) for 15 min, once daily, 6 days as a course of treatment for 3 courses. At the end of moxibustion, the AD model was established by injection of Aß25-35 aggregation solution into the bilateral hippocampus. The sham operation group was only injected with the same amount of 0.9% Nacl solution. The spatial learning-memory ability of rats was detected by Morris water maze test, the ultrastructure of hippocampal neurons was observed by transmission electron microscope (TEM). The histopathological changes of hippocampus tissue were observed by HE staining, and the protein expression levels of TLR4 and NF-κB p65 in the hippocampus detected by Western blot, and the positive expressions of Iba-1, CD80 and CD206 in the hippocampal CA1 region were detected by immunofluorescence labeling. The contents of inflammatory factors IL-1ß, TNF-α and IL-10 in the hippocampus were measured by ELISA. RESULTS: Compared with the sham operation group, the escape latency was significantly increased (P<0.01), and the number of platform quadrant crossing times was decreased (P<0.01) in the model group. In comparison with the model group, the increased escape latency and the decreased platform quadrant crossing times were reversed in the pre-moxibustion group (P<0.01). TEM and light microscope observation showed loose arrangement of cells, enlarged cell space, degeneration, swelling and deformation of hippocampal neurons, rupture of membranes of a large number of cells, reduction of mitochondria, dilation of endoplasmic reticulum, and matrix vacuoles, uneven distribution of organelles and cytoplasm, and being difficult in distinguishing the nuclear cytoplasm in the model group, which was relatively milder in the pre-moxibustion group. The expression levels of hippocampal NF-κB p65 and TLR4, the mean immunofluorescence density of Iba-1 and CD80, as well as the contents of IL-1ß and TNF-α in hippocampal CA1 region were significantly increased in the model group than those in the sham operation group (P<0.01), and obviously decreased in the pre-moxibustion group than those in the model group (P<0.05, P<0.01). Whereas the expression of CD206 and the content of IL-10 were evidently decreased in the model group than those in the sham operation group (P<0.01), and strikingly increased in the pre-moxibustion group than those in the model group (P<0.01). No significant differences were found between the sham operation group and the normal group in all the indexes mention above (P>0.05). CONCLUSION: Pre-moxibustion at GV20, BL23 and ST36 can improve learning-memory ability in AD rats, which may be associated with its functions in promoting the polarization of microglia from M1 to M2 and reducing the neuroinflammatory response by way of TLR4/NF-κB signaling pathway.

Radiotherapy prognosis-associated gene GCNT3 promotes the proliferation, migration and invasion of lung adenocarcinoma cells.

Lung cancer is a life-threatening malignant tumour that is prevalent worldwide. Here, the GCNT3 gene in lung adenocarcinoma was studied via public databases, and cytology and molecular biology experiments were performed to further explore the role of this gene in lung adenocarcinoma. In this study, abnormally high GCNT3 expression levels were observed in tumour tissues compared with normal tissues at both the mRNA and protein levels. In the pancancer analysis, abnormal GCNT3 expression was observed in many tumour types. Moreover, the survival analysis revealed that among patients receiving radiotherapy, those with high GCNT3 expression levels had a worse prognosis. Cell and molecular biology experiments showed that the proliferation, migration and invasion capabilities of the A549 cell line were decreased after knockdown of GCNT3, and epithelial-mesenchymal transformation was significantly inhibited. In subsequent studies, we found that the sensitivity of cells to radiotherapy was enhanced after GCNT3 knockdown. Overall, our findings reveal that GCNT3 is an important factor affecting the radiotherapy sensitivity of lung adenocarcinoma, and GCNT3 inhibition deserves further study as a radiotherapy sensitising strategy.

ATM/IKK alpha axis regulates the crosstalk between autophagy and apoptosis in selenite-treated Jurkat cells.

Selenium is an essential trace element. High dosage of selenite exhibits a great potential in treating leukemia. Previous study discovered selenite could promote leukemia cells apoptosis through inducing DNA damage and cell cycle arrest, while the switch mechanisms of these events and autophagy were still unclear. Current study discovered selenite promoted autophagy and apoptosis of leukemia Jurkat cells. In this process, DNA damage related ATM/IKK alpha axis was activated. This axis could stabilize pro-apoptotic P73, and promote autophagy through regulating NF-kappaB signaling pathway. Moreover, survivin-2B was also confirmed to be necessary for the ATM-induced nuclear location of IKK alpha, and therefore stood at the node position of apoptosis and autophagy cascades inside Jurkat cells. Finally, our in vivo experiments proved that selenite exhibited some anti-tumor effects on Jurkat cells-bearing mice. Moreover, alterations of ATM and IKK alpha expression observed in vivo were similar to that identified in vitro. Therefore, our findings had fully confirmed survivin-2B dependent activation of ATM/IKK alpha axis might be another crosstalk between autophagy and apoptosis of selenite-treated leukemia cells.

Association between socio-economic factors and the risk of overweight and obesity among Chinese adults: a retrospective cross-sectional study from the China Health and Nutrition Survey.

BACKGROUND: With the rising prevalence of obesity and overweight, increasing number of scholars paid attention to the negative effects on human health and life. Recent years, many studies have focused on the relation of socio-economic factors with the risk of overweight or obesity, but findings have been inconsistent. This study investigated the relationship between socio-economic factors and the risk of overweight and obesity among Chinese adults. METHODS: This study was based on the survey of the China Health and Nutrition Survey in 2015, with 9245 Chinese adults aged 18-65 years old. Overweight and obesity were assessed by physical measurements of weight, height, and waist circumference. Multiple logistic models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of the association. RESULTS: Overall, the prevalence rates of general obesity and abdominal obesity were 15.5% and 22.6%, respectively. We found that education and per capita household income were positively associated with overweight and obesity risk in men. However, the association between education and obesity status was negative in women [general obesity: OR = 0.64, 95% CI (0.50-0.81); abdominal obesity: OR = 0.62, 95% CI (0.51-0.76)]. Occupational status was only associated with general overweight in men. CONCLUSIONS: Results suggested that higher education and per capita household income were associated with an increased risk of overweight and obesity among Chinese men, whereas the associations were negative for women. We recommended that men with high levels of education and income, women with low levels of education, can engage in some physical activity, modify dietary, and adopt a new way of life to maintain their weight and general health.

YTHDF2 Inhibits the Migration and Invasion of Lung Adenocarcinoma by Negatively Regulating the FAM83D-TGFß1-SMAD2/3 Pathway.

OBJECTIVE: YTH domain family 2 (YTHDF2) is an important N6-methyladenosine (m6A) reader, but its role in lung adenocarcinoma remains elusive. This study assessed its function in lung adenocarcinoma. METHODS: YTHDF2 expression in lung adenocarcinoma was explored using public databases, such as The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumour Analysis Consortium (CPTAC). The effect of YTHDF2 on a lung adenocarcinoma cell line was explored by performing cytological and molecular experiments. Molecules downstream of YTHDF2 were identified using proteomics, and the related pathways were verified through cytological and molecular biology experiments. RESULTS: YTHDF2 expression was upregulated in lung adenocarcinoma, and patients with high YTHDF2 expression experienced prolonged overall survival. In two lung cancer cell lines, YTHDF2 knockdown inhibited proliferation but promoted migration, invasion, and the epithelial-mesenchymal transition. The proteomic analysis identified 142 molecules downstream of YTHDF2, and 11 were closely related to survival. Further experiments revealed that YTHDF2 inhibited expression of the family with sequence similarity 83D (FAM83D)-TGFß1-SMAD2/3 pathway components. This study is the first to show that YTHDF2 regulated the downstream TGFß1-SMAD2/3 pathway through FAM83D in lung adenocarcinoma. CONCLUSION: YTHDF2 inhibits the migration and invasion of lung adenocarcinoma cells by regulating the FAM83D-TGFß1-pSMAD2/3 pathway, which may play an important role in lung cancer metastasis.