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The LJP61A suppressed macrophage foam cell formation and atherosclerotic progression by modulating Ca2+-calpain mediated autophagy inhibition.

The accumulation and sustained release of drugs in the colonic inflammatory region are the favorable strategy for treating ulcerative colitis (UC). In this study, we developed a synergistic anti-inflammatory drug (quercetin/EGCG)-loaded micelle using hydrolytic quinoa protein (HQP) and cationic lotus root starch (CLRS) by a layer-by-layer assembly method. The encapsulation efficiency of quercetin and EGCG in the Que-HQP-EGCG-CLRS micelles reached 91.5 and 89.4%, respectively. This composite micelle exhibited a core-shell structure, where Que-HQP-EGCG was the core and CLRS was the coating shell. Moreover, the in vitro experiments indicated that these micelles can make Que/EGCG pass through gastric environments stably and delay their release in the intestine. Animal experiments further confirmed that the Que-HQP-EGCG-CLRS micelles can efficiently accumulate in the colonic inflammatory region and enable sustained release of drugs (more than 24 h), thus notably alleviating the symptoms of UC. These results suggested that Que-HQP-EGCG-CLRS micelles have good gastric stability, colonic inflammatory-accumulated effect, and sustained drug release ability, which are a promising co-delivery system for UC treatment.

This study aimed to investigate the association between preoperative dipstick albuminuria (DA) and acute kidney injury (AKI) in high-risk patients following non-cardiac surgery.This was a single-center prospective cohort study. Adult patients with high risk of AKI undergoing non-cardiac surgery were enrolled. The primary outcome was AKI, defined according to KDIGO criteria within 7 days following non-cardiac surgery. DA status was determined by urinalysis performed within 24 h of hospital admission. Multivariate logistic regression model was used to analyze the association between preoperative DA and postoperative AKI.During the study period, 552 patients were enrolled and 8.5% of them developed postoperative AKI. The overall rate of preoperative positive DA was 26.4% with 30 and ≥ 100 mg/dL DA accounting for 19.2% and 7.2%, respectively. Patients with more severe preoperative DA had much higher rate of postoperative AKI (5.2% in patients with negative or trace DA, 13.2% in patients with 30 mg/dL DA and 30.0% in patients with ≥ 100 mg/dL DA, P 0.001). After adjusting for several perioperative variables, preoperative 30 mg/dL DA (OR 2.575; 95% CI 1.049-6.322; P = 0.039) and ≥ 100 mg/dL DA (OR 3.868; 95% CI 1.246-12.010; P = 0.019) showed an independent association with postoperative AKI. In addition, patients with higher DA status demonstrated significantly increased level of postoperative urine biomarkers and their ratio to urine creatinine.Preoperative DA was independently associated with AKI in high-risk patients following non-cardiac surgery. Preoperative routine urinalysis for determination of DA status was suggested in early risk stratification.

In the present work, four groups of spherical chromium carbide reinforced NiCrBSi hardmetal coatings were prepared on AISI 4145 steel by plasma transferred arc (PTA) technique. The corrosion behavior of the four as-received hardmetal coatings in 0.5 mol/L H2SO4 solution was investigated by polarization curve and electrochemical impedance spectroscopy (EIS). The results revealed that more Cr-rich carbides (Cr3C2, Cr7C3 and M23(C, B)6) are formed in the chromium carbide reinforced coatings, while for the NiCrBSi hardmetal coating only Cr7C3 carbide was detected by XRD. The polarization results show that the chromium carbide reinforced NiCrBSi hardmetal coatings have positive corrosion potential and lower corrosion current, providing a better protective effect to the substrate metal. The combined effects of Cr-rich carbide ceramic phases and a more stable passive film of Cr2O3 greatly improved the corrosion resistances of the chromium carbide reinforced NiCrBSi hardmetal coatings. The coating with the highest spherical chromium carbide addition has more pores because of the thermal stress due to the difference of thermal expansion coefficient between the NiCrBSi bonding phase and chromium carbide reinforced phase. The negative effects of the pores weaken the corrosion resistance, and the coating with the 30% chromium carbide content shows the best corrosion resistance. For NiCrBSi hardmetal coatings with higher reinforced chromium carbide content, the repeatability of the corrosion current obtained by polarization fitting is not as good as that of coatings with lower chromium carbide content. The repeatability of polarization results becomes worse when the specimens keep in a more stable passive state.

To study the influence of electrothermal effect of ESD protection device on the reliability of inte-grated circuit,a theoretical model of ESD protection device thermal resistance is constructed in the paper based on the Conservation of Energy Principle. By analyzing the temperature relativity between electricity parameter and thermology parameter of ESD protection device characterized by self-heating thermal resistance, the quantitative relationship expression of physical parameter and geometric parameter is obtained, which can be used to improve ESD protection device elec-tro-thermal effect. The simulation testing and the real tape-out testing of ESD protection device self-heating thermal resistance based on ggNMOS are shown and compared. It is concluded that self-heating thermal resistance is an effective index for the protection device electrothermal char-acterization. Based on the established model, the self-heating thermal resistance could be decreased to improve the homogeneity of the heat transference. The uneven distribution of device temperature can be reduced, and the overall reliability of chips can be improved.

Acute kidney injury (AKI) is a common and adverse complication following non-cardiac surgery. Evidence have shown urine microscopy could help early detection, differentiating the causes and predicting the progression of AKI. However, little evidence is available on AKI after non-cardiac surgery. Thus, we investigated the association between urine microscopy and severe AKI in critically ill patients after non-cardiac surgery.This was a single-center prospective cohort study. The primary outcome was severe AKI, defined as stage 2 or 3 according to maximal KDIGO criteria within 7 days following non-cardiac surgery. Urine microscopy immediately, 6 and 12 hours after surgical intensive care unit (SICU) admission were examined and graded by a urine microscopy score (UMS) based on the observed quantification of renal tubular cells and casts in the sediment. Then, multivariate Logistic regression models were used to analyze the associations between UMS and postoperative severe AKI.From May 20, 2019 to November 24, 2020, 661 patients were enrolled with 147 patients (22.2%) developing postoperative severe AKI. Multivariate Logistic regression model showed elevated UMS (≥1) 6 and 12 hours after SICU admission were independently associated with postoperative severe AKI (OR 2.200, 95% CI: 1.182-4.095, P=0.013 and OR 2.949, 95% CI: 1.657-5.248, P0.001, respectively). Furthermore, higher UMS 6 hours after SICU admission demonstrated correlation with greater risk of severe AKI with OR 3.887 (95% CI: 1.430-10.563) for UMS ≥3 and OR 2.429 (95% CI: 1.237-4.770) for UMS =1-2. The specificity and sensitivity of UMS ≥1 for severe AKI was 93.8% (95% CI: 91.7-95.9%) and 15.6% (95% CI: 9.7-21.5%), respectively. While the negative and positive predictive value was 79.5% (95% CI: 76.3-82.7%) and 41.8% (95% CI: 28.8-54.8%), respectively. In addition, patients with higher UMS (≥3, 1-2 and 0) had significantly more postoperative complications and longer SICU stay; and they also showed a trend toward other adverse postoperative outcomes.Early urine microscopy was independently associated with severe AKI in critically ill patients following non-cardiac surgery with higher UMS related to greater risk.ClinicalTrials.gov identifier: NCT03880110.

The relationship between the severity of impairment in basic activities of daily living (ADLs) function and postoperative outcomes in older surgical patients remains unclear. This study aimed to clarify the association between the severity of preoperative functional impairment and the composite postoperative outcome of major morbidity and mortality in older patients undergoing digestive tract surgery.This was a retrospective cohort study. We collected perioperative data of older patients (age ≥ 65 years) who underwent digestive tract surgery in our institution. The severity of functional impairment was assessed using the Barthel Index scale before surgery. The major morbidity and mortality were defined as Clavien-Dindo grade III or greater postoperative complications during hospital stay. The association between the severity of functional impairment and the major morbidity and mortality was assessed using a multivariable logistic regression model.131 of 1076 patients (12.2%) developed major morbidity and mortality. After controlling for confounding factors, high Barthel Index scores were correlated with decreased risk of major morbidity and mortality (OR 0.986, 95% CI 0.976-0.997, P = 0.011); preoperative severe (OR 2.862, 95% CI 1.172-6.989, P = 0.021), but not mild or moderate (OR 1.019, 95% CI 0.602-1.726, P = 0.943) functional impairment was independently associated with an increased risk of major morbidity and mortality, when compared with independent functional status.Preoperative severe functional impairment in basic ADLs was independently associated with a higher risk of major postoperative morbidity and mortality in older patients undergoing digestive tract surgery.

Background The subgenual anterior cingulate cortex (sgACC) appears to play a central role in the pathophysiology of major depressive disorder (MDD). To wit, its functional interactive profile with the left dorsal lateral prefrontal cortex (DLPFC) has been shown to be related to treatment outcomes with transcranial magnetic stimulation (TMS) treatment outcomes. Nevertheless, previous research on sgACC functional connectivity (FC) in MDD has yielded inconsistent results, partly due to small sample sizes and limited statistical power of prior work.Methods Here, leveraging a large multi-site sample (1660 MDD patients vs. 1341 healthy controls) from Phase II of the Depression Imaging REsearch ConsorTium (DIRECT), we systematically delineated case-control difference maps of sgACC FC and examined their clinical relevance to previously identified TMS targets. We also investigated case-control FC difference maps of left DLPFC sub-fields.Results In MDD patients we found significantly increased FC between sgACC and thalamus and reduced FC to a broad array of brain regions, including somatosensory area, occipital lobe, medial and lateral temporal lobe, and insular cortex, when global signal regression (GSR) was not implemented. Intriguingly, we found enhanced left DLPFC-sgACC FC in MDD patients when GSR was performed. We leveraged an prior independent sample to explore the possible relationship between the case-control differences regarding sgACC’s FC profiles and the treatment out comes of TMS. In sites in which open TMS treatment was administered, case-control differences in sgACC FC, with GSR, were related to clinical improvement. Next we tested whether the position of peak of the FC maps (previously identified TMS target) could be altered in MDD patients as compred with healthy controls (HC)s. We found the optimized TMS target differed in MDD patients. Several DLPFC sub-fields yielded case-control differences in whole-brain FC maps.Conclusion In summary, we reliably delineated MDD-related abnormalities of sgACC FC profiles in a large sample. GSR was essential in applying case-control difference maps to identify optimized TMS targets. Our results highlight the functional heterogeneity of the left DLPFC and of precise TMS targets therein.

BackgroundFrailty predicts an increased risk of postoperative morbidity and mortality. Comparison of the predictive performance between two deficit accumulation models of frailty, the modified frailty index (mFI) and the revised-Risk Analysis Index (RAI-rev), is poorly understood. This study compared the predictive abilities of the above two frailty indices in predicting life-threatening morbidity and mortality among older patients following elective high-risk abdominal surgery.MethodsThis retrospective cohort study extracted perioperative data of older patients (age ≥65 years) undergoing elective high-risk abdominal surgery at a single institution between January 2018 and December 2020. Preoperative frailty was screened by mFI and RAI-rev scoring systems. The primary outcome was the composite of postoperative life-threatening morbidity and mortality during hospitalization. Multivariable logistic regression analyses were performed to investigate the association of the two frailty indices with the primary outcome. Receiver-operating characteristic (ROC) curve was employed to test the predictive performances of the two frailty instruments in predicting the composite primary outcome. The difference between the area under the curves (AUCs) was assessed by DeLong’s test.Results1,132 older patients (mean age, 73.4 ± 6.2 years; 63.9% male) were included. Of these, 107 (9.5%) developed postoperative life-threatening morbidity and mortality. In multivariable logistic regression analyses, rising continuous frailty scores (mFI: adjusted OR 1.319 per 0.09-point increase in score, 95% CI 1.151–1.511, p p = 0.002) as well as dichotomized frailty measures (mFI ≥0.27: adjusted OR 2.059, 95% CI 1.328–3.193, p = 0.001; RAI-rev ≥45: adjusted OR 1.862, 95% CI 1.188–2.919, p = 0.007) were associated with increased odds of the primary outcome separately. ROC curve analysis showed that the discrimination of mFI and RAI-rev scores for the life-threatening morbidity and mortality was poor and comparable (AUC: 0.598 [95% CI 0.569–0.627] vs. 0.613 [95% CI 0.583–0.641]; DeLong’s test: Z = 0.375, p = 0.7075).ConclusionHigh mFI and RAI-rev scores were associated with an increased risk of life-threatening morbidity and mortality in older patients undergoing elective high-risk abdominal surgery. However, both frailty indices displayed poor discrimination for postoperative life-threatening morbidity and mortality.

The selectivity of chemotherapeutic agents for liver cancer is poor. When they kill tumour cells, they produce serious adverse reactions in the whole body and multidrug resistance (MDR) is also a major hurdle in liver cancer chemotherapy. Combination therapy is a useful method for overcoming MDR and reducing toxic and side effects. In this study, we developed a long-circulating codelivery system, in which doxorubicin (DOX) and schizandrin A (SchA) are combined against MCF-7/ADR cells. The DOX-SchA long-circulating liposome (DOX-SchA-Lip) was prepared using ammonium sulphate gradient method. The two drugs were co-encapsulated into the distearoyl phosphatidylethanolamine-polyethylene glycol (DSPE-mPEG2000) liposome and the liposome had an average particle size of (100 ± 3.5) nm and zeta electrical potential of (-31.3 ± 0.5) mV. The average encapsulation rate of DOX was 97.98% and that of SchA was 86.94%. DOX in liposome had good sustained-release effect. The results showed that DOX-SchA-Lip could significantly prolong the half-life (t1/2z) of the DOX and SchA, increase their circulation time in vivo, improve its bioavailability and reduce their side effects. Liposome can effectively induce early apoptosis of HepG2/ADR cells and the cell cycle was blocked in S-phase by DOX-SchA-Lip in a dose-dependent manner. The IC50 of compound liposome to HepG2 and HepG2/ADR were 0.55 μmol/L and 1.38 μmol/L, respectively, which could significantly reverse the resistance of HepG2/ADR and the reversion multiple was 30.28. It was verified that DOX-SchA-Lip can effectively kill tumour cells and reverse MDR.

Aberrant topological organization of whole-brain networks has been inconsistently reported in studies of patients with major depressive disorder (MDD), reflecting limited sample sizes. To address this issue, we utilized a big data sample of MDD patients from the REST-meta-MDD Project, including 821 MDD patients and 765 normal controls (NCs) from 16 sites. Using the Dosenbach 160 node atlas, we examined whole-brain functional networks and extracted topological features (e.g., global and local efficiency, nodal efficiency, and degree) using graph theory-based methods. Linear mixed-effect models were used for group comparisons to control for site variability; robustness of results was confirmed (e.g., multiple topological parameters, different node definitions, and several head motion control strategies were applied). We found decreased global and local efficiency in patients with MDD compared to NCs. At the nodal level, patients with MDD were characterized by decreased nodal degrees in the somatomotor network (SMN), dorsal attention network (DAN) and visual network (VN) and decreased nodal efficiency in the default mode network (DMN), SMN, DAN, and VN. These topological differences were mostly driven by recurrent MDD patients, rather than first-episode drug naive (FEDN) patients with MDD. In this highly powered multisite study, we observed disrupted topological architecture of functional brain networks in MDD, suggesting both locally and globally decreased efficiency in brain networks.

Background and aimsFindings about the associations between transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 and nonalcoholic fatty liver disease have not been consistently replicated, particularly in steatosis and fibrosis. The present study aimed to investigate the associations between the rs58542926T allele and the spectrum of NAFLD and its related metabolic phenotypes.MethodsSystematic literature research was performed to analyse the associations between rs58542926 and the spectrum of NAFLD and its related metabolic phenotypes. A random effects meta-analysis with a dominant genetic model was applied.ResultsData from 123,800 individuals across 44 studies were included in the current meta-analysis.rs58542926 T allele was associated with an increased risk of NAFLD in both adults (OR=1.62; 95% CI: 1.40, 1.86) and children (OR=2.87; 95% CI: 1.85, 4.46). Children had a stronger association with NAFLD (P=0.01). rs58542926 T allele was also positively associated with steatosis progression (mean difference=0.22; 95% CI: 0.05, 0.39) and fibrosis stage (OR=1.50; 95% CI: 1.20, 1.88) in adults. The TM6SF2 rs58542926 T allele was positively associated with ALT in both adults and children (both PPPPConclusionTM6SF2 rs58542926 is involved in the entire spectrum of NAFLD and its related metabolic phenotype, and differences in serum lipid levels were observed between adults and children.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021288163.

Is the brain at rest during the so-called resting-state? Ongoing experiences in the resting-state vary in unobserved and uncontrolled ways across time, individuals, and populations. However, the role of self-generated thoughts in resting-state fMRI remains largely unexplored. In this study, we collected real-time self-generated thoughts during “resting-state” fMRI scans via the think-aloud method (i.e., think-aloud fMRI), which required participants to report whatever they were currently thinking. We first investigated brain activation patterns during a think-aloud condition and found that significantly activated brain areas included all brain regions required for speech. We then calculated the relationship between divergence in thought content and brain activation during think-aloud and found that divergence in thought content was associated with many brain regions. Finally, we explored the neural representation of self-generated thoughts by performing representational similarity analysis (RSA) at three neural scales: a voxel-wise whole-brain searchlight level; a region-level whole-brain analysis using the Schaefer 400-parcels; at the systems level using the Yeo seven-networks. We found that “resting-state” self-generated thoughts were distributed across a wide range of brain regions, involving all seven Yeo networks. This study highlights the value of considering ongoing experiences during resting-state fMRI, as well as providing preliminary methodological support for think-aloud fMRI.

Background Regional anesthesia and analgesia reduce the stress response to surgery and decrease the need for volatile anesthesia and opioids, thereby preserving cancer-specific immune defenses. This study therefore tested the primary hypothesis that combining epidural anesthesia–analgesia with general anesthesia improves recurrence-free survival after lung cancer surgery. Methods Adults scheduled for video-assisted thoracoscopic lung cancer resections were randomized 1:1 to general anesthesia and intravenous opioid analgesia or combined epidural–general anesthesia and epidural analgesia. The primary outcome was recurrence-free survival (time from surgery to the earliest date of recurrence/metastasis or all-cause death). Secondary outcomes included overall survival (time from surgery to all-cause death) and cancer-specific survival (time from surgery to cancer-specific death). Long-term outcome assessors were blinded to treatment. Results Between May 2015 and November 2017, 400 patients were enrolled and randomized to general anesthesia alone (n = 200) or combined epidural–general anesthesia (n = 200). All were included in the analysis. The median follow-up duration was 32 months (interquartile range, 24 to 48). Recurrence-free survival was similar in each group, with 54 events (27%) with general anesthesia alone versus 48 events (24%) with combined epidural–general anesthesia (adjusted hazard ratio, 0.90; 95% CI, 0.60 to 1.35; P = 0.608). Overall survival was also similar with 25 events (13%) versus 31 (16%; adjusted hazard ratio, 1.12; 95% CI, 0.64 to 1.96; P = 0.697). There was also no significant difference in cancer-specific survival with 24 events (12%) versus 29 (15%; adjusted hazard ratio, 1.08; 95% CI, 0.61 to 1.91; P = 0.802). Patients assigned to combined epidural–general had more intraoperative hypotension: 94 patients (47%) versus 121 (61%; relative risk, 1.29; 95% CI, 1.07 to 1.55; P = 0.007). Conclusions Epidural anesthesia–analgesia for major lung cancer surgery did not improve recurrence-free, overall, or cancer-specific survival compared with general anesthesia alone, although the CI included both substantial benefit and harm. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background Experimental and observational research suggests that combined epidural–general anesthesia may improve long-term survival after cancer surgery by reducing anesthetic and opioid consumption and by blunting surgery-related inflammation. This study therefore tested the primary hypothesis that combined epidural–general anesthesia improves long-term survival in elderly patients. Methods This article presents a long-term follow-up of patients enrolled in a previous trial conducted at five hospitals. Patients aged 60 to 90 yr and scheduled for major noncardiac thoracic and abdominal surgeries were randomly assigned to either combined epidural–general anesthesia with postoperative epidural analgesia or general anesthesia alone with postoperative intravenous analgesia. The primary outcome was overall postoperative survival. Secondary outcomes included cancer-specific, recurrence-free, and event-free survival. Results Among 1,802 patients who were enrolled and randomized in the underlying trial, 1,712 were included in the long-term analysis; 92% had surgery for cancer. The median follow-up duration was 66 months (interquartile range, 61 to 80). Among patients assigned to combined epidural–general anesthesia, 355 of 853 (42%) died compared with 326 of 859 (38%) deaths in patients assigned to general anesthesia alone: adjusted hazard ratio, 1.07; 95% CI, 0.92 to 1.24; P = 0.408. Cancer-specific survival was similar with combined epidural–general anesthesia (327 of 853 [38%]) and general anesthesia alone (292 of 859 [34%]): adjusted hazard ratio, 1.09; 95% CI, 0.93 to 1.28; P = 0.290. Recurrence-free survival was 401 of 853 [47%] for patients who had combined epidural–general anesthesia versus 389 of 859 [45%] with general anesthesia alone: adjusted hazard ratio, 0.97; 95% CI, 0.84 to 1.12; P = 0.692. Event-free survival was 466 of 853 [55%] in patients who had combined epidural–general anesthesia versus 450 of 859 [52%] for general anesthesia alone: adjusted hazard ratio, 0.99; 95% CI, 0.86 to 1.12; P = 0.815. Conclusions In elderly patients having major thoracic and abdominal surgery, combined epidural–general anesthesia with epidural analgesia did not improve overall or cancer-specific long-term mortality. Nor did epidural analgesia improve recurrence-free survival. Either approach can therefore reasonably be selected based on patient and clinician preference. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background Depression is a common and serious complication in new mothers. We investigated the hypothesis that neuraxial labor analgesia is associated with a decreased risk of postpartum depression. Methods In this multicenter prospective cohort study with propensity score matching, 599 nulliparous women with single term cephalic pregnancy who planned vaginal delivery were enrolled and self-selected neuraxial analgesia or not. The primary outcome was 6-week postpartum depression assessed with the Chinese version Edinburgh Postnatal Depression Scale; a score of ≥10 was set as the threshold of postpartum depression. Logistic regression models were established to assess the association between neuraxial labor analgesia and postpartum depression. Results Of the 577 parturients who completed the study, 417 (72.3%) received neuraxial analgesia and 160 (27.7%) did not. After propensity score matching, 433 parturients were included in the analysis; of whom, 279 (64.4%) received neuraxial analgesia and 154 (35.6%) did not. The incidence of postpartum depression was lower in parturients with neuraxial analgesia than in those without (14.9% [62/417] vs. 23.8% [38/160], P=0.012 before matching; 13.3% [37/279] vs. 23.4% [36/154], P=0.007 after matching). After adjustment for confounding factors, neuraxial analgesia was associated with decreased odds of postpartum depression (odds ratio [OR] 0.50, 95% CI 0.28-0.88, P=0.015 before matching; OR 0.40, 95% CI 0.21-0.77, P=0.006 after matching). Limitations As an observational study, unidentified confounders might influence the results. Conclusions In nulliparae with single term cephalic pregnancy preparing to give vaginal delivery neuraxial analgesia during labor was associated with a decreased risk of 6-week postpartum depression.

Background:. Vasovagal syncope (VVS) greatly impairs quality of life. The therapeutic efficacy of oral rehydration saline (ORS) for unselected VVS patients is not satisfactory due to the diverse mechanisms of the disease. Body mass index (BMI) was demonstrated to reflect blood volume to a certain extent. Therefore, the present study explored the capability of BMI to predict the therapeutic response of children with VVS to ORS treatment. Methods:. Seventy-four children with VVS who visited the Syncope Unit of Pediatrics at Peking University First Hospital from November 2010 to June 2019 receiving ORS treatment were enrolled for this retrospective case-control study. A comparison of demographic, clinical, and hemodynamic characteristics was performed between responders and non-responders. The correlation between baseline BMI and response time was analyzed. To determine the value of baseline BMI in predicting the therapeutic efficacy of ORS in children with VVS, a receiver operating characteristic curve analysis was performed. Results:. Fifty-two children were identified as responders, and the remaining 22 children were identified as non-responders. The baseline BMI of the responders was much lower than that of the non-responders (16.4 [15.5, 17.8] kg/m2vs. 20.7 ±e6 kg/m2, P

BackgroundNeuraxial analgesia is widely used to relieve labor pain; its effects on long-term neurodevelopment of offspring remain unclear. This study was designed to investigate the influence of maternal neuraxial labor analgesia on offspring mental development.MethodsThis was a predefined secondary analysis of a 2-year prospective longitudinal study. Nulliparous women with single-term cephalic pregnancy preparing for vaginal delivery self-selected neuraxial analgesia or not during labor. Mothers and their offspring were followed up 2 years later. children's mental development was assessed with the bayley scales of infant development. A multivariable logistic model was used to identify factors associated with below-average mental development (Mental Development Index ResultsA Total of 508 pairs of mothers and children completed a 2-year follow-up. after propensity score matching, 387 pairs were included in the analysis. In both cohorts, the proportions with below-average mental development were slightly lower in children whose mothers received neuraxial labor analgesia, although not statistically significant [in the full cohort: 9.8 % (36/368) vs. 15.7% (22/140), P = 0.060; In the matched cohort: 8.3% (21/254) vs. 14.3% (19/133), P = 0.065]. A higher 2-year depression score (in the full cohort: Odds Ratio 1.15, 95% CI 1.08–1.22, P < 0.001; In the matched cohort: Odds Ratio 1.09, 95% CI 1.01–1.18, P = 0.037), but not neuraxial analgesia exposure, was associated with an increased risk of below-average mental development.ConclusionsMaternal depression at 2 years was associated with the risk of below-average mental development, whereas maternal exposure to neuraxial labor analgesia was not.Clinical Trial RegistrationThe study was registered with www.chictr.org.cn (ChiCTR-OCH-14004888) and ClinicalTrials.gov (NCT02823418).

Dignity-conserved nursing has been widely studied by scholars all over the world; however, there is no clear direction in which this field is trending.To conduct a bibliometric analysis that systematically characterises publications on dignity research in the nursing field from 2011 to 2020.Bibliometric and visual analysis of retrieved articles.The Web of Science Core Collection database was used to retrieve all articles which addressed dignity in nursing from 2011 to 2020. The WoSCC's own analysis tool, CiteSpace and VOSviewer, were used to obtain visual analysis results. Reporting follows the STROBE checklist.A total of 1429 papers on dignity care are included in this study. We found that the number of papers on this topic increased steadily, and the United States topped the list with 366 articles in total. The institute with the most publications was King's College London, and the most widely published journal was Nursing Ethics. We were able to identify four major research topics, namely dignity in: (a) palliative care, (b) dementia and the elderly, (c) health care and (d) nursing ethics. Terminally ill patient, home, value, rehabilitation and psychological distress were the five keywords with the highest burst strength.The interest in dignity care research has been steadily increasing from 2011 and is reflected in the number of published papers. The United States and Western Europe are leading in this field, both having a high number of cutting-edge researchers and high-level scientific research institutions. In the domain of dignity care, several stable and high-yield core author groups have been formed. While the existing research mainly focuses on four hot spots, psychological distress, advanced cancer, maternity care and content analysis may be the research frontiers.

Atherosclerosis is a kind of lipid-driven chronic inflammatory disease of arteries and is the principal pathological basis of life-threatening cardiovascular disease events, such as strokes and heart attacks. Clinically, statins are the most commonly prescribed drugs for the treatment of atherosclerosis, but prolonged use of these drugs exhibit many adverse reactions and have limited efficacy. Polysaccharides are important natural biomacromolecules widely existing in plants, animals, microorganisms and algae. They have drawn considerable attention worldwide due to their multiple healthy functions, along with their non-toxic property. Importantly, a growing number of studies have demonstrated that bioactive polysaccharides exhibit prominent efficiency in controlling atherosclerotic risk factors like hyperlipemia, hypertension, oxidative stress, and inflammation. In recent decades, various bioactive polysaccharides with different structural features and anti-atherosclerotic potential from natural sources have been isolated, purified, and characterized. The aim of this review is to focus on the research progress of natural polysaccharides in reducing the risks of atherosclerosis based on evidence of in vitro and in vivo studies from 1966 to 2022. PRACTICAL APPLICATIONS: In the future, it is still necessary to strengthen the research on the development and mechanism of polysaccharides with anti-atherosclerotic potential. These anti-atherosclerotic polysaccharides with different structural characteristics and physiochemical properties from different sources will constitute a huge source of materials for future applications, especially in functional foods and drugs. The information summarized here may serve as useful reference materials for further investigation, production, and application of these polysaccharides in functional foods and therapeutic agents.

The nucleus accumbens (NAc) is considered a hub of reward processing and a growing body of evidence has suggested its crucial role in the pathophysiology of major depressive disorder (MDD). However, inconsistent results have been reported by studies on reward network-focused resting-state functional MRI (rs-fMRI). In this study, we examined functional alterations of the NAc-based reward circuits in patients with MDD via meta- and mega-analysis. First, we performed a coordinated-based meta-analysis with a new SDM-PSI method for all up-to-date rs-fMRI studies that focused on the reward circuits of patients with MDD. Then, we tested the meta-analysis results in the REST-meta-MDD database which provided anonymous rs-fMRI data from 186 recurrent MDDs and 465 healthy controls. Decreased functional connectivity (FC) within the reward system in patients with recurrent MDD was the most robust finding in this study. We also found disrupted NAc FCs in the DMN in patients with recurrent MDD compared with healthy controls. Specifically, the combination of disrupted NAc FCs within the reward network could discriminate patients with recurrent MDD from healthy controls with an optimal accuracy of 74.7%. This study confirmed the critical role of decreased FC in the reward network in the neuropathology of MDD. Disrupted inter-network connectivity between the reward network and DMN may also have contributed to the neural mechanisms of MDD. These abnormalities have potential to serve as brain-based biomarkers for individual diagnosis to differentiate patients with recurrent MDD from healthy controls.

The PBRM1 (PB1) gene which encodes the specific subunit BAF180 of the PBAF SWI/SNF complex, is highly mutated (~ 40%) in clear cell renal cell carcinoma (ccRCC). However, its functions and impact on cell signalling are still not fully understood. Aerobic glycolysis, also known as the 'Warburg Effect', is a hallmark of cancer, whether PB1 is involved in this metabolic shift in clear cell renal cell carcinoma remains unclear. Here, with established stable knockdown PB1 cell lines, we performed functional assays to access the effects on 786-O and SN12C cells. Based on the RNA-seq data, we selected some genes encoding key glycolytic enzymes, including PFKP, ENO1, PKM and LDHA, and examined the expression levels. The AKT-mTOR signalling pathway activity and expression of HIF1α were also analysed. Our data demonstrate that PB1 deficiency promotes the proliferation, migration, Xenograft growth of 786-O and SN12C cells. Notably, knockdown of PB1 activates AKT-mTOR signalling and increases the expression of key glycolytic enzymes at both mRNA and protein levels. Furthermore, we provide evidence that deficient PB1 and hypoxic conditions exert a synergistic effect on HIF 1α expression and lactate production. Thus, our study provides novel insights into the roles of tumour suppressor PB1 and suggests that the AKT-mTOR signalling pathway, as well as glycolysis, is a potential drug target for ccRCC patients with deficient PB1.

Objective To evaluate the effect of multilevel single-shot thoracic paravertebral blockade (PVB) on the occurrence of chronic postsurgical pain (CPSP) in patients undergoing breast cancer surgery. Design A randomized controlled trial with two parallel groups. Setting A tertiary hospital. Methods Patients scheduled for breast cancer surgery were randomized to receive either ultrasound-guided multilevel single-shot PVB from T2 to T5 (the PVB group) or nothing (the control group). Surgery was then performed under general anesthesia. Patients were followed up for 12 months after surgery. The primary end point was incidence of CPSP at six months after surgery. Results A total of 218 patients were enrolled and randomized; of these, 208 and 204 completed six- and 12-month follow-up, respectively. The incidence of CPSP at six months was significantly lower in the PVB group (12.5% [13/104]) than in the control group (24.0% [25/104], relative risk = 0.52, 95% CI = 0.28–0.96, P = 0.031). Pain scores within 48 hours both at rest and with movement were lower in the PVB group than the control group (P = 0.006 and P Conclusions For patients undergoing breast cancer surgery, multilevel single-shot PVB reduces the incidence of CPSP at six months; it also improves early postoperative analgesia and reduces neuropathic pain at six and 12 months after surgery.

Background. Despite the recent large number of studies comparing endoscopic and laparoscopic resection for small gastrointestinal stromal tumors (GISTs) (diameter ≤ 5 cm), the results remain conflicting. The objective of this work was to perform a cumulative meta-analysis to assess the advantages and disadvantages of endoscopic resection vs. laparoscopic resection. Methods. The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched medical databases up to January 2020. Meta-analytical random or fixed effects models were used in pooled analyses. Meta-regression, cumulative meta-analyses, and subgroup analyses were performed to improve the accuracy of the conclusion. Sensitivity analyses were applied to assess the robustness of the results. Results. A total of 12 cohort studies with 1383 participants comparing endoscopic resection and laparoscopic resection were identified, while three cohort studies with 167 participants comparing endoscopic resection and laparoscopic and endoscopic cooperative surgery were found. We found that endoscopic resection had shorter operation times (weighted mean difference [WMD] = –27.1 min, 95% confidence interval [CI]: –40.8 min to –13.4 min) and lengths of hospital stay (WMD = –1.43 d, 95% CI: –2.31 d to –0.56 d) than did laparoscopic resection. The results were stable and reliable. There were no significant differences in terms of blood loss, hospitalization costs, incidence of complications or recurrence rates. For tumor sizes 2 – 5 cm, endoscopic resection increased the risk of positive margins (relative risk [RR] = 5.78, 95% CI: 1.31 – 25.46). Although operation times for endoscopic resection were shorter than those of laparoscopic and endoscopic cooperative surgery (WMD = –41.03 min, 95% CI: –59.53 min to –22.54 min), there was a higher incidence of complications (RR = 4.03, 95% CI: 1.57 – 10.34). Conclusions. In general, endoscopic resection is an alternative method for gastric GISTs ≤ 5 cm. Laparoscopic and endoscopic cooperative surgery may work well in combination. Further randomized controlled trials are recommended to validate or update these results.

Cordycepin (3'-deoxyadenosine) from Cordyceps militaris has been reported to have anti-tumor effects. However, the molecular target and mechanism underlying cordycepin impeding pancreatic cancer cell growth in vitro and in vivo remain vague. In this study, we reported functional target molecule of cordycepin which inhibited pancreatic cancer cells growth in vitro and in vivo. Cordycepin was confirmed to induce apoptosis by activating caspase-3, caspase-9 and cytochrome c. Further studies suggested that MAPK pathway was blocked by cordycepin via inhibiting the expression of Ras and the phosphorylation of Erk. Moreover, cordycepin caused S-phase arrest and DNA damage associated with activating Chk2 (checkpoint kinase 2) pathway and downregulating cyclin A2 and CDK2 phosphorylation. Very interestingly, we showed that cordycepin could bind to FGFR2 (KD = 7.77 × 10-9) very potently to inhibit pancreatic cancer cells growth by blocking Ras/ErK pathway. These results suggest that cordycepin could potentially be a leading compound which targeted FGFR2 to inhibit pancreatic cells growth by inducing cell apoptosis and causing cell cycle arrest via blocking FGFR/Ras/ERK signaling for anti-pancreatic cancer new drug development.

The present work aims to investigate the effects and underlying mechanism of a homogeneous Laminaria japonica polysaccharide (LJP61A) on acute kidney injury (AKI) in mice. According to the results of biochemical and pathological analysis, we concluded that LJP61A could protect kidney from the damage of adriamycin in AKI mice. Compared to the model group, the mRNA level of cytokines (TNF-α, IL-1β and MCP-1) and protein level of mesenchymal markers demsin were decrease by the treatment of LJP61A while the protein levels of podocyte structure markers (Nephrin and WT-1) were increased. Moreover, the adriamycin-induced enhancement of phosphor-p65, phosphor-p38, phosphor-ERK1/2 and phosphor-JNK in the kidney of AKI mice were significantly suppressed by LJP61A. Similar variation was observed in the mRNA and protein levels of TGF-β1 and Smad3. These results suggested that LJP61A prevented acute kidney injury possibly via regulating TGF-β1-mediated Smad3, MAPKs and NF-κB signaling pathways.

Background: Genome-wide association studies (GWASs) have consistently identified MAP2K5 as an obesity susceptibility gene. To deepen our understanding of the potential causal genetic variants of this region, a fine-mapping study of MAP2K5 was conducted.Methods and Results: SNPs rs7175517 (G > A) and rs4776970 (T > A) were identified as the leading SNPs associated with BMI in both Chinese and the United Kingdom populations. Second, colocalization of GWAS and expression quantitative trait loci (eQTL) analyses and bioinformatic analyses indicated that rs7175517 is the functionally leading variant in the MAP2K5 gene region. Dual-luciferase assays indicated that the G allele of rs7175517 reduced the mRNA expression of MAP2K5 in HEK293T cells. The possible mechanism was that the G allele interacted with more RNA repressors from nuclei extracts, which was evidenced by electrophoretic mobility shift assays (EMSAs). Furthermore, the pathway enrichment analyses of the products from DNA pull-down and protein mass spectrometry demonstrated that the G allele of rs7175517 might interact with RNA catabolic or splicing transcription factors, which consequentially increased adiposity deposition.Conclusion: SNP rs7175517 of the MAP2K5 gene was the putative causal variant associated with BMI. More precisely designed in vitro or animal experiments are warranted to further delineate the function of MAP2K5 in adipogenesis.