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Background and aimsAn increasing number of studies have confirmed that non-textbook outcomes (non-TO) are a risk factor for the long-term outcome of malignant tumors. It is particularly important to identify the predictive factors of non-TO to improve the quality of surgical treatment. We attempted to construct two nomograms for preoperative and postoperative prediction of non-TO after laparoscopic hepatectomy for hepatocellular carcinoma (HCC).MethodsPatients who underwent curative-intent hepatectomy for HCC between 2014 and 2021 at two Chinese hospitals were analyzed. Using univariate and multivariate analyses, the independent predictors of non-TO were identified. The prediction accuracy is accurately measured by the receiver operating characteristic (ROC) curve and calibration curve. ROC curves for the preoperative and postoperative models, Child–Pugh grade, BCLC staging, and 8th TNM staging were compared relative to predictive accuracy for non-TO.ResultsAmong 515 patients, 286 patients (55.5%) did not achieve TO in the entire cohort. Seven and eight independent risk factors were included in the preoperative and postoperative predictive models by multivariate logistic regression analysis, respectively. The areas under the ROC curves for the postoperative and preoperative models, Child–Pugh grade, BCLC staging, and 8th TNM staging in predicting non-TO were 0.762, 0.698, 0.579, 0.569, and 0.567, respectively.ConclusionOur proposed preoperative and postoperative nomogram models were able to identify patients at high risk of non-TO following laparoscopic resection of HCC, which may guide clinicians to make individualized surgical decisions, improve postoperative survival, and plan adjuvant therapy against recurrence.

OBJECTIVES:. In COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO), our primary objective was to determine the frequency of intracranial hemorrhage (ICH). Secondary objectives were to estimate the frequency of ischemic stroke, to explore association between higher anticoagulation targets and ICH, and to estimate the association between neurologic complications and in-hospital mortality. DATA SOURCES:. We searched MEDLINE, Embase, PsycINFO, Cochrane, and MedRxiv databases from inception to March 15, 2022. STUDY SELECTION:. We identified studies that described acute neurological complications in adult patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requiring ECMO. DATA EXTRACTION:. Two authors independently performed study selection and data extraction. Studies with 95% or more of its patients on venovenous or venoarterial ECMO were pooled for meta-analysis, which was calculated using a random-effects model. DATA SYNTHESIS:. Fifty-four studies (n = 3,347) were included in the systematic review. Venovenous ECMO was used in 97% of patients. Meta-analysis of ICH and ischemic stroke on venovenous ECMO included 18 and 11 studies, respectively. The frequency of ICH was 11% (95% CI, 8–15%), with intraparenchymal hemorrhage being the most common subtype (73%), while the frequency of ischemic strokes was 2% (95% CI, 1–3%). Higher anticoagulation targets were not associated with increased frequency of ICH (p = 0.06). In-hospital mortality was 37% (95% CI, 34–40%) and neurologic causes ranked as the third most common cause of death. The risk ratio of mortality in COVID-19 patients with neurologic complications on venovenous ECMO compared with patients without neurologic complications was 2.24 (95% CI, 1.46–3.46). There were insufficient studies for meta-analysis of COVID-19 patients on venoarterial ECMO. CONCLUSIONS:. COVID-19 patients requiring venovenous ECMO have a high frequency of ICH, and the development of neurologic complications more than doubled the risk of death. Healthcare providers should be aware of these increased risks and maintain a high index of suspicion for ICH.

Goats with diverse economic phenotypic traits play an important role in animal husbandry. However, the genetic mechanisms underlying complex phenotypic traits are unclear in goats. Genomic studies of variations provided a lens to identify functional genes. In this study, we focused on the worldwide goat breeds with outstanding traits and used whole-genome resequencing data in 361 samples from 68 breeds to detect genomic selection sweep regions. We identified 210–531 genomic regions with six phenotypic traits, respectively. Further gene annotation analysis revealed 332, 203, 164, 300, 205, and 145 candidate genes corresponding with dairy, wool, high prolificacy, poll, big ear, and white coat color traits. Some of these genes have been reported previously (e.g., KIT, KITLG, NBEA, RELL1, AHCY, and EDNRA), while we also discovered novel genes, such as STIM1, NRXN1, LEP, that may be associated with agronomic traits like poll and big ear morphology. Our study found a set of new genetic markers for genetic improvement in goats and provided novel insights into the genetic mechanisms of complex traits.

BackgroundDelirium detection is challenging due to the fluctuating nature and frequent hypoactive presentation. This study aimed to determine an optimal strategy that detects delirium with higher sensitivity but lower effort in older patients admitted to the intensive care unit (ICU) after surgery.MethodsThis was a secondary analysis of the database from a randomized trial. Seven hundred older patients (aged ≥65 years) who were admitted to the ICU after elective noncardiac surgery were enrolled. Delirium was assessed with the Confusion Assessment Method for the ICU (CAM-ICU) twice daily during the first 7 days postoperatively. The sensitivity of different strategies in detecting delirium were analyzed and compared.ResultsOf all enrolled patients, 111 (15.9%; 95% CI: 13.3% to 18.8%) developed at least one episode of delirium during the first 7 postoperative days. Among patients who developed delirium, 60.4% (67/111) had their first delirium onset on postoperative day 1, 84.7% (94/111) by the end of day 2, 91.9% (102/111) by the end of day 3, and 99.1% (110/111) by the end of day 4. Compared with delirium assessment twice daily for 7 days, twice-daily measurements for 5 days detected 100% of delirium patients with 71% efforts; twice-daily measurements for 4 days detected 99% (95% CI: 94% to 100%) of delirium patients with 57% efforts; twice-daily assessment for 3 days detected 92% (95% CI: 85% to 96%) of delirium patients with only 43% efforts.ConclusionsFor older patients admitted to the ICU after elective noncardiac surgery, it is reasonable to detect delirium with the CAM-ICU twice daily for no more than 5 days, and if the personnel and funds are insufficient, 4 days could be sufficient.

BackgroundOsteoarticular tuberculosis (TB) is an uncommon form of extrapulmonary TB. In this study, we analyzed the epidemiological characteristics, common sites, and drug resistance profiles of osteoarticular TB infections occurring in southwest China.MethodsA total of 3,254 cases of patients clinically diagnosed with osteoarticular TB infections between 2013 and 2021 were retrospectively analyzed. Patients' demographic and clinical characteristics were collected. Drug sensitivity testing was performed using the microporous plate ratio method. Chi-squared analysis was used to analyze the rates of and trends in mycobacterial isolates.ResultsOf the 3,254 patients, 1,968 (60.5%) were men and boys, and 1,286 (39.5%) were women and girls; patients' ages ranged from 1 to 91 years, with an average of 42 ± 19.3 years. In terms of disease, 2,261 (69.5%) had spinal TB, mainly thoracic (815, 36%) or lumbar (1,080, 48%); joint TB was found in 874 cases (26.9%), mainly occurring in the knee (263, 30%) or hip (227, 26%); and both spinal and joint TB were observed in 119 cases (3.7%). Drug susceptibility tests were performed on 241 isolated strains of MTB; 70 strains (29.0%) were resistant to at least one drug, and MDR-TB and XDR-TB were observed in 7.1 and 1.2% of strains, respectively.ConclusionsIn southwest China over this period, osteoarticular TB mainly affected middle-aged and young men with poor nutritional status. Patients from ethnic minority areas also accounted for a large proportion of cases. Spinal TB is prone to occur in the lumbar and thoracic vertebrae, and joint TB is prone to occur in the lower limb joints. Additionally, there has been an increasing trend in the number of TB cases over the past 9 years, and drug resistance has also increased.

Background: Intracellular copper homeostasis requires a complex system. It has shown considerable prospects for intervening in the tumor microenvironment (TME) by regulating copper homeostasis and provoking cuproptosis. Their relationship with hepatocellular carcinoma (HCC) remains elusive.Methods: In TCGA and ICGC datasets, LASSO and multivariate Cox regression were applied to obtain the signature on the basis of genes associated with copper homeostasis and cuproptosis. Bioinformatic tools were utilized to reveal if the signature was correlated with HCC characteristics. Single-cell RNA sequencing data analysis identified differences in tumor and T cells’ pathway activity and intercellular communication of immune-related cells. Real-time qPCR analysis was conducted to measure the genes’ expression in HCC and adjacent normal tissue from 21 patients. CCK8 assay, scratch assay, transwell, and colony formation were conducted to reveal the effect of genes on in vitro cell proliferation, invasion, migration, and colony formation.Results: We constructed a five-gene scoring system in relation to copper homeostasis and cuproptosis. The high-risk score indicated poor clinical prognosis, enhanced tumor malignancy, and immune-suppressive tumor microenvironment. The T cell activity was markedly reduced in high-risk single-cell samples. The high-risk HCC patients had a better expectation of ICB response and reactivity to anti-PD-1 therapy. A total of 156 drugs were identified as potential signature-related drugs for HCC treatment, and most were sensitive to high-risk patients. Novel ligand-receptor pairs such as FASLG, CCL, CD40, IL2, and IFN-Ⅱ signaling pathways were revealed as cellular communication bridges, which may cause differences in TME and immune function. All crucial genes were differentially expressed between HCC and paired adjacent normal tissue. Model-constructed genes affected the phosphorylation of mTOR and AKT in both Huh7 and Hep3B cells. Knockdown of ZCRB1 impaired the proliferation, invasion, migration, and colony formation in HCC cell lines.Conclusion: We obtained a prognostic scoring system to forecast the TME changes and assist in choosing therapy strategies for HCC patients. In this study, we combined copper homeostasis and cuproptosis to show the overall potential risk of copper-related biological processes in HCC for the first time.

Large numbers of microbes can be present in seminal fluid, and there are differences in the semen microbiota between normal and abnormal semen samples. To evaluate the semen microbiota in patients with leukocytospermia, 87 seminal fluid samples, including 33 samples with a normal seminal leukocyte count and 54 samples with leukocytospermia, were obtained for a cross-sectional analysis. Twenty samples with a normal seminal leukocyte count had normal sperm parameters (Control group), and 13 samples with a normal seminal leukocyte count were from asthenozoospermia patients (Ast group). However, 32 samples with leukocytospermia were from asthenozoospermia patients (LA group), and only 22 samples with leukocytospermia had normal sperm parameters (Leu group). The 16S ribosomal RNA (rRNA) gene sequencing method was used to sequence the microbiota in the seminal fluid, and multiple bioinformatics methods were utilized to analyze the data. Finally, the results showed that the worse sperm parameters were observed in the leukocytospermia-related groups. Semen microbiota analysis found that there was increased alpha diversity in the leukocytospermia-related groups. Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes were the primary phyla in the seminal fluid. Two microbiota profiles, namely, Lactobacillus-enriched and Streptococcus-enriched groups, were identified in this study. The majority of the samples in the groups with a normal seminal leukocyte count could be categorized as Lactobacillus-enriched, whereas the majority of the leukocytospermia samples could be categorized as Streptococcus-enriched. Our study indicated that males with leukocytospermia have worse sperm parameters and a different semen microbiota composition compared to males with a normal seminal leukocyte count.

Prion disease represents a group of fatal neurogenerative diseases in humans and animals that are associated with energy loss, axonal degeneration, and mitochondrial dysfunction. Axonal degeneration is an early hallmark of neurodegeneration and is triggered by SARM1. We found that depletion or dysfunctional mutation of SARM1 protected against NAD+ loss, axonal degeneration, and mitochondrial functional disorder induced by the neurotoxic peptide PrP106–126. NAD+ supplementation rescued prion-triggered axonal degeneration and mitochondrial dysfunction and SARM1 overexpression suppressed this protective effect. NAD+ supplementation in PrP106–126-incubated N2a cells, SARM1 depletion, and SARM1 dysfunctional mutation each blocked neuronal apoptosis and increased cell survival. Our results indicate that the axonal degeneration and mitochondrial dysfunction triggered by PrP106–126 are partially dependent on SARM1 NADase activity. This pathway has potential as a therapeutic target in the early stages of prion disease.

The existing emotion recognition researches generally use neural network and attention mechanism to learn emotional features,which have relatively single feature representation.Moreover,neuroscience studies have shown that EEG signals of different frequencies and channels have different responses to emotion.Therefore,this paper proposes a method of fusing frequency and electrode channel convolutional attention for EEG emotion recognition.Specifically,EEG signals are firstly decomposed into different frequency bands and the corresponding frame-level features are extracted.Then the pre-activated residual network is employed to learn deep emotion-relevant features.At the same time,the frequency and electrode channel convolutional attention module is integrated into each pre-activated residual unit of residual network to model the frequency and channel information of EEG signals,thus generating final representation of EEG features.Experiments on DEAP and DREAMER datasets show that the proposed method helps to enhance the importing of emotion-salient information in EEG signals when compared with single-layer attention mechanism,and generates better recognition performance.

Objective: To investigate the molecular mechanism of AwB subtype by performing serological and gene detection in a Chinese individual. Methods: One case of AwB subtype was determined by ABO serology using standard serological method, and 7 exons of ABO gene and their flanks were amplified by PCR, and then cloned and sequenced. Glycosyl Transferase A (GTA) mutants were constructed by Chimera software, and was mapped and analyzed by PyMOL software. Results: Serological identification showed that this individual had AwB subtype. DNA cloning and gene sequen-cing analysis showed that the A gene from the proband was A cis-expressed allele of A1.02 and A3.03, and the genotype was ABO*Avar/B.01. In the ISBT database, the A allele of this variant should be a novel allele, with missense mutations in c. 467C>T and c. 838C>T, which could result in p.P.156L and p.L.280F amino acid replacement in GTA. Analysis of the spatial structure of GTA showed, p.L280F resulted in the phenotypes, and did not lead to changes in the overall structure of GTA proteins, which altered the hydrogen bond network between amino acid 280 and surrounding amino acid residues, resulting in local conformation changes. Conclusions: AwB subtype caused by a novel A allele-is reported for the first time. The formation mechanism may be as follows: p.L280F mutations in glycosyltransferases encoded by the A1.02 allele alter the interactions between adjacent amino acids, resulting in reduced activity of the A enzyme,and AwB subtype occurs when co-expressing with the B allele.

Chen, Xu, et al. performed a population genetics analysis of the eight species in the Ovis genus to assess the evolutionary and demographic history of these wild species and its domesticated counterpart. The authors identified a number of introgression events at different time periods, likely associated with the domestication process as well as identify a number of possible genomic targets of domestication.

Taking the upper sub-member of Sha 4 in Well Fanye 1 and Well Niuye 1 in Dongying Sag, Jiyang Depression, Bohai Bay Basin as a typical example, this paper adopts the method of combining macro and micro laminar characterization and complementing each other. The characteristics of laminar development are studied by means of fine description of rock thin sections by cores and electron microscopic observation Reconstruction of the Bohai Bay Basin in sand four period of ancient sedimentary environment, it is concluded that the sand on the four period of development of four complete filling sedimentary cycle. Using Milankovitch cycles method, reveals the ancient climate control mechanism of lithofacies, formed by organic laminae under hot and humid climate and a small amount of calcite laminated lithofacies, in hot and humid climate, the lithofacies is mainly composed of organic lamina and a small amount of calcite lamina, while in cold and dry climate, the lithofacies is mainly composed of calcite lamina, and the lithofacies is mainly composed of organic lamina, silty lamina and gypsum lamina. Micro-laminar research is an important scientific issue in unconventional oil and gas eology. It can provide basic data for unconventional oil and gas exploration, such as the types, distribution and extension of laminar, especially the determination of sampling targets. Different laboratory samples can be analyzed according to the laminar types.

Dapagliflozin has been used to treat patients with type 1 diabetes mellitus; however, the actual drug efficacy of dapagliflozin on glycated hemoglobin (HbA1c) and whether there is a rebound from dapagliflozin efficacy on HbA1c remain unknown. The present study aimed to explore the actual therapeutic effect and rebound situation of dapagliflozin on HbA1c in type 1 diabetes mellitus patients. A total of 1,594 type 1 diabetes mellitus patients were enrolled for analysis using a non-linear mixed effect model from randomized controlled trials from published literature works including two 5 mg/day dapagliflozin dosage groups and three 10 mg/day dapagliflozin dosage groups. The change rate of HbA1c from a baseline value was chosen as a dapagliflozin pharmacodynamic evaluation index. After deducting control group effects, the therapeutic effect of 5 and 10 mg/day dapagliflozin on HbA1c in type 1 diabetes mellitus patients had no significant difference. In addition, the actual maximal efficacy (AEmax) of dapagliflozin on HbA1c was -6.24% at week 9. When it reached the AEmax, the dapagliflozin pharmacodynamic rebound on HbA1c occurred, and when the treatment was continued for 0.5 and 1 year, the actual efficacies were -4.70% (75% AEmax) and -3.27% (52% AEmax), respectively. This was the first time to clarify the actual therapeutic effect and rebound situation of dapagliflozin on HbA1c in type 1 diabetes mellitus patients, providing a reference value for clinical practices.

BackgroundThe sivelestat is a neutrophil elastase inhibitor thought to have an effect against acute lung injury (ALI) in patients after scheduled cardiac surgery. However, the beneficial effect of sivelestat in patients undergoing emergent cardiovascular surgery remains unclear. We aim to evaluate the effect of sivelestat on pulmonary protection in patients with ALI after emergent cardiovascular surgery.MethodsFirstly, a case-control study in 665 patients undergoing emergent cardiovascular surgery from January 1st, 2020 to October 26th, 2022 was performed. 52 patients who received sivelestat (0.2mg/kg/h for 3 days) and 613 age- and sex-matched controls. Secondly, a propensity-score matched cohort (sivelestat vs control: 50 vs 50) was performed in these 665 patients. The primary outcome was a composite of adverse outcomes, including 30-day mortality, ECMO, continuous renal replacement therapy (CRRT) and IABP, etc. The secondary outcome included pneumonia, ventricular arrhythmias and mechanical ventilation time, etc.ResultsIn propensity-matched patients, the 30-day mortality (16% vs 24%, P=0.32), stroke (2% vs 8%, P=0.17), ECMO(6% vs 10%, P=0.46), IABP(4% vs 8%, P=0.40) and CRRT(8% vs 20%, P=0.08) had no differences between sivelestat and control group; sivelestat could significantly decrease pneumonia (40% vs 62%, P=0.03), mechanical ventilation time (median: 96hours, IQR:72-120hours vs median:148hours, IQR:110-186hours, P

BackgroundKetamine is approved for antidepressant therapy, but evidence regarding its use in women with perinatal depression is lacking. Herein, we investigated the effects of low-dose ketamine in women with prenatal depressive symptoms and tested the feasibility of a future large randomized trial.MethodsThis was a randomized, double-blind, placebo-controlled pilot trial. Sixty-six women with prenatal depressive symptoms who were scheduled for elective cesarean delivery were randomized to receive either low-dose ketamine (0.5 mg/kg) or placebo (normal saline). The study drugs were intravenously infused over a 40-minute period after clamping the umbilical cord. The primary outcome was depression score assessed with the Edinburgh Postnatal Depression Scale at 48 h postpartum. Among other and safety outcomes, occurrence of nausea or vomiting was observed, pain intensity was assessed with the numeric rating scale. The feasibility of implementing the protocol was also evaluated.ResultsA total of 64 parturients were included in the intention-to-treat analysis. The depression score at 48 h did not differ between groups: median 9 (interquartile range 6 to 13) with ketamine vs. 8 (6 to 10) with placebo; median difference 1, 95% CI −1 to 3; P = 0.608. The pain intensity at 4 h postpartum was less severe in the ketamine group (median difference −1, 95% CI −1 to 0, P = 0.002). Among safety outcomes, intraoperative nausea or vomiting was less common in patients given ketamine (0.0% [0/33] with ketamine vs. 21.2% [7/33] with placebo, P = 0.011). Recruitment was satisfactory and the protocol was acceptable to participants and clinicians.ConclusionsA single low-dose ketamine infusion did not decrease the depression score at 2 days, but reduced intraoperative nausea and vomiting and lowered pain intensity at 4 h after cesarean delivery among women with prenatal depressive symptoms. The study protocol is feasible for a large randomized trial.Clinical Trial RegistrationThe study was registered with ClinicalTrials.gov (identifier: NCT03336541; 08/11/2017).

Thoracic surgery has increased drastically in recent years, especially in light of the severe outbreak of the 2019 novel coronavirus disease (COVID-19). Routine “passive” chest computed tomography (CT) screening of inpatients detects some pulmonary diseases requiring thoracic surgeries timely. As an essential device for thoracic anesthesia, the double-lumen tube (DLT) is particularly important for anesthesia and surgery. With the continuous upgrading of the DLTs and the widespread use of fiberoptic bronchoscopy (FOB), the position of DLT in thoracic surgery is gradually becoming more stable and easier to observe or adjust. However, DLT malposition still occurs during transferring patients from a supine to the lateral position in thoracic surgery, which leads to lung isolation failure and hypoxemia during one-lung ventilation (OLV). Recently, some innovative DLTs or improved intervention methods have shown good results in reducing the incidence of DLT malposition. This review aims to summarize the recent studies of the incidence of left-sided DLT malposition, the reasons and effects of malposition, and summarize current methods for reducing DLT malposition and prospects for possible approaches. Meanwhile, we use bibliometric analysis to summarize the research trends and hot spots of the DLT research.

ObjectiveHyperglycemia is common in critically ill patients after surgery and is associated with worse perioperative outcomes. Yet, the impact of postoperative hyperglycemia on long-term outcomes remains unclear. We therefore analyzed the association between early postoperative hyperglycemia and 3-year overall survival in older patients who were admitted to the intensive care unit after surgery.MethodsThis was a post hoc analysis of database obtained from a previous randomized trial and 3-year follow-up. The underlying trial enrolled 700 patients aged 65 years or older who were admitted to the intensive care unit after elective non-cardiac surgery. Early postoperative time-weighted average blood glucose was calculated and was divided into three levels, i.e., 10.0 mmol/L. The primary outcome was 3-year overall survival. The association between time-weighted average blood glucose level and 3-year overall survival was analyzed with Cox proportional hazard regression models. Subgroup analyses were also performed in patients with or without diabetes, and in patients following cancer or non-cancer surgery.ResultsA total of 677 patients (mean age 74 years, 60% male sex) were included in the final analysis. Within 3 years after surgery, deaths occurred in 22.1% (30/136) of patients with time-weighted average blood glucose 10.0 mmol/L (unadjusted hazard ratio 1.91, 95% CI 1.28 to 2.85, P = 0.002). After adjustment for confounding factors, the risk of 3-year mortality remained higher in patients with time-weighted average blood glucose from 8.0 to 10.0 mmol/L (adjusted hazard ratio 2.28, 95% CI 1.47 to 3.54, P < 0.001) and in those >10.0 mmol/L (adjusted hazard ratio 2.00, 95% CI 1.29 to 3.10, P = 0.002). Similar results were obtained in the subgroups of patients without diabetes and patients following cancer surgery.ConclusionFor older patients admitted to the intensive care unit after elective non-cardiac surgery, high early blood glucose (time-weighted average blood glucose ≥ 8.0 mmol/L) was associated with poor 3-year overall survival. The impact of moderate glycemic control on long-term survival deserves further investigation.

Traditional pavement materials used in the orthotropic steel bridge deck suffer from various pavement distresses and thus reduce the service life of the steel bridge. Therefore, this study proposed a novel engineered material named polyester polyurethane concrete (PPUC) for the steel bridge deck pavement. Indoor laboratory experiments and numerical comparison analysis were conducted to comprehensively assess the feasibility of PPUC as the steel bridge deck pavement and ordinary Portland cement (OPC), guss asphalt concrete (GAC), asphalt mastic concrete (SMAC) and epoxy asphalt concrete (EAC) were used as references compared with PPUC. After the specimens of PPUC were prepared by mixing polyester polyurethane binder (PPUB) and aggregate with the binder-aggregate ratio of 15%, the specimens were subjected to compressive test, splitting tensile test, flexural tensile strength test, wheel tracking test, low-temperature cracking test, freeze-thaw splitting test, shear test and pull-out test. The mechanical performance comparison of different pavement structures with different materials was also analyzed using finite element analysis method. Results show that PPUC presents higher mechanical properties (compressive, tensile and flexural strength) compared to OPC, and it has good durability properties compared to SMAC, GAC, and EAC, such as high temperature stability, low temperature cracking resistance and water stability. In addition, PPUC has strong adhesive property with steel deck and does not change significantly with temperature changes. The finite element simulation results show that the maximum tensile strength and maximum compressive strength of PPUC in the single-layer structure are 0.51 MPa and 3.52 MPa respectively, which are much smaller than the experimental values and those of other materials. The maximum tensile strength and maximum shear strength of PPUC in the PPUC + SMAC composite structure are 0.232 MPa and 0.148 MPa respectively, which are also much smaller than the experimental values and those of other structures. The mechanical performance comparison results indicate that PPUC pavement structure can improve the overall stiffness of the steel bridge deck and protect the wear layer. These results support that the PPUC has a promising application for the steel bridge deck pavement.

Background: Esophageal Squamous Cell Cancer (ESCC) is an aggressive disease associated with a poor prognosis. As a newly defined form of regulated cell death, ferroptosis plays a crucial role in cancer development and treatment and might be a promising therapeutic target. However, the expression patterns of ferroptosis-related genes (FRGs) in ESCC remain to be systematically analyzed.Methods: First, we retrieved the transcriptional profile of ESCC from TCGA and GEO datasets (GSE47404, GSE23400, and GSE53625) and performed unsupervised clustering to identify different ferroptosis patterns. Then, we used the ssGSEA algorithm to estimate the immune cell infiltration of these patterns and explored the differences in immune cell abundance. Common genes among patterns were finally identified as signature genes of ferroptosis patterns.Results: Herein, we depicted the multi-omics landscape of FRGs through integrated bioinformatics analysis and identified three ESCC subtypes with distinct immune characteristics: clusters A-C. Cluster C was abundant in CD8+ T cells and other immune cell infiltration, while cluster A was immune-barren. By comparing the differently expressed genes between clusters of diverse datasets, we defined a gene signature for each cluster and successfully validated it in the TCGA-ESCC dataset.Conclusion: We provided a comprehensive insight into the expression pattern of ferroptosis genes and their interaction with immune cell infiltration. Additionally, we established a gene signature to define the ferroptosis patterns, which might be used to predict the response to immunotherapy.

We report a novel prediction from single-field inflation that even a tiny step in the inflaton potential can change our perception of primordial non-Gaussianities of the curvature perturbation. Our analysis focuses on the tail of probability distribution generated by an upward step transition between two stages of slow-roll evolution. The nontrivial background dynamics with off-attractor behavior is identified. By using a non-perturbative δN analysis, we explicitly show that a highly non-Gaussian tail can be generated by a tiny upward step, even when the conventional nonlinearity parameters fNLlocal, gNLlocal, etc. remain small. With this example, we demonstrate for the first time the sensitive dependence of non-perturbative effects on the tail of probability distribution. Our scenario has an inconceivable application to primordial black holes by either significantly boosting their abundance or completely forbidding their appearance.

The aim of the present study is to investigate the quantitative effects of sodium–glucose cotransporter-2 (SGLT-2) inhibitors on the quality of life in heart failure (HF) patients. A total of 14,674 HF patients from two dapagliflozin and three empagliflozin studies is included for analysis via the nonlinear mixed-effect modeling (NONMEM) software, among which the change rate of the Kansas City Cardiomyopathy Questionnaire (KCCQ) score is used as the evaluation index. There is no significant difference in the pharmacodynamics influencing the quality of life in HF patients between the SGLT-2 inhibitors: 10 mg/day dapagliflozin and 10 mg/day empagliflozin. For the clinical summary score (CSS), total symptom score (TSS), and overall summary score (OSS), the Emax of the SGLT-2 inhibitors on the quality of life in HF patients is 3.74%, 4.43%, and 4.84%, respectively, and ET50 is 2.23, 4.37, and 7.15 weeks, respectively. In addition, the time duration of achieving 25%, 50%, 75%, and 80% Emax is 0.75, 2.23, 6.69, and 8.92 weeks for the CSS; 1.46, 4.37, 13.11, and 17.48 weeks for the TSS; and 2.39, 7.15, 21.45, and 28.6 weeks for the OSS, respectively. Therefore, to reach the plateau period (80% of Emax) of SGLT-2 inhibitors on the CSS, TSS, and OSS, 10 mg/day dapagliflozin (or 10 mg/day empagliflozin) is required to be taken for 8.92 weeks, 17.48 weeks, and 28.6 weeks, respectively. This is the first time that the quantitative effects of SGLT-2 inhibitors on the quality of life in HF patients are being explored.

Abstract Background Dexmedetomidine promotes normal sleep architecture; the drug also improves analgesia. We therefore tested the hypothesis that supplementing intravenous analgesia with dexmedetomidine reduces delirium in older patients recovering from orthopedic surgery. Methods In this double-blinded randomized controlled trial, we enrolled 712 older (aged 65–90 years) patients scheduled for major orthopedic surgery. Postoperative analgesia was provided by patient-controlled intravenous sufentanil, supplemented by randomly assigned dexmedetomidine (1.25 μg/mL) or placebo, for up to three days. The primary outcome was the incidence of delirium assessed twice daily with the Confusion Assessment Method. Among secondary outcomes, pain severity was assessed twice daily and sleep quality once daily, each with an 11-point scale where 0 = no pain/the best possible sleep and 10 = the worst pain/the worst possible sleep. Results The incidence of postoperative delirium was 7.3% (26 of 354) with placebo and 4.8% (17 of 356) with dexmedetomidine; relative risk 0.65, 95% CI 0.36 to 1.18; P = 0.151. Dexmedetomidine reduced pain both at rest (median difference -1 to 0 points, P ≤ 0.001) and with movement (-1 points, P

Background & aimsThe long-term prognosis of patients with metabolic syndrome (MS) and hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) after radical hepatectomy remains unclear. The purpose of this study was to elucidate the effect of MS on long-term survival for patients with HBV-related HCC after hepatectomy.MethodsPatients with HBV-HCC after hepatectomy were included. Patients were stratified into MS-HBV-HCC and HBV-HCC groups. Clinical features and surgical outcomes were compared between the two groups, and COX regression analysis was used to determine independent risk factors associated with overall survival (OS) and recurrence-free survival (RFS).Result389 patients (MS-HBV-HCC group: n=50, HBV-HCC group: n=339) were enrolled for further analysis. Baseline characteristics showed that patients with MS-HBV-HCC were associated with a high rate of elderly patients, ASA score, and co-morbid illness, but a lower rate of anatomy hepatectomy. There were no significant differences in perioperative complications. After excluding patients who relapsed or died within 90 days after surgery, multivariate Cox regression analysis showed MS was an independent risk factor of OS (HR 1.68, 95% CI 1.05-2.70, P = 0.032) and RFS (HR 1.78, 95% CI 1.24-2.57, P = 0.002).ConclusionMS is an independent risk factor for poor OS and RFS in HBV-infected HCC patients after radical hepatectomy. This suggests that we need to strengthen postoperative follow-up of the relevant population and encourage patients to develop a healthy lifestyle.

PurposeTo investigate the influence of changes in T1 slope (T1S) and cervical sagittal vertical axis (CSVA) on cervical laminoplasty outcomes.MethodsEighty-one patients with cervical spondylotic myelopathy (CSM) treated with cervical laminoplasty were enrolled in this study. Demographic parameters included age and follow-up time. Imaging data included occiput-C2 lordosis (OC2), C2–C7 Cobb angle (CL), T1S, CSVA. Outcome assessment indicators included the Japanese Orthopedic Association (JOA) score, JOA recovery rate, and neck disability index (NDI). All patients were grouped based on preoperative T1S and variation in CL after surgery, respectively. Patients with decreased CL postoperatively were further grouped according to whether they were combined with T1S reduction.ResultsThere were no significant differences in the final JOA score, JOA recovery rate, or NDI between patients with different T1S. Patients with loss of CL postoperatively had lower JOA score and JOA recovery rate, but higher NDI than patients with sustained CL. Furthermore, patients with CL loss but compensate for it with reduction in T1S had lower CSVA, higher JOA score and JOA recovery rate than those with CL loss alone.ConclusionsDecreased T1S postoperatively prevents the tendency of the cervical spine to tilt forward by regulating CSVA and facilitates recovery of neurological function after cervical laminoplasty.

Knowledge of adequate diets can improve an individual's health status. Although previous studies have identified the main resources from which Chinese people acquire dietary knowledge, it is still unclear whether information sources regarding diets (ISRDs) can increase individuals' knowledge of adequate diets (KAD) and which ISRDs are most effective in conveying KAD to the Chinese population. In this study, we interviewed 4,710 residents in Eastern China regarding their ISRDs and KAD. Descriptive statistics, ANOVA, and multivariate linear regression were used to analyze the effectiveness of different ISRDs in transmitting KAD to Chinese individuals and to determine the relationship between ISRDs and KAD. Results showed that the KAD scores of the respondents were low overall in Eastern China. Providing dietary information through expert lectures, books, newspapers, magazines, and social media could significantly improve the average KAD score of Chinese individuals. Respondents with a greater number of ISRDs were more likely to have higher KAD scores. These findings suggest that the number of ISRDs should be increased. In particular, emphasis should be placed on the role of expert lectures, books, newspapers, magazines, and social media.

ObjectiveThis study investigated the effects of 12 weeks of specifically designed physical activity intervention on working memory and motor competence in preschool children and explored the correlation between working memory changes and motor competence changes by the intervention.MethodsFour classes of preschool children were grouped into an intervention group and a control group. Children in the intervention group received a 12-week physical activity intervention, while children in the control group followed their daily routine as usual. Before and after the intervention period, children were assessed with the 1-back task and Movement Assessment Battery for Children, second edition (MABC-2) to measure their working memory and motor competence, respectively.ResultsRegarding working memory, the accuracy on the 1-back task increased significantly in the intervention group relative to the control group. The intervention group demonstrated a greater decrease in response time from pre- to posttest than the control group, but the difference was not statistically significant. Regarding motor competence, children's manual dexterity, aiming and catching and total score increased significantly in the intervention group relative to the control group, while no significant difference in static and dynamic balance was observed between the two groups. Furthermore, the correlation results showed that changes in the efficacy and efficiency of working memory were positively related to changes in static and dynamic balance and the total score on the MABC-2.ConclusionThese findings demonstrated that 12 weeks of specifically designed physical activity intervention could improve preschool children's efficacy of working memory as well as manual dexterity, aiming and catching and global motor competence. The improvement in the efficacy and efficiency of working memory was positively related to the improvement in static and dynamic balance and global motor competence.

The decline in natural mating behavior is the primary reason underlying in the poor population growth of captive giant pandas. However, the influencing factors and underlying mechanisms remain unclear to data. It is speculated that the decline in natural mating behavior could be related to the psychological stress caused by captivity, which restricts their free choice of mates. In order to test this hypothesis, we performed urinary metabolomics analysis using Ultra-High-Performance Liquid Chromatography-Mass Spectrometry (UHPLC/-MS) combined with 16S rDNA sequencing for exploring the physiological mechanism underlying the decline in the natural mating behavior of captive giant panda. The results demonstrated that the decline in mating ability could be related to abnormalities in arginine biosynthesis and neurotransmitter synthesis. Additionally, the relative abundance of bacteria from the Firmicutes, Proteobacteria, and Actinobacteria phyla and the Acinetobacter, Weissella, and Pseudomonas genus was significantly reduced in the group with low natural mating behavior. These findings imply that the inhibition of arginine synthesis induced by environmental changes could be related to the poor libido and failure of mate selection in captive giant pandas during the breeding period. The results also demonstrate the relationship between the altered urinary microbes and metabolites related to arginine and neurotransmitter synthesis. These findings may aid in understanding the mechanism underlying environment-induced mate selection in captive giant pandas and propose a novel strategy for determining the sexual desire of giant pandas based on urinary microbes. The method would be of great significance in improving the natural reproductive success rate of captive giant pandas.

Cancer is one of the most serious diseases threatening human health, so it is particularly important to develop effective tumor-targeting drugs. As the first CDK4/6 inhibitor, palbociclib effectively inhibits tumor proliferation by blocking the cell cycle to the G1 phase. 10-HCPT is a Topo I inhibitor; however, its clinical application has been greatly limited due to its high toxicity. Based on the successful development of double target inhibitors, three novel palbociclib derivatives (HP-1, HP-2, and HP-3) were designed and synthesized from Palbociclib and 10-HCPT, and their biological activities were investigated. At first, the possible binding sites of the three compounds to Topo I and CDK4/6 were predicted by molecular docking. Then, we evaluated the anti-proliferative effects of the three palbociclib derivatives. In general, human lung cancer cells were more sensitive to HP-1, HP-2, and HP-3, especially NCI-H460. In addition, cell cycle arrest and apoptosis induction were investigated by flow cytometry. The three palbociclib derivatives, especially HP-1, had obvious cell cycle arrest phenomenon on NCI-H460 cells and induced apoptosis of NCI-H460 cells significantly. In the end, it was proved that these three drugs had obvious cyclin-dependent kinase inhibitory activities. In short, all the data showed that HP-1, HP-2, and HP-3 could play anti-cancer roles by acting on dual targets and had the characteristics of high efficiencies and low toxicities, which opened up a new idea for the study of palbociclib derivatives.

BackgroundSleep disturbances are prevalent in patients requiring invasive mechanical ventilation in the intensive care unit (ICU) and are associated with worse outcomes. Sedative-dose dexmedetomidine may improve sleep quality in this patient population but is associated with adverse events. Herein, we tested the effect of low-dose dexmedetomidine infusion on nighttime sleep quality in postoperative ICU patients with invasive ventilation.MethodsIn this pilot randomized trial, 80 adult patients who were admitted to the ICU after non-cardiac surgery and required invasive mechanical ventilation were randomized to receive either low-dose dexmedetomidine (0.1 to 0.2 μg/kg/h, n = 40) or placebo (n = 40) for up to 72 h. The primary endpoint was overall subjective sleep quality measured using the Richards–Campbell Sleep Questionnaire (score ranges from 0 to 100, with a higher score indicating better quality) in the night of surgery. Secondary outcomes included sleep structure parameters monitored with polysomnography from 9:00 PM on the day of surgery to the next 6:00 AM.ResultsAll 80 patients were included in the intention-to-treat analysis. The overall subjective sleep quality was median 52 (interquartile 20, 66) with placebo vs. 61 (27, 79) with dexmedetomidine, and the difference was not statistically significant (median difference 8; 95% CI: −2, 22; P = 0.120). Among 68 patients included in sleep structure analysis, those in the dexmedetomidine group tended to have longer total sleep time [median difference 54 min (95% CI: −4, 120); P = 0.061], higher sleep efficiency [median difference 10.0% (95% CI: −0.8%, 22.3%); P = 0.060], lower percentage of stage N1 sleep [median difference −3.9% (95% CI: −11.8%, 0.5%); P = 0.090], higher percentage of stage N3 sleep [median difference 0.0% (95% CI: 0.0%, 0.4%); P = 0.057], and lower arousal index [median difference −0.9 (95% CI −2.2, 0.1); P = 0.091] but not statistically significant. There were no differences between the two groups regarding the incidence of adverse events.ConclusionAmong patients admitted to the ICU after surgery with intubation and mechanical ventilation, low-dose dexmedetomidine infusion did not significantly improve the sleep quality pattern, although there were trends of improvement. Our findings support the conduct of a large randomized trial to investigate the effect of low-dose dexmedetomidine in this patient population.Clinical trial registrationClinicalTrial.gov, identifier: NCT03335527.

BackgroundEarly identification of patients who will benefit from immune checkpoint inhibitors (ICIs) has recently become a hot issue in cancer immunotherapy. Peripheral cytokines are key regulators in the immune system that can induce the expression of immune checkpoint molecules; however, the association between peripheral cytokines and the efficiency of ICIs remains unclear.MethodsA systematic review was conducted in several public databases from inception through 3 February 2022 to identify studies investigating the association between peripheral cytokines (i.e., IL-1β, IL-2, IL-2RA, IL-2R, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, TNF-α, IFN-γ, and TGF-β) and ICI treatment. Survival data, including overall survival (OS) and/or progression-free survival (PFS), were extracted, and meta-analyses were performed.ResultsTwenty-four studies were included in this analysis. The pooled results demonstrated that the pretreatment peripheral levels of IL-6 (univariate analysis: HR = 2.53, 95% CI = 2.21–2.89, p < 0.00001; multivariate analysis: HR = 2.21, 95% CI = 1.67–2.93, p < 0.00001) and IL-8 (univariate analysis: HR = 2.17, 95% CI = 1.98–2.38, p < 0.00001; multivariate analysis: HR = 1.88, 95% CI= 1.70–2.07, p < 0.00001) were significantly associated with worse OS of cancer patients receiving ICI treatment in both univariate and multivariate analysis. However, high heterogeneity was found for IL-6, which might be attributed to region, cancer type, treatment method, sample source, and detection method.ConclusionThe peripheral level of IL-8 may be used as a prognostic marker to identify patients with inferior response to ICIs. More high-quality prospective studies are warranted to assess the predictive value of peripheral cytokines for ICI treatment.

The present study aimed to explore the effect of carnitine supplementation on body weight in patients with polycystic ovary syndrome (PCOS) and predict an appropriate dosage schedule using a machine-learning approach. Data were obtained from literature mining and the rates of body weight change from the initial values were selected as the therapeutic index. The maximal effect (Emax) model was built up as the machine-learning model. A total of 242 patients with PCOS were included for analysis. In the machine-learning model, the Emax of carnitine supplementation on body weight was −3.92%, the ET50 was 3.6 weeks, and the treatment times to realize 25%, 50%, 75%, and 80% (plateau) Emax of carnitine supplementation on body weight were 1.2, 3.6, 10.8, and 14.4 weeks, respectively. In addition, no significant relationship of dose-response was found in the dosage range of carnitine supplementation used in the present study, indicating the lower limit of carnitine supplementation dosage, 250 mg/day, could be used as a suitable dosage. The present study first explored the effect of carnitine supplementation on body weight in patients with PCOS, and in order to realize the optimal therapeutic effect, carnitine supplementation needs 250 mg/day for at least 14.4 weeks.

ObjectiveCervical sagittal parameters have been widely used to predict clinical outcomes in patients with cervical spondylotic myelopathy (CSM). This study aims to coin a novel cervical sagittal parameter defined as the ratio of cervical sagittal vertical axis to T1 slope (CSVA/T1S) and to investigate the correlation between CSVA/T1S and postoperative HRQOL after laminoplasty.MethodsA total of 102 CSM patients treated with cervical laminoplasty from our database were retrospectively reviewed. All patients were followed up for >12 months. Radiological parameters were measured using lateral cervical radiographs, including occiput-C2 lordosis (OC2), cervical lordosis (CL), CSVA, and T1S. Clinical parameters included the Japanese Orthopedic Association (JOA) score, neck disability index (NDI), and JOA recovery rate. Patients were grouped by preoperative T1S, T1S-CL, and CSVA/T1S value, respectively. Clinical and radiological outcomes were compared between the groups.ResultsPatients with high CSVA/T1S had greater OC2 and CSVA but lower CL than those in the low CSVA/T1S group pre-and postoperatively. With respect to HRQOL results, the final NDI was 12.46 ± 9.11% in the low CSVA/T1S group, which was significantly lower than that in the high CSVA/T1S group (17.68 ± 8.81%, P = 0.040). Moreover, only CSVA/T1S was detected to be significantly correlated with final NDI (r = 0.310, P = 0.027). No significant correlation was found between clinical results and other cervical sagittal parameters, including T1S, CSVA, and T1S-CL.ConclusionsPreoperative CSVA/T1S was correlated with postoperative NDI in patients with CSM after cervical laminoplasty. Patients with low preoperative CSVA/T1S achieved better neurological function improvement after cervical laminoplasty. Cervical laminoplasty could be an appropriate choice for patients with lower preoperative CSVA/T1S.

Abstract Coal, especially the inertinite in it, is highly sensitive to climate changes, showing an obvious response to paleoclimate conditions, in particular, to paleo-oxygen concentration (pO2). In this study, the inertinite abundance data of typical coal-forming periods in China were systematically collected and analyzed. Its characteristics and control factors were studied, and its evolution was established. Based on inertinite abundance data, pO2 evolution curves of various coal-forming periods in China were established, which fluctuated between 15% and 30% during the entire Phanerozoic. The inertinite abundance in coal deposits during Paleozoic in China was basically consistent with that of other areas of the world, while it was quite different globally from the Mesozoic to the Cenozoic. The results show that the inertinite abundance in coal deposits is controlled by pO2 and other factors including climatic zones, plant differentiation, sedimentary environments, and tectonic activities. The inertinite abundance in coal deposits in China during the Jurassic was high, suggesting dry paleoclimate of inland China.

VSe2 is with high electrical conductivity and high work function, thus it is beneficial for the carrier transport in the optoelectronic devices. However, the performance and mechanism of its effect on the photoelectronic devices conversion efficiency is still beyond understood. In this work, we fabricate VSe2 film between back contact and absorber layer Cu2ZnSn(S,Se)4 (CZTSSe) film. We demonstrate that the VSe2 film in back contact region increases solar cell efficiency by 39%. Besides improving the carrier transport in the back contact region, the increasing can also be attributed to the reduction of the decomposition reaction of CZTSSe during the nucleation of CZTSSe as VSe2 fabricated between back contact and absorber layer. The present work not only provides an effective method to improve the performance of the optoelectronic device, but also shows an attractive application of metallic TMDs in optoelectronic device and solar cell energy generation.