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Hemagglutinins (HAs) are the receptor-binding and membrane fusion glycoproteins of influenza viruses. They recognize sialic acid-containing, cell-surface glycoconjugates as receptors but have limited affinity for them, and, as a consequence, virus attachment to cells requires their interaction with several virus HAs. Receptor-bound virus is transferred into endosomes where membrane fusion by HAs is activated at pH between 5 and 6.5, depending on the strain of virus. Fusion activity requires extensive rearrangements in HA conformation that include extrusion of a buried "fusion peptide" to connect with the endosomal membrane, form a bridge to the virus membrane, and eventually bring both membranes close together. In this review, we give an overview of the structures of the 16 genetically and antigenically distinct subtypes of influenza A HA in relation to these two functions in virus replication and in relation to recognition of HA by antibodies that neutralize infection.

Objective: The objective of this study is to investigate the diagnosis of dynamic volume computed tomography (CT) for pulsatile tinnitus caused by sigmoid sinus diverticulum (SSD) and bone defects. Methods: Data obtained by dynamic volume CT from 35 patients with SSD were retrospectively collected. Then the ear morphological parameters, including bone defect, transverse sinus stenosis, position of the jugular bulb, jugular bulb diverticulum, defect of the jugular bulb wall, gross venous sinus thrombosis and SSD, and blood perfusion parameters, including cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT), were evaluated and compared between the tinnitus side and the asymptomatic side of the ear. Results: The maximum diameters of the bone defects on the tinnitus side were greater than those on the asymptomatic side (Horizontal 6.36±2.35mm vs. 1.12±0.78mm; Longitudinal 4.87±1.25 vs. 0.88±0.06mm). Dynamic volume CT visually displayed the SSD herniated into the adjacent mastoid via the bone defect. Transverse sinus stenosis, high position of the jugular bulb, jugular bulb diverticulum, defect of the jugular bulb wall, and gross venous sinus thrombosis were present more frequently on the tinnitus side than on the asymptomatic side (P < 0.05). Moreover, CBF, CBV, and MTT were significantly greater on the tinnitus side than on the asymptomatic side (P < 0.05). Conclusion: Dynamic volume CT examination is an effective method for the diagnosis of pulsatile tinnitus caused by SSD with bone defects.

Cervical neuroblastic tumors (NTs) are rare but less aggressive cancer with an above-average survival rate. Little has been published regarding the management and surgical outcomes of patients with cervical NTs based on pathology category. This study compared and identified the preoperative characteristics of cervical NTs in different pathology categories and evaluated the outcomes of patients undergoing surgical resection.Upon the institutional review board's approval, a retrospective chart review was performed at Beijing Children's Hospital from April 2013 to August 2020. Demographics of patients, imaging data, lab test results, operation details and outcomes were recorded and analyzed.Of 32 cervical NTs, 24(80%) were classified as neuroblastoma (NB) /ganglioneuroblastoma-nodular (GNBn) and 8(20%) as ganglioneuroblastoma-intermixed (GNBi)/ ganglioneuroma (GN). Patients with GNBi/GN were older than those with NB/GNBn (44.5 months (IQR 16-81) vs 9 months (IQR 1-47); P = 0.001). GNBi/GN patients presented more frequently with stage 1 disease compared with NB/GNBn patients (100% vs. 29.2%, P = 0.001), less frequently with tumor-related symptoms (0% vs. 70.8%, P = 0.001), artery encased tumor (0% vs. 41.7%, P = 0.035), and surgical complications (25% vs. 70.8%, P = 0.038). GNBi/GN patients were also less likely to show elevated neuron specific enolase (NSE) (12.5% vs. 79.2%, P = 0.002).Cervical NB/GNBn and GNBi/GN patients had distinct characteristic clinical presentations and surgical outcomes. For children with features suggestive of benign disease (older age, asymptomatic, normal serum tumor markers) and no artery image-defined risk factors (IDRFs), upfront resection can be considered.

Does a previous history of naturally conceived tubal ectopic pregnancy (TEP) affect subsequent pregnancy and perinatal outcomes when a freeze-all policy is applied?A large retrospective study was performed involving women who had undergone their first frozen-thawed embryo transfer (FET) cycles, using vitrified-warmed embryos, from January 2013 to April 2018 at a tertiary care centre. Participants were divided into two groups: a study group consisting of women with a history of TEP preceding IVF, and a control group consisting of women without an initial TEP. The live birth rate (LBR) and perinatal outcomes were evaluated via a propensity score matching method.A total of 23,270 women were included for potential analysis and finally 2168 pairs of women were generated for comparison after propensity score matching. The LBR in the study group was similar to that in the control group (45.7% versus 44.0%, P = 0.259). No differences were noted regarding rates of ectopic pregnancy (5.4% versus 4.1%, P = 0.122), miscarriage (11.5% versus 13.5%, P = 0.158) or intrauterine implantation (35.8% versus 35.8%, P = 0.974) between the groups. Regarding birth outcomes, the mean gestational age and birthweight and the incidences of preterm birth and low birthweight were comparable between the groups for both singletons and twins.The present study demonstrated that a prior history of TEP was not associated with adverse reproductive and perinatal outcomes in subsequent FET cycles. With the increasing utilization of FET globally, these results are important as they can help guide physicians during patient counselling.

To assess HOXC9 expression in non-small cell lung cancer (NSCLC) using bioinformatics analysis with experimental validation and to investigate its role and potential mechanisms in NSCLC.Public databases were explored to investigate the gene expression, clinical outcomes, immune infiltration, and potential molecular mechanisms of HOXC9 in NSCLC. Next, HOXC9 expression levels in NSCLC were verified by RT-PCR and nucleic acid electrophoresis. In vitro experiments were performed to assess the effects of HOXC9 on proliferation, migration, and invasion of NSCLC cells.HOXC9 expression was increased in NSCLC and correlated with poor prognosis in lung adenocarcinoma. In addition, HOXC9 expression levels were significantly correlated with immune cell infiltration of tumors and biomarkers of immune cells. Overexpression of HOXC9 promoted NSCLC cell proliferation, migration, and invasion in vitro. Finally, the circCENPF/hsa-miR-184 axis was identified as the most promising upstream regulatory pathway of HOXC9 in lung adenocarcinoma.HOXC9 expression may reflect the prognosis and immune microenvironment infiltration in NSCLC, emerging as a potential oncogene and a new target for immunotherapy.

High malignancy and mortality in colon cancer require clarifying the underlying mechanisms of colon cancer carcinogenesis and exploring new targets or drugs for the clinical treatment of colon cancer. Resveratrol (Res), a natural compound, shows cytotoxicity against various tumors. However, the specific anti-cancer mechanism of Res remains unclear. In the present study, we aimed to explore the anti-cancer activity of Res against colon cancer cells and the possible mechanism. The results showed that Res could inhibit cell proliferation and induce cell cycle arrest and apoptosis in HCT116 cells. Western blotting and Polymerase chain reaction (PCR) showed that Res increased the phosphorylated YAP (pYAP) levels and decreased YAP total protein level and decreased the mRNA expression of the YAP signaling downstream genes CTGF and CYR61. The effects of Res on pYAP were enhanced by YAP inhibitor verteporfin (VP). VP also enhanced the effects of Res on decreasing viability and inducing apoptosis. Furthermore, the molecular docking analysis indicated Res could bind with YAP-TEAD through van der Waals, pi-alkyl, and pi-pi stacked interactions. Our findings suggested that the anti-cancer activity of Res may be mediated via activating Hippo/YAP signaling and partially disturbing the interaction between YAP and TEAD. All this evidence supports that Res may be an efficacious drug for colon cancer treatment.

Fish oil is one of the most popular supplements in the UK and other developed countries. However, the relationship between fish oil use and chronic obstructive pulmonary disease (COPD) is unclear.To prospectively examine the association of habitual fish oil supplementation with incident COPD risk and to evaluate potential effect modification by genetic predisposition.This study included 484,414 participants (mean and standard deviation [SD] age: 56.5 [8.1] years) from the UK Biobank who completed a touchscreen questionnaire on habitual fish oil supplement use between 2006 and 2010 and were followed up through 2018. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) with adjustment for sociodemographic and lifestyle behaviours, health conditions, and other potential confounding factors. A weighted genetic risk score (GRS) for COPD was derived from 112 validated single nucleotide polymorphisms.During a median follow-up of 9.0 years, 8860 incident COPD events were recorded. A total of 31.4% (152,230) of the study participants reported habitual fish oil supplementation at baseline. Habitual fish oil supplementation was significantly associated with a lower risk of incident COPD (adjusted HR: 0.88; 95% CI: 0.84-0.93). The association with COPD did not differ by GRS strata (P for interaction = 0.880). The results from subgroup and sensitivity analyses supported the robustness of our findings.Our findings suggest that habitual fish oil supplementation is associated with a lower risk of incident COPD, irrespective of genetic predisposition.

BACKGROUND: The endocannabinoid system is present in multiple organ systems and is involved in smooth muscle regulation, immune function, neuroendocrine modulation, and metabolism of tissues. Limited data are available regarding the presence and role of this system in reproductive tissues. Components of the endocannabinoid system have been identified in myometrial and placental tissues. However, no study has investigated differential expression of the endocannabinoid system in labor. OBJECTIVES: The purpose of this study was to identify and quantify two components of the endocannabinoid system, the CB(1) cannabinoid receptor and cannabinoid receptor interacting protein 1a (CRIP1a) in uterine and placental tissues, and to determine if there is differential expression in tissues exposed to labor. We hypothesized that CB(1) cannabinoid receptor concentration would be altered in uterine and placental tissue exposed to labor compared with tissues not exposed to labor. STUDY DESIGN: Uterine and placental tissue samples were collected in nine laboring and 11 nonlaboring women undergoing cesarean delivery. CB(1) cannabinoid receptor and CRIP1a presence and quantification were evaluated using western blot, immunohistochemistry, and real-time quantitative polymerase chain reaction. Statistical comparisons of laboring and nonlaboring subjects were made for uterine and placental tissue using a Mann–Whitney test. RESULTS: Immunohistochemistry demonstrated positive staining for CB(1) cannabinoid receptors and CRIP1a in uterine tissue. The protein abundance of CB(1) cannabinoid receptor in uterine tissue was significantly lower in tissues exposed to labor (p=0.01). The protein abundance of CRIP1a was lower in uterine tissue exposed to labor but did not reach statistical significance (p=0.06). mRNA expression of CB(1) cannabinoid receptor (p=0.20) and CRIP1a (p=0.63) did not differ in labored compared with nonlabored uterine tissues. CONCLUSIONS: Our findings of diminished protein density of CB(1) cannabinoid receptor in uterine tissue exposed to labor support the hypothesis that the endocannabinoid system plays a role in parturition. Our data add to the growing body of evidence indicating the endocannabinoid system is of importance for successful reproduction and support the need for additional research investigating this complex system as it pertains to labor. ClinicalTrials.gov ID: NCT03752021.

Background Obsessive-compulsive disorder (OCD) is characterized by both internalizing (anxiety) and externalizing (compulsivity) symptoms. Currently, little is known about their interrelationships and their relative contributions to disease heterogeneity. Our goal is to resolve affective and cognitive symptom heterogeneity related to internalized and externalized symptom dimensions by determining subtypes of children with OCD symptoms, and to identify any corresponding neural differences. Methods A total of 1269 children with OCD symptoms screened using the Child Behavior Checklist Obsessive-Compulsive Symptom scale and 3987 matched control subjects were obtained from the Adolescent Brain Cognitive Development (ABCD) Study. Consensus hierarchical clustering was used to cluster children with OCD symptoms into distinct subtypes. Ten neurocognitive task scores and 20 Child Behavior Checklist syndrome scales were used to characterize cognitive/behavioral differences. Gray matter volume, fractional anisotropy of major white matter fiber tracts, and functional connectivity among networks were used in case-control studies. Results We identified two subgroups with contrasting patterns in internalized and externalized dimensions. Group 1 showed compulsive thoughts and repeated acts but relatively low anxiety symptoms, whereas group 2 exhibited higher anxiety and perfectionism and relatively low repetitive behavior. Only group 1 had significant cognitive impairments and gray matter volume reductions in the bilateral inferior parietal lobe, precentral gyrus, and precuneus gyrus, and had white matter tract fractional anisotropy reductions in the corticostriatal fasciculus. Conclusions Children with OCD symptoms are heterogeneous at the level of symptom clustering and its underlying neural basis. Two subgroups represent distinct patterns of externalizing and internalizing symptoms, suggesting that anxiety is not its major predisposing factor. These results may have implications for the nosology and treatment of preteenage OCD.

Brain cancer is an aggressive type of cancer with poor prognosis. While the immune system protects against cancer in the early stages, the tumor exploits the healing arm of inflammatory reactions to accelerate its growth and spread. Various immune cells penetrate the developing tumor region, establishing a pro-inflammatory tumor milieu. Additionally, tumor cells may release chemokines and cytokines to attract immune cells and promote cancer growth. Inflammation and its associated mechanisms in the progression of cancer have been extensively studied in the majority of solid tumors, especially brain tumors. However, treatment of the malignant brain cancer is hindered by several obstacles, such as the blood-brain barrier, transportation inside the brain interstitium, inflammatory mediators that promote tumor growth and invasiveness, complications in administering therapies to tumor cells specifically, the highly invasive nature of gliomas, and the resistance to drugs. To resolve these obstacles, nanomedicine could be a potential strategy that has facilitated advancements in diagnosing and treating brain cancer. Due to the numerous benefits provided by their small size and other features, nanoparticles have been a prominent focus of research in the drug-delivery field. The purpose of this article is to discuss the role of inflammatory mediators and signaling pathways in brain cancer as well as the recent advances in understanding the nano-carrier approaches for enhancing drug delivery to the brain in the treatment of brain cancer.

The choice of treatment is an unavoidable challenge faced in the day to day medical decision making pertaining to patients with organic heart disease. As a professional discipline, cardiac surgery focuses on creating and using the most advanced evidence-based patient decision aids (PtDAs) to achieve high-quality decision-making.To describe the basic situation, influencing factors, and the outcome of indicators of PtDAs among cardiac surgery patients.Seven electronic databases were systematically searched for relevant reviews on the application of PtDAs among cardiac surgery patients. The methodological framework proposed by Arskey and O'Malley was used to guide the scoping review. The extracted data was analyzed qualitatively and quantitatively.After dual, blinded screening of titles and abstracts, 12 articles were included in the review. 10 were quantitative studies, 1 was a mixed study, 1 was a qualitative study.Compared with the burden of heart disease and the huge evidence base, the application of PtDAs in cardiac surgery is obviously insufficient. The published literature mainly provide information about the factors to be solved from the perspective of researchers, and also summarize obstacle factors. This is the basis for the application and construction of PtDAs in cardiac surgery patients.

Astrocytes are the most abundant cells in the brain. They have many important functions in the central nervous system (CNS), including the maintenance of glutamate and ion homeostasis, the elimination of oxidative stress, energy storage in glycogen, tissue repair, regulating synaptic activity by releasing neurotransmitters, and participating in synaptic formation. Astrocytes have special highly ramified structure. Their branches contact with synapses of neurons inwardly, with fine structure and wrapping synapses; their feet contact with blood vessels of brain parenchyma outward, almost wrapping the whole brain. The adjacent astrocytes rarely overlap and communicate with each other through gap junction channels. The ideal location of astrocytes enables them to sense the weak changes of their surroundings and provide the structural basis for the energy supply of neurons. Neurons and astrocytes are closely coupled units of energy metabolism in the brain. Neurons consume a lot of ATPs in the process of neurotransmission. Astrocytes provide metabolic substrates for neurons, maintain high activity of neuron, and facilitate information transmission of neurons. This article reviews the characteristics of glucose metabolism, lipid metabolism, and amino acid metabolism of astrocytes. The metabolic interactions between astrocytes and neurons, astrocytes and microglia were also detailed discussed. Finally, we classified analyzed the role of metabolic disorder of astrocytes in the occurrence and development of neurodegenerative diseases.

The refractory macular edema (RME) seriously affects the patient's vision due to its repetition and ineffective drug response. RME is mainly related to the inflammatory pathway and angiogenesis pathway. At present, microglia activation and angiogenesis have also been widely focused on. With the promotion of the concept of precision diagnosis and treatment, intraocular fluid is becoming a popular evidence-based method. The detection and evaluation of aqueous humor factors can provide more accurate evidences and guidance for the treatment of RME. The purpose of this article is to review the treatment prediction and assessment progress of aqueous humor cytokines for the RME, giving evidence to provide a basis for expanding the diagnosis and treatment ideas of RME and guiding the development of personalized medical treatment.

Cancer immunotherapy, a major breakthrough in cancer treatment, has been successfully applied to treat a number of tumors. However, given the presence of factors in the tumor microenvironment (TME) that impede immunotherapy, only a small proportion of patients achieve a good clinical response. With the ability to increase permeability and cross biological barriers, nanomaterials have been successfully applied to deliver immunotherapeutic agents, thus realizing the anti-cancer therapeutic potential of therapeutic agents. This has driven a wave of research into systems for the delivery of immunotherapeutic agents, which has resulted in widespread interest in nanomaterial-based drug delivery systems. Nanomaterial-based drug delivery systems are able to overcome the challenges from TME and thus achieve good results in cancer immunotherapy. If it can make a breakthrough in improving biocompatibility and reducing cytotoxicity, it will be more widely used in clinical practice. Different types of nanomaterials may also have some subtle differences in enhancing cancer immunotherapy. Moreover, delivery systems made of nanomaterials loaded with drugs, such as cytotoxic drugs, cytokines, and adjuvants, could be used for cancer immunotherapy because they avoid the toxicity and side effects associated with these drugs, thereby enabling their reuse. Therefore, further insights into nanomaterial-based drug delivery systems will provide more effective treatment options for cancer patients.

The most important consideration in determining treatment strategies for undifferentiated early gastric cancer (UEGC) is the risk of lymph node metastasis (LNM). Therefore, identifying a potential biomarker that predicts LNM is quite useful in determining treatment.To develop a machine learning (ML)-based integral procedure to construct the LNM gray-level co-occurrence matrix (GLCM) prediction model.We retrospectively selected 526 cases of UEGC confirmed through pathological examination after radical gastrectomy without endoscopic treatment in four tertiary hospitals between January 2015 to December 2021. We extracted GLCM-based features from grayscale images and applied ML to the classification of candidate predictive variables. The robustness and clinical utility of each model were evaluated based on the following factors: Receiver operating characteristic curve (ROC), decision curve analysis, and clinical impact curve.GLCM-based feature extraction significantly correlated with LNM. The top 7 GLCM-based factors included inertia value 0° (IV_0), inertia value 45° (IV_45), inverse gap 0° (IG_0), inverse gap 45° (IG_45), inverse gap full angle (IG_all), Haralick 30° (Haralick_30), Haralick full angle (Haralick_all), and Entropy. The areas under the ROC curve (AUCs) of the random forest classifier (RFC) model, support vector machine, eXtreme gradient boosting, artificial neural network, and decision tree ranged from 0.805 [95% confidence interval (CI): 0.258-1.352] to 0.925 (95%CI: 0.378-1.472) in the training set and from 0.794 (95%CI: 0.237-1.351) to 0.912 (95%CI: 0.355-1.469) in the testing set, respectively. The RFC (training set: AUC: 0.925, 95%CI: 0.378-1.472; testing set: AUC: 0.912, 95%CI: 0.355-1.469) model that incorporates Entropy, Haralick_all, Haralick_30, IG_all, IG_45, IG_0, and IV_45 had the highest predictive accuracy.The evaluation results indicate that the method of selecting radiological and textural features becomes more effective in the LNM discrimination against UEGC patients. Additionally, the ML-based prediction model developed using the RFC can be used to derive treatment options and identify LNM, which can hence improve clinical outcomes.

Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible pulmonary interstitial disease that seriously affects the patient's quality of life and lifespan. The pathogenesis of IPF has not been clarified, and its treatment is limited to pirfenidone and nintedanib, which only delays the decline of lung function. Alveolar epithelial type 2 (AT2) cells are indispensable in the regeneration and lung surfactant secretion of alveolar epithelial cells. Studies have shown that AT2 cell dysfunction initiates the occurrence and progression of IPF. This review expounds on the AT2 cell dysfunction in IPF, involving senescence, apoptosis, endoplasmic reticulum stress, mitochondrial damage, metabolic reprogramming, and the transitional state of AT2 cells. This article also briefly summarizes potential treatments targeting AT2 cell dysfunction.

This study aimed to explore the role of phospholipase C epsilon1 (PLCE1) in the growth and progression of oral squamous cell carcinoma (OSCC) and determine its potential as a biomarker with respect to diagnosis, prognosis and treatment of OSCC.The expression level of PLCE1 in tissue specimens was detected by immunohistochemistry (182 OSCC cases and 76 controls) and its relationship to clinicopathological parameters was analyzed. Then, the diagnostic value of PLCE1 in OSCC was verified by constructing the receiver operating characteristic (ROC) curve. Kaplan-Meier and Cox analysis were performed to investigate the role of PLCE1 in predicting the prognosis of OSCC patients. Furthermore, the effects of PLCE1 on the occurrence and development of OSCC were revealed by knocking down the level of PLCE1.PLCE1 was mainly located in the cytoplasm of OSCC cells, and its level in OSCC tissues was obviously higher than in adjacent normal tissues. While the expression of PLCE1 did not correlate with clinicopathological parameters of OSCC. The area under the ROC curve (AUC) of PLCE1 was 0.865 with a sensitivity of 75.8% and a specificity of 78.8%. Besides, high expression of PLCE1 suggested a worse prognosis in OSCC patients than those with low expression. The knockdown of PLCE1 obviously inhibited proliferation, migration, and invasion of OSCC cells, and induce G0 cell cycle phase arrest and apoptosis, thus preventing the progression of OSCC.PLCE1 may cause carcinogenesis and development of OSCC, which provide a novel possibility in diagnosis, prognosis and treatment of OSCC.

Numerous studies have concentrated on neoadjuvant therapies for treating triple-negative breast cancer (TNBC) that improve the pathological complete response (pCR) rate but remain controversial. We conducted a network meta-analysis (NMA) to objectively explore the efficacy and safety of different neoadjuvant regimens.Phase II/III randomized clinical trials that compared different neoadjuvant therapies for TNBC were included. NMA and pairwise meta-analysis were performed using WinBUGS (version 1.4.3) and Review Manager 5.3.Forty-four studies with 8459 patients met the eligibility criteria. The NMA of pCR showed that programmed cell death Protein-1 and programmed cell death Ligand-1 inhibitors (PD-1/PD-L1), bevacizumab (Bev), zoledronic acid (ZOL), and platinum salts plus poly polymerase inhibitors (Pt+PARPi) may be favorable for TNBC neoadjuvant therapy. Chemotherapy combined with platinum salts or nanoparticle albumin-bound paclitaxel (Nab-p) has additional beneficial effects. However, neo-type drugs may also have increased toxicity.PD-1/PD-L1, Bev, ZOL, and Pt+ PARPi-containing regimens improved the pCR rate compared to traditional chemotherapy, including anthracyclines and taxanes. Chemotherapy with platinum salts or Nab-p improved the pCR rate. Nevertheless, the balance between efficacy and toxicity should be evaluated rigorously. PD-1/PD-L1-containing regimens appear to be the most favorable for TNBC neoadjuvant therapy, with good efficacy and tolerance.

The on-demand replacement of multifunctional hydrogel wound dressings helps to avoid bacterial colonization, and the on-demand painless peeling of tissue adhesive hydrogels on the wound site remains a major challenge to be solved. In this work, we design and develop a series of multifunctional dynamic Schiff base network hydrogels composed of cystamine-modified hyaluronic acid, benzaldehyde-functionalized poly(ethylene glycol)-co-poly(glycerol sebacate), and polydopamine@polypyrrole nanocomposite (PDA@PPy) with mild on-demand removability to enhance drug-resistant bacteria-infected wound healing. These hydrogels exhibited ideal injectable and self-healing properties, excellent tissue adhesion, in vivo hemostasis, good antioxidation, and conductivity. PDA@PPy inspired by melanin endows hydrogels with excellent antioxidant capacity, UV-blocking ability, and photothermal anti-infection ability. Based on the dynamic oxidation-reduction response of disulfide bonds inspired by the dissociation of the tertiary spatial structure transformation of poly-polypeptide chains, these hydrogels can achieve rapid painless on-demand removal under mild conditions by adding dithiothreitol. These multifunctional hydrogels significantly promoted collagen deposition and angiogenesis in the MRSA-infected full-thickness skin repair experiment. All the results showed that these multifunctional hydrogels with painless on-demand removal property showed great potential in clinical treatment of infected wounds.

Nonylphenol (NP) is a widely used chemical, which has been considered a kind of endocrine-disrupting chemical and is involved in the occurrence and development of many types of cancers. Our recent studies demonstrated that NP exposure is related to colorectal cancer (CRC) progression. In this study, we also found epithelial-mesenchymal transition (EMT) promoted by NP treatment in CRC cells. However, the mechanism of NP on tumor metastasis is still unclear. In this study, we focused on the effect of the regulator of cell cycle (RGCC) induced by NP treatment. The cancer genome atlas (TCGA) analysis suggested that the expression of RGCC increased in CRC tissues, and our clinical samples showed that the expression of RGCC in tumor tissues is positively correlated with the serum level of NP in CRC patients. Further studies revealed that overexpression of RGCC could enhance the NP-induced EMT process in CRC cells and activate ERK signaling pathways. Inhibiting ERK signaling by ERK inhibitors or the knockdown of RGCC could attenuate the NP-induced EMT process. In addition, both RGCC overexpression and NP treatment could activate ERK pathways and attenuate the effect of ERK inhibitors on the EMT process in CRC cells. Altogether, this study demonstrated that NP could induce cell invasion and migration by increasing the expression of RGCC to enhance the EMT process, which might be through the activation of ERK signaling pathways. This finding supported a potential target for studying NP exposure-related colorectal cancers.

To assess the safety and efficacy of laparoscopic versus open repair of congenital duodenal obstruction (CDO), we conducted a systematic review and meta-analysis (CDO).A literature search was conducted to identify studies that compared laparoscopic surgery (LS) and open surgery (OS) for neonates with CDO. Meta-analysis was used to pool and compare variables such as operative time, time to feeding, length of hospital stay, anastomotic leak or stricture, postoperative ileus, wound infection, and overall postoperative complications.Among the 1348 neonatal participants with CDO in the ten studies, 304 received LS and 1044 received OS. When compared to the OS approach, the LS approach resulted in shorter hospital stays, faster time to initial and full feeding, longer operative time, and less wound infection. However, no significant difference in secondary outcomes such as anastomotic leak or stricture, postoperative ileus, and overall postoperative complications was found between LS and OS.LS is a safe, feasible and effective surgical procedure for neonatal CDO when compared to OS. Compared with OS, LS has a faster time to feeding, a shorter hospital stay, and less wound infection. Furthermore, in terms of anastomotic leak or stricture, postoperative ileus, and overall postoperative complications, LS is equivalent to OS. We conclude that LS should be considered an acceptable option for CDO.

The triglyceride glucose (TyG) index is closely associated with subclinical atherosclerosis. However, the association remains inconclusive among obese and nonobese individuals.This prospective study was conducted in 5751 adults with normal carotid intima-media thickness (CIMT) at baseline. We divided the population into four groups based on the TyG index, which was calculated by the following formula: Ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Information on CIMT was acquired by ultrasonography. Incident elevated CIMT was defined as IMT values greater than 0.9 mm at follow-up. Odds ratios (ORs) and 95% confidence intervals (CIs) of the associations between TyG index and elevated CIMT were estimated using multivariable logistic regression models.After a median follow-up of 4.3 years, 722 (12.6%) individuals had progressed to elevated CIMT. Compared with the second quartile of the TyG index, the first and fourth quartile both conferred higher risks of elevated CIMT after adjusting for potential confounders. In the total population, the ORs for the first and fourth quartile were 1.29 (95% CI, 1.00-1.66) and 1.42 (95% CI, 1.11-1.83), respectively. Restricted cubic splines demonstrated an approximately U-shaped association between TyG index and elevated CIMT among the total and nonobese adults (P for nonlinearity.05), but not in those with general or abdominal obesity.A U-shaped association was observed between TyG index and elevated CIMT only among nonobese Chinese adults.背景: 甘油三酯血糖(TyG)指数与亚临床动脉粥样硬化密切相关。然而，肥胖者和非肥胖者之间的联系仍然没有定论。 方法: 这项前瞻性研究在5751名基线颈动脉内膜中层厚度(CIMT)正常的成年人中进行。根据TyG指数将人群分为四组，计算公式为:Ln(空腹甘油三酯[mg/dL]×空腹血糖[mg/dL]/2)。超声检查获得CIMT的相关信息。升高的CIMT定义为随访时IMT值大于0.9 mm。用多变量Logistic回归模型估计TyG指数与CIMT升高之间关联的优势比(OR)和95%置信区间(CI)。 结果: 经过平均4.3年 的随访，有722例(12.6%)患者进展为CIMT升高。与TyG指数的第二个四分位数相比，在校正了潜在的混杂因素后，第一和第四个四分位数都具有更高的CIMT升高风险。在总人口中，第一和第四个四分位数的OR值分别为1.29(95%CI，1.00~1.66)和1.42(95%CI，1.11~1.83)。限制立方样条法显示TyG指数与非肥胖者和非肥胖者的CIMT升高呈近似的U型相关(P0.05)，但在一般肥胖者或腹型肥胖者中不存在。 结论: 仅在非肥胖的中国成年人中，TyG指数与CIMT升高呈U型相关。.

Neural precursor cell expressed developmentally downregulated 4-like (NEDD4L), a member of the E3 ubiquitin-protein ligases, encoded by NEDD4L gene, was found to be involved in in salt sensitivity by regulating sodium reabsorption in salt-sensitive rats. The authors aimed to explore the associations of NEDD4L genetic variants with salt sensitivity, blood pressure (BP) changes and hypertension incidence in Chinese adults. Participants from 124 families in Northern China in the Baoji Salt-Sensitive Study Cohort in 2004, who received the chronic salt intake intervention, including a 7-day low-salt diet (3.0 g/day) and a 7-day high-salt diet (18 g/day), were analyzed. Besides, the development of hypertension over 14 years was evaluated. NEDD4L single nucleotide polymorphism (SNP) rs74408486 was shown to be significantly associated with systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) responses to low-salt diet, while SNPs rs292449 and rs2288775 were significantly associated with pulse pressure (PP) response to high-salt diet. In addition, SNP rs4149605, rs73450471, and rs482805 were significantly associated with the longitudinal changes in SBP, DBP, MAP, or PP at 14 years of follow-up. SNP rs292449 was significantly associated with hypertension incidence over the 14-year follow-up. Finally, this gene-based analysis found that NEDD4L was significantly associated with longitudinal BP changes and the incidence of hypertension over the 14-year follow-up. This study indicated that gene polymorphism in NEDD4L serve an important function in salt sensitivity, longitudinal BP change and development of hypertension in the Chinese population.

Objective. To investigate the effects of loratadine tablets in combination with other drugs on nasal physiological function and T lymphocyte subsets in patients with allergic rhinitis (AR). Methods. A total of 120 AR patients treated in our hospital from February 2018 to February 2021 were randomly divided into control group and research group. The control group was given mometasone furoate nasal spray combined with loratadine tablets, while the research group was given budesonide combined with loratadine. The efficacy, duration of clinical symptom remission, immune function indicators, T lymphocyte subset, nasal physiological function, and incidence of adverse reactions were compared between the two groups. Results. The efficacy results of the two groups showed that the effective rate of the research group was 96.67%, while the effective rate of the control group was 83.33%. The effective rate in the research group was higher compared to the control group (χ2: 5.925 P < 0.05 ). The results of clinical symptom relief time showed that the clinical symptom relief time of nasal congestion, itching, runny nose, and sneezing in the research group was lower than that in the control group, and the difference was statistically significant ( P < 0.05 ). The results of the comparison of immune function indicators showed that the IL-6, IL-8, and IgE of the research group were lower than those of the control group, while the Th1/Th2 of the research group were higher than those of the control group. There were no statistically significant differences in T lymphocyte subsets before nursing, but after treatment, the T lymphocyte subsets of the two groups decreased, and the level of CD3+, CD4+, CD8+, CD4+, and CD4+/CD8+ lymphocytes in the research group was lower than that of the control group, and the difference was statistically significant ( P < 0.05 ). Before treatment, there exhibited no significant difference in nasal physiological function, but after treatment, the nasal physiological function of the two groups was enhanced, and the MTT, NR, and MCR of the research group were lower than those of the control group, and the difference was statistically significant ( P < 0.05 ). Finally, the incidence of adverse reactions in the research group was lower compared to the control group, and the difference was statistically significant ( P < 0.05 ). Conclusion. Budesonide and loratadine are effective in improving patient efficacy, T lymphocyte subsets, and nasal physiological function, and are safer.

The paranasal area is closely associated with midfacial esthetics. However, there is no special technique available to achieve ideal esthetics paranasal restoration. The present study aims to apply the 3D printed PolyEtherEtherKetone (PEEK) implants as an innovative solution for esthetic paranasal reconstruction. On the basis of the CT scan, the patient-specific PEEK implant and a surgical guiding plate were manufactured aided by a computer. Preoperative and postoperative CBCT data were utilized to evaluate esthetic outcomes. The average follow-up period was 13 months. All patients' wounds healed by first intention. The statistical analysis of preoperative and postoperative esthetic indices revealed light levels of postoperative paranasal depression ( P0.001) and the wrinkle severity rating scale for nasolabial folds ( P0.001). Moreover, the nasolabial angle increased ( P0.05). The established 3D-printing PEEK implanted prosthesis can individually correct the depressed deformity of the paranasal region, and achieve favorable clinical esthetic outcomes.

Aims: To assess the independent and joint impact of visit-to-visit fasting blood glucose variability (VVV-FBG) and mean fasting glucose level (M-FBG) on all-cause mortality.Materials and methods: This prospective cohort study included 48,843 Chinese with type 2 diabetes. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) to evaluate the association of VVV-FBG and M-FBG with all-cause mortality. The potential nonlinear associations were examined by restricted cubic splines, and additive interaction was evaluated by the relative excess risk due to interaction (RERI). Cox generalized additive models (CGAM) and bivariate response surface models were further used to assess the joint effects of VVV-FBG and M-FBG.Results: A total of 4087 deaths was observed during a median follow-up of 6.99 years. Compared with patients with values at the 5th percentile of ARV and M-FBG, we observed a 23% and 38% increased risk of premature deaths among those with values at the 95th percentile of ARV (HR: 1.23, 95% CI 1.10,1.37) and M-FBG (HR: 1.38, 95% CI 1.26,1.51), respectively. The interaction between glycemic variability (ARV) and M-FBG was significant on both the additive scale [RERI: 0.80 (0.29, 1.32)] and multiplicative scale [HR: 1.90 (1.10, 3.28)]. Subjects with high VVV-FBG and high M-FBG conferred the highest risk of all-cause mortality (HR: 1.89, 95% CI: 1.64,2.17), compared to low VVV-FBG and low M-FBG. The CGAM revealed significant synergistic effects between glycemic variability and M-FBG (P < 0.05). Moreover, bivariate surface plot revealed that the risk of death increased more rapidly in type 2 diabetes patients at the lower M-FBG level combined with lower glycemic variability level.Conclusions: The coexistence of great glycemic variability and high level of glucose might exacerbate the independent risk of premature mortality in type 2 diabetes patients, highlighting the importance of achieving normal and stable glucose levels simultaneously in the management of glucose. This article is protected by copyright. All rights reserved.

Valerate and caproate are two subtypes of short-chain fatty acids produced by gut microbiota. We aimed to measure the serum valerate and caproate levels and analyze the associations between them and renal prognosis of diabetic nephropathy (DN).The serum samples of patients with biopsy-confirmed diagnosis of DN were collected in the First Affiliated Hospital of Zhejiang University, from April 1, 2013, to March 31, 2018. One hundred patients were included and divided into an early DN group (eGFR ≥ 60 ml/min, n = 42) and an advanced DN group (eGFR 60 ml/min, n = 58). The valerate and caproate were measured using gas chromatography-mass spectrometry. Participants were followed up until the cutoff date of August 31, 2018, or if they met the primary endpoint of end-stage renal disease (ESRD).There were 71 males and 29 females in this study, and 29 patients developed ESRD. We observed a significant lower concentration of valerate and caproate in the advanced DN group. There were negative correlations between valerate and glomerular classification (r = - 0.20, P = 0.03) and between caproate and interstitial fibrosis and tubular atrophy (IFTA) (r = - 0.24, P = 0.01). And there were positive correlations between valerate or caproate and eGFR (r = 0.22, P = 0.02; r = 0.38, P 0.01). Multivariate Cox analysis revealed higher levels of valerate and caproate were negatively related to progression to ESRD (HR = 0.024, P = 0.016; HR = 0.543, P = 0.030). The area under the curve values of valerate and caproate levels were 0.66 and 0.63, respectively, in predicting progression to ESRD.This study showed alterations in serum valerate and caproate in DN and demonstrates lower valerate and caproate levels with progression of DN to ESRD.

Anti-neurofascin 155 (NF155) antibody has been discovered in chronic demyelinating conditions. However, the positive rate and clinical description were insufficient in acute demyelinating conditions, such as Guillain-Barré syndrome (GBS). This study aimed to explore the positive rate of anti-NF155 antibody in GBS patients and determine whether there were unique clinical characteristics in these patients.Serum anti-NF155 antibody was detected from 94 GBS patients and 50 sex- and age-matched healthy controls using cell-based assay and tissue-based assay with immunostaining of mouse teased sciatic nerve fibers. Clinical characteristics, laboratory data, and electrophysiology examinations were retrospectively collected.Seven of 94 (7.45%) GBS patients were positive for anti-NF155 antibody, and the main IgG subclass was IgG1. Compared with anti-NF155 antibody-negative GBS patients, anti-NF155 antibody-positive GBS patients had a higher GBS disability score at nadirs (p = .010), higher modified Erasmus GBS outcome score (p = .022), higher rate of abnormal compound motor action potential (CMAP) amplitude (p = .002), higher frequency of prolonged F-wave latency (p .001), lower frequency of abnormal sensory conduction velocity (p .001) and sensory nerve action potential amplitude (p .001), more axonal type (p = .040), and poorer therapeutic effect (p = .017).Anti-NF155 antibody exists in a small portion of GBS patients. Anti-NF155 antibody-positive GBS patients possibly have a more severe clinical course, less sensory nerves involved, higher proportion of axonal type, poorer therapeutic effect, and worse prognosis, but the pathogenicity of the anti-NF155 antibody in GBS needs further study.

The exercise pressor reflex (EPR), a neurocirculatory control mechanism, is exaggerated in hypertensive humans and rats. Disease-related abnormalities within the afferent arm of the reflex loop, including mechano- and metabosensitive receptors located at the terminal end of group III/IV muscle afferents, may contribute to the dysfunctional EPR in hypertension. Using control (WKY) and spontaneous hypertensive (SHR) rats, we examined dorsal root ganglion (DRG) gene and protein expression of molecular receptors recognized as significant determinants of the EPR. Twelve lumbar DRGs (6 left, 6 right) were harvested from each of 10 WKY [arterial blood pressure (MAP): 96 ± 9 mmHg] and 10 SHR (MAP: 144 ± 9 mmHg). DRGs from the left side were used for protein expression (Western blotting; normalized to GAPDH), whereas right-side DRGs (i.e., parallel structure) were used to determine mRNA levels (RNA-sequencing, normalized to TPM). Analyses focused on metabosensitive (ASIC3, Bradykinin receptor B2, EP4, P2X3, TRPv1) and mechanosensitive (Piezo1/2) receptors. Although Piezo1 was similar in both groups ( P = 0.75), protein expression for all other receptors was significantly higher in SHR compared with WKY. With the exception of a greater Bradykinin-receptor B2 in SHR ( P < 0.05), mRNA expression of all other receptors was not different between groups ( P > 0.18). The higher protein content of these sensory receptors in SHR indirectly supports the previously proposed hypothesis that the exaggerated EPR in hypertension is, in part, due to disease-related abnormalities within the afferent arm of the reflex loop. The upregulated receptor content, combined with normal mRNA levels, insinuates that posttranscriptional regulation of sensory receptor protein expression might be impaired in hypertension.

C2 pedicle screw placement in patients with basilar invagination (BI) is fraught with risks because of a high incidence of anatomical variations and high-riding vertebral artery (HRVA). However, no study can be found in the literature that attempted to identify the ideal entry point and trajectory through the C2 pedicle in BI patients with HRVA.To investigate the parameters of ideal entry point and trajectory for C2 pedicle screw placement in BI patients with HRVA and compare them with those in BI patients without HRVA and patients without BI as control. These parameters would serve as a guide to pedicle screw placement.A retrospective comparative study.A total of 396 patients (198 consecutive BI patients and 198 matched patients without BI as control) and 792 unilateral pedicles from April 2017 to October 2021 at two medical centers were included.The insertion parameters of mediolateral angle, surface distance, cephalad angle, and vertical distance from the superior border of the lamina were the primary outcome measures for the reference of C2 pedicle screw placement. Furthermore, factors that affect the primary insertion parameters were assessed via multiple linear regression analyses.According to the diagnosis of BI and HRVA, the unilateral pedicles were assigned into HRVA of BI, non-HRVA of BI, HRVA of control, and non-HRVA of control groups. Subgroup analyses based on Goel types A and B were also performed. Moreover, vertebral artery (VA) anomalies that might result in potentially serious complications were identified and systematically compared.The measurements of insertion parameters in BI patients with HRVA indicated a mean mediolateral angle of 27.42°, a mean cephalad angle of 43.02°, a mean surface distance of 9.74 mm, and a mean vertical distance from the superior border of the lamina of 3.85 mm. Compared with that in BI patients without HRVA, the measurements suggested that the entry point in BI patients with HRVA should be shifted upward by 0.38 mm and the trajectory should be angled cephalad by 6.05° and medially by 4.78°. In the control group, changes in the insertion parameters between HRVA and non-HRVA showed a similar trend to the BI group. Multiple linear regression showed that mediolateral angle was significantly associated with the male gender (B=-0.930, p=.017) and the diagnoses of HRVA (B=6.964, p.001), Goel type A (B=-1.656, p=.003), and Goel type B (B=0.981, p=.030). Moreover, cephalad angle was significantly associated with the length of lateral mass (B=-0.319, p=.001) and the diagnoses of HRVA (B=3.254, p.001) and Goel type A (B=6.924, p.001). The VA anomalies were significantly higher in the BI group than in the control group.The insertion parameters of the ideal entry point and trajectory for C2 screw placement in BI patients with HRVA were remarkably different from those of non-HRVA of BI, HRVA of control, and non-HRVA of control cohorts. Preoperative 3D computed tomography (CT) and CT angiography are highly recommended in such patients to improve intraoperative safety and reduce postoperative complications.

To compare the effectiveness and safety of sacrospinous ligament fixation (SSLF) and uterosacral ligaments suspension (ULS) for surgical correction of pelvic organ prolapse (POP).Comparative studies were identified in PubMed, EMBASE, MEDLINE, Cochrane library, Medicine and clinicaltrials.gov databases. Randomized controlled trials, prospective and retrospective cohort studies were included. Primary outcomes were collected including anatomical success rate (Defined as anterior or posterior vaginal wall beyond the hymen), surgical success rate, recurrence and total complication rate, while secondary outcomes were specific complications rates. Data were analyzed using Revman (Version 5.4).After searching databases and removing the duplicate studies, a total of 57 articles had entered the screening stage. Finally, 9 moderate and high quality studies (4 randomized controlled trials and 5 retrospective studies) with 4516 participants were included. For primary outcomes, there was no statistical difference between the 2 groups regarding surgical success rate (RR = 1.00; 95% CI: 0.91-1.01; IIn conclusion, SSLF and ULS have the same efficacy and safety for patients. However, SSLF seems to have lower complication rates of vaginal granulation tissue and urethral injury and is gradually favored by surgeons because of its short operation time and simple operation. We still need more high-quality research, especially in terms of the incidence of complications.

Patients with chronic kidney disease (CKD) are at higher risk for coronavirus disease 2019 (COVID-19)-related morbidity and mortality. However, a significant portion of CKD patients showed hesitation toward vaccination in telephone survey of our center. Yet no serial data available on humoral response in patients with CKD, especially those on immunosuppression. We conducted a pilot, prospective study to survey the safety and humoral response to inactivated SARS-CoV-2 vaccine in CKD patients receiving a 2-dose immunization of inactivated SARS-CoV-2 vaccine. We found the neutralizing antibody titers in CKD patients was significantly lower than that in healthy controls, hypertension patients, and diabetes patients. Notably, immunosuppressive medication rather than eGFR levels or disease types showed effect on the reduction of immunogenicity. Interestingly, a third dose significantly boosted neutralizing antibody in CKD patients while immunosuppressants impeded the boosting effects. In conclude, our data demonstrates that CKD patients, even for those on immunosuppression treatment, can benefit from a third vaccination boost by improving their humoral immunity.

Aim: The underlying mechanisms by which circular RNAs (circRNAs) regulate non-small-cell lung cancer (NSCLC) progression remain elusive. This study investigated the role of circRNA circTTBK2 in NSCLC tumorigenesis. Materials & methods: Quantitative reverse transcriptase polymerase chain reaction analysis of circTTBK2 in NSCLC tissues and cell lines was performed. Cell proliferation, migration, invasion and tumorigenesis were confirmed in vitro and in vivo using CCK-8, EdU incorporation, Transwell assays and xenograft technique. The circTTBK2/miR-873-5p/TEAD1/DERL1 axis was verified by RNA immunoprecipitation, chromatin immunoprecipitation and luciferase reporter assays. Results: Overexpressed circTTBK2 in NSCLC tissues indicates poor prognosis of NSCLC patients. circTTBK2 harbors miR-873-5p, and miR-873-5p directly targets TEAD1. TEAD1 transcriptionally activates DERL1. Conclusion: This study revealed a novel machinery of circTTBK2/miR-873-5p/TEAD1/DERL1 for NSCLC tumorigenesis.

Giant cell tumors (GCTs) and giant cell granulomas (GCGs) are giant cell-rich lesions that occur extremely rarely in the temporal bone and have similar clinical presentations.We aimed to analyze the clinical features and introduce our staging system and surgical treatment.Forty-six patients pathologically diagnosed with a giant cell lesion involving the temporal bone between October 2001 and October 2020 were reviewed retrospectively. The clinical characteristics, surgical approaches, and risk factors for recurrence were analyzed.GCTs and GCGs presented as masses centered on the temporomandibular joint with similar imaging features, including a thin, calcified shell and central scattered calcifications on a computed tomography scan. Differences were detected on magnetic resonance imaging in 29.6% (4/14) of GCG and 50% (16/32) of GCT cases; the remaining cases were not distinguishable. Based on our staging system and surgical strategy, 31.8% (7/22) of GCT and 10% (1/10) of GCG cases experienced recurrence, which compares to recurrence rates of 60% in GCT cases and 20% in GCG cases in previous studies.Specific clinical and preoperative imaging features help to make a diagnosis of temporal giant cell-rich lesions. Our staging system and surgical strategy could help surgeons tailor the surgical strategy.

Non-small cell lung cancer (NSCLC) is the prevalent histological subtype of lung cancer. In this study, we performed ultraperformance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS)-based metabolic profiling of 227 tissue samples from 79 lung cancer patients with adenocarcinoma (AC) or squamous cell carcinoma (SCC). Orthogonal partial least squares-discriminant analysis (oPLS-DA) analyses showed that AC, SCC, and NSCLC tumors were discriminated from adjacent noncancerous tissue (ANT) and distant noncancerous tissue (DNT) samples with good accuracies (91.3, 100, and 88.3%), sensitivities (85.7, 100, and 83.9%), and specificities (94.3, 100, and 90.7%), using 12, 4, and 7 discriminant metabolites, respectively. The discriminant panel for AC detection included valine, sphingosine, glutamic acid γ-methyl ester, and lysophosphatidylcholine (LPC) (16:0), levels of which in tumor tissues were significantly altered. Valine, sphingosine, LPC (18:1), and leucine derivatives were used for SCC detection. The discrimination between AC and SCC had 96.8% accuracy, 98.2% sensitivity, and 85.7% specificity using a five-metabolite panel, of which valine and creatine had significant differences. The classification models were further verified with external validation sets, showing a promising prospect for NSCLC tissue detection and subtyping.

The aim was to examine the subgroups of work engagement in frontline nurses during the COVID-19 pandemic.The pandemic may affect the work engagement of nurses who have direct contact with infected patients and lead to a poor quality of care. Identifying classification features of work engagement and tailoring interventions to support frontline nurses is imperative.This study utilized a cross-sectional study design.Three hundred fifty-five nurses were enrolled in this cross-sectional study from 14 February to 15 April 2020. A latent profile analysis was performed to identify classification features of work engagement. Multiple logistic regression analyses were used to examine predictors of profile membership.A four-profile model provided the best fit. The four profiles were titled 'low work engagement' (n = 99), 'high vigour-low dedication and absorption' (n = 58), 'moderate work engagement' (n = 63) and 'high work engagement' (n = 135). A regression analysis suggested that young nurses and nurses who were the only children of their family were more likely to be in the 'low work engagement' and 'high vigour-low dedication and absorption' groups.This study highlights the importance of tailoring interventions for frontline supporting nurses by considering their distinct work engagement patterns, especially during the COVID-19 pandemic, to improve the promotion of work satisfaction and quality of care.This was the first study to explore the latent profiles of work engagement in frontline nurses during the COVID-19 pandemic. Over 40% of nurses were in the 'low work engagement' and 'high vigour-low dedication and absorption' groups and reported low levels of work engagement. Understanding different patterns of work engagement in frontline nurses can help nursing managers provide emotional, material and organizational support based on the features of each latent profile, which may improve the quality of care and patient safety.

The pathogenesis of amyotrophic lateral sclerosis (ALS) remains unclear. The recent studies have suggested that the protein abnormalities could play some important roles in ALS because several protein mutations were found in individuals with this disease. However, proteins that are currently known to be associated with ALS only explain the pathogenesis of this disease in a minority of cases, thus, further screening is needed to identify other ALS-related proteins. In this study, we systematically analyzed and compared the brain proteomic alterations between a mouse model of ALS, the Tg(SOD1*G93A)1Gur model, and wild-type mice using isobaric tags for relative and absolute quantitation (iTRAQ) as well as bioinformatics methods. The results revealed some significant up- and downregulated proteins at the different developmental stages in the ALS-like mice as well as the possibly related cellular components, molecular functions, biological processes, and pathways in the development of ALS. Our results identified some possible proteins that participate in the pathogenesis of ALS as well as the cellular components that are damaged by these proteins, we additionally identified the molecular functions, the biological processes, and the pathways of these proteins as well as the molecules that are associated with these pathways. This study represents an important preliminary investigation of the role of proteomic abnormalities in the pathogenesis of ALS, both in human patients and other animal models. We present some novel findings that may serve as a basis for further investigation of abnormal proteins that are involved in the pathogenesis of ALS.

Toll-like receptors (TLRs) are important components of the innate and adaptive immune systems, and abnormal TLR expression has been linked to a variety of cancers. However, there was a lack of clarity on the association of TLR stimulation with the carcinogenesis of cancer. The study's goal was to analyse the clinical importance of TLRs expression at the mRNA level in pan-cancer datasets, as well as the link between TLR expression and carcinogenesis, progression, and clinical prognosis. The expression profile of TLRs derived from UCSC pan-cancer data was analysed in multiple dimensions, including clinical analysis, immunological subtype analysis, tumour microenvironment (TME) analysis, tumour stem cell correlation analysis, and drug sensitivity analysis. Additionally, we analyse protein-protein interactions, functional enrichment, and chromatin accessibility, as well as TLR expression in single-cell sequencing data. Our multi-omics analysis results imply that TLRs may operate as a biological marker for carcinogenesis and progression, a potential target for anti-tumour therapy, and a prognostic biomarker, laying the theoretical groundwork for future translational medicine research. TLRs are involved in the formation of malignancies and can be explored in further detail as potential prognostic indicators. Key MessagesToll-like receptors (TLRs) are key factors in the process of the innate and adaptive immune response, and their aberrant expression of TLRs have been widely reported in various cancer. However, the association between TLRs stimulation and tumorigenesis of cancer has not been well clarified.In this study, in the pan-cancer data, integrated TLR family gene expression analysis, clinical correlation analysis, immune subtype correlation analysis, tumour microenvironment correlation analysis, tumour stem cell correlation analysis, and drug sensitivity correlation analysis were performed.TLRs play an important role in the development of tumours and can be studied in depth as potential prognostic markers. Toll-like receptors (TLRs) are key factors in the process of the innate and adaptive immune response, and their aberrant expression of TLRs have been widely reported in various cancer. However, the association between TLRs stimulation and tumorigenesis of cancer has not been well clarified. In this study, in the pan-cancer data, integrated TLR family gene expression analysis, clinical correlation analysis, immune subtype correlation analysis, tumour microenvironment correlation analysis, tumour stem cell correlation analysis, and drug sensitivity correlation analysis were performed. TLRs play an important role in the development of tumours and can be studied in depth as potential prognostic markers.

Lactate dehydrogenase (LDH) is a biomarker for cancer. However, the relationship between serum LDH levels and the survival of patients with brain metastasis has been fully revealed. We aimed to evaluate the serum LDH levels and assess its prognostic value in patients with BM.The serum LDH levels were collected from 2507 patients with BM. Patients were categorized into four groups according to the quartile of serum LDH levels. The association between serum LDH levels and overall survival (OS) was evaluated using Cox regression models and Kaplan-Meier curves. Three predictive models were used to evaluate patients.The Kaplan-Meier curve for survival by the serum LDH group demonstrates clear separation between four groups (P 0.001). The participants in the lower group had longer OS than those in the higher group. After adjusting in multivariate Cox regression models remained significant for patients in the Q4 compared with patients in the Q1 (Q4:Q1 OR 1.58, 95% CI 1.38-1.80). Furthermore, the GPA-LDH model generates a pooled area under the curve of 0.630 (95% CI 0.600, 0.660).Serum LDH levels and OS in patients with brain metastasis is an inverse association. Moreover, Serum LDH levels can improve the prognosis of the GPA model.

Bilateral hepatolithiasis is an intractable disease and repeated attacks of acute cholangitis seriously threaten patient health. The surgical approaches evolve along with gradually greater understanding of its pathophysiology.This is a retrospective cohort study for bilateral hepatolithiasis from January 1958 to December 2018. Before May 1993 (Group A, n = 70), three surgical approaches were adopted: 37 patients with common bile duct exploration (CBDE), 29 with choledochoenterostomy (CE) and four with partial hepatectomy (PH). After June 1993 (Group B, n = 150), 101 patients underwent Oddi sphincter-preserved cholangioplasty with hepatico-subcutaneous stoma (OSPCHS), and 16 with CBDE, 21 with CE, 12 with PH. The perioperative and long-term outcomes were compared.After 1993, the cholangitis recurrence rate significantly decreased from 49.2% to 20.9%, and the stone recurrence rate from 76.3% to 37.1% (both P .001). Also, the stone-/cholangitis-free durations were prolonged significantly (median: 50.8 vs 26.4/49.6 vs 16.2 months, both P .001). Preoperative cholangitis was an independent risk factor for stone recurrence (hazard ratio [HR] = 1.863, P = .018), and residual stone for cholangitis recurrence (HR = 2.838, P .001). OSPCHS and PH were protective surgical approaches for recurrent stone (CBDE: reference; OSPCHS: HR = .469, P = .016, PH: HR = .219, P = .018) and cholangitis (CBDE: reference; OSPCHS: HR = .421, P = .010, PH: HR = .283, P = .093).For bilateral hepatolithiasis, the management should focus on hepatobiliary lesion eradication and Oddi sphincter function preservation.

Objectives Cervical cancer (CC) is the common female malignant tumour with non-negligible morbidity and mortality. Eleutheroside E (EE) has anti-oxidative stress, anti-inflammatory and anti-proliferation effects in diverse disease models. However, its anti-tumour role remains unclear. Methods The cell viability, apoptosis rate and protein expressions were detected by CCK-8, flow cytometry and western blot assays, respectively. The metabolic profile was performed by GC/MS analysis. Furthermore, the effect of EE on CC was verified in nude mice. Key findings EE notably decreased the viability and increased the cell apoptosis, which could be reversed with 740Y-P treatment. EE treatment changed the metabolic categories of SiHa cells. The fatty acids signalling pathway was the most outstanding differential pathway. Myo-inositol prominently enhanced the level of phosphorylated Akt in a dose-dependent way. Moreover, EE declined the tumour volume and weight and the proliferation, but promoted the apoptosis in vivo. EE reduced the relative expression of phosphorylated PI3K and Akt. However, all these in-vivo results were observably antagonized with myo-inositol treatment. Conclusions EE plays an anti-tumour role in CC via inhibiting the PI3K pathway and reprogramming the metabolic responses.

The multicenter and randomized DEFINITION II (Two-Stent vs Provisional Stenting Techniques for Patients With Complex Coronary Bifurcation Lesions) trial showed less 1-year target lesion failure (TLF) after a 2-stent approach for complex coronary bifurcation lesions compared with provisional stenting (PS). The authors report the 3-year clinical outcome of the DEFINITION II trial.The aim of the present study was to investigate the difference in TLF at 3 years after a planned 2-stent approach vs PS for complex coronary bifurcation lesions stratified by DEFINITION (Definitions and Impact of Complex Bifurcation Lesions on Clinical Outcomes After Percutaneous Coronary Intervention Using Drug-Eluting Stents) criteria.A total of 653 patients with complex coronary bifurcation lesions were randomly assigned to either the 2-stent group or the PS group in the DEFINITION II trial and were followed for 3 years. The primary endpoint was the occurrence of TLF at 3 years. Stent thrombosis was the safety endpoint.At 3 years, TLF had occurred in 52 patients (16.0%) in the PS group and in 34 (10.4%) patients in the 2-stent group (HR: 0.63; 95% CI: 0.41-0.97; P = 0.035), driven mainly by increased target vessel myocardial infarction (8.0% vs 3.7%; HR: 0.45; 95% CI: 0.23-0.89; P = 0.022) and target lesion revascularization (8.3% vs 4.3%; HR: 0.50; 95% CI: 0.26-0.96; P = 0.038). There was no difference in TLF between the 2 groups between year 1 and year 3.For patients with complex coronary bifurcations who reach 1-year postprocedure without experiencing endpoint events, there is still a risk for future events. The type of procedure performed initially is no longer a future event risk determinant. (Two-Stent vs Provisional Stenting Techniques for Patients With Complex Coronary Bifurcation Lesions; NCT02284750).

Hippocampal deficits and metabolic dysregulations such as dyslipidemia have been frequently reported in schizophrenia and are suggested to contribute to the pathophysiology of schizophrenia. Hippocampus is particularly susceptible to environmental challenges including metabolism and inflammation. However, evidence linking hippocampal alterations and metabolic dysregulations are quite sparse in drug-naïve schizophrenia. A total of 166 drug-naïve patients with first-episode schizophrenia (FES) and 78 healthy controls (HC) underwent measures for several serum metabolic markers, structural and resting-state functional magnetic resonance imaging (rs-fMRI), as well as diffusion tensor imaging (DTI). Seed-to-voxel functional connectivity (FC) and probabilistic tractography were performed to assess the functional and microstructural connectivity of the bilateral hippocampi. Clinical symptoms were evaluated with Positive and Negative Syndrome Scale (PANSS). Patients with FES showed significantly decreased total cholesterol (Chol) level. Patients showed elevated FC between the left hippocampus and bilateral thalami while showing decreased microstructural connectivity between the left hippocampus and bilateral thalami. Multiple regression analyses showed that FC from the left hippocampus to the right superior frontal gyrus (SFG), bilateral frontal pole (FP), and right thalamus were negatively associated with the Chol level, while no association was observed in the HC group. Our study validated alterations in both functional and microstructural thalamo-hippocampal connectivities, and abnormal cholesterol level in FES. Moreover, decreased cholesterol level is associated with elevated thalamo-hippocampal functional connectivity in patients with FES, suggesting that dyslipidemia may interact with the hippocampal dysfunction in FES.

Clinical studies have shown that subsets of patients with cancer achieve a significant benefit from Aurora kinase inhibitors, suggesting an urgent need to identify biomarkers for predicting drug response. Chromodomain helicase DNA binding protein 1 (CHD1) is involved in chromatin remodeling, DNA repair, and transcriptional plasticity. Prior studies have demonstrated that CHD1 has distinct expression patterns in cancers with different molecular features, but its impact on drug responsiveness remains understudied. Here, we show that CHD1 promotes the susceptibility of prostate cancer cells to inhibitors targeting Aurora kinases, while depletion of CHD1 impairs their efficacy in vitro and in vivo. Pan-cancer drug sensitivity analyses revealed that high expression of CHD1 was associated with increased sensitivity to Aurora kinase A (AURKA) inhibitors. Mechanistically, KPNA2 served as a direct target of CHD1 and suppressed the interaction of AURKA with the coactivator TPX2, thereby rendering cancer cells more vulnerable to AURKA inhibitors. Consistent with previous research reporting that loss of PTEN elevates CHD1 levels, studies in a genetically engineered mouse model, patient-derived organoids, and patient samples showed that PTEN defects are associated with a better response to AURKA inhibition in advanced prostate cancer. These observations demonstrate that CHD1 plays an important role in modulating Aurora kinases and drug sensitivities, providing new insights into biomarker-driven therapies targeting Aurora kinases for future clinical studies. Significance: CHD1 plays a critical role in controlling AURKA activation and promoting Aurora kinase inhibitor sensitivity, providing a potential clinical biomarker to guide cancer treatment.

Background. The discovery of noncoding RNAs (ncRNAs) offers new options for cancer-targeted therapy. This study is aimed at exploring the regulatory function of LINC00092 on breast cancer (BC) oxidative stress and glycolysis, along with internal mechanism concerning pyruvate carboxylase (PC). Methods. Bioinformatics analysis was used to explore LINC00092 (or friend leukemia virus integration 1 (FLI1)) expression on BC progression, as well as oxidative stress and glycolysis in BC. After LINC00092 overexpression or silence, BC cell viability, proliferation, migration, invasion, oxidative stress, glycolysis, and AKT/mTOR pathway were detected. Following 2-DG, SC79, or MK2206 treatment, effects of LINC00092 on BC cells were measured. Moreover, regulatory activity of LINC00092 in PC expression was analyzed. Whether PC participated in the modulation of LINC00092 on BC cell functions was explored. Results. LINC00092 was lowly expressed in BC and negatively related to BC progression. FLI1 bound to LINC00092 promoter to positively modulate LINC00092. LINC00092 overexpression inhibited BC cell proliferation, migration, invasion, oxidative stress, glycolysis, and AKT/mTOR pathway and likewise suppressed BC growth in vivo. Silence of LINC00092 had opposite influences. 2-DG partially reversed the LINC00092 silence-resulted increase of BC cell proliferation. SC79 alleviated the function of LINC00092 overexpression on BC cell functions. MK2206 had the contrary influence of SC79. Besides, LINC00092 bound to PC to modulate ubiquitination degradation of PC protein. PC took part in the influences of LINC00092 on BC cell functions. Conclusions. LINC0092 modulates oxidative stress and glycolysis of BC cells via the PC-mediated AKT/mTOR pathway, which is possibly a target for BC diagnosis and therapy.

ATP-binding cassette subfamily A (ABCA) has received wide recognition because it possesses the capacity to translocate its derivatives, xenobiotics, vitamins, and cholesterol across biological membranes. Some ABCA members have causative relevance to inborn diseases, and a number of studies have explored their functions in cancer progression and metastasis. Here, we explored the interrelation between ABCA genes and lung adenocarcinoma (LUAD). We specified the expression and functions of ABCA members in LUAD using the GEPIA, GEO, Human Protein Atlas, UALCAN, TIMER, and Kaplan-Meier Plotter databases. ABCA5, ABCA6, ABCA8, ABCA9, and ABCA10 were found to be significantly less expressed in LUAD and correlated with TP53 mutation in patients with LUAD. Furthermore, ABCA5, ABCA6, and ABCA8 were relevant to overall survival of patients with LUAD. In conclusion, this study showed that ABCA members may be related to the TP53 mutation of LUAD. Moreover, it may serve as a potential marker for the prognosis of LUAD.

The eye is one of the most important organs of the human body. Eye diseases are closely related to other systemic diseases, both of which influence each other. Numerous systemic diseases lead to special clinical manifestations and complications in the eyes. Typical diseases include diabetic retinopathy, hypertensive retinopathy, thyroid associated ophthalmopathy, optic neuromyelitis, and Behcet’s disease. Systemic disease-related ophthalmopathy is usually a chronic disease, and the analysis of imaging markers is helpful for a comprehensive diagnosis of these diseases. Recently, artificial intelligence (AI) technology based on deep learning has rapidly developed, leading to numerous achievements and arousing widespread concern. Presently, AI technology has made significant progress in research on imaging markers of systemic disease-related ophthalmopathy; however, there are also many limitations and challenges. This article reviews the research achievements, limitations, and future prospects of AI image analysis technology in systemic disease-related ophthalmopathy.

To investigate the prevalence of preterm birth (PTB) and the risk factors for different gestational age subgroups of preterm birth in China.We carried out a descriptive cross-sectional study encompassing all singleton live births (24The prevalence of PTB was 7.4% (15,833/215,254) in singleton births. After adjusting for maternal age, parity, and potential risk factors in univariate analysis, the high-risk factors for PTB at32 weeks were placental abruption (aOR=41.52; 95% CI, 25.89-66.58), placenta previa (aOR=40.04; 95% CI, 32.00-50.09), chorioamnionitis (aOR=11.06; 95% CI, 8.738-14.02), and hypertension disorders in pregnancy (HDP) (aOR=3.564; 95% CI, 2.930-4.335). Intrahepatic cholestasis of pregnancy (ICP) was significantly associated with PTB at 34-36 weeks (aOR=5.763; 95% CI, 5.049-6.577), particularly with spontaneous PTB (aOR=10.04; 95% CI, 8.79-11.47). Gestational diabetes mellitus (GDM) was significantly associated with PTB at 34-36 weeks only (aOR=1.156; 95% CI, 1.054-1.267).Placental abruption, placenta previa, chorioamnionitis, and HDP were more predictive of early PTB; GDM and ICP were more predictive of late PTB.

Chirality-based nanomaterials, especially semiconductors nanoparticles (NPs), are the emerging research in biomedicine field. Herein, chiral manganese dioxide (L/D-MnO

Previous suicide attempt is a strong risk factor for subsequent suicide and other causes of mortality, but evidence from China is sparse. In this study, follow up face-to-face interviews were conducted with suicide attempters or a key informant, and any subsequent deaths were examined through local cause-of-death censoring databases to ascertain details surrounding the death. Competitive risk models and Cox proportional hazard regression models were used to ascertain significant risk factors of suicide, non-suicide and overall deaths following suicide attempt. Predictive nomograms were also constructed to predict the probability of suicide, non-suicide, and overall deaths. A total of 1103 suicide attempters were successfully interviewed with an average follow-up time of 7.48 (7.38-7.57) years. The cumulative rates of suicide at 1, 2, 3, 5 and 10 years were 0.27%, 0.63%, 0.91%, 1.56%, and 1.83%, respectively. Factors significantly associated with subsequent suicide were advancing age, history of suicide attempt, and mental disorders. Significant risk factors for non-suicide death included males, advancing age, and physical illness. Overall deaths during the follow-up period were associated with males, advancing age, physical illness, and mental disorders. Predictive models showed good ability with satisfactory C-indexes (between 0.77 and 0.86) and excellent calibration performance in predicting the varying causes of subsequent death among suicide attempters in rural China.