Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury.

BACKGROUND: Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) plays a crucial role in metabolizing and detoxifying endogenous and exogenous substances. However, its contribution to the progression of liver damage remains unclear. AIM: To determine the role and mechanism of UGT1A1 in liver damage progression. METHODS: We investigated the relationship between UGT1A1 expression and liver injury through clinical research. Additionally, the impact and mechanism of UGT1A1 on the progression of liver injury was analyzed through a mouse model study. RESULTS: Patients with UGT1A1 gene mutations showed varying degrees of liver damage, while patients with acute-on-chronic liver failure (ACLF) exhibited relatively reduced levels of UGT1A1 protein in the liver as compared to patients with chronic hepatitis. This suggests that low UGT1A1 levels may be associated with the progression of liver damage. In mouse models of liver injury induced by carbon tetrachloride (CCl4) and concanavalin A (ConA), the hepatic levels of UGT1A1 protein were found to be increased. In mice with lipopolysaccharide or liver steatosis-mediated liver-injury progression, the hepatic protein levels of UGT1A1 were decreased, which is consistent with the observations in patients with ACLF. UGT1A1 knockout exacerbated CCl4- and ConA-induced liver injury, hepatocyte apoptosis and necroptosis in mice, intensified hepatocyte endoplasmic reticulum (ER) stress and oxidative stress, and disrupted lipid metabolism. CONCLUSION: UGT1A1 is upregulated as a compensatory response during liver injury, and interference with this upregulation process may worsen liver injury. UGT1A1 reduces ER stress, oxidative stress, and lipid metabolism disorder, thereby mitigating hepatocyte apoptosis and necroptosis.

PU.1 induces tumor-associated macrophages promoting glioma progression through BTK-mediated Akt/mTOR pathway activation.

Glioma, the most common primary malignant brain tumor, is characterized by infiltrating immune cells that contribute to tumor progression and therapeutic resistance. Tumor-associated macrophages (TAMs) constitute a significant proportion of these infiltrating immune cells and have been implicated in glioma progression. However, the underlying molecular mechanisms by which TAMs promote glioma progression remain elusive. In this study, we investigated the role of PU.1, a crucial transcription factor involved in myeloid cell development, in glioma-associated macrophage polarization and activation. First, bioinformatics and analysis of clinical glioma samples demonstrated a positive correlation between PU.1 expression in TAMs and disease severity. Further experiments using in vitro coculture systems revealed that the expression of PU.1 is increased in glioma cells vs. control cells. Importantly, PU.1-overexpressing macrophages exhibited a protumorigenic phenotype characterized by enhanced migration, invasion, and proliferation. Mechanistically, we found that PU.1-induced activation of the Bruton tyrosine kinase (BTK) signaling pathway led to Akt/mTOR pathway activation in macrophages, which further enhanced their protumorigenic functions. Furthermore, pharmacological inhibition of the BTK or Akt/mTOR pathway reversed the protumorigenic effects of macrophages in vitro and impaired their ability to promote glioma progression in vivo. In conclusion, our study elucidates a novel mechanism by which PU.1 induces the polarization and activation of TAMs in the glioma microenvironment. We highlight the significance of BTK-mediated Akt/mTOR pathway activation in driving the protumorigenic functions of TAMs. Targeting PU.1 and its downstream signaling pathways in TAMs may provide a promising therapeutic strategy to suppress glioma progression and improve patient outcomes.

Link between mutations in ACVRL1 and PLA2G4A genes and chronic intestinal ulcers: A case report and review of literature.

BACKGROUND: Genetic factors of chronic intestinal ulcers are increasingly garnering attention. We present a case of chronic intestinal ulcers and bleeding associated with mutations of the activin A receptor type II-like 1 (ACVRL1) and phospholipase A2 group IVA (PLA2G4A) genes and review the available relevant literature. CASE SUMMARY: A 20-year-old man was admitted to our center with a 6-year history of recurrent abdominal pain, diarrhea, and dark stools. At the onset 6 years ago, the patient had received treatment at a local hospital for abdominal pain persisting for 7 d, under the diagnosis of diffuse peritonitis, acute gangrenous appendicitis with perforation, adhesive intestinal obstruction, and pelvic abscess. The surgical treatment included exploratory laparotomy, appendectomy, intestinal adhesiolysis, and pelvic abscess removal. The patient's condition improved and he was discharged. However, the recurrent episodes of abdominal pain and passage of black stools started again one year after discharge. On the basis of these features and results of subsequent colonoscopy, the clinical diagnosis was established as inflammatory bowel disease (IBD). Accordingly, aminosalicylic acid, immunotherapy, and related symptomatic treatment were administered, but the symptoms of the patient did not improve significantly. Further investigations revealed mutations in the ACVRL1 and PLA2G4A genes. ACVRL1 and PLA2G4A are involved in angiogenesis and coagulation, respectively. This suggests that the chronic intestinal ulcers and bleeding in this case may be linked to mutations in the ACVRL1 and PLA2G4A genes. Oral Kangfuxin liquid was administered to promote healing of the intestinal mucosa and effectively manage clinical symptoms. CONCLUSION: Mutations in the ACVRL1 and PLA2G4A genes may be one of the causes of chronic intestinal ulcers and bleeding in IBD. Orally administered Kangfuxin liquid may have therapeutic potential.

Why emotional neglect brings suicidal ideation? The mediating effect of meaning in life and the moderating effect of post-stress growth.

BACKGROUND: Emotional neglect during childhood has long-lasting negative effects on individuals, and it is often hidden and unrecognized. Previous research has not fully understood its unique effects on mental health outcomes, especially when considering the co-occurrence with other forms of maltreatment. The meaning-making coping and growth model suggests that individuals achieve positive psychological outcomes by constructively integrating negative experiences into their self-concept, which may be a protective mechanism against the detrimental effects of emotional neglect. OBJECTIVE: This study aimed to examine the relationship between emotional neglect and suicidal ideation among undergraduates, accounting for the presence of emotional abuse and physical neglect, and to investigate the mediating role of meaning in life and the moderating role of post-stress growth in this relationship. METHODS: A self-reported survey was conducted with 3132 undergraduate students from a university in South China. The survey assessed emotional neglect, emotional abuse, physical neglect, suicidal ideation, post-stress growth, and meaning in life. RESULTS: Meaning in life partially mediated the relationship between emotional neglect and suicidal ideation. Post-stress growth moderated the association between emotional neglect and the sense of meaning in life, in particular the moderation effect was stronger when emotional abuse was weaker. CONCLUSIONS: Meaning in life mediated the relationship between emotional neglect and suicide ideation. Post-stress growth moderated the mediation effect such that it was weakened among individual with a higher level of post-stress growth. This study contributes to the understanding of the psychopathological processes following emotional neglect and the development of positive personal changes thereafter.

Collagen and actin network mediate antiviral immunity against Orsay virus in C. elegans intestinal cells.

C. elegans is a free-living nematode that is widely used as a small animal model for studying fundamental biological processes and disease mechanisms. Since the discovery of the Orsay virus in 2011, C. elegans also holds the promise of dissecting virus-host interaction networks and innate antiviral immunity pathways in an intact animal. Orsay virus primarily targets the worm intestine, causing enlarged intestinal lumen as well as visible changes to infected cells such as liquefaction of cytoplasm and convoluted apical border. Previous studies of Orsay virus identified that C. elegans is able to mount antiviral responses by DRH-1/RIG-I mediated RNA interference and Intracellular Pathogen Response, a uridylyltransferase that destabilizes viral RNAs by 3' end uridylation, and ubiquitin protein modifications and turnover. To comprehensively search for novel antiviral pathways in C. elegans, we performed genome-wide RNAi screens by bacterial feeding using existing bacterial RNAi libraries covering 94% of the entire genome. Out of the 106 potential antiviral gene hits identified, we investigated those in three new pathways: collagens, actin remodelers, and epigenetic regulators. By characterizing Orsay virus infection in RNAi and mutant worms, our results indicate that collagens likely form a physical barrier in intestine cells to inhibit viral infection by preventing Orsay virus entry. Furthermore, evidence suggests that actin remodeling proteins (unc-34, wve-1 and wsp-1) and chromatin remodelers (nurf-1 and isw-1) exert their antiviral activities by regulating the intestinal actin (act-5), a critical component of the terminal web which likely function as another physical barrier to prevent Orsay infection.

Chemical Profile of Turnip According to the Plant Part and the Cultivar: A Multivariate Approach.

Turnip (Brassica rapa subsp. rapa) is a cruciferous plant cultivated worldwide that serves as a source of nutrients and bioactive compounds. Most turnip studies have focused on a few compounds or on part of the plant. The establishment of a complete chemical profile of different plant parts would facilitate its use for nutritional and medicinal purposes. In the current study, mineral elements, soluble sugars, free amino acids (FAA), total phenols (TP), total flavonoids (TF), and glucosinolates (GS) were quantified in the leaves, stems, and roots. Results were compared for 20 strains of turnip. The outcomes showed significant differences between parts of the plant and strains. The leaves exhibited the highest TF, TP, indispensable FAA, and microelement levels, and they showed a higher GS. Moreover, the stems had a high content of GS and macroelements. Furthermore, the roots showed high levels of free sugars and total FAA. The findings of this work provide the basis for utilizing each part of the turnip plant based on its chemical composition.

Complex roles of Hippo-YAP/TAZ signaling in hepatocellular carcinoma.

BACKGROUND: The Hippo signaling pathway is an evolutionarily conserved signaling module that controls organ size in different species, and the disorder of the Hippo pathway can induce liver cancer in organisms, especially hepatocellular carcinoma (HCC). The exact mechanism that causes cancer is still unknown. Recent studies have shown that it is a classical kinase cascade that phosphorylates the Mst1/2-sav1 complex and activates the phosphorylation of the Lats1/2-mob1A/B complex for inactivating Yap and Taz. These kinases and scaffolds are regarded as primary regulators of the Hippo pathway, and help in activating a variety of carcinogenic processes. Among them, Yap/Taz is seen to be the main effector molecule, which is downstream of the Hippo pathway, and its abnormal activation is related to a variety of human cancers including liver cancer. Currently, since Yap/Taz plays a variety of roles in cancer promotion and tumor regeneration, the Hippo pathway has emerged as an attractive target in recent drug development research. METHODS: We collect and review relevant literature in web of Science and Pubmed. CONCLUSION: This review highlights the important roles of Yap/Taz in activating Hippo pathway in liver cancer. The recent findings on the crosstalks between the Hippo and other cancer associated pathways and moleculars are also discussed. In this review, we summarized and discussed recent breakthroughs in our understanding of how key components of the Hippo-YAP/TAZ pathway influence the hepatocellular carcinoma, including their effects on tumor occurrence and development, their roles in regulating metastasis, and their function in chemotherapy resistance. Further, the molecular mechanism and roles in regulating cross talk between Hippo-YAP/TAZ pathway and other cancer-associated pathways or oncogenes/cancer suppressor genes were summarized and discussed. More, many other inducers and inhibitors of this signaling cascade and available experimental therapies against the YAP/TAZ/TEAD axis were discussed. Targeting this pathway for cancer therapy may have great significance in the treatment of hepatocellular carcinoma. Graphical summary of the complex role of Hippo-YAP/TAZ signaling in hepatocellular carcinoma.

Tea Polyphenols Inhibit the Activity and Toxicity of Staphylococcus aureus by Destroying Cell Membranes and Accumulating Reactive Oxygen Species.

Staphylococcus aureus can cause bacterial food intoxication and seriously affect human health. Tea polyphenols (TP) are a kind of natural, safe, and broad-spectrum bacteriostatic substances, with a wide range of bacteriostatic effects. In the study, we explored the possible bacteriostatic mode of TP. The minimum inhibitory concentration of TP against S. aureus was 64 µg/mL. Protein, DNA, and K+ leak experiments, fluorescence microscopy, and transmission electron microscopy suggested that TP disrupt cell membranes, leading to intracellular component loss. By studying the effect of TP on the toxicity of S. aureus, it was found that the expression levels of two toxin genes, coa and spa, were downregulated by 2.37 and 32.6, respectively. Furthermore, after treatment with TP, a large number of reactive oxygen species (ROS) were propagated and released, leading to oxidative stress in cells. We speculated that the bacteriostatic mechanism of TP may be through the destruction of the cell membrane and ROS-mediated oxidative stress. Meanwhile, the hemolysis activity proved the safety of TP. Our results suggested that TP may be a potential antimicrobial agent for food.

Collagen and actin network mediate antiviral immunity against Orsay in C. elegans intestinal cells.

C. elegans is a free-living nematode that is widely used as a small animal model for studying fundamental biological processes and disease mechanisms. Since the discovery of the Orsay virus in 2011, C. elegans also holds the promise of dissecting virus-host interaction networks and innate antiviral immunity pathways in an intact animal. Orsay primarily targets the worm intestine, causing enlarged intestinal lumen as well as visible changes to infected cells such as liquefaction of cytoplasm and rearrangement of the terminal web. Previous studies of Orsay identified that C. elegans is able to mount antiviral responses by DRH-1/RIG-I mediated RNA interference and Intracellular Pathogen Response, a uridylyltransferase that destabilizes viral RNAs by 3' end uridylation, and ubiquitin protein modifications and turnover. To comprehensively search for novel antiviral pathways in C. elegans, we performed genome-wide RNAi screens by bacterial feeding using existing bacterial RNAi libraries covering 94% of the entire genome. Out of the 106 antiviral genes identified, we investigated those in three new pathways: collagens, actin remodelers, and epigenetic regulators. By characterizing Orsay infection in RNAi and mutant worms, our results indicate that collagens likely form a physical barrier in intestine cells to inhibit viral infection by preventing Orsay entry. Furthermore, evidence suggests that the intestinal actin (act-5), which is regulated by actin remodeling proteins (unc-34, wve-1 and wsp-1), a Rho GTPase (cdc-42) and chromatin remodelers (nurf-1 and isw-1), also provides antiviral immunity against Orsay possibly through another physical barrier presented as the terminal web.

Postoperative jaundice related to UGT1A1 and ABCB11 gene mutations: A case report and literature review.

BACKGROUND: Patients with obstructive jaundice caused by intrahepatic bile duct stones can be effectively managed by surgery. However, some patients may develop postoperative complications, liver failure, and other life-threatening situations. Here, we report a patient with mutations in the uridine 5'-diphospho-glucuronosyltransferase 1A1 (UGT1A1) and bile salt export pump (adenosine triphosphate-binding cassette subfamily B member 11, ABCB11) genes who presented multiple intrahepatic bile duct stones and cholestasis, and the jaundice of the patient increased after partial hepatectomy. CASE SUMMARY: A 52-year-old male patient admitted to the hospital on October 23, 2021, with a progressive exacerbation of jaundice, was found to have multiple intrahepatic bile duct stones with the diagnoses of obstructive jaundice and acute cholecystitis. Subsequently, the patient underwent left hepatectomy with biliary exploration, stone extraction, T-tube drainage, and cholecystectomy without developing any intraoperative complications. The patient had a dark urine color with worsening jaundice postoperatively and did not respond well to plasma exchange and other symptomatic and supportive treatments. Since the progressive increase in postoperative bilirubin could not be clinically explained with any potential reason, including, if not at all, viral infection, cholangitis, autoimmune liver disease, and other causes, the patient underwent whole-exon screening for any genetic diseases, which surprisingly identified UGT1A1 and ABCB11 gene mutations related to glucuronidation of indirect bilirubin as well as bile acid transport in hepatocytes, respectively. Thus, we hypothesized that postoperative refractory cholestasis might result from UGT1A1 and ABCB11 gene mutations and further recommended liver transplantation to the patient, who eventually declined it and died from liver failure six months later. CONCLUSION: Surgery may aggravate cholestasis in patients with multiple intrahepatic bile duct stones and cholestasis associated with UGT1A1 and ABCB11 gene mutations. A liver transplant may be the best option if active medical treatment fails.

SERPINB9 is commonly amplified and high expression in cancer cells correlates with poor immune checkpoint blockade response.

Immunotherapies, in particular immune checkpoint blockade (ICB), have improved the clinical outcome of cancer patients, although many fail to mount a durable response. Several resistance mechanisms have been identified, but our understanding of the requirements for a robust ICB response is incomplete. We have engineered an MHC I/antigen: TCR-matched panel of human NSCLC cancer and T cells to identify tumor cell-intrinsic T cell resistance mechanisms. The top differentially expressed gene in resistant tumor cells was SERPINB9. This serine protease inhibitor of the effector T cell-derived molecule granzyme B prevents caspase-mediated tumor apoptosis. Concordantly, we show that genetic ablation of SERPINB9 reverts T cell resistance of NSCLC cell lines, whereas its overexpression reduces T cell sensitivity. SERPINB9 expression in NSCLC strongly correlates with a mesenchymal phenotype. We also find that SERPINB9 is commonly amplified in cancer, particularly melanoma in which it is indicative of poor prognosis. Single-cell RNA sequencing of ICB-treated melanomas revealed that SERPINB9 expression is elevated not only in cells from post- versus pre-treatment cancers, but also in ICB-refractory cancers. In NSCLC we commonly observed rare SERPINB9-positive cancer cells, possibly accounting for reservoirs of ICB-resistant cells. While underscoring SERPINB9 as a potential target to combat immunotherapy resistance, these results suggest its potential to serve as a prognostic and predictive biomarker.

Dietary fiber ameliorates sleep disturbance connected to the gut-brain axis.

Circadian rhythms play an important role in maintaining normal physiological and psychological functions of the body, including regulating sleep patterns. External factors such as poor eating habits and work and rest patterns of modern people can disrupt the circadian rhythm, resulting in sleep disorders such as difficulty falling asleep and frequent waking up. The gut flora uses the "gut-brain axis" as a bridge to establish a connection with sleep, mainly including immune pathways, neural pathways, and endocrine pathways. Meanwhile, this article emphasizes that increasing the intake of dietary fiber in the daily dietary structure is beneficial for ameliorating sleep disorders. This is attributed to the metabolism of dietary fiber in the colon, increasing the type and quantity of probiotics and their representative metabolites, short-chain fatty acids (SCFAs), in the gut. They modulate sleep disorders by significantly improving the damaged gut barrier, stimulating the secretion of sleep cytokines, inhibiting inflammatory pathways, and increasing serotonin secretion. These provide new strategies for improving human sleep disorders from the perspective of the gut microbiota.

Intracellular alpha-fetoprotein mitigates hepatocyte apoptosis and necroptosis by inhibiting endoplasmic reticulum stress.

BACKGROUND: Endoplasmic reticulum (ER) stress contributes to the pathogenesis of chronic liver diseases, but how hepatocytes respond to ER stress has not been clarified. Alpha-fetoprotein (AFP) is secreted by hepatoma cells and elevated levels of serum AFP are associated with development of liver malignancies. AIM: To investigate whether and how AFP could regulate ER stress and hepatocyte injury. METHODS: The distribution of AFP and the degrees of ER stress in liver tissues and liver injury were characterized by histology, immunohistochemistry, and Western blot in biopsied human liver specimens, two mouse models of liver injury and a cellular model. The levels of AFP in sera and the supernatants of cultured cells were quantified by chemiluminescence. RESULTS: High levels of intracellular AFP were detected in liver tissues, particularly in the necrotic areas, from patients with chronic liver diseases and mice after carbon tetrachloride (CCl4) administration or induction of ER stress, but not from the controls. The induced intracellular AFP was accompanied by elevated activating transcription factor-6 (ATF6) expression and protein kinase R-like ER kinase (PERK) phosphorylation in mouse livers. ER stress induced AFP expression in LO2 cells and decreased their viability. ATF6, but not PERK, silencing mitigated the ER-stress-induced AFP expression in LO2 cells. Conversely, AFP silencing deteriorated the ER stress-mediated LO2 cell injury and CCl4 administration-induced liver damages by increasing levels of cleaved caspase-3, the C/enhancer binding protein homologous protein expression, mixed lineage kinase domain-like pseudokinase and PERK phosphorylation, but decreasing ATF6 expression. CONCLUSION: ER stress upregulated intra-hepatocyte AFP expression by activating ATF6 during the process of liver injury and intracellular AFP attenuated hepatocyte apoptosis and necroptosis by alleviating ER stress.

Propofol Versus Sevoflurane General Anaesthesia for Selective Impairment of Attention Networks After Gynaecological Surgery in Middle-Aged Women: A Randomised Controlled Trial.

Purpose: Attention is an essential component of cognitive function that may be impaired after surgery with anaesthesia. Propofol intravenous anaesthesia and sevoflurane inhalational anaesthesia are frequently used in gynaecological surgery. However, which type of anaesthetic has fewer cognitive effects postoperatively remains unclear. We compared the differences in attention network impairment after surgery in women receiving propofol versus sevoflurane general anaesthesia. Patients and Methods: Eighty-three patients with gynaecological diseases who were 40-60 years of age were involved in the study. All patients underwent elective gynaecological surgery under either total intravenous anaesthesia or sevoflurane inhalational anaesthesia, depending on randomisation. The efficiencies of the three attention networks were captured using the attention network test preoperatively and on the 1st and 5th postoperative days. Results: Both groups of patients showed differences in impairments on the 1st and 5th postoperative days. Pairwise comparisons indicated that the alerting and orienting networks of patients in the propofol group were impaired to a greater extent than those of patients in the sevoflurane group on the 1st postoperative day, while the executive control network was impaired to a lesser extent. On the 5th postoperative day, the alerting networks of both groups recovered to the baseline level. Patients in the propofol group still showed impairment of the orienting network, while patients in the sevoflurane group recovered to baseline. For the executive control network, patients in the sevoflurane group still exhibited more severe impairment than those in the propofol group. Conclusion: In middle-aged women, propofol impaired orienting and alerting networks more than sevoflurane, while sevoflurane showed more residual impairment of the executive control network.

Effective Doses of Nalbuphine Combined with Propofol in Painless Hysteroscopy.

Purpose: Nalbuphine is becoming a common analgesic used in hysteroscopic operations. The aim of this study was to identify the median effective dose (ED50) and 95% effective dose (ED95) of nalbuphine combined with propofol in painless hysteroscopy. Patients and Methods: Twenty-five patients aged 18-60 years with an American Society of Anesthesiologists classification of I-II who were scheduled for painless hysteroscopy were recruited. The initial dose of nalbuphine was set at 0.15 mg/kg and varied by 0.01 mg/kg according to the Dixon sequential method. The ED50/ED95 of nalbuphine combined with propofol for hysteroscopy was calculated by the probit method. Results: The ED50 of nalbuphine was 0.122 (95% confidence interval (CI) 0.092-0.137) mg/kg, and the ED95 of nalbuphine was 0.153 (95% CI 0.138-0.361) mg/kg. Conclusion: The ED50/ED95 values of nalbuphine combined with propofol in painless hysteroscopy are 0.122 mg/kg and 0.153 mg/kg, respectively. Nalbuphine at 0.153 mg/kg combined with propofol is effective and safe for painless hysteroscopy.

Comparison between I-gel® and endotracheal intubation in terms of the incidence of postoperative sore throat following thyroid surgery: a randomized observational trial.

BACKGROUND: Postoperative sore throat (POST) is a common complication following thyroid surgery with an endotracheal tube (ET). The I-gel® is a supraglottic airway device that has greater advantages in airway management compared with ET. This prospective trial aimed to explore the potential benefits of I-gel® compared with ET on POST. METHODS: In this trial, 106 patients, classified using the American Society of Anesthesiologists (ASA) physical status classification system, belonging to classes I and II, aged 18-65 years old who were prearranged for elective radical thyroidectomy, were randomly divided into the ET and I-gel® groups. All patients underwent total intravenous anesthesia (propofol, sufentanil, and cisatracurium). The incidence and severity of POST and postoperative hoarseness (PH) at 1, 6, 24, and 48 h following the operation were assessed and compared between the two groups. Moreover, the hemodynamic data during anesthesia were recorded and compared. Opioid consumption (sufentanil, propofol, and remifentanil) and postoperative nausea and vomiting were recorded. The visual analog scale scores for pain at the incision site 1, 6, 24, and 48 h postoperatively and Ramsay Sedation Scale scores were also evaluated and recorded. RESULTS: No significant difference was observed in the incidence of POST 1, 6, 24, and 48 h postoperatively (61.2% vs. 51.0%, P=0.309; 75.5% vs. 83.7%, P=0.316; 83.7% vs. 85.7%, P=0.779; and 12.2% vs. 22.4%, P=0.182, respectively) and the severity of sore throat (P=0.392) following surgery between the ET and I-gel® groups. The incidence of PH in the I-gel® group was significantly lower than that in the ET group 1, 6, 24, and 48 h postoperatively (all P<0.05). Compared with the ET group, a significantly less fluctuation in heart rate 1 min after intubation (P=0.045) and extubation (P=0.001) was observed in the I-gel® group. CONCLUSIONS: Although the I-gel® cannot reduce the incidence and severity of POST in patients with normal BMIs following thyroid surgery, it can reduce the occurrence and severity of PH compared with ET. The I-gel® showed superior results in terms of insertion time and better hemodynamic condition during intubation.

Pathogenesis of sporadic Alzheimer's disease by deficiency of NMDA receptor subunit GluN3A.

The Ca2+ hypothesis for Alzheimer's disease (AD) conceives Ca2+ dyshomeostasis as a common mechanism of AD; the cause of Ca2+ dysregulation, however, is obscure. Meanwhile, hyperactivities of N-Methyl-D-aspartate receptors (NMDARs), the primary mediator of Ca2+ influx, are reported in AD. GluN3A (NR3A) is an NMDAR inhibitory subunit. We hypothesize that GluN3A is critical for sustained Ca2+ homeostasis and its deficiency is pathogenic for AD. Cellular, molecular, and functional changes were examined in adult/aging GluN3A knockout (KO) mice. The GluN3A KO mouse brain displayed age-dependent moderate but persistent neuronal hyperactivity, elevated intracellular Ca2+ , neuroinflammation, impaired synaptic integrity/plasticity, and neuronal loss. GluN3A KO mice developed olfactory dysfunction followed by psychological/cognitive deficits prior to amyloid-ß/tau pathology. Memantine at preclinical stage prevented/attenuated AD syndromes. AD patients' brains show reduced GluN3A expression. We propose that chronic "degenerative excitotoxicity" leads to sporadic AD, while GluN3A represents a primary pathogenic factor, an early biomarker, and an amyloid-independent therapeutic target.

LncRNA LINC00460 takes a stimulating role on hepatocellular carcinoma stemness property.

Abundant researches have stated that long noncoding RNAs (lncRNAs) are crucial molecules in intricate progression of various cancers in terms of their influence on cell stemness. However, no research has discussed the role of LINC00460 in the stemness of hepatocellular carcinoma (HCC). RT-qPCR and western blot were utilized to respectively examine the RNA and protein levels. Aldehyde dehydrogenase 1 (ALDH1) assays and sphere formation assay were performed to detect cell stemness property in vitro and in vivo subcutaneous xenograft tumor assay was performed to detect tumor growth. Interaction between RNAs was explored by luciferase reporter assays and RNA pull-down assays. Our results showed that LINC00460 was markedly over-expressed in HCC and silencing LINC00460 impaired cell stemness. Additionally, LINC00460 knockdown curbed proliferation, migration, invasion and epithelial-to-mesenchymal transition (EMT) and drove apoptosis of HCC cells. Further, LINC00460 bound to miR-503-5p and miR-654-3p to protect t-complex 1 (TCP1) from being inhibited by miR-503-5p/miR-654-3p. Rescue experiments confirmed the effect of LINC00460/miR-503-5p/miR-654-3p/TCP1 on HCC cell stemness. In conclusion, LINC00460 aggravated cell stemness in HCC via targeting miR-503-5p/miR-654-3p and TCP1, suggesting that LINC00460 may work as a potential signature for cell stemness in HCC.[Figure: see text].

Nalbuphine and dexmedetomidine as adjuvants to ropivacaine in ultrasound-guided erector spinae plane block for video-assisted thoracoscopic lobectomy surgery: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Adjuvants to local anesthetics, such as nalbuphine and dexmedetomidine, can be used to improve the quality and duration of peripheral nerve block effects. Dexmedetomidine has been successfully used as an adjuvant of erector spinae plane block (ESPB) with ropivacaine in video-assisted thoracoscopic lobectomy surgeries (VATLS). This study aimed to compare the effects of nalbuphine and dexmedetomidine used as adjuvants to ropivacaine for ESPB in VATLS. METHODS: A total of 102 patients undergoing VATLS with ESPB were enrolled and randomized into 3 groups, each of which received a different adjuvant to ropivacaine. The visual analogue scale score, onset and duration of sensory block, use of patient-controlled analgesia (PCA), rate of rescue analgesia, duration of postoperative hospitalization, incidence of postoperative nausea and vomiting, and chronic pain were measured and observed. RESULTS: The visual analogue scale score, total PCA use, rate of rescue analgesia, and postoperative chronic pain in the ropivacaine with dexmedetomidine (RD), and ropivacaine with nalbuphine (RN) groups were lower than those in the ropivacaine (RC) group (P < .05). The duration of sensory block was longer and the first use of PCA occurred later in the RD and RN groups than they did in the RC group (P < .05). CONCLUSIONS: As an adjuvant to ropivacaine in ESPB, nalbuphine and dexmedetomidine are comparable in terms of the associated analgesia, sensory block duration, need for rescue analgesia, and incidence of chronic pain in patients after VATLS.