Astrocyte atrophy induced by L-PGDS/PGD2/Src signaling dysfunction in the central amygdala mediates postpartum depression.

BACKGROUND: Postpartum depression (PPD) is a serious psychiatric disorder that has significantly adverse impacts on maternal health. Metabolic abnormalities in the brain are associated with numerous neurological disorders, yet the specific metabolic signaling pathways and brain regions involved in PPD remain unelucidated. METHODS: We performed behavioral test in the virgin and postpartum mice. We used mass spectrometry imaging (MSI) and targeted metabolomics analyses to investigate the metabolic alternation in the brain of GABAAR Delta-subunit-deficient (Gabrd-/-) postpartum mice, a specific preclinical animal model of PPD. Next, we performed mechanism studies including qPCR, Western blot, immunofluorescence staining, electron microscopy and primary astrocyte culture. In the specific knockdown and rescue experiments, we injected the adeno-associated virus into the central amygdala (CeA) of female mice. RESULTS: We identified that prostaglandin D2 (PGD2) downregulation in the CeA was the most outstanding alternation in PPD, and then validated that lipocalin-type prostaglandin D synthase (L-PGDS)/PGD2 downregulation plays a causal role in depressive behaviors derived from PPD in both wild-type and Gabrd-/- mice. Furthermore, we verified that L-PGDS/PGD2 signaling dysfunction-induced astrocytes atrophy is mediated by Src phosphorylation both in vitro and in vivo. LIMITATIONS: L-PGDS/PGD2 signaling dysfunction may be only responsible for the depressive behavior rather than maternal behaviors in the PPD, and it remains to be seen whether this mechanism is applicable to all depression types. CONCLUSION: Our study identified abnormalities in the L-PGDS/PGD2 signaling in the CeA, which inhibited Src phosphorylation and induced astrocyte atrophy, ultimately resulting in the development of PPD in mice.

CT analysis of frontal recess air cell and fluid dynamics simulation of frontal sinus in people with different frontal sinus development after Draf1-3 surgery.

OBJECTIVE: To explore the effects of Draf1-3 on frontal sinus airflow and frontal sinus irrigation in people with different frontal sinus development METHODS: The development of the frontal sinus and the distribution of the frontal recess cells were evaluated by CT scan in 150 adults (300 sides). The airflow changes into the frontal sinus and frontal recess after Draf were analyzed by Fluent software under a steady state and quiet inspiratory state. Nasal irrigation after Draf in adults with well-developed frontal sinus was simulated using 120 mL saline at a rate of 12 mL/s in a position at 45° to observe the changes in transient flow distribution. RESULTS: The moderately developed type of the frontal sinus was the most common. The airflow patterns in the frontal sinus and frontal recess in the moderate development group were laminar, while several large vortexes were formed between the frontal sinus and frontal recess in the well-development group. The Draf exerted more significant effects on the patterns, pressure, and velocity of the airflow in the frontal sinus and frontal recess in the well development group than in the moderate development group. The volume fraction of saline in the frontal sinus increased significantly from Draf1 to Draf3, and the time required for a complete infiltration of saline in the frontal sinus mucosa was significantly reduced. CONCLUSIONS: Draf1-3 has different effects on the airflow field of the frontal sinus with different developmental types; and Draf1-3 can significantly improve the postoperative flushing of the frontal sinus.

[A prospective study of the effect of functional endoscopic sinus surgery on the recovery of olfactory function in patients with chronic rhinosinusitis with nasal polyposis].

Objective:To investigate the efficacy of functional endoscopic sinus surgery（FESS） in the treatment of olfactory dysfunction in patients with chronic rhinosinusitis with nasal polyps （CRSwNP） , at the same time, it provides an evidence for the prognosis evaluation of olfaction and the clinical application of oERPs to evaluate the plasticity of olfaction cortex. Methods:From October 2021 to October 2022, 45 patients with CRSwNP who underwent FESS nine-step standardized treatment in our department were recruited as the research subjects, divided into 22 patients with eosinophilic CRSwNP（ECRS）and 23 patients with non-eosinophilic CRSwNP（nECRS）. VAS-olfactory dysfunction （VAS-OD） score, SNOT-22 olfactory score, Sniffin' Sticks test and oERPs collection and processing were performed before the operation. All items were evaluated again 3 months after the operation. Results:VAS-OD and SNOT-22 olfactory score were significantly lower in all CRSwNP patients after the operation than those before the operation[F（1, 43） =357.429, P<0.001; F（1, 43） =185.657, P<0.001], the scores of T, D, I and TDI scores in Sniffin' Sticks test were significantly higher than those before the operation[F（1, 43） =126.302, P<0.001; F（1, 43） =311.301, P<0.001; F（1, 43） =131.401, P<0.001; F（1, 43） =295.885, P<0.001]; The decrease of VAS-OD and SNOT-22 olfactory score in the ECRS group was smaller than that in the nECRS group[F（1, 43） =4.825, P=0.033; F（1, 43） =9.916, P=0.003], T, D and TDI scores were significantly lower in nECRS group than those in nECRS group[F（1, 43） =6.719, P=0.013; F（1, 43） =4.890, P=0.032; F（1, 43） =4.469, P=0.040]; There was a positive correlation between preoperative eosinophil-to-lymphocyte ratio（ELR） and SNOT-22 olfactory score and how much it changes（r=0.455, P=0.002; r=-0.414, P=0.005）, a negative correlation between T, TDI score and how much they change respectively（r=-0.431, P=0.003; r=-0.385, P=0.009; r=-0.383, P=0.010; r=-0.316, P=0.035）. The latency of P3 was significantly shorter after operation than that before operation in all CRSwNP patients[F（1, 14） =24.840, P<0.001], however, the amplitude has no significant surgical effect. Conclusion:FESS could significantly improve the olfactory function of CRSwNP patients, while changes in plasticity may occur in the olfactory cortex. In addition, the preoperative peripheral blood eosinophil granulocyte level can predict the postoperative olfactory improvement.

Postoperative residual neuromuscular block in a woman with severe preeclampsia treated with magnesium sulfate and nicardipine: A case report and literature review.

Calcium channel blockers and magnesium sulfate are frequently used together, particularly in women with underlying chronic hypertension and pre-eclampsia. A review of the literature showed prolonged neuromuscular blockade after treatment with magnesium sulfate. Since magnesium and calcium have opposite effects on the neuromuscular junctions, muscle weakness may become a postoperative manifestation of magnesium sulfate and calcium antagonist treatment in the obstetric population; however, limited information is available regarding this postulation. Here, we report a case wherein rocuronium activity was markedly prolonged due to pretreatment with magnesium sulfate and nicardipine after general anesthesia during an emergency cesarean delivery.

LncRNA NEAT1 regulates the growth, migration, and invasion of the human esophageal cancer cells via the miR-377/E2F3 axis.

Esophageal cancer is a highly aggressive and lethal human malignancy. The current study was established with the aim of studying the role of the lncRNA NEAT1 in regulating the growth and progression of esophageal cancer. Esophageal cancer tissues and cell lines showed significantly (P<0.05) upregulated transcript levels of lncRNA NEAT1. The expression of NEAT1 was also upregulated in metastatic tissues compared to nonmetastatic. The elimination of lncRNA NEAT1 led to a significant decrease (P<0.05) decrease in the viabilities of cancer cells due to the induction of apoptosis. Cancer cell migration and invasion were also significantly reduced (P<0.05) upon lncRNA NEAT1. In silico analysis indicated that miR-377 targets lncRNA NEAT1 at the post-transcriptional level, whose overexpression in cancer cells was found to mimic the tumor-suppressive regulatory effects of lncRNA-NEAT1. At the molecular level, the regulatory effects of lncRNA NEAT1 were shown to be modulated by the miR-377/E2F3 signaling axis. The results suggest that the molecular targeting of the lncRNA NEAT1 and miR-377/E2F3 axis could prove beneficial in the management of esophageal cancer.

[Clinical practice of infratemporal fossa benign tumor endoscopic transnasal/oral surgery in 36 patients].

Objective:According to the characteristics of endoscopic transnasal and transoral surgery for infratemporal fossa tumors, we divided and named subzones of the infratemporal fossa, to explore the approaches of endoscopic transnasal and transoral surgery for infratemporal fossa tumors, and to analyze their advantages and disadvantages. Methods:We retrospectively analyzed the clinical data of 36 patients with benign tumors of infratemporal fossa successfully resected through nose or mouth under endoscope, summarized and analyzed the localization characteristics of these tumors in infratemporal fossa, and made a subzone naming rule of infratemporal fossa. We also summarized the selection principles, advantages and disadvantages of endoscopic transnasal and transoral surgical approaches. Results:The infratemporal fossa area is divided into ABC area. Area A is the fat pad area posterolateral of maxillary sinus. Area B is further divided into B1 （above the plane of maxillary sinus floor, anterior styloid process）, B2 （below the plane of maxillary sinus floor, anterior styloid process）, and B3 （posterior styloid process to anterior vertebra）; Area C is retropharyngeal and eustachian tube area. The location of the tumor in the infratemporal fossa determines the choice of transnasal and transoral approaches. All tumors were completely removed, and no tumor recurred during the follow-up. A few patients had temporary local sensory function decline, and recovered during the follow-up. Conclusion:The infratemporal fossa region naming rule according to the characteristics of endoscopic transoral and transnasal surgery approach is simple and practical, which can effectively guide the operation of the infratemporal fossa region and has clinical application value.

[Application research and development of objective examination of olfactory function].

The sense of smell is one of the five most primitive human sensory functions, and it plays a very important role in our daily lives. Despite numerous methods for evaluating olfactory function, there is still a lack of standardization of olfactory tests and the results are often inconsistent. Furthermore, the related research on objective evaluation started relatively late. Along with the deciphering of the olfactory pathway, the technical level of olfactory objective inspection has been greatly improved and significant progress has also been made in terms of clinical application, such as: olfactory pathway MRI and fMRI imaging, OERPs, BEAM for various olfactory disorders and early diagnosis of neurodegenerative disorders, as well as related research based on bionic olfactory sensing technology. This article mainly introduces the recent research progress of several commonly used objective olfactory tests and provides reference for more accurate evaluation of olfactory function.

Optimum programmed intermittent epidural bolus interval time between 8 mL boluses of Ropivacaine 0.1% with sufentanil 0.3 µg/mL with dural puncture epidural technique for labor analgesia: A biased-coin up-and-down sequential allocation trial.

OBJECTIVE: The combination of dural puncture epidural (DPE) technique and programmed intermittent epidural bolus (PIEB) is a novel alternative labor analgesia regimen providing rapid analgesia onset and improved analgesia quality. However, the optimum PIEB settings for using the DPE technique remain unclear. DESIGN: Biased-coin up-and-down sequential allocation design. SETTING: Labor analgesia. PATIENTS: Forty nulliparous women requesting labor analgesia. INTERVENTIONS: Dural was punctured using a 25-gauge Whitacre needle. 12 mL of 0.1% ropivacaine with 0.3 µg/mL of sufentanil was used for initiation. Labor analgesia was maintained using the same solution with a fixed 8 mL volume beginning 1 h after initiation. The interval for the first patient was 60 min and varied for subsequent patients according to the biased-coin design (groups 60, 50, 40, and 30; interval 60, 50, 40, and 30 min, respectively). MEASUREMENTS: The primary outcome was adequate analgesia, defined as no request of patient-controlled epidural analgesia or provider boluses for 6 h after the epidural analgesia initiation or until the maternal cervix was fully dilated, whichever came first. The secondary outcomes included sensory blockade level, motor strength, maternal hypotension, and pruritus. RESULTS: The estimated effective interval in 90% of participants was 41.5 min (95% CI 39.5-43.5 min) and 40.5 min (95% CI 33.7-47.5 min) by the truncated Dixon and Mood method and the isotonic regression method, respectively, for the 40 women included. The proportions of patients with the highest sensory block level achieving or above T6 were 60%, 26%, 27%, and 0% in groups 30, 40, 50, and 60, respectively. One patient presented a Bromage score of 1. There was a low incidence of hypotension in all the groups with no need for vasopressor treatment. CONCLUSIONS: The optimum PIEB interval time between 8 mL boluses of ropivacaine 0.1% and sufentanil 0.3 µg/mL when using the DPE technique was approximately 41 min.

[Research advances on endoscopic surgical approach for infratemporal fossa tumors].

The tumors occurring in infratemporal fossa （ITF） and parapharyngeal space account for 0.5%-1.0% of head and neck tumors, 80% of which are benign and 20% are malignant. At present, a variety of ITF surgical approaches have been described in domestic and foreign literatures. However, the selection of surgical approaches in clinical practice is still based on the habits and experience of the operators, there is still a lack of standardized clinical guidance. This article mainly introduces the advantages and disadvantages of the latest anatomical division of ITF and the corresponding endoscopic surgical approach as well as the research progress, so as to provide reference for the selection of the optimal surgical approach for ITF tumors.

Amygdala dynorphin/κ opioid receptor system modulates depressive-like behavior in mice following chronic social defeat stress.

Major depression disorder is a severe and recurrent neuropsychological disorder characterized by lowered mood and social activity and cognitive impairment. Owing to unclear molecular mechanisms of depression, limited interventions are available in clinic. In this study we investigated the role of dynorphin/κ opioid receptor system in the development of depression. Mice were subjected to chronic social defeat stress for 14 days. Chronic social defeat stress induced significant social avoidance in mice characterized by decreased time duration in the interaction zone and increased time duration in the corner zone. Pre-administration of a κ opioid receptor antagonist norBNI (10 mg/kg, i.p.) could prevent the development of social avoidance induced by chronic social defeat stress. Social avoidance was not observed in κ opioid receptor knockout mice subjected to chronic social defeat stress. We further revealed that social defeat stress activated c-fos and ERK signaling in the amygdala without affecting the NAc, hippocampus and hypothalamus, and ERK activation was blocked by systemic injection of norBNI. Finally, the expression of dynorphin A, the endogenous ligand of κ opioid receptor, was significantly increased in the amygdala following social defeat stress; microinjection of norBNI into the amygdala prevented the development of depressive-like behaviors caused by social defeat stress. The present study demonstrates that upregulated dynorphin/κ opioid receptor system in the amygdala leads to the emergence of depression following chronic social defeat stress, and sheds light on κ opioid receptor antagonists as potential therapeutic agents for the prevention and treatment of depression following chronic stress.

The Protective Effect of Picroside II on Isoflurane-Induced Neuronal Injury in Rats via Downregulating miR-195.

INTRODUCTION: Numerous pieces of evidence demonstrated that isoflurane induces hippocampal cell injury and cognitive impairments. Picroside II has been investigated for its anti-apoptosis and antioxidant neuroprotective effects. We aimed to explore the protective effects of picroside II and the role of microRNA-195 (miR-195) on isoflurane-induced neuronal injury in rats. METHODS: The Morris water maze test was used to evaluate the effects of isoflurane on rats regarding escape latency and time in quadrant parameters. Real-time quantitative PCR was used to detect the expression levels of miR-195 and pro-inflammatory cytokines, including inter-leukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) mRNA, in the hippocampal tissues and neuronal cells. RESULTS: The picroside II significantly improves isoflurane-induced higher escape latency and lower time spent in the quadrant compared with the control rats. Picroside II also promotes cell viability and suppresses cell apoptosis of isoflurane-induced neuronal cells. Besides, picroside II suppresses the expression of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) and miR-195 in vivo and in vitro. Furthermore, overexpression of miR-195 abrogates the effects of picroside II on the expression of pro-inflammatory cytokines. The appropriate dose of picroside II is 20 mg/kg. CONCLUSION: Picroside II could protect the nervous system possibly through inhibiting the inflammatory response in the isoflurane-induced neuronal injury of rats. The protective effect of picroside II may be achieved by downregulating the expression of miR-195 and then inhibiting the inflammatory response.

The Emerging Role of Neutrophil Extracellular Traps in Arterial, Venous and Cancer-Associated Thrombosis.

Neutrophils play a vital role in the formation of arterial, venous and cancer-related thrombosis. Recent studies have shown that in a process known as NETosis, neutrophils release proteins and enzymes complexed to DNA fibers, collectively called neutrophil extracellular traps (NETs). Although NETs were originally described as a way for the host to capture and kill bacteria, current knowledge indicates that NETs also play an important role in thrombosis. According to recent studies, the destruction of vascular microenvironmental homeostasis and excessive NET formation lead to pathological thrombosis. In vitro experiments have found that NETs provide skeletal support for platelets, red blood cells and procoagulant molecules to promote thrombosis. The protein components contained in NETs activate the endogenous coagulation pathway to promote thrombosis. Therefore, NETs play an important role in the formation of arterial thrombosis, venous thrombosis and cancer-related thrombosis. This review will systematically summarize and explain the study of NETs in thrombosis in animal models and in vivo experiments to provide new targets for thrombosis prevention and treatment.

Development of a novel miR-3648-related gene signature as a prognostic biomarker in esophageal adenocarcinoma.

BACKGROUND: Esophageal adenocarcinoma (EA) is a typical immunogenic malignant tumor with a dismal 5-year survival rate lower than 20%. Although miRNA-3648 (miR-3648) is expressed abnormally in EA, its impact on the tumor immune microenvironment remains unknown. In this study, we sought to identify immune-related genes (IRGs) that are targeted by miR-3648 and develop an EA multigene signature. METHODS: The gene expression data of 87 EA tumor samples and 67 normal tissue samples from The Cancer Genome Atlas (TCGA) database and the Genotype-Tissue Expression (GTEx) database were downloaded, respectively. Weighted gene co-expression network analysis (WGCNA), the CIBERSORT algorithm, and Cox regression analysis were applied to identify IRGs and to construct a prognostic signature and nomogram. RESULTS: MiR-3648 was expectedly highly expressed in EA tumor tissues (P=2.6e-8), and related to the infiltration of activated natural killer cells (NK cells) and activated CD4 T lymphocytes (CD4 cells). A total of 70 miR-3648-targeted genes related to immune cell infiltration were identified. Among them, 4 genes (C10orf55, DLL4, PANX2, and NKAIN1) were closely related to overall survival (OS), and were thus selected to construct a 4-gene risk score (RS). The RS had a superior capability to predict OS [area under the curve (AUC) =0.740 for 1 year; AUC =0.717 for 3 years; AUC =0.622 for 5 years]. A higher score was indicative of a poorer prognosis than a lower score [hazard ratio (HR) =2.71; 95% confidence interval (CI): 1.45-5.09; P=0.002]. Furthermore, the nomogram formed by combining the RS and the TNM classification of malignant tumors (TNM stage) improved the accuracy of survival prediction [Harrell's concordance index (C-index) =0.698]. CONCLUSIONS: MiR-3648 may play a critical role in EA pathogenesis. The novel 4-gene signature may serve as a prognostic tool to manage patients with EA.

Enhanced recovery after cesarean delivery: a challenge for anesthesiologists.

Enhanced recovery after cesarean (ERAC) delivery is an evidence-based, multi-disciplinary approach throughout pre-, intra-, post-operative period. The ultimate goal of ERAC is to enhance recovery and improve the maternal and neonatal outcomes. This review highlights the role of anesthesiologist in ERAC protocols. This review provided a general introduction of ERAC including the purposes and the essential elements of ERAC protocols. The tool used for evaluating the quality of ERAC (ObsQoR-11) was discussed. The role of anesthesiologist in ERAC should cover the areas including management of peri-operative hypotension, prevention and treatment of intra- and post-operative nausea and vomiting, prevention of hypothermia and multi-modal peri-operative pain management, and active pre-operative management of unplanned conversion of labor analgesia to cesarean delivery anesthesia. Although some concerns still remain, ERAC implementation should not be delayed. Regular assessment and process improvement should be imbedded into the protocol. Further high-quality studies are warranted to demonstrate the effectiveness and efficacy of the ERAC protocol.

A case of anosmia and hypogeusia as a complication of propofol.

Anesthetics represent an uncommon cause of taste and smell disorders. We describe a case of anosmia and hypogeusia for 6 weeks after recovery from a uterine curettage operation in a 32-year-old woman. The case is unusual because propofol was the only anesthetic used during surgery and anesthesia. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed no abnormality. This case may highly suggest that propofol could induce smell and taste disorders.

[Investigation of occupational noise exposure and hearing loss in large automobile manufacturing enterprise during 2006-2010 in Guangzhou, China].

OBJECTIVE: To analyze the relationship between occupational noise exposure and hearing loss among workers in large automobile manufacturing enterprise during 2006-2010 in Guangzhou, China. METHODS: A retrospective cohort study was conducted. The subjects were divided into noise exposure group and control group. Their hearing examination results and noise exposure levels in different workplaces were collected during 2006-2010, and the relationship between noise exposure in workplaces and hearing loss was analyzed. RESULTS: The incidence of hearing loss for the noise exposure group was 9.34%, versus 2.75% for the control group; the noise exposure group had a significantly higher risk of hearing loss than the control group (R = 3.378, 95%CI = 1.467∼ 9.083). The noise intensity and over-limit rate were significantly higher in the stamping, welding, and general assembly workshops than in other workshops. The risk of hearing loss significantly increased with years of noise exposure in 80, 85, and 90 dB (A) groups (χ(2) = 6.377, P = 0.041; χ(2) = 8.570, P = 0.014; χ(2) = 7.037, P = 0.030). The risk of hearing loss also increased with noise intensity in all working age groups (χ(2) = 5.068, P = 0.024; χ(2) = 71.497, P < 0.01; χ(2) = 24.226, P < 0.01). CONCLUSION: Noise exposure increases the risk of noise-induced hearing loss in workers. The incidence of hearing loss increases with the noise intensity in workplaces and years of noise exposure. The noise exposure level and incidence of hearing loss are higher in the stamping workshop than in other workshops. Controlling the noise intensity in automobile manufacturing enterprise may reduce the risk of hearing loss in workers.

MiR-138 inhibits tumor growth through repression of EZH2 in non-small cell lung cancer.

BACKGROUND/AIMS: MicroRNAs (miRNAs) play important roles in tumorigenesis. We investigated the roles and mechanisms of miR-138 in human non-small cell lung cancer (NSCLC). METHODS: The expression of miR-138 was first examined in NSCLC cell lines and tumour tissues by real-time PCR The in vitro and in vivo functional effect of miR-138 was examined further. A luciferase reporter assay was conducted to confirm target association between miR-138 and the enhancer of zeste homolog 2 (EZH2). RESULTS: miR-138 was frequently downregulated in NSCLC cells and tissues. Overexpression of miR-138 inhibited proliferation of NSCLC cells in vitro and tumor growth in vivo. The EZH2 oncogene, which is often overexpressed in various human cancers and acts as an important regulator of cell growth and tumor invasion, was identified as a novel target of miR-138. miR-138 can bind to the 3' untranslated region (3' UTR) of EZH2 and suppress the expression of EZH2 at both mRNA and protein levels. Furthermore, knockdown of EZH2 phenocopied the tumor suppressive effects of miR-138 in cell models, whereas ectopic expression of EZH2 rescued the suppressive effects of miR-138. CONCLUSION: These findings define a tumor suppressor function for miR-138 in NSCLC and further suggest that miR-138 may represent a potential therapeutic target for NSCLC patients.