Serum calcium level at 32 weeks of gestation could be applied as a predictor of preterm delivery: a retrospective study.

Preterm delivery (PTD) is associated with severe adverse maternal and neonatal outcomes and higher medical costs. Therefore, PTD warrants more attention. However, predicting PTD remains a challenge for researchers. This study aimed to investigate potential prenatal predictors of PTD. We retrospectively recruited pregnant women who experienced either PTD or term delivery (TD) and underwent laboratory examinations at 32 weeks of gestation. We compared the test results between the two groups and performed logistic regression analysis and receiver operating characteristic (ROC) curve analysis to identify risk factors and predictive factors for PTD. Our investigation revealed that the PTD cohort exhibited statistically significant elevations in lymphocyte count, mean corpuscular hemoglobin concentration, calcium, uric acid, alkaline phosphatase, triglycerides, and total bile acids. Conversely, the PTD group demonstrated statistically significant reductions in mean corpuscular volume, homocysteine, neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), neutrophils to (white blood cells-neutrophils) ratio (dNLR), and (neutrophils × monocytes) to lymphocyte ratio (SIRI). The ROC curve analysis revealed that calcium had an area under the curve (AUC) of 0.705, with a cut-off value of 2.215. Logistic regression analysis showed that premature rupture of membranes was an independent risk factor for PTD. Our study demonstrated that serum calcium levels, NLR, dNLR, and other laboratory tests conducted at 32 weeks of gestation can serve as predictors for PTD. Furthermore, we identified premature rupture of membranes as a risk factor for PTD.

Oxycodone enhances antitumor effect of paclitaxel on human breast cancer SKBR3 cells in vitro.

BACKGROUND: The influences of Oxycodone (OXY) combined with Paclitaxel (PTX) on breast cancer cells are unclear. The present study aimed to examine the effects of OXY combined with PTX on the proliferation, apoptosis, and migration of human breast cancer SKBR3 cells and the underlying mechanism. METHODS: The proliferation, apoptosis and invasion of SKBR3 cells were assessed by CCK-8, colony formation assay, flowcytometric, Transwell assay and scratch assays, respectively. In addition, Western blotting was used to detect the expression of related proteins in these cells. The autophagic bodies were observed under a transmission electron microscope. RESULTS: OXY (0.25, 0.5 and 1 mM) significantly inhibited the viability, colony-forming, migration, and invasion of SKBR3 cells as compared to the control group. Furthermore, OXY (0.25, 0.5 and 1 mM) markedly induced the apoptosis of SKBR3 cells and the levels of apoptosis-related proteins. In addition, OXY (0.25, 0.5 and 1 mM) and PTX inhibited the proliferation of SKBR3 cells synergistically as compared to PTX group in vitro. Moreover, OXY (0.25, 0.5 and 1 mM) significantly elevated the PTX-induced apoptosis in SKBR3 cells via downregulating the expression of N-cadherin, Becline-1 LC3-Ⅱ, p-Akt and p-mTOR and upregulating E-cadherin expression. Compared with the control group, OXY (1 mM) treatment induced autophagy in SKBR3 cells. CONCLUSIONS: The present study indicates that OXY can enhance the antitumor effect of PTX on breast cancer in vitro. Hence, the combination of OXY with PTX may serve as a potential strategy for the treatment of breast cancer.

A scientometric analysis of research on the role of NMDA receptor in the treatment of depression.

Background: There have been numerous studies on NMDA receptors as therapeutic targets for depression. However, so far, there has been no comprehensive scientometric analysis of this field. Thus, we conducted a scientometric analysis with the aim of better elucidating the research hotspots and future trends in this field. Methods: Publications on NMDAR in Depression between 2004 and 2023 were retrieved from the Web of Science Core Collection (WoSCC) database. Then, VOSviewer, CiteSpace, Scimago Graphica, and R-bibliometrix-were used for the scientometric analysis and visualization. Results: 5,092 qualified documents were identified to scientometric analysis. In the past 20 years, there has been an upward trend in the number of annual publications. The United States led the world in terms of international collaborations, publications, and citations. 15 main clusters were identified from the co-cited references analysis with notable modularity (Q-value = 0.7628) and silhouette scores (S-value = 0.9171). According to the keyword and co-cited references analysis, treatment-resistant depression ketamine (an NMDAR antagonist), oxidative stress, synaptic plasticity, neuroplasticity related downstream factors like brain-derived neurotrophic factor were the research hotspots in recent years. Conclusion: As the first scientometric analysis of NMDAR in Depression, this study shed light on the development, trends, and hotspots of research about NMDAR in Depression worldwide. The application and potential mechanisms of ketamine in the treatment of major depressive disorder (MDD) are still a hot research topic at present. However, the side effects of NMDAR antagonist like ketamine have prompted research on new rapid acting antidepressants.

Effect of cuff inflation with lidocaine, saline, and air on tracheal tube cuff pressure during laparoscopic resection of colorectal neoplasms: a randomized clinical trial.

BACKGROUND: Tracheal tube cuff pressure will increase after pneumoperitoneum when the cuff is inflated with air, high pressure can cause tracheal mucosal damage. This prospective trial aimed to assess if inflating with normal saline or lidocaine can prevent increase of tracheal tube cuff pressure and tracheal mucosal damage in laparoscopic surgeries with general anesthesia. Whether changes of tracheal tube cuff transverse diameter (CD) can predict changes of tracheal tube cuff pressure. METHODS: Ninety patients scheduled for laparoscopic resection of colorectal neoplasms under general anesthesia were randomly assigned to groups air (A), saline (S) or lidocaine (L). Endotracheal tube cuff was inflated with room-temperature air in group A (n = 30), normal saline in group S (n = 30), 2% lidocaine hydrochloride injection in group L (n = 30). After intubation, tracheal tube cuff pressure was monitored by a calibrated pressure transducers, cuff pressure was adjusted to 25 cmH2O (T0.5). Tracheal tube cuff pressure at 15 min after pneumoperitoneum (T1) and 15 min after exsufflation (T2) were accessed. CD were measured by ultrasound at T0.5 and T1, the ability of ΔCD (T1-0.5) to predict cuff pressure was accessed. Tracheal mucous injury at the end of surgery were also recorded. RESULTS: Tracheal tube cuff pressure had no significant difference among the three groups at T1 and T2. ΔCD had prediction value (AUC: 0.92 [95% CI: 0.81-1.02]; sensitivity: 0.99; specificity: 0.82) for cuff pressure. Tracheal mucous injury at the end of surgery were 0 (0, 1.0) in group A, 0 (0, 1.0) in group S, 0 (0, 0) in group L (p = 0.02, group L was lower than group A and S, p = 0.03 and p = 0.04). CONCLUSIONS: Compared to inflation with air, normal saline and 2% lidocaine cannot ameliorate the increase of tracheal tube cuff pressure during the pneumoperitoneum period under general anesthesia, but lidocaine can decrease postoperative tracheal mucosa injury. ΔCD measured by ultrasound is a predictor for changes of tracheal tube cuff pressure. TRIAL REGISTRATION: Chinese Clinical Trial Registry, identifier: ChiCTR2100054089, Date: 08/12/2021.

Efficacy and safety of perioperative application of esketamine on postoperative depression: a meta-analysis of randomized controlled studies.

BACKGROUND: Postoperative depression has a profound impact on patients' postoperative rehabilitation and overall quality of life. Preventing postoperative depression is of significant value because conventional antidepressants have a slow onset of action. Esketamine showed prompt and sustained antidepressant efficacy. Nevertheless, the safety and effectiveness of perioperative esketamine in preventing postoperative depression are still unknown. The purpose of this meta-analysis was to assess the safety and effectiveness of perioperative intravenous esketamine in relation to its ability to prevent postoperative depression. MATERIALS AND METHODS: Randomized controlled trials were searched in the following databases: Web of Science, Cochrane Central Registry of Controlled Trials, PubMed, and Embase. The primary outcome assessed is the postoperative depression scores. Postoperative pain ratings and adverse effects constituted secondary outcomes. Subgroup analyses were carried out on the basis of multiple variables, including the absence or presence of preoperative depression, the mode of esketamine administration, the dosage of esketamine, and the type of anesthesia. RESULTS: A total of 16 studies encompassed 1161 patients who received esketamine intervention, whereas 1106 patients served as controls. Esketamine was efficacious in reducing postoperative depression scores when administered perioperatively, and the esketamine group maintained a lower postoperative depression score than the control group more than four weeks after surgery. Esketamine effectively alleviated postoperative pain scores without increasing the occurrence of postoperative nausea and vomiting, dizziness, drowsiness, nightmares, and dissociation. CONCLUSION: The administration of esketamine during the perioperative has the potential to decrease postoperative depression and pain scores without increasing the incidence of adverse effects.

Oxytocin ameliorates cognitive impairments by attenuating excitation/inhibition imbalance of neurotransmitters acting on parvalbumin interneurons in a mouse model of sepsis-associated encephalopathy.

Inflammation plays a crucial role in the initiation and progression of sepsis, and it also induces alterations in brain neurotransmission, thereby contributing to the development of sepsis-associated encephalopathy (SAE). Parvalbumin (PV) interneurons are pivotal contributors to cognitive processes in various central dysfunctions including SAE. Oxytocin, known for its ability to augment the firing rate of gamma-aminobutyric acid (GABA)ergic interneurons and directly stimulate inhibitory interneurons to enhance the tonic inhibition of pyramidal neurons, has prompted an investigation into its potential effects on cognitive dysfunction in SAE. In the current study, we administered intranasal oxytocin to the SAE mice induced by lipopolysaccharide (LPS). Behavioral assessments, including open field, Y-maze, and fear conditioning, were used to evaluate cognitive performance. Golgi staining revealed hippocampal synaptic deterioration, local field potential recordings showed weakened gamma oscillations, and immunofluorescence analysis demonstrated decreased PV expression in the cornu ammonis 1 (CA1) region of the hippocampus following LPS treatment, which was alleviated by oxytocin. Furthermore, immunofluorescence staining of PV co-localization with vesicular glutamate transporter 1 or vesicular GABA transporter indicated a balanced excitation/inhibition effect of neurotransmitters on PV interneurons after oxytocin administration in the SAE mice, leading to improved cognitive function. In conclusion, cognitive function improved after oxytocin treatment. The number of PV neurons in the hippocampal CA1 region and the balance of excitatory/inhibitory synaptic transmission on PV interneurons, as well as changes in local field potential gamma oscillations in the hippocampal CA1 region, may represent its specific mechanisms.

Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: randomised clinical trial.

OBJECTIVE: To determine whether a single low dose of esketamine administered after childbirth reduces postpartum depression in mothers with prenatal depression. DESIGN: Randomised, double blind, placebo controlled trial with two parallel arms. SETTING: Five tertiary care hospitals in China, 19 June 2020 to 3 August 2022. PARTICIPANTS: 364 mothers aged ≥18 years who had at least mild prenatal depression as indicated by Edinburgh postnatal depression scale scores of ≥10 (range 0-30, with higher scores indicating worse depression) and who were admitted to hospital for delivery. INTERVENTIONS: Participants were randomly assigned 1:1 to receive either 0.2 mg/kg esketamine or placebo infused intravenously over 40 minutes after childbirth once the umbilical cord had been clamped. MAIN OUTCOME MEASURES: The primary outcome was prevalence of a major depressive episode at 42 days post partum, diagnosed using the mini-international neuropsychiatric interview. Secondary outcomes included the Edinburgh postnatal depression scale score at seven and 42 days post partum and the 17 item Hamilton depression rating scale score at 42 days post partum (range 0-52, with higher scores indicating worse depression). Adverse events were monitored until 24 hours after childbirth. RESULTS: A total of 364 mothers (mean age 31.8 (standard deviation 4.1) years) were enrolled and randomised. At 42 days post partum, a major depressive episode was observed in 6.7% (12/180) of participants in the esketamine group compared with 25.4% (46/181) in the placebo group (relative risk 0.26, 95% confidence interval (CI) 0.14 to 0.48; P<0.001). Edinburgh postnatal depression scale scores were lower in the esketamine group at seven days (median difference -3, 95% CI -4 to -2; P<0.001) and 42 days (-3, -4 to -2; P<0.001). Hamilton depression rating scale scores at 42 days post partum were also lower in the esketamine group (-4, -6 to -3; P<0.001). The overall incidence of neuropsychiatric adverse events was higher in the esketamine group (45.1% (82/182) v 22.0% (40/182); P<0.001); however, symptoms lasted less than a day and none required drug treatment. CONCLUSIONS: For mothers with prenatal depression, a single low dose of esketamine after childbirth decreases major depressive episodes at 42 days post partum by about three quarters. Neuropsychiatric symptoms were more frequent but transient and did not require drug intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT04414943.

3'-Deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.

JOURNAL/nrgr/04.03/01300535-202410000-00028/figure1/v/2024-02-06T055622Z/r/image-tiff Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasome. 3'-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3'-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3'-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3'-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3'-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3'-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3'-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3'-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.

Efficacy and safety of perioperative application of esketamine on postpartum depression: A meta-analysis of randomized controlled studies.

Postpartum depression (PPD) seriously impairs the physical and mental health of mothers and their offspring, so how to prevent the occurrence of PPD has essential significance. Esketamine is a common general anesthetic that produces rapid and sustained antidepressant effects. However, the efficacy and safety of perioperative esketamine administration for PPD prevention remain uncertain. We conducted a meta-analysis to determine the effect of perioperative intravenous esketamine on PPD. Randomized controlled trials were included. The primary outcome was the prevalence of PPD and postpartum Edinburgh Postnatal Depression Scale (EPDS) scores. Secondary outcomes included postoperative pain scores and esketamine-related adverse effects. Seven studies included 669 patients treated with esketamine and 619 comparisons. Esketamine could effectively reduce EPDS scores and the incidence of PPD after cesarean section. Even at 42 days postpartum, the incidence of PPD was still significantly lower in the esketamine group. Esketamine did not increase the incidence of postoperative nausea and vomiting, dizziness, and drowsiness. In the esketamine low-dose subgroup, postoperative nausea and vomiting were significantly lower in the esketamine group. The two groups had no significant difference in postoperative pain scores. In conclusion, using esketamine during the perioperative period can reduce the incidence of PPD without increasing adverse effects.

Perinatal outcome of emergency cesarean section under neuraxial anesthesia versus general anesthesia: a seven-year retrospective analysis.

OBJECTIVE: An emergency cesarean section (CS), which is extremely life-threatening to the mother or fetus, seems to be performed within an adequate time horizon to avoid negative fetal-maternal denouement. An effective and vigilant technique for anesthesia remains vital for emergency cesarean delivery. Therefore, this study aimed to validate the impact of various anesthesia tactics on maternal and neonatal outcomes. METHOD: This was a retrospective cohort study of parturient patients who were selected for emergency CS with the assistance of general or neuraxial anesthesia between January 2015 and July 2021 at our institution. The 5-min Apgar score was documented as the primary outcome. Secondary outcomes, including the 1 min Apgar score, decision-to-delivery interval (DDI), onset of anesthesia to incision interval (OAII), decision to incision interval (DII), duration of operation, length of hospitalization, height and weight of the newborn, use of vasopressors, blood loss, neonatal resuscitation rate, admission to neonatal intensive care unit (NICU), duration of NICU and complications, were also measured. RESULTS: Of the 539 patients included in the analysis, 337 CSs were performed under general anesthesia (GA), 137 under epidural anesthesia (EA) and 65 under combined spinal-epidural anesthesia (CSEA). The Apgar scores at 1 min and 5 min in newborns receiving GA were lower than those receiving intraspinal anesthesia, and no difference was found between those receiving EA and those receiving CSEA. The DDI of parturients under GA, EA, and CSE were 7[6,7], 6[6,7], and 14[11.5,20.5], respectively. The DDI and DII of GA and EA were shorter than those of CSE, and the DDI and DII were similar between GA and EA. Compared to that in the GA group, the OAII in the intraspinal anesthesia group was significantly greater. GA administration correlated with more frequent resuscitative interventions, increased admission rates to NICU, and a greater incidence of neonatal respiratory distress syndrome (NRDS). Nevertheless, the duration of NICU stay and the incidence rates of neonatal hypoxic ischemic encephalopathy (HIE) and pneumonia did not significantly differ based on the type of anesthesia performed. CONCLUSION: Compared with general anesthesia, epidural anesthesia may not be associated with a negative impact on neonatal or maternal outcomes and could be utilized as an alternative to general anesthesia in our selected patient population following emergency cesarean section; In addition, a comparably short DDI was achieved for emergency cesarean delivery under epidural anesthesia when compared to general anesthesia in our study. However, the possibility that selection bias related to the retrospective study design may have influenced the results cannot be excluded.

miR­3120/Hsc70 participates in forced swim stress­induced mechanical hyperalgesia in rats in an inflammatory state.

The heat shock cognate 71 kDa protein (Hsc70) is a stress­inducible ATPase that can protect cells against harmful stimuli. Transient receptor potential vanilloid 1 (TRPV1) is a well­documented nociceptor. Notably, Hsc70 can inhibit TRPV1 expression and function, suggesting that Hsc70 may have pain regulation potential. However, the role of Hsc70 in stress­induced hyperalgesia remains unclear. In the present study, the participation of Hsc70 and its regulator microRNA (miR)­3120 were investigated in forced swim (FS) stress­induced mechanical hyperalgesia in rats in an inflammatory state. Complete Freund's adjuvant (CFA) hind paw injection was performed to induce inflammatory pain in rats (CFA rats). Furthermore, in FS + CFA rats, FS stress was performed for 3 days before CFA injection. The levels of Hsc70, miR­3120 and their downstream molecule TRPV1 were measured in the dorsal root ganglion (DRG) with western blotting, immunofluorescence, reverse transcription­quantitative polymerase chain reaction and fluorescence in situ hybridization. The results revealed that FS stress significantly exacerbated CFA­induced mechanical pain. Furthermore, CFA upregulated Hsc70 and TRPV1 expression, which was partially inhibited or further enhanced by FS stress, respectively. In FS + CFA rats, intrathecal injection of a lentiviral vector overexpressing Hsc70 (LV­Hsc70) could decrease TRPV1 expression and improve the mechanical pain. Additionally, the expression levels of miR­3120, a regulator of Hsc70, were markedly upregulated on day 3 following FS stress. Finally, miR­3120 was identified to be colocalized with Hsc70 and expressed in all sizes of DRG neurons. In CFA rats, DRG injection of miR­3120 agomir to induce overexpression of miR­3120 resulted in similar TRPV1 expression and behavioral changes as those caused by FS stress, which were abolished in the presence of LV­Hsc70. These findings suggested that miR­3120/Hsc70 may participate in FS stress­induced mechanical hyperalgesia in rats in an inflammatory state, possibly via disinhibiting TRPV1 expression in the DRG neurons.

Modified Dixon sequential method to determine the effective dose of alfentanil compounded with propofol for day-case hysteroscopy.

Background: Propofol combined with alfentanil is suitable for intravenous anesthesia for day-case hysteroscopy. Objective: To investigate the median effective dose (ED50) and 95% effective dose (ED95) of alfentanil compounded with propofol for day-case hysteroscopy. Design: In all, 29 patients who volunteered for painless hysteroscopy in 2022 were recruited. 1.5 mg/kg propofol was given as a sedative to all patients. The trial was conducted using the modified Dixon sequential method, with an initial dose of 10 µg/kg of alfentanil, and the subject's alfentanil dose depended on whether the prior hysteroscopy had failed, which was defined as inadequate cervical dilatation and hysteroscope placement with the patient exhibiting body movement, frowning, or a MOAA/S score >1. If the hysteroscopy failed (i.e. a positive response), the subsequent subject's alfentanil dosage was raised, and conversely (i.e. a negative response), the dose was decreased, with the adjacent dose ratio always being 1:1.2. The formal test begins with the first crossover wave and lasts until seven crossover waves materialize. Methods: The probit method was used to calculate the ED50, ED95, and corresponding 95% confidence intervals (CIs) of alfentanil compounded with propofol for hysteroscopy. Results: The ED50 and ED95 of alfentanil combined with propofol for day-case hysteroscopy were 5.701 (95% CI: 3.841-7.069) µg/kg and 8.817 (95% CI: 7.307-20.868) µg/kg, respectively. Conclusion: Alfentanil at 8.817 µg/kg in conjunction with propofol is a successful and safe approach for day-case painless hysteroscopy. Trial registration: The trial registry name: Modified sequential method to determine the half-effective dose of alfentanil compounded with propofol for ambulatory hysteroscopy. The URL of registration is https://www.chictr.org.cn/showproj.html?proj=171786, where the full trial protocol can be accessed. Registration number: ChiCTR2200061619.

Alfentanil combined with propofol is suitable for day-case hysteroscopy Why was this study done? Hysteroscopy is a procedure in which a hysteroscope is placed after the cervix is dilated to observe lesions in the uterine cavity. This study explores the effective dose of alfentanil combined with propofol for day-case (i.e., patients admitted and discharged on the same day) hysteroscopy to provide patients with comforting anesthesia (i.e., pain relief) during hysteroscopy. What did the researchers do? The research team recruited 29 patients who volunteered for painless hysteroscopy in 2022. All patients received alfentanil and propofol for intravenous anesthesia. If anesthesia was not effective, subsequent subjects increased the dose of anesthetic medication, and vice versa, the dose was decreased. According to this method, we can find the optimal dose of anesthetic drugs in hysteroscopy. What did the researchers find? The effective dose of alfentanil combined with propofol in patients undergoing painless hysteroscopy was 8.817 µg/kg. What do the findings mean? Alfentanil at 8.817 µg/kg in conjunction with propofol is a successful and safe approach for day-case painless hysteroscopy.

Laboratory markers to identify acute histological chorioamnionitis in febrile parturients undergoing epidural analgesia: a retrospective study.

BACKGROUND: This study aimed to investigate the effect of the pathological staging of acute histological chorioamnionitis (HCA) on laboratory indicators and to conduct further studies to reassess the threshold values used by clinicians to identify acute HCA in febrile parturients undergoing epidural analgesia. METHODS: A retrospective study of febrile mothers receiving epidural analgesia at Nanjing Maternal and Child Health Care Hospital from January 1, 2018 to December 31, 2018. The participants were grouped by the progression of acute HCA, and the laboratory parameters were compared between groups. The ability of C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and monocyte-leukocyte ratio (M%), alone or in combination, to identify acute HCA in febrile parturients undergoing epidural analgesia was assessed using logistic regression and ROC curves. RESULTS: The area under the curve (AUC) of the best logistic regression model predicting HCA climbed to 0.706 (CRP + MLR). Maternal CRP, NLR, and MLR significantly and progressively increased with the progression of acute HCA (p < 0.0001). Based on the ROC curves, the following thresholds were selected to define increased laboratory indicators for identifying acute HCA: CRP ≥ 6.90 mg/L, NLR ≥ 11.93, and MLR ≥ 0.57. In addition, the AUC of the best logistic regression model predicting HCA ≥ stage 2 was 0.710, so these inflammatory markers were more precise in predicting HCA ≥ stage 2. CONCLUSION: Increased CRP (≥ 6.90 mg/L), NLR (≥ 11.93), and MLR (≥ 0.57) may help clinicians to identify early potential acute HCA in febrile parturients receiving epidural analgesia and to monitor progression to optimize clinical treatment options. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry on November 24, 2021 ( http://www.chictr.org.cn , ChiCTR2100053554).

Research Trends and Hot Spots of Allopregnanolone Research in the Last 20 Years: A Bibliometric Analysis.

Background: Allopregnanolone is a kind of neuroactive steroid or neurosteroid in the central nervous system that acts as an endogenenous GABAA receptor positive modulator. However, at present, no comprehensive bibliometric analysis regarding allopregnanolone research is available. In our study, we intend to analyze the research trends and hot spots related to allopregnanolone in the past 20 years. Methods: We searched for allopregnanolone related articles and reviews between 2004 and 2023 from the Web of Science Core Collection database. Then, the bibliometric analysis was conducted using VOSviewer, CiteSpace, Microsoft Excel 2019, as well as the online bibliometric analysis platform (http://bibliometric.com/). Results: A total of 1841 eligible publications were identified. The number of annual publications and citations was generally on the rise. Among countries, the United States ranked first in overall publications, citations, international cooperation, and the number of research institutions. The University of North Carolina was the most active institution, conducting numerous preclinical and clinical work that focusing on allopregnanolone treatment for diverse psychiatric or neurologic disorders. As for authors, Dr. Frye CA, Morrow AL, and Pinna G were identified as the top three prolific scholars due to their great publications and citations. Based on the publication clusters and citation bursts analysis, the keyword co-occurrence network, the strongest citation bursts, and co-cited references analysis, the hot spots in recent years included "depression", "postpartum depression", "GABAA receptor", and so on. Conclusion: Allopregnanolone is still a popular area of research, and the United States leads the way in this area. Dr. Frye CA, Morrow AL, Pinna G, and their teams contributed greatly to the mechanism study and translation study of allopregnanolone. The use of allopregnanolone for the treatment of psychiatric or neurologic disorders, especially postpartum depression, is the current hot spot. However, the underlying mechanisms of anti-depression are still not clear, deserving more in-depth research.

Satellite glial cell-secreted exosomes after in-vitro oxaliplatin treatment presents a pro-nociceptive effect for dorsal root ganglion neurons and induce mechanical hypersensitivity in naïve mice.

BACKGROUND: The pathophysiological mechanism underlying chemotherapy-induced neuropathic pain (CINP) remains unclear. Sensory neuronal hypersensitivity in the dorsal root ganglion (DRG) is essential for the onset and maintenance of chronic pain. Satellite glial cells (SGCs) in the DRG potentially affect the function of sensory neurons, possibly by mediating extracellular or paracrine signaling. Exosomes play an essential role in cell-cell communication. However, the role of SGC-secreted exosomes in glia-neuron communication and CINP remains unclear. METHODS: SGCs and sensory neurons were cultured from the DRG of mice. The SGCs were treated with 4 µM oxaliplatin for 24 h. Glial fibrillary acid protein (GFAP) and connexin-43 (Cx-43) expressions in the SGCs were examined with immunocytochemistry (ICC). Enzyme-linked immunosorbent assay (ELISA) detected cytokine release in the SGCs after oxaliplatin treatment. Subsequently, SGC-secreted exosomes were collected using ultracentrifugation and identified by nanoparticle tracking analysis, transmission electron microscopy, and western blotting. Subsequently, DRG neurons were incubated with SGC-secreted exosomes for 24 h. The percentage of reactive oxygen species (ROS)-positive neurons was detected using flow cytometry, and acid-sensing ion channel 3 (ASIC3) and transient receptor potential vanilloid 1 (TRPV1) expression were examined by western blotting. SGC-secreted exosomes were intrathecally injected into naïve mice. The mechanical withdrawal threshold was assessed 24, 48, and 72 h following the injection. TRPV1 expression in the DRG was examined 72 h after intrathecal injection. Furthermore, differentially expressed (DE) miRNAs within the SGC-secreted exosomes were detected using RNA sequencing and bioinformatics analysis. Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathway analyses were performed to predict the function of the target genes of DE miRNAs. Finally, the DE miRNAs with pain regulation potential were identified in silico. RESULTS: After in-vitro oxaliplatin treatment, ICC showed an increase in the immunoreactivity of GFAP and Cx-43 in the SGCs. ELISA results suggested an increased release of tumor necrosis factor-α and interleukin (IL)-1ß, but a decreased release of IL-10. Oxaliplatin treatment increased the secretion of exosomes in the SGCs from 4.34 to 5.99 × 1011 (particles/ml). The exosome-specific markers CD9 and TSG101 were positive, whereas calnexin was negative for the obtained exosomes. Additionally, the SGC-secreted exosomes were endocytosed by DRG neurons after co-incubation. Moreover, after incubation with conditioned SGC-secreted exosomes (after 4 µM oxaliplatin treatment), the percentage of ROS-positive DRG neurons increased and ASIC3 and TRPV1 expressions were upregulated. After the intrathecal injection of the conditioned SGC-secreted exosomes, the mice presented with mechanical hypersensitivity and TRPV1 expression upregulation in the DRG. Notably, 25 and 120 significantly upregulated and downregulated miRNAs, respectively, were identified in the conditioned SGC-secreted exosomes. When predicting the function of target genes of DE miRNAs, certain GO terms, such as synapse organization, neurogenesis regulation, histone modification, and pain-related KEGG or Reactome pathways, including vascular endothelial growth factor A-vascular endothelial growth factor receptor 2, mammalian target of rapamycin, and mitogen-activated protein kinase signaling pathways, related to nervous system function were predicted. Finally, 27 pain regulation-related miRNAs, including miR-324-3p, miR-181a-5p, and miR-122-5p, were identified in silico. CONCLUSION: Our study demonstrates that SGC-secreted exosomes after in-vitro oxaliplatin treatment present a pro-nociceptive effect for DRG neurons and induce mechanical hypersensitivity in naïve mice, possibly via the contained miRNA cargo. Identifying the candidate miRNAs and verifying their functions in vivo are required to elucidate the exosomes mediating 'glia-neuron' communication under CINP condition.

Remimazolam Supplemented to General Anesthesia Alleviates Stress and Cognitive Impairment in Elder Patients After Hip Surgery.

OBJECTIVE: Stress and cognitive impairment are common postoperative complications in elder patients who have undergone hip surgery. The objective of the work is to evaluate the effects of remimazolam supplemented to combined general anesthesia in improving stress and cognitive performance. METHODS: A total of 120 patients were included to receive a low dose of remimazolam (0.1 mg/kg/h) intravenously combined with general anesthesia or general anesthesia alone during hip surgery. Assessments were used for evaluating cognitive and psychological performance respectively before surgery (T0), 24 h (T5), and 72 h (T6) after surgery. Physiological parameters including mean artery pressure, heart rate, and blood oxygen levels (SpO2) were measured at T0, 30 min after anesthesia (T1), and completion of surgery (T2). Stress indexes including serum cortisol and norepinephrine levels were measured at T0, T5, and T6. The visual analog scale pain scores were also acquired at 6 h after surgery, 12 h after surgery, and T6. Serum interleukin-6 and tumor necrosis factor-α levels were acquired at T0, T2, and T6. RESULTS: Heart rate and SpO2 levels in the combination group were significantly improved compared to the control group. Serum cortisol and norepinephrine levels were the highest at T1 and decline over time until T5 in both groups, the two stress indexes of the combination group were significantly lower at T1 and T2. CONCLUSION: Remimazolam supplemented to combined general anesthesia demonstrated significant benefit in reducing stress and cognitive dysfunction in elder patients who underwent hip surgery.

Evaluation of clinical effects of Esketamine on depression in patients with missed miscarriage: A randomized, controlled, double-blind trial.

BACKGROUND: Patients with missed miscarriages are usually accompanied by varying degrees of depression, which is closely related to the patient's prognosis. We investigated whether Esketamine could alleviate postoperative depression symptoms in patients with missed miscarriages who underwent painless curettage. METHODS: This study was a randomized, parallel-controlled, double-blind, single-center trial. A total of 105 patients with preoperative 1d (EPDS) ≥ 10 were randomly assigned to the Propofol; Dezocine; Esketamine group. Patients record EPDS at 7 and 42 days after the operation. Secondary outcomes included VAS for 1 h postoperation, total propofol usage, adverse reactions, And the expressions of inflammatory factors of TNF-α, IL-1ß, IL-6, IL-8, and IL-10. RESULTS: Compared with the P and D group, patients in the S group had lower EPDS scores at 7 day (8.63 ± 3.14, 9.17 ± 3.23 vs. 6.34 ± 2.87 P = 0.0005) and 42 days (9.40 ± 2.67, 8.49 ± 3.05 vs.5.31 ± 2.49 P < 0.0001) after the operation. Respectively, Compared with the P group, the VAS scores (3.51 ± 1.12 vs. 2.80 ± 0.83, 2.40 ± 0.81, P = 0.0035) and the dosage of propofol used during operation (198.7 ± 47.48 vs. 145.5 ± 19.31, 142.9 ± 21.01 P < 0.0001) were lower in the D and S groups, and lower postoperative inflammatory response at 1 day after surgery. Other outcomes among the three groups were not found to the difference. CONCLUSIONS: Esketamine effectively treated postoperative depressive symptoms of patients with a missed miscarriage, decreasing propofol consumption and inflammatory response.

Correlation between pleth variability index and ultrasonic inferior vena cava-collapsibility index in parturients with twin pregnancies undergoing cesarean section under spinal anesthesia.

BACKGROUND: To explore the correlation and consistency of non-invasive pleth variability index (PVI) combined with ultrasonic measurement of inferior vena cava-collapsibility index (IVC-CI) in parturients with twin pregnancies undergoing cesarean section under spinal anesthesia. METHODS: Forty-seven twin pregnancies women undergoing elective cesarean section were selected. The ASA score was rated as I-II, aged from 18 to 45 years. Spinal anesthesia was performed at L3-4. PVI and IVC-CI, general data (BMI, gestational weeks, operation duration, blood loss), MAP, temperature sensory block level and adverse reactions were recorded at baseline (T1) and completion of testing the level of spinal anesthesia (T2). RESULTS: The correlation coefficient analysis of baseline IVC-CI% and PVI revealed that the Pearson's coefficient was 0.927, > 0.4. Thus, pre-anesthesia IVC-CI% had a strong correlation with PVI, with R2 of 85.69%. The correlation coefficient analysis of post-anesthesia IVC-CI% and PVI revealed that the Pearson's coefficient was 0.904, > 0.4. Thus, post-anesthesia IVC-CI% had a strong correlation with PVI, with R2 of 81.26%. CONCLUSION: PVI is strongly consistent with ultrasound measurement of IVC-CI twin pregnancies, which can be used as a valuable index for predicting the volume in parturients with twin pregnancies undergoing cesarean section under spinal anesthesia. Trial registration This study was registered on ClinicalTrials.gov with clinical trial registration number of ChiCTR2200055364 (08/01/2022).