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.

Development and validation of immunogenic cell death-applied prediction model for esophageal carcinoma.

Evidence suggests that immunogenic cell death (ICD) releases cancer antigens that promote cytotoxic T-cell responses, potentially improving immunotherapy. However, the relationship between ICDs and esophageal cancer (EC) remains unclear. This study aimed to determine the role of ICDs in EC and to construct an ICD-based prognostic panel. RNA-seq data of EC and the corresponding clinical information were downloaded from the UCSC-Xena platform to explore the association between ICD gene expression and EC prognosis. The GSE53625 dataset was used to validate the proposed model. Differentially expressed genes (DEGs) between different molecular subtypes were identified to construct a new ICD-related prognosis panel and generate molecular subtypes using ConsensusClusterPlus. We created a prognostic profile based on the ICD and a nomogram based on the risk score. Compared with normal samples, ICD gene expression of malignant samples were significantly increased. 161 patients with EC were successfully divided into three subtypes (SubA, SubB, and SubC). Patients with EC in the SubC group had the best survival and lowest ICD score, whereas patients in the SubB group had the worst prognosis. DEGs between subtypes were evaluated, and risk panels were established using LASSO-Cox regression analysis. The prognosis of low-risk patients was significantly better than that of high-risk patients in both cohorts. The area under the curve of the receiver operating characteristic curve indicated that the risk group had a good prognostic value. Our study identified the molecular subtypes of EC and ICD-based prognostic signatures. Our three-gene risk panel could serve as a biomarker for effectively assessing the prognostic risk of patients with EC.

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.

Molecular Landscape of ERBB2 Alterations in 14,956 Solid Tumors.

ERBB2 abnormalities frequently occur and serve as rationale therapeutic targets in cancer. In this study, clinical and next-generation sequencing data from 14,956 patients across more than 20 tumor types were collected. A total of 406 (2.7%) patients were identified with ERBB2 amplifications, and 303 (2.0%) patients with pathogenic somatic ERBB2 mutations. ERBB2 amplifications fell most frequently in breast (15.9%) and stomach (8.3%) cancers. Somatic ERBB2 SNVs/indels occurred most common in bladder/urinary tract (7.3%) and intestine (6.1%) cancers. The top mutated ERBB2 SNVs/indels were p.Y772_A775dup (25.5%) and p.S310F/Y (19.9%). Significantly higher rates of ERBB2 SNV/indels were found in women compared to men (2.8% vs. 1.5%, p < 0.0001). CDK12 was the most common co-amplification gene with ERBB2 in cancers with a high frequency of ERBB2 amplifications. Patients with ERBB2 amplifications or mutations had higher TMB compared with patients with non-ERBB2 alterations. The study provided the landscape of ERBB2 alterations across a variety of solid tumors that may benefit from anti-HER2 agents.

Hippocampal Inhibitory Synapsis Deficits Induced by α5-Containing GABAA Receptors Mediate Chronic Neuropathic Pain-Related Cognitive Impairment.

Chronic neuropathic pain often leads to cognitive impairment, but the exact mechanism remains unclear. Gamma-aminobutyric acid A receptors (GABAARs) are the major inhibitory receptors in the brain, of which the α5-containing GABAARs (GABAARs-α5) are implicated in a range of neuropsychiatric disorders with cognitive deficits. However, whether GABAARs-α5 are involved in chronic neuropathic pain-related cognitive impairment remains unknown. In this study, the rats with chronic neuropathic pain induced by right sciatic nerve ligation injury (SNI) exhibited cognitive impairment with declined spontaneous alternation in Y-maze test and discrimination index in novel object recognition test. The GABAARs-α5 expressing on parvalbumin and somatostatin interneurons increased remarkably in hippocampus, resulting in decreased mean frequency of spontaneous inhibitory postsynaptic currents in hippocampal pyramidal neurons. Significantly, antagonizing the GABAARs-α5 by L655708 rescued weakened inhibitory synaptic transmission and cognitive impairment induced by chronic neuropathic pain. Taken together, these data suggest that the GABAARs-α5 play a crucial role in chronic neuropathic pain-induced cognitive impairment by weakening inhibitory synaptic transmission, which may provide insights into the pharmacologic treatment of chronic neuropathic pain-related cognitive impairment.

Deficit of perineuronal net induced by maternal immune activation mediates the cognitive impairment in offspring during adolescence.

Maternal immune activation (MIA) during pregnancy is considered a risk factor for neurodevelopment in the offspring, resulting in behavioral abnormalities. Furthermore, adolescence is a vulnerable period for developing different psycho-cognitive deficits. Here, we aimed to observe the cognitive consequences of prenatal MIA exposure in adolescents and explored the underlying mechanisms. We divided dams into CON and MIA groups after inducing a mouse model of MIA using lipopolysaccharide (120 µg/kg) on gestational day 15. Open field (OF), elevated plus maze (EPM), and novel object recognition (NOR) tests were performed on postnatal day (PD) 35-37. The expression of hippocampal Wisteria floribunda agglutinin (WFA)+ perineuronal net (PNN), parvalbumin (PV), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adapter molecule-1(Iba-1) were evaluated using immunofluorescence, and the expression of matrix metalloprotein-9 (MMP-9) in the hippocampus was assessed using the western blot. Following the infusion of chondroitinase ABC (ChABC) into CA1 in the offspring from the CON group on PD 30, they were divided into ChABC and Sham groups. OF, EPM, and NOR were performed on PD 35-37. Compared to the CON group, decreased exploration time of the novel object and preference ratio were observed in the MIA group. Meanwhile, the MIA group presented significantly decreased WFA+ PNN in CA1, increased Iba-1+ microglia, and MMP-9 in the hippocampus. Additionally, the density of PV+ neurons and GFAP+ astrocytes was comparable between both groups. After digesting the PNN, the exploration time of novel object and preference ratio decreased in the ChABC group compared to the Sham group. Conclusively, the PNN deficit in CA1 caused by prenatal MIA might, at least partially, induce cognitive impairment in adolescents. Microglia and MMP-9 may also be potential candidates for PNN deficit after MIA.

Intestinal dysbacteriosis-propelled T helper 17 cells activation mediate the perioperative neurocognitive disorder induced by anesthesia/surgery in aged rats.

BACKGROUND: Perioperative neurocognitive disorders (PND) is a common postoperative disease in elderly patients, but its pathogenesis remains unclear. METHODS: Exploratory laparotomy was performed to establish PND model under sevoflurane anesthesia. 16S rRNA high-throughput sequencing was used to detect the changes of intestinal flora. Antibiotics were used to relatively eliminate intestinal flora before anesthesia/surgery, and behavior tests, such as open field, Y maze, and fear conditioning tests were applied to detect the changes of memory ability. The number of Th17 cells and Foxp3 cells was detected by flow cytometry in the Peyer's patches (PP), mesenteric lymph nodes (MLN), blood and brain. Western blot was used to detect the expression of IL17, IL17RA, IL6 and IL10 in the hippocampus. Immunofluorescence was used to detect the expression of IL17, IL17R and IBA1 (ionized calcium binding adaptor molecule1) in the hippocampus. RESULTS: Anesthesia/surgery caused intestinal flora imbalance and induced neurocognitive impairment, increased the number of Th17 cells in the PP, MLN, blood and brain, increased the level of IL17, IL17R and inflammatory factors production in the hippocampus. Antibiotics administration before anesthesia/surgery significantly decreased the number of Th17 cells and the level of IL17, IL17R and inflammatory factors production, and improved the memory function. In addition, we found that IL17R was co-labeled with IBA1 in a large amount in the hippocampus through immunofluorescence double-staining. CONCLUSION: Our study suggested that intestinal dysbacteriosis-propelled T helper 17 cells activation and IL17 secretion might play an important role in the pathogenesis of PND induced by anesthesia/surgery in aged rats.

Circular RNA circ_0008274 upregulates granulin to promote the progression of hepatocellular carcinoma via sponging microRNA -140-3p.

Circular RNA (circRNA) features prominently in the progression of hepatocellular carcinoma (HCC), of which the biological function and potential mechanism of circ_0008274 in HCC are obscure. The present study aims to explore circ_ 0008274's biological functions and underlying mechanisms in HCC. The expressions of circ_0008274, miR-140-3p and Granulin (GRN) mRNA in HCC tissues and cells were investigated by quantitative real-time polymerase chain reaction. Besides, GRN protein expression was measured by Western blot. Furthermore, chi-square test was used to probe the interrelation between circ_0008274 expression and clinicopathological parameters. In addition, cell counting kit-8 (CCK-8) and EdU assays were applied to detect cell proliferation. Moreover, transwell assay was used to detect cell migration and invasion. What's more, bioinformatics prediction, dual-luciferase reporter gene assay and RNA Immunoprecipitation experiments were used to corroborate the targeting interrelations among circ_0008274, miR-140-3p and GRN. Herein we reported that circ_0008274 was highly expressed in HCC, and its high expression enhanced the proliferation, migration, and invasion of HCC cells, while depleting circ_0008274 inhibited the malignant biological behaviors of HCC cells. Mechanistically, circ_0008274 upregulates GRN expressions via adsorbing miR-140-3p to expedite the progression of HCC.

Elevated Level of Serum C-reactive Protein Predicts Postoperative Delirium among Patients Receiving Cervical or Lumbar Surgery.

OBJECTIVE: To explore the relationship between elevated serum C-reactive protein (CRP) level and postoperative delirium (POD). METHODS: 206 patients scheduled to receive cervical or lumbar vertebra surgery under general anesthesia for more than 2 hours in a single medical center were observed and analyzed. Patients' serum CRP, delirious status (using the confusion assessment method (CAM)), and delirious score (using the memorial delirium assessment scale (MDAS)) were examined before surgery and 1-2 days after surgery. The association of a serum CRP elevation value from before to after surgery (D-CRP) with delirium occurrence within 2 days after surgery was assessed with a binary logistic regression model, while the association of D-CRP with the postoperative delirious score was assessed with a linear regression model. The effect of D-CRP on predicting delirium occurrence was evaluated with the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: D-CRP was significantly positively associated with postoperative delirium occurrence (OR = 1.047, 95%CI = 1.013, 1.082), and D-CRP was also significantly linearly associated with the postoperative delirious score (ß = 0.014, 95%CI = 0.006, 0.023). AUC of ROC was 0.711 (P = 0.014), suggesting that D-CRP had moderate efficacy on predicting postoperative delirium occurrence (P < 0.05). CONCLUSIONS: Elevated serum CRP after surgery may be a risk factor for and a predictor of postoperative delirium.

Combination of Polypropylene Mesh and in Situ Injectable Mussel-Inspired Hydrogel in Laparoscopic Hernia Repair for Preventing Post-Surgical Adhesions in the Piglet Model.

Polypropylene (PP) mesh has been used successfully for a long time in clinical practice as an impressive prosthesis for ventral hernia repair. To utilize a physical barrier for separating mesh from viscera is a general approach for preventing adhesions in clinical practice. However, a serious abdominal adhesion between the mesh and viscera can possibly occur post-hernia, especially with the small intestine; this can lead to a series of complications, such as chronic pain, intestinal obstruction, and fistula. Thus, determining how to prevent abdominal adhesions between the mesh and viscera is still an urgent clinical problem. In this study, a dopamine-functionalized polysaccharide derivative (oxidized-carboxymethylcellulose-g-dopamine, OCMC-DA) was synthesized; this was blended with carboxymethylchitosan (CMCS) to form a hydrogel (OCMC-DA/CMCS) in situ at the appropriate time. The physical and chemical properties of the hydrogel were characterized successfully, and its excellent biocompatibility was presented by the in vitro cell test. The combination of this hydrogel and PP mesh was used in laparoscopic surgery for repairing the abdominal wall defect, where the hydrogel could become fixed in situ on the PP mesh to form an anti-adhesion gel-mesh. The results showed that the gel-mesh could prevent abdominal adhesions effectively in the piglet model. Moreover, the histology and immunohistochemical staining proved that the gel-mesh could effectively alleviate the inflammation reaction and deposition of collagen around the mesh, and it did not disturb the integration between mesh and abdominal wall. Thus, the gel-mesh has superior tissue compatibility.

Structural characterization of an active polysaccharide of longan and evaluation of immunological activity.

An active polysaccharide (LPD2) was isolated from longan pulp by comparing the effects of polysaccharides on the phagocytosis of macrophages. LPD2 was composed of arabinose, mannose, glucose, and galactose in a molar ratio of 0.25:0.49:1:0.5 with average molecular weight of 9.64 × 106 Da. The main linkages of the sugar residues of LPD2 were (1→4)-ß-Glc and (1→6)-ß-Man. LPD2 significantly enhanced the lymphocytes proliferation, phagocytosis and NO and IL-6 secretion by macrophage. The anti-TLR2 and anti-TLR4 mAbs markedly suppressed LPD2-mediated NO and IL-6 production. Furthermore, anti-TLR4 or anti-TLR2 plus anti-TLR4 treatment significantly decreased LPD2-induced increase of MyD88, IRAK4, TRAF6 and INOS mRNA expression. Moreover, western blotting analysis showed that LPD2 enhanced the expression of target proteins in MyD88/IRAK4-TRAF6- INOS pathways. These results suggested that LPD2 induced macrophage activation partly via the TLR2- and TLR4-mediated MyD88/IRAK4-TRAF6 signaling pathways. Knowing the structural features and activities of active polysaccharide of longan gives the insights into longan polysaccharide application as an immunomodulatory agent.

Mussel-inspired copolymer-coated polypropylene mesh with anti-adhesion efficiency for abdominal wall defect repair.

Polypropylene (PP) meshes are one of the most commonly used prosthesis materials in repairing abdominal wall defects. However, their application is usually limited due to possible serious abdominal adhesions between the mesh and the viscera. Instilling PP meshes with excellent anti-adhesion characteristics is still a formidable challenge. In this work, in order to prevent intestinal adhesion to the PP mesh, an effective method was developed to prepare anti-adhesive PP meshes, which was inspired by mussel adhesive proteins. A functional monomer, namely, dopamine methacrylamide, was first synthesized. Then, it was copolymerized with poly(ethylene glycol) methacrylate on the surface of O2-plasma-treated PP (OPP) meshes to form comb-like copolymer poly[poly(ethylene glycol) methacrylate-co-dopamine methacrylamide] (PEDMA), which was simultaneously grafted in situ on the OPP mesh surface through the catechol group of PEDMA, subsequently yielding an anti-adhesive PP mesh (OPP-g-PEDMA). The properties of PEDMA and OPP-g-PEDMA meshes were characterized by NMR, GPC, TGA, FTIR, XPS, SEM, and water contact angle measurements. NIH-3T3 cells were employed to assess the cytocompatibility of OPP-g-PEDMA in vitro. Furthermore, the rat abdominal wall defect model was used to evaluate the efficacy of adhesion prevention. The results show that OPP-g-PEDMA not only possesses fantastic biocompatibility but also satisfactory anti-adhesion property involving minimal chronic inflammation, as well as lower adhesion formation rate and adhesion tenacity scores (less than 1.0). This type of OPP-g-PEDMA mesh is a promising candidate in effectively preventing peritoneal adhesion during abdominal wall defect repair.

Intestinal microbiota are involved in the immunomodulatory activities of longan polysaccharide.

It is difficult for polysaccharides to be directly absorbed through the intestine, which implies other utilization mechanisms involved in the bioactivity performance of polysaccharide. In this study, the multi-omics approach was applied to investigate the impacts of longan polysaccharide on mouse intestinal microbiome and the interaction between the polysaccharide-derived microbiome and host immune system. According to the result, the longan polysaccharide showed a significant improvement in the typical intestinal immunity index of mice. Meanwhile, at the taxonomy level, the intestinal microbiota from the control group and polysaccharide group were highly distinct in organismal structure. At the functional level, a significant decline in the microbial metabolites of pyruvate, butanoate fructose and mannose in the control group was found. Additionally, a significant increase was observed in the succinic acid and the short-chain fatty acid, including acetic acid, propionic acid and butyric acid, in the polysaccharide group. Furthermore, the multi-omic based network analysis indicated that the intake of longan polysaccharide resulted in the changes of the intestinal microbiota as well as the gut metabolites, which led to the enhancement of host's immune function under the stress conditions. These results indicated the polysaccharide-derived changes in intestinal microbiota were involved in the immunomodulatory activities.

Laparoendoscopic single-site distal pancreatectomy in pigs.

AIM: To explore the technique for laparoendoscopic single-site distal pancreatectomy. METHODS: Laparoendoscopic single-site spleen-preserving distal pancreatectomy was performed in pigs using a novel flexible multichannel port, a curved laparoscopic multifunctional operative device and a fish hook retractor, which provided a favorable operative field. RESULTS: Six pigs were involved in this study, and five survived the procedure. The first animal died following injury to the superior mesenteric vein and uncontrolled intraoperative bleeding. Except for this failure, the mean operative time was 155 min (range: 102-236 min). A steep learning curve was observed in the study, with a mean operative time of 177 min in the first two operations vs 134 min in the last three operations. The mean blood loss was 50 mL, and the postoperative course was uneventful. The animals were sacrificed three weeks after the procedures, and no pancreatic leakage or abdominal infection was found macroscopically. CONCLUSION: Laparoendoscopic single-site distal pancreatectomy is a safe and feasible procedure and can be implemented in humans in selected cases at qualified surgical centers.