Isolation and identification of active components from Grifola frondosa and its anti-EV71 virus effect.

BACKGROUND: It is reported that anti-enterovirus 71 (EV71) drugs have some side effects on human health. Notably, fungi plays a crucial role in promoting human health and anti-virus. Grifola frondosa is a type of large medicinal and edible fungi, rich in active substances. The present study aimed to investigate the anti-EV71 effect of G. frondosa and the potential active substances. RESULTS: In the present study, the water extract of G. frondosa was subjected to ethanol precipitation to obtain the water-extracted supernatant of G. frondosa (GFWS) and water-extracted precipitation of G. frondosa. Their inhibitory effects on EV71 virus were studied based on a cell model. The results showed that GFWS had stronger security and anti-EV71 effects. In addition, the chemical constituents of GFWS were identified by ultra-high performance liquid chromatography-tandem mass spectrometry, which were selected for further separation and purification. Three compounds, N-butylaniline, succinic acid and l-tryptophan, were isolated from GFWS by NMR spectroscopy. It is noteworthy that N-butylaniline and l-tryptophan were isolated and identified from the G. frondosa fruiting bodies for the first time. Our study found that l-tryptophan has anti-EV71 virus activity, which reduced EV71-induced apoptosis and significantly inhibited the replication process after virus adsorption. Furthermore, it could also bind to capsid protein VP1 to prevent the virus from attaching to the cells. CONCLUSION: l-tryptophan was an inhibitor of the EV71 virus, which could be used in infant nutrition and possibly provide a new drug to treat hand, foot and mouth disease. © 2024 Society of Chemical Industry.

Immunotoxicity Evaluation of Trihalophenolic Disinfection By-Products in Mouse and Human Mononuclear Macrophage Systems: The Role of RNA Epitranscriptomic Modification in Mammalian Immunity.

BACKGROUND: 2,4,6-Trichlorophenol (TCP), 2,4,6-tribromophenol (TBP) and 2,4,6-triiodophenol (TIP) are three widely detected trihalophenolic disinfection by-products (DBPs). Previous studies have mainly focused on the carcinogenic risk and developmental toxicity of 2,4,6-trihalophenols. Very little is known about their immunotoxicity in mammals. OBJECTIVES: We investigated the effects of 2,4,6-trihalophenols on mammalian immunity using a mouse macrophage model infected with bacteria or intracellular parasites and aimed to elucidate the underlying mechanisms from an epitranscriptomic perspective. The identified mechanisms were further validated in human peripheral blood mononuclear cells (PBMCs). METHODS: The mouse macrophage cell line RAW264.7 and primary mouse peritoneal macrophages were exposed to different concentrations of TCP, TBP, and TIP. The pro-inflammatory marker Ly6C, the survival of the bacterium Escherichia coli (E. coli), and the parasite burden of Toxoplasma gondii (T. gondii) were assessed. Furthermore, the global gene expression profiling of macrophages following exposure to 2,4,6-trihalophenols was obtained through RNA-sequencing (RNA-seq). The effects of 2,4,6-trihalophenols on RNA N6-methyladenosine (m6A) methyltransferases and total RNA m6A levels were evaluated using Western blotting and dot blot, respectively. Transcriptome-wide m6A methylome was analyzed by m6A-seq. In addition, expression of m6A regulators and total RNA m6A levels in human PBMCs exposed to 2,4,6-trihalophenols were detected using quantitative reverse transcriptase polymerase chain reaction and dot blot, respectively. RESULTS: Mouse macrophages exposed to TCP, TBP, or TIP had lower expression of the pro-inflammatory marker Ly6C, with a greater difference from control observed for TIP-exposed cells. Consistently, macrophages exposed to such DBPs, especially TIP, were susceptible to infection with the bacterium E. coli and the intracellular parasite T. gondii, indicating a compromised ability of macrophages to defend against pathogens. Intriguingly, macrophages exposed to TIP had significantly greater m6A levels, which correlated with the greater expression levels of m6A methyltransferases. Macrophages exposed to each of the three 2,4,6-trihalophenols exhibited transcriptome-wide redistribution of m6A. In particular, the m6A peaks in genes associated with immune-related pathways were altered after exposure. In addition, differences in m6A were also observed in human PBMCs after exposure to 2,4,6-trihalophenols. DISCUSSION: These findings suggest that 2,4,6-trihalophenol exposure impaired the ability of macrophages to defend against pathogens. This response might be associated with notable differences in m6A after exposure. To the best of our knowledge, this study presents the first m6A landscape across the transcriptome of immune cells exposed to pollutants. However, significant challenges remain in elucidating the mechanisms by which m6A mediates immune dysregulation in infected macrophages after 2,4,6-trihalophenol exposure. https://doi.org/10.1289/EHP11329.

Probiotic Fermentation of Kelp Enzymatic Hydrolysate Promoted its Anti-Aging Activity in D-Galactose-Induced Aging Mice by Modulating Gut Microbiota.

SCOPE: To investigate anti-aging effects of probiotic-fermented kelp enzymatic hydrolysate culture (KMF), probiotic-fermented kelp enzymatic hydrolysate supernatant (KMFS), and probiotic-fermented kelp enzymatic hydrolysate bacteria suspension (KMFP) in D-galactose-induced aging mice. METHODS AND RESULTS: The study uses a probiotic-mixture of Lactobacillus reuteri, Pediococcus pentosaceus, and Lactobacillus acidophilus strains for kelp fermentation. KMF, KMFS, and KMFP prevent D-galactose-induced elevation of malondialdehyde levels in serum and brain tissue of aging mice, and they increase superoxide dismutase and catalase levels and total antioxidant capacity. Furthermore, they improve the cell structure of mouse brain, liver, and intestinal tissue. Compared with the model control group, the KMF, KMFS, and KMFP treatments regulate mRNA and protein levels of genes associated with aging, the concentrations of acetic acid, propionic acid, and butyric acid in the three treatment groups are more than 1.4-, 1.3-, and 1.2-fold increased, respectively. Furthermore, the treatments affect the gut microbiota community structures. CONCLUSIONS: These results suggest that KMF, KMFS, and KMFP can modulate gut microbiota imbalances and positively affect aging-related genes to achieve anti-aging effects.

Probiotics-Fermented Grifola frondosa Total Active Components: Better Antioxidation and Microflora Regulation for Alleviating Alcoholic Liver Damage in Mice.

Alcoholic liver damage is caused by long-term drinking, and it further develops into alcoholic liver diseases. In this study, we prepared a probiotic fermentation product of Grifola frondosa total active components (PFGF) by fermentation with Lactobacillus acidophilus, Lactobacillus rhamnosus, and Pediococcus acidilactici. After fermentation, the total sugar and protein content in the PFGF significantly decreased, while the lactic acid level and antioxidant activity of the PFGF increased. Afterward, we investigated the alleviating effect of PFGF on alcoholic liver injury in alcohol-fed mice. The results showed that the PFGF intervention reduced the necrosis of the liver cells, attenuated the inflammation of the liver and intestines, restored the liver function, increased the antioxidant factors of the liver, and maintained the cecum tissue barrier. Additionally, the results of the 16S rRNA sequencing analysis indicated that the PFGF intervention increased the relative abundance of beneficial bacteria, such as Lactobacillus, Ruminococcaceae, Parabacteroids, Parasutterella, and Alistipes, to attenuate intestinal inflammation. These results demonstrate that PFGF can potentially alleviate alcoholic liver damage by restoring the intestinal barrier and regulating the intestinal microflora.

Ameliorating Effect on Glycolipid Metabolism of Spirulina Functional Formulation Combination from Traditional Chinese Medicine.

Insulin resistance is the major factor involved in the pathogenesis of type 2 diabetes. Although the oral drug metformin (MH) is widely used to reduce hyperglycemia, it is associated with adverse effects. Therefore, there is an urgent need to search for safe and natural foods that do not cause adverse effects as alternatives to commercial drugs. In this study, the active substances from Spirulina platensis, Grifola frondosa, Panax ginseng, and chromium-rich yeast were used to obtain Spirulina functional formulations (SFFs), and its therapeutic effects on mice with glycolipid metabolism disorder (GLD) were investigated. Results showed that SFFs not only improved glycolipid metabolism and reduced inflammation in mice with GLD but also showed good regenerative effects on the liver, jejunum, and cecum tissues. Moreover, SFFs could inhibit the growth of harmful microbes in the intestine and promote the proliferation of beneficial bacteria, thereby promoting the production of short-chain fatty acids and further regulating GLD. Additionally, SFFs significantly increased the expression of INS, INSR, IRS-1, PI3K, AKT-1, and GLUT-4 genes and significantly decreased that of GSK-3ß in the INS/PI3K/GLUT-4 signaling pathway. Therefore, the findings of this study suggest that SFFs can be further developed as a new class of therapeutic agents against GLD.

The involvement of branched-chain amino acids (BCAAs) in aromatic trihalogenated DBP exposure-induced kidney damage in mice.

Disinfection by-products (DBPs) are inevitably generated in the process of disinfection. Among them, aromatic halogenated DBPs, such as 2,4,6-trichlorophenol (TCP), 2,4,6-tribromophenol (TBP) and 2,4,6-triiodophenol (TIP), have attracted considerable interest for their high toxicity. A systematic nephrotoxicity evaluation of 2,4,6-trihalophenols is still lacking. In this study, mice were exposed to TCP, TBP and TIP ranging from environmental-related low concentration to high concentration that commonly used in animal study (0.5-200 µg/L). Kidney histopathology, urine protein detection and urine metabolomics were performed. Remarkable changes including kidney damage, proteinuria and glomerular mesangial cell proliferation were observed after three 2,4,6-trihalophenol exposure, even at low concentration of 0.5 µg/L. The nephrotoxicity rank order was TIP > TBP > TCP. Additionally, in vivo exposure to 2,4,6-trihalophenols also led to apparent changes in urinary metabolic profiles. Biosynthesis pathways of branched-chain amino acids (BCAAs, containing valine, leucine and isoleucine) were disturbed even at the early stage of exposure (4 weeks). Intriguingly, it has been reported that BCAAs could promote the proliferation of glomerular mesangial cells. Thus, in vitro cell experiments were further performed on mouse glomerular mesangial cell line MES-13. Consistently with in vivo results, cell proliferation was observed in MES-13 cells after exposure to 2,4,6-trihalophenols, especially to TBP and TIP. Meanwhile, TCP at high concentration, TBP and TIP at not only high concentration but also low concentration, induced BCAAs accumulation in glomerular mesangial cells, which was completely commensurate to that observed in cell proliferation assay. Then the proliferation of MES-13 cells induced by 2,4,6-trihalophenols was remarkably inhibited after BCAAs interference. Here we provide direct link between disturbed BCAAs and the nephrotoxicity of 2,4,6-trihalophenols. 2,4,6-trihalophenols could induce excess BCAAs, which further led to proliferation of glomerular mesangial cells and renal injury. This study revealed the nephrotoxicity of aromatic trihalogenated DBPs and provided new insights into the potential toxic mechanisms.

In vivo toxicity evaluations of halophenolic disinfection byproducts in drinking water: A multi-omics analysis of toxic mechanisms.

Halophenolic disinfection byproducts (DBPs) in drinking water have attracted considerable concerns in recent years due to their wide occurrence and high toxicity. The liver has been demonstrated as a major target organ for several halophenolic DBPs. However, little is known about the underlying mechanisms of liver damage caused by halophenolic DBPs. In this study, 2,4,6-trichlorophenol (TCP), 2,4,6-tribromophenol (TBP) and 2,4,6-triiodiophenol (TIP) were selected as representative halophenolic DBPs and exposed to C57BL/6 mice at an environmentally-relevant concentration (0.5 µg/L) and two toxicological concentrations (10 and 200 µg/L) for 12 weeks. Then, a combination of histopathologic and biochemical examination, liver transcriptome, serum metabolome, and gut microbiome was adopted. It was found that trihalophenol exposure significantly elevated the serum levels of alkaline phosphatase and albumin. Liver inflammation was observed at toxicological concentrations in the histopathological examination. Transcriptome results showed that the three trihalophenols could impact immune-related pathways at 0.5 µg/L, which further contributed to the disturbance of pathways in infectious diseases and cancers. Notably, TBP and TIP had higher immunosuppressive effects than TCP, which might lead to uncontrolled infection and cancer. In terms of serum metabolic profiles, energy metabolism pathway of citrate cycle and amino acid metabolism pathways of valine, leucine, and isoleucine were also significantly affected. Integration of the metabolomic and transcriptomic data suggested that a 12-week trihalophenol exposure could prominently disturb the glutathione metabolism pathway, indicating the impaired antioxidation and detoxification abilities in liver. Moreover, the disorder of the intestinal flora could interfere with immune regulation and host metabolism. This study reveals the toxic effects of halophenolic DBPs on mammalian liver and provides novel insights into the underlying mechanisms of hepatotoxicity.

6,8-(1,3-Diaminoguanidine) luteolin and its Cr complex show hypoglycemic activities and alter intestinal microbiota composition in type 2 diabetes mice.

Flavonoid compounds such as luteolin exhibit hypolipidemic effects, and there are few reports on the hypoglycemic activity of luteolin derivatives. In this research, 6,8-(1,3-diaminoguanidine) luteolin (DAGL) and its Cr complex (DAGL·Cr) were obtained as a result of structural modifications to luteolin, and the hypoglycemic activities and the composition of intestinal microbiota in T2DM mice were investigated. This study found that DAGL and DAGL·Cr could significantly restore body weight, FBG, OGTT, AUC, and GSP in T2DM mice. Moreover, the pancreatic islet function index and the biochemical indicators of serum and the liver were also significantly improved. The histopathological results also showed that DAGL and DAGL·Cr had a stronger repair ability in the liver and the pancreas. It was also revealed that the potential hypoglycemic mechanism of DAGL and DAGL·Cr was involved in the simultaneous regulation of PI3K/AKT-1/GSK-3ß/GLUT-4 and PI3K/AKT-1/mTOR/S6K1/IRS-1. Furthermore, DAGL and DAGL·Cr could also regulate the structure of the intestinal microbiota and increase the content of SCFA to relieve the symptoms of hyperglycemia in T2DM mice. This included a significant reduction in the ratio of Firmicutes and Bacteroidetes (F/B), and at the genus level, an increase in the relative abundance of Alistipe and Ruminiclostridium, and improvement in the content of SCFA in the feces of T2DM mice. In conclusion, in this study, DAGL and DAGL·Cr were found to improve hyperglycemia in T2DM mice by improving the pancreatic islet function index, regulating the biochemical indicators of serum and the liver, repairing damaged tissues, and regulating the PI3K/AKT-1 signaling pathway as well as reducing F/B, increasing the relative abundance of intestinal beneficial microbiota, and the content of SCFA in the feces. The hypoglycemic effect of DAGL·Cr on the body weight, serum IL-10, serum IL-6, and pancreatic islet function index was significantly better than that of DAGL.

LncRNA PVT1 contributes to invasion and doxorubicin resistance of bladder cancer cells through promoting MDM2 expression and AURKB-mediated p53 ubiquitination.

In most bladder cancer (BC) patients, cancer cells will eventually develop chemical resistance causing increased mortality. This study aimed to explore the mechanism of lncRNA plasmacytoma variant translocation 1 (PVT1) in regulating doxorubicin (ADM) resistance of BC cells. We observed that PVT1 expression was upregulated in ADM-resistant BC cells compared with ADM-sensitive BC cells. Downregulation of PVT1 suppressed ADM-resistant BC cell proliferation and invasion, promoted apoptosis, and increased sensitivity to ADM, while PVT1 overexpression promoted ADM-sensitive BC cell growth and their resistance to ADM. Further study uncovered that PVT1 could interact with and promote mouse double minute 2 (MDM2) expression, and upregulated MDM2-mediated Aurora kinase B (AURKB). Furthermore, Nutlin-3, an inhibitor of MDM2, could counteract the promotive effects of PVT1 overexpression on ADM resistance of ADM-sensitive BC cell, the expression of multidrug-resistance-related proteins, and the inhibition of p53-mediated tumor suppressor genes. And, overexpression of MDM2 or AURKB reversed the promotive effects of PVT1 silence on the ADM sensitivity of ADM-resistant BC cell, and the inhibitory effect on expression multidrug resistance proteins. Mechanically, AURKB increased MDM2-mediated p53 ubiquitination. Taken together, PVT1 promoted BC cell proliferation and drug resistance via elevating MDM2 expression and AURKB-mediated p53 ubiquitination.

Early onset of severe lymphopenia during definitive radiotherapy correlates with mean body dose and predicts poor survival in cervical cancer.

BACKGROUND: Lymphopenia during definitive radiotherapy (RT) has been shown to reduce survival in patients with cervical cancer. However, there are few studies on the significance of onset time of lymphopenia during RT in patients with cervical cancer. OBJECTIVE: This study aimed to exam the prognostic significance of early onset of severe lymphopenia (EOSL) during definitive RT in patients with cervical cancer. METHODS: Newly diagnosed cervical cancer patients treated with definitive RT from January 2015 to December 2019 were eligible for this retrospective study. EOSL was defined as first onset of grade 3-4 lymphopenia ⩽ 3 weeks from the start of RT. Mean body dose (MBD) was the mean radiation dose absorbed by the body during the whole course of external beam RT (EBRT) and was directly obtained from the dose volume histogram (DVH) of the EBRT planning. Logistic regression analysis and restricted cubic spline (RCS) models were applied to assess relationships between clinicopathological factors and EOSL. Survival analysis was performed using Kaplan-Meier curves and log-rank test. A COX regression model was developed to predict overall survival (OS). RESULTS: A total of 104 patients were included and 59.6% had EOSL. MBD (P= 0.04), concurrent cisplatin (P= 0.011), and pre-RT absolute lymphocyte count (ALC) (P= 0.001) were associated with EOSL. A linear relationship (P for non-linearity = 0.803) between MBD and risk of EOSL was found. Patients with EOSL had decreased OS (2-yr 75.1% vs 91.1%, P= 0.021) and progression-free survival (PFS) (2-yr 71.2% vs 83.7%, P= 0.071). An OS prediction COX model was developed with C-index of 0.835 and AUC of 0.872. CONCLUSIONS: EOSL during definitive RT correlates with MBD and predicts poor survival in patients with cervical cancer.

Opioids for the Prevention of Post-dural Puncture Headache in Obstetrics: A Systematic Review and Meta-analysis of Efficacy and Safety.

BACKGROUND: Post-dural puncture headache (PDPH), or spinal headache, is the most common serious complication resulting from iatrogenic puncture of the dura during epidural or spinal anesthesia and cerebrospinal fluid (CSF) leak in pregnant women. OBJECTIVE: To analyze the effectiveness and safety of opioids as a prophylaxis approach in treating obstetric patients who underwent unintentional dural puncture during the initiation of neuraxial anesthesia. STUDY DESIGN: A systematice review and meta-analysis. SETTING: No restriction regarding study type. METHODS: PubMed, Embase, and the Cochrane library were searched for available papers published up to September 2020. RESULTS: According to the eligibility criteria, 10 studies were included with post-dural puncture headache (PDPH) incidence as the primary outcome and the number of epidural blood patch (EBP) required as the second outcome. The risk estimates of each study were reported as odds ratios (ORs). The results showed morphine does not decrease the incidence of PDPH (OR = 0.45, 95% CI: 0.15 - 1.34, P = 0.153, I2 = 74.4%, Pheterogeneity = 0.004) and the use of EBP (OR = 0.40, 95% CI: 0.08 - 1.95, P = 0.259, I2=73.7%, Pheterogeneity = 0.004). Fentanyl does not decrease the incidence of PDPH (OR = 0.35, 95% CI: 0.01-13.77, P = 0.576, I2 = 81.0%, Pheterogeneity = 0.022). LIMITATIONS: The small number of included studies, high heterogeneity, and variety in study designs. CONCLUSIONS: Exposure to opioids for any reason after the diagnosis of unintentional dural puncture is not associated with a reduced risk of PDPH and does not decrease the need for therapeutic EBP.

A Space-Time Analysis of Rural Older People's Outdoor Mobility and Its Impact on Self-Rated Health: Evidence from a Taiwanese Rural Village.

With the aggravation of rural aging, the well-being and self-rated health level of older people in rural communities are significantly lower than those in urban communities. Past studies hold that mobility is essential to the quality of life of the elderly, and well-being depends on their own adaptation strategies in the built environment. Therefore, this study combines three key factors related to active aging: environment, health and mobility, and assumes that the elderly with good health status will have environmental proactivity and a wider range of daily mobility in a poor rural built environment. This study attempts to track daily mobility by using a space-time path method in time geography and then to explore the relationship between outdoor mobility and older people's self-rated health. A 1-week mobility path survey for 20 senior citizens of Xishi Village, a typical rural village in Taiwan, was conducted by wearing a GPS sports watch. A questionnaire survey and in-depth interviews were done to provide more information about the seniors' personal backgrounds and lifestyles. The results show that when the built environment is unfit to the needs of daily activities, half of the participants can make adjustment strategies to go beyond the neighborhoods defined by administrative units. Correlation analysis demonstrated that mental health is associated with daily moving time and distance. In addition, men have higher self-rated health scores than women, and there are significant statistical differences between married and widowed seniors in daily outing time and distance. This exploratory study suggests that in future research on rural health and active aging in rural areas, understanding the daily outdoor mobility of the elderly can help to assess their health status and living demands and quickly find out whether there is a lack of rural living services or environmental planning.

Combination Effect of Outdoor Activity and Screen Exposure on Risk of Preschool Myopia: Findings From Longhua Child Cohort Study.

Evidence regarding screen use and outdoor activity during very early childhood (i. e., from aged 1 to 3 years) and their potential combined links to the later preschool myopia is limited. This information is needed to release effective public health messages and propose intervention strategies against preschool myopia. We collected information regarding very early childhood screen use, outdoor activity and the kindergartens vision screenings of 26,611 preschoolers from Longhua Child Cohort Study by questionnaires. Logistic regression models were used to examine the associations between reported outdoor activity, screen use from 1 to 3 years of age, and preschool myopia. Throughout very early childhood, from 1 to 3 years, the proportion of children exposed to screens increased (from 35.8 to 68.4%, p < 0.001), whereas the proportion of children who went outdoors ≥7 times/week (67.4-62.1%, p < 0.001) and who went outdoors for ≥60 min/time (53.3-38.0%, p < 0.001) declined. Exposure to fixed screen devices [adjusted odds ratio (AOR) = 2.66, 95% confidence interval (CI) = 2.09-3.44], mobile screen devices (AOR = 2.76, 95% CI = 2.15-3.58), and limited outdoor activity (AOR = 1.87, 95% CI = 1.42-2.51) during early childhood were associated with preschool myopia. Among children whose parents were myopic, the interactions between outdoor activity and fixed or mobile screen use on later preschool myopia were significant; the ORs and 95% CI were 3.34 (1.19-9.98) and 3.04 (1.06-9.21), respectively. Our findings suggest the possibility that the impact of screen exposure during early childhood on preschool myopia could be diminished by outdoor activity for children whose parents have myopia.

Association between greater residential greenness and decreased risk of preschool myopia and astigmatism.

OBJECTIVE: Rapid urbanization has led to reduced greenness in many areas, this has been linked to adverse health outcomes. The aim was to determine the association between residential greenness experienced during very early childhood with preschool myopia and astigmatism and to explore the potential mediating role of screen time on any associations. METHOD: Information regarding socio-demographic characteristics, home address, screen time during early childhood, and refraction data from vision screenings of 53,575 preschoolers from Longhua Child Cohort Study were collected via questionnaires. Residential greenness was calculated as the average of satellite-derived Normalized Difference Vegetation Index in buffers of 100, 250, and 500 m around each child's home address. Logistic and linear regression models were used to examine the relationships between residential greenness, screen time, and preschool myopia and astigmatism. RESULT: The mean (SD) age of the 53,575 preschoolers was 5.0 (0.7) years, and 24,849 (46.4%) were girls. A total of 1236 (2.3%) preschoolers had myopia and 5347 (10.0%) had astigmatism. In the adjusted model, a higher neighborhood greenness level within 100 m buffers around the home address was associated with decreased risk of myopia (adjusted odds ratios (AOR): 0.62, 95% confidence interval (CI): 0.38-0.99), and higher neighborhood greenness levels within 100, 250, and 500 m decreased the risk of astigmatism, and their AORs (95% CIs) were 0.55 (0.43-0.70) for 100 m, 0.59 (0.41-0.83) for 250 m, 0.61 (0.42-0.90) for 500 m, respectively. Greater screen time during early childhood increased the risk of myopia (AOR = 1.33) and astigmatism (AOR = 1.23). Reduction in screen time fully mediated the benefits of greater residential greenness on preschool myopia, but partially mediated that on preschool astigmatism (p < 0.05). CONCLUSION: Higher residential greenness reduces the risk of preschool myopia and astigmatism; the benefits of residential greenness were mediated through reduced daily screen time.

Perioperative patient blood management during parallel transverse uterine incision cesarean section in patient with pernicious placenta previa: A retrospective cohort analysis.

Pernicious placenta previa (PPP) is the main cause of severe obstetric postpartum hemorrhage and hysterectomy and often requires donor blood transfusion. Prophylactic internal iliac artery (IIA) balloon occlusion (BO) combined with cell salvage is increasingly being deployed in parallel transverse uterine incision (PTUI) cesarean section (CS). The aim of this study was to explore the differences in blood management in PTUI CS with or without prophylactic IIA BO and to evaluate the safety and efficacy of cell salvage to reduce the need for donor blood transfusion during PTUI CS.This retrospective study included all women who were diagnosed with PPP and PA and underwent PTUI CS from October 1, 2016, to October 31, 2018. Sixty-four patients were included: 34 underwent prophylactic IIA BO (IIA group), whereas 30 were treated without prophylactic IIA BO (control group). The primary outcome was a composite measure of perioperative blood management outcomes, including the estimated blood loss (EBL), donor blood transfusion, salvaged blood returned, fresh frozen plasma (FFP), pre- and postoperative serum hemoglobin and hematocrit. In addition, the baseline conditions of mother and neonates were compared.EBL was significantly higher in the IIA group compared to the control group (2883.5 mL in the IIA group vs 1868.7 mL in the control group, P = .001). Overall, the donor blood transfusion rate was 23.5% (8/34), averaging 4.2 U, in the IIA group versus 30% (9/30), averaging 3.4 U, in the control group, which were not significantly different. The FFP transfusion rate was 47%, averaging 765.6 mL, in the IIA group versus 20%, averaging 816.7 mL, in the control group. In the IIA group, 97.1% used cell savage and had salvaged blood returned, averaging 954.9 mL. In the control group, 90% had salvaged blood returned, averaging 617.9 mL. No cases of amniotic fluid embolism were observed with leukocyte depletion filters.Prophylactic IIA BO during PTUI CS in women with PPP and PA does not lead to a statistically significant reduction in EBL. Cell salvage was associated with a reduction in the rate of donor blood transfusion during PTUI CS.

Anesthesia management of a premature neonate during minimally invasive sclerotherapy of a large chest wall mass: A case report.

RATIONALE: The most common critical incidents in pediatric anesthesia are perioperative respiratory adverse events (PRAE), which occur more often in neonates and account for one-third of anaesthesia-related cardiac arrests. It is crucial to maintain an open stable airway during anesthesia in neonates, as this population has a low oxygen reserve, small airways, and the loss of protective airway reflexes under general anesthesia. PATIENT CONCERNS: A 6-day-old premature newborn underwent minimally invasive sclerotherapy under general anesthesia. For high-risk premature neonates, the selections of the anesthesia and airway device are extremely important, as those factors directly affect the prognosis. DIAGNOSES: B ultrasound and computed tomography (CT) revealed a large mass from the left chest wall to axilla, which was suspected to be a lymphocele. INTERVENTIONS: Minimally invasive sclerotherapy was performed under inhalation anesthesia. After the initiation of anesthesia, a laryngeal mask was placed to control airway. Anesthesia was maintained intraoperatively via sevoflurane inhalation with spontaneous breathing. No accidental displacements or PRAE occurred. OUTCOME: The operation and anesthesia process was stable and safe. The patient discharged at 2 days postoperatively. LESSONS: Minimally invasive sclerotherapy in a premature neonate is an operation with an extremely short operation time and minimal trauma, but a very high anesthesia risk and risk of PRAE. Anesthesia management is very important in a premature neonate undergoing a very short surgery under general anesthesia. Total sevoflurane inhalation general anesthesia and laryngeal mask airway control with spontaneous breathing may be an ideal option to reduce PRAE during very short surgery in a premature neonate.

Protocadherin 8 (PCDH8) Inhibits Proliferation, Migration, Invasion, and Angiogenesis in Esophageal Squamous Cell Carcinoma.

BACKGROUND Protocadherin 8 (PCDH8) functions as a tumor-suppressor gene in many types of cancer. This study aimed to investigate the role of PCDH8 in esophageal squamous cell carcinoma (ESCC). MATERIAL AND METHODS Cell proliferation, apoptosis, transwell assay, tube formation assays, and tumor xenograft experiment were performed to explore the role of PCDH8 in the progression of ESCC. RESULTS PCDH8 was found to be downregulated in ESCC cells. Ectopic expression of PCDH8 blocked proliferation, invasion, and migration and induced apoptosis in ESCC cells. Furthermore, vascular endothelial growth factor A (VEGFA) secretion and the AKT signaling pathway were also inhibited when PCDH8 was upregulated. PCDH8 overexpression suppressed epithelial-mesenchymal transition (EMT) and pro-angiogenic activity of ESCC cells. In a mouse model of ESCC xenograft tumors, PCDH8 overexpression remarkably restrained tumor cell growth, with the tumor inhibition rate of 75.2%. PCDH8 was the target of miR-200c and had a negative correlation with miR-200c. CONCLUSIONS PCDH8 exerts a tumor-suppressive effect against ESCC cells. However, further studies are required to elucidate the exact molecular mechanism underlying the antitumor activity of PCDH8 in ESCC.