An evaluation of dexmedetomidine in combination with midazolam in pediatric sedation: a systematic review and meta-analysis.

BACKGROUND: Dexmedetomidine and midazolam are commonly used sedatives in children. We conducted a systematic review and meta-analysis to compare the safety and effectiveness of sedation provided by dexmedetomidine combined with midazolam versus other sedatives including chloral hydrate, midazolam and other sedatives in pediatric sedation. METHODS: The Embase, Web of Science, Cochrane Library, and PubMed databases, and Clinicaltrials.gov register of controlled trials were searched from inception to June 2022. All randomized controlled trials used dexmedetomidine-midazolam in pediatric sedation were enrolled. The articles search, data extraction, and quality assessment of included studies were performed independently by two researchers. The success rate of sedation was considered as the primary outcome. The secondary outcomes included onset time of sedation, recovery time of sedation and occurrence of adverse events. RESULTS: A total of 522 studies were screened and 6 RCTs were identified; 859 patients were analyzed. The administration of dexmedetomidine combined with midazolam was associated with a higher sedation success rate and a lower incidence of nausea and vomiting in computed tomography, magnetic resonance imaging, Auditory Brainstem Response test or fiberoptic bronchoscopy examinations than the other sedatives did (OR = 2.92; 95% CI: 1.39-6.13, P = 0.005, I2 = 51%; OR = 0.23, 95% CI: 0.07-0.68, P = 0.008, I2 = 0%, respectively). Two groups did not differ significantly in recovery time and the occurrence of adverse reactions (WMD = - 0.27, 95% CI: - 0.93 to - 0.39, P = 0.42; OR 0.70; 95% CI: 0.48-1.02, P = 0.06, I2 = 45%. respectively). However, the results of the subgroup analysis of ASA I-II children showed a quicker onset time in dexmedetomidine-midazolam group than the other sedatives (WMD=-3.08; 95% CI: -4.66 to - 1.49, P = 0.0001, I2 = 30%). CONCLUSIONS: This meta-analysis showed that compared with the control group, dexmedetomidine combined with midazolam group provided higher sedation success rates and caused a lower incidence of nausea and vomiting in completing examinations, indicating a prospective outpatient clinical application for procedural sedation.

Novel insights into the glucose metabolic alterations of freshwater snails: a pathway to molluscicide innovation and snail control strategies.

As ecosystem disruptors and intermediate hosts for various parasites, freshwater snails have significant socioeconomic impacts on human health, livestock production, and aquaculture. Although traditional molluscicides have been widely used to mitigate these effects, their environmental impact has encouraged research into alternative, biologically based strategies to create safer, more effective molluscicides and diminish the susceptibility of snails to parasites. This review focuses on alterations in glucose metabolism in snails under the multifaceted stressors of parasitic infections, drug exposure, and environmental changes and proposes a novel approach for snail management. Key enzymes within the glycolytic pathway, such as hexokinase and pyruvate kinase; tricarboxylic acid (TCA) cycle; and electron transport chains, such as succinate dehydrogenase and cytochrome c oxidase, are innovative targets for molluscicide development. These targets can affect both snails and parasites and provide an important direction for parasitic disease prevention research. For the first time, this review summarises the reverse TCA cycle and alternative oxidase pathway, which are unique metabolic bypasses in invertebrates that have emerged as suitable targets for the formulation of low-toxicity molluscicides. Additionally, it highlights the importance of other metabolic pathways, including lactate, alanine, glycogenolysis, and pentose phosphate pathways, in snail energy supply, antioxidant stress responses, and drug evasion mechanisms. By analysing the alterations in key metabolic enzymes and their products in stressed snails, this review deepens our understanding of glucose metabolic alterations in snails and provides valuable insights for identifying new pharmacological targets.

Size selection of intrahepatic lesions for cryoablation contributes to abscopal effect and long-term survival in patients with liver metastatic melanoma receiving PD-1 blockade therapy.

OBJECTIVES: In this study, we aimed to examine parameters of cryoablation, tumor characteristics, and their correlations with distant tumor response and survival of liver metastatic melanoma patients receiving cryoablation and PD-1 blockade (cryo-PD-1) combination treatment. MATERIALS AND METHODS: A retrospective study was conducted among 45 melanoma patients who received combined PD-1 blockade therapy and cryoablation for liver metastasis from 2018 to 2022. Cox regression was utilized to determine the associations between factors and overall survival (OS). Changes in cytokines and immune cell compositions in peripheral blood samples following the combined treatment were investigated, along with their correlations with treatment response. RESULTS: The mean cycle of cryo-PD-1 combination treatment was 2.2 (range, 1-6), and the 3-month overall response rate (RECIST 1.1 criteria) was 26.7%. Of the 21 patients who failed previous PD-1 blockade therapy after diagnosis of liver metastasis, 4 (19.0%) achieved response within 3 months since combination treatment. The diameter of ablated lesion ≤ 30 mm, metastatic organs ≤ 2, and pre-treatment LDH level ≤ 300 U/L were independent prognostic factors for favorable OS. Further analysis showed patients with intrahepatic tumor size of 15-45 mm, and ablated lesion size of ≤ 30 mm had significantly higher 3-month response rate (42.9% vs 12.5%; P = 0.022) and survival time (30.5 vs 14.2 months; P = 0.045) than their counterparts. The average increase in NLR among patients with ablated tumor size of ≤ 3 cm and > 3 cm were 3.59 ± 5.01 and 7.21 ± 12.57, respectively. The average increase in serum IL-6 levels among patients with ablated tumor size of ≤ 3 cm and > 3 cm were 8.62 ± 7.95 pg/ml and 15.40 ± 11.43 pg/ml, respectively. CONCLUSION: Size selection of intrahepatic lesions for cryoablation is important in order to achieve abscopal effect and long-term survival among patients with liver metastatic melanoma receiving PD-1 blockade therapy.

Efficacy and safety of GLP-1RAs for people with obesity: A systematic review based on RCT and Bayesian network meta-analysis.

BACKGROUND: GLP-1 receptor agonists (GLP-1RAs) reduce glucagon and glycogen secretion, inhibit appetite and slow gastric empties and have recently been approved to treat obesity. OBJECTIVE: To explore the safety and efficacy of GLP-1RAs in the treatment of obesity and clarify the optimal GLP-1RAs treatment regimen. METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were searched for English randomized controlled trials (RCTs) on GLP-1RAs in the treatment and management of obesity published before July 18, 2023. Literature screening and data extraction were performed independently by three researchers. Bayesian random effect model was used to compare the effects of interventions. Continuous variables were expressed as mean difference with 95% CI, and dichotomous variables were reported as RR with 95% CI. RESULTS: A total of 29 studies with 10,333 participants were included in the present study. The combination of cagrilintide and semaglutide (short for cagrANDsema) was an optimal strategy for weight loss and glycosylated hemoglobin (HbA1c) reduction. Compared to placebo, cagrANDsema reduced weight by - 14.13 kg (95% CI: -16.49, -11.73) and HbA1c by - 0.33% (95% CI: -0.41, -0.25). Moreover, this study indicated that orforglipron and semaglutide also had relatively good effects on weight loss. Meta-regression results indicated that higher dose levels might have better effects on weight loss. CONCLUSIONS: CagrANDsema exerts the best effect for weight loss. In terms of current dose levels, a higher dose gets better weight-loss effects without increasing the risk of adverse events.

Oral midazolam vs. intranasal dexmedetomidine plus oral midazolam for sedation of pediatric outpatients: a double-blinded randomized controlled trial.

BACKGROUND: Moderate to deep sedation is required for dental treatment of children with dental anxiety. Midazolam is the most commonly used sedative, whereas intranasal dexmedetomidine is increasingly used in pediatric sedation. OBJECTIVE: The aim of this trial was to compare the sedative efficacy of oral midazolam alone with that of intranasal dexmedetomidine plus oral midazolam during dental treatment of children with dental anxiety. DESIGN: In total, 83 children (aged 3-12 years) scheduled to undergo dental sedation were randomized to receive oral midazolam (0.5 mg/kg) and intranasal placebo, or oral midazolam (0.5 mg/kg) plus intranasal dexmedetomidine (2 µg/kg). The primary outcome was the rate of successful sedation for dental treatment. Secondary outcomes were the onset time and adverse events during and after treatment. Data analyses involved descriptive statistics and nonparametric tests. RESULTS: The rate of successful sedation was significantly higher in combination group (P = 0.007), although the sedation onset time was significantly longer in combination group (17.5 ± 2.4 min) than in monotherapy group (15.7 ± 1.8) (P = 0.003). No children required medical intervention or oxygen therapy for hemodynamic disturbances, and the incidences of adverse events had no significant difference between groups (P = 0.660). CONCLUSION: Combined treatment with oral midazolam (0.5 mg/kg) and intranasal dexmedetomidine (2 µg/kg) is more significantly effective for managing the behavior of non-cooperative children during dental treatment, compared to oral midazolam (0.5 mg/kg) alone. (Chinese Clinical Trial Registry: ChiCTR2100042300) TRIAL REGISTRATION: ChiCTR2100042300, Clinical trial first registration date: 17/01/2021.

Exploring the spatial pattern of house collapse rates caused by extreme rainfall in central China: The role of natural and social factors.

The collapse of houses represents a prominent hazard associated with floods, mudslides, and other disastrous events resulting from extreme rainfall. Nevertheless, previous research in this area has been insufficiently dedicated to comprehending the factors that specifically contribute to house collapse triggered by extreme rainfall. This study endeavors to address this knowledge gap by proposing a hypothesis that the occurrence of house collapse, induced by extreme rainfall, demonstrates spatial heterogeneity and is subject to the interactive impacts of various factors. In the study, we investigate the relationship between house collapse rates and natural and social factors in the provinces of Henan, Shanxi, and Shaanxi provinces in 2021. These provinces are representative of flood-prone areas in central China. Spatial scan statistics and GeoDetector model were used to analyze spatial hotspot areas of house collapse rates and determinant power of natural and social factors on the spatial heterogeneity of house collapse rates, respectively. Our analysis reveals that the spatial hotspot areas predominantly concentrated in regions characterized by high rainfall, including areas along riverbanks and low-lying regions. Multiple factors contribute to the variations in house collapse rates. Among these factors, precipitation (q = 0.32) is the most significant, followed by the ratio of brick-concrete houses (q = 0.24), per capita GDP (q = 0.13), elevation (q = 0.13) and other factors. Notably, the interaction of precipitation and slope explains 63 % of the damage pattern, making it the strongest causal factor. The results substantiate our initial hypothesis and underscore the fact that the pattern of damage does not solely rely on a singular factor but rather on the interaction of multiple factors. These findings hold significance in advancing the formulation of more precise strategies aimed at bolstering safety measures and safeguarding properties within regions susceptible to flooding.

[Metabolomics study of Berberidis Radix in intervening ulcerative colitis based on UPLC-Q-TOF-MS].

The effect of Tujia medicine Berberidis Radix on endogenous metabolites in the serum and feces of mice with ulcerative colitis(UC) induced by dextran sulfate sodium(DSS) was analyzed by metabolomics technology to explore the metabolic pathway and underlying mechanism of Berberidis Radix in the intervention of UC. The UC model was induced in mice by DSS. Body weight, disease activity index(DAI), and colon length were recorded. The levels of tumor necrosis factor-α(TNF-α) and interleukin-10(IL-10) in colon tissues were determined by ELISA. The levels of endogenous metabolites in the serum and feces were detected by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were employed to characterize and screen differential metabolites. The potential metabolic pathways were analyzed by MetaboAnalyst 5.0. The results showed that Berberidis Radix could significantly improve the symptoms of UC mice and increase the level of the anti-inflammatory factor IL-10. A total of 56 and 43 differential metabolites were identified in the serum and feces, respectively, belonging to lipids, amino acids, fatty acids, etc. After the intervention by Berberidis Radix, the metabolic disorder gradually recovered. The involved metabolic pathways included biosynthesis of phenylalanine, tyrosine, and tryptophan, linoleic acid metabolism, phenylalanine metabolism, and glycerophospholipid metabolism. Berberidis Radix can alleviate the symptoms of mice with DSS-induced UC, and the mechanism may be closely related to the re-gulation of lipid metabolism, amino acid metabolism, and energy metabolism.

Berberine attenuates uric acid-induced cell injury by inhibiting NLRP3 signaling pathway in HK-2 cells.

Hyperuricemia (HUA) is a common chronic metabolic disease that can cause renal failure and even death in severe cases. Berberine (BBR) is an isoquinoline alkaloid derived from Phellodendri Cortex with strong antioxidant, anti-inflammatory, and anti-apoptotic properties. The purpose of this study was to investigate the protective effects of berberine (BBR) against uric acid (UA)-induced HK-2 cells and unravel their regulatory potential mechanisms. The CCK8 assay was carried out to detect cell viability. The expression levels of inflammatory factors interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) and Lactate dehydrogenase (LDH) were measured using Enzyme-linked immunosorbent assays (ELISA). The expression of the apoptosis-related protein (cleaved-Caspase3, cleaved-Caspase9, BAX, BCL-2) was detected by western blot. The effects of BBR on the activities of the NOD-like receptor family pyrin domain containing 3 (NLRP3) and the expression of the downstream genes were determined by RT-PCR and western blot in HK-2 cells. From the data, BBR significantly reversed the up-regulation of inflammatory factors (IL-1ß, IL-18) and LDH. Furthermore, BBR down-regulated protein expression of pro-apoptotic proteins BAX, cleaved caspase3 (cl-Caspase3), cleaved caspase9 (cl-Caspase9), and enhanced the expression of antiapoptotic protein BCL-2. Simultaneously, BBR inhibited the activated NLPR3 and reduced the mRNA levels of NLRP3, Caspase1, IL-18, and IL-1ß. Also, BBR attenuated the expression of NLRP3 pathway-related proteins (NLRP3, ASC, Caspase1, cleaved-Caspase1, IL-18, IL-1ß, and GSDMD). Furthermore, specific NLRP3-siRNA efficiently blocked UA-induced the level of inflammatory factors (IL-1ß, IL-18) and LDH and further inhibited activated NLRP3 pathway. Collectively, our results suggested that BBR can alleviate cell injury induced by UA. The underlying unctionary mechanism may be through the NLRP3 signaling pathway.

Interactions between Orthodontic Treatment and Gingival Tissue.

In recent years, as the number of adults seeking orthodontic treatment has increased, so too has the number of periodontal tissue problems, particularly regarding the impact on periodontal tissue of receiving orthodontic treatment. Orthodontic treatment improves the occlusion and appearance of teeth by moving the teeth appropriately. These movements have a significant impact on the interactions between the teeth and periodontal tissues. Orthodontic treatment can also recover tooth alignment for patients with tooth displacement caused by periodontitis; however, orthodontic treatment also often has adverse effects on periodontal soft tissue, such as gingivitis, gingival enlargement and gingival recession. The purpose of this review is to summarise the current evidence and solid knowledge of periodontal soft tissue problems in orthodontic treatment and outline some prevention strategies.

Improving cascade outcomes for active TB: A global systematic review and meta-analysis of TB interventions.

BACKGROUND: To inform policy and implementation that can enhance prevention and improve tuberculosis (TB) care cascade outcomes, this review aimed to summarize the impact of various interventions on care cascade outcomes for active TB. METHODS AND FINDINGS: In this systematic review and meta-analysis, we retrieved English articles with comparator arms (like randomized controlled trials (RCTs) and before and after intervention studies) that evaluated TB interventions published from January 1970 to September 30, 2022, from Embase, CINAHL, PubMed, and the Cochrane library. Commentaries, qualitative studies, conference abstracts, studies without standard of care comparator arms, and studies that did not report quantitative results for TB care cascade outcomes were excluded. Data from studies with similar comparator arms were pooled in a random effects model, and outcomes were reported as odds ratio (OR) with 95% confidence interval (CI) and number of studies (k). The quality of evidence was appraised using GRADE, and the study was registered on PROSPERO (CRD42018103331). Of 21,548 deduplicated studies, 144 eligible studies were included. Of 144 studies, 128 were from low/middle-income countries, 84 were RCTs, and 25 integrated TB and HIV care. Counselling and education was significantly associated with testing (OR = 8.82, 95% CI:1.71 to 45.43; I2 = 99.9%, k = 7), diagnosis (OR = 1.44, 95% CI:1.08 to 1.92; I2 = 97.6%, k = 9), linkage to care (OR = 3.10, 95% CI = 1.97 to 4.86; I2 = 0%, k = 1), cure (OR = 2.08, 95% CI:1.11 to 3.88; I2 = 76.7%, k = 4), treatment completion (OR = 1.48, 95% CI: 1.07 to 2.03; I2 = 73.1%, k = 8), and treatment success (OR = 3.24, 95% CI: 1.88 to 5.55; I2 = 75.9%, k = 5) outcomes compared to standard-of-care. Incentives, multisector collaborations, and community-based interventions were associated with at least three TB care cascade outcomes; digital interventions and mixed interventions were associated with an increased likelihood of two cascade outcomes each. These findings remained salient when studies were limited to RCTs only. Also, our study does not cover the entire care cascade as we did not measure gaps in pre-testing, pretreatment, and post-treatment outcomes (like loss to follow-up and TB recurrence). CONCLUSIONS: Among TB interventions, education and counseling, incentives, community-based interventions, and mixed interventions were associated with multiple active TB care cascade outcomes. However, cost-effectiveness and local-setting contexts should be considered when choosing such strategies due to their high heterogeneity.

Andrographolide sodium bisulfite ameliorates dextran sulfate sodium-induced colitis and liver injury in mice via inhibiting macrophage proinflammatory polarization from the gut-liver axis.

Ulcerative colitis (UC), an inflammatory disease, is widely thought to be associated with colonic barrier damage and inflammatory response. With the destruction of the colonic barrier, lipopolysaccharide (LPS) enters the liver through the portal vein and causes liver injury. Liver injury in turn exacerbates UC to form a vicious cycle, so the treatment of liver injury cannot be ignored. Andrographolide (Andro) has a protective effect against colitis and liver injury, but with low bioavailability. Andrographolide sodium bisulfite (ASB), a water-soluble sulfonate of Andro, has better bioavailability, whether it has a better curative effect against UC and liver injury is rarely reported. Hence, we investigated the protective effect and potential mechanism of ASB against dextran sulfate sodium (DSS)-induced UC and liver injury in mice. The results showed that treatment with ASB significantly relieved the clinical symptoms of UC and liver injury by reducing disease activity index, inhibiting gut-derived LPS leakage, and improving colonic and hepatic injury, and its curative effect was better than Andro. Moreover, ASB effectively decreased the YAP-mediated colonic inflammation and TLR4/MyD88/NF-κB-mediated pro-inflammatory factor release in the liver. Both colonic and hepatic inflammation were associated with macrophage proinflammatory polarization, but they were significantly inhibited by ASB. ASB showed good safety in the treatment of UC and liver injury and has no nephrotoxicity as previously described. In conclusion, ASB has an effective protective effect on DSS-induced UC and liver injury, mainly by suppressing macrophage proinflammatory polarization from the gut-liver axis.

Vulnerability to typhoons: A comparison of consequence and driving factors between Typhoon Hato (2017) and Typhoon Mangkhut (2018).

Typhoon disasters have caused casualties, property loss, and other negative impacts to social and economic development. Vulnerability is an important component of typhoon risk. However, little is known about the contributions of vulnerability factors and their interaction effects on typhoon-induced losses at a fine scale. Focusing on the vulnerability measures of Typhoon Hato in 2017 and Typhoon Mangkhut in 2018, this study aims to quantify the contribution and interactive effects of physical and socioeconomic factors on vulnerability based on the GeoDetector method and determine the factors that account for most of the change in vulnerability. The results show that from Typhoon Hato in 2017 to Typhoon Mangkhut in 2018, the vulnerability of the economy and houses decrease on average. Rain intensity and wind intensity are the dominant factors of disaster loss for Typhoon Hato and Typhoon Mangkhut, respectively. Vegetation cover and landform explain vulnerability better than average slope in most instances. For different loss types, the dominant socioeconomic vulnerability factor is different. For both typhoons, emergency transfer has a higher determining power (q) ranking for the population vulnerability, while the percentage of the GDP made up of primary industry have higher q ranking for economic vulnerability. The dominant interaction effects between two vulnerability factors differ depending on the typhoon and loss type but show a nonlinear enhancement effect in most cases. Moreover, changes in the maximum 4-hour accumulated rainfall account for most of the change in vulnerability between Hato and Mangkhut. Overall, the results can be conducive to understanding the complexity of vulnerability to typhoons and provide a reference for possible indicators for vulnerability assessment models, and determining the reasons for changes in vulnerability can be constructive to the formulation of specific policies for disaster prevention and mitigation.

Protective effect of oxyberberine against acute lung injury in mice via inhibiting RhoA/ROCK signaling pathway.

Acute lung injury (ALI), hallmarked with alveolar epithelial barrier impairment and pulmonary edema induced by acute inflammation, presents a severe health burden to the public, due to the limited available interventions. Oxyberberine (OBB), having improved anti-inflammatory activity and safety, is a representative component with various activities derived from berberine, whereas its role against ALI with alveolar epithelial barrier injury remains uncertain. To investigate the influence and underlying mechanisms of OBB on ALI, we induced acute inflammation in mice and A549 cells by using lipopolysaccharide (LPS). Changes in alveolar permeability were assessed by analyzing lung histopathology, measuring the dry/wet weight ratio of the lungs, and altering proinflammatory cytokines and neutrophils levels in the bronchoalveolar lavage fluid (BALF). Parameters of pulmonary permeability were assessed through ELISA, western blotting, quantitative real-time PCR, and immunofluorescence analysis. U46619, the agonist of RhoA/ROCK, was employed to further investigate the mechanism of OBB on ALI. Unexpectedly, we found OBB mitigated lung impairment, pulmonary edema, inflammatory reactions in BALF and lung tissue, reduction in ZO-1, and addition of connexin-43. Besides, OBB markedly reduced the expression of RhoA in association with its downstream factors, which are linked to the intercellular junctions and permeability both in vivo and in vitro. Nevertheless, U46619 abolished the benefits obtained from OBB in A549 cells. In conclusion, these outcomes indicated that OBB exerted RhoA/ROCK inhibitor-like effect to moderate alveolar epithelial barrier impairment and permeability, ultimately preventing ALI progression.

Correlates of time to clinical presentation for symptomatic individuals with gonorrhoea in South China: results from a cross-sectional study.

OBJECTIVES: This study aimed to determine the variation in the interval between the onset of symptoms and clinical presentation, and its associated factors among symptomatic individuals with gonorrhoea. DESIGN: A cross-sectional study was conducted between 1 June and 30 July 2017. SETTING: 129 sexually transmitted disease clinics from 21 cities of Guangdong, China. PARTICIPANTS: Using convenience sampling method to recruit symptomatic individuals with gonorrhoea over 18 years old. OUTCOME MEASURE: Time to clinical presentation. RESULTS: Among 1664 participants, the median age was 29 (24-36) years old, and the majority were male (92.5%) and married (52.9%). The median time to clinical presentation was 3 (2-6) days. About 471 (28.3%) patients had sexual contact while symptomatic. After adjusting for covariates, participants who were female (aß=0.44, 95% CI: 0.22 to 0.80), from east Guangdong region (aß=0.44, 95% CI: 0.22 to 0.80) and had the absence of dysuria (aß=0.26, 95% CI: 0.06 to 0.46) had increased time to clinical presentation. Participants who had commercial sex in the past 6 months (aß=-0.11, 95% CI: -0.21 to -0.01) had decreased time to clinical presentation. Participants who were female (adjusted odds ratio (aOR)=1.66, 95% CI: 1.08 to 2.50) and delayed in seeking healthcare more than 7 days (aOR=46.71, 95% CI: 24.27 to 89.93) were more likely to have sexual contact while symptomatic. CONCLUSION: The time to clinical presentation for individuals with symptomatic gonorrhoea is variable and a high proportion of participants continued to have sexual behaviour while symptomatic. Strategies to increase health literacy may help to minimise the sequelae of gonorrhoea and reduce onward transmission.

The relationship between nuclear factor-erythrocyte-related factor 2 and antioxidant enzymes in the placenta of patients with gestational diabetes and the metabolism of umbilical cord endothelial cells.

The paper aimed to explore the relationship between nuclear factor erythroid 2 related factor 2 (Nrf2), antioxidant enzymes and the metabolism of umbilical cord endothelial cells in the placenta of patients with gestational diabetes (GDM). A total of 200 pregnant women who underwent an obstetric examination at the Municipal Maternity and Child Health Hospital from March 2018 to December 2019 were selected, with an average age of 30.91±3.24. According to the plasma glucose level and oral glucose tolerance test (OGTT), pregnant women were divided into a control group and an observation group. Blood samples were collected from these pregnant women, serum was removed, put into a centrifuge tube and stored in the refrigerator of the laboratory at - 80 °C. Placental tissue was collected for biochemical analysis. GSH level was detected by absorbance kit, and serum MDA content was detected by spectrophotometry. The expression levels of Heme oxygenase-1(HO-1), Nrf2, and NQO1 protein in placental tissue were analyzed by gel electrophoresis. Western blot analysis was used to detect the protein expression levels of Bach1 and Keap1 in endothelial cells. PCR real-time analysis was used to detect the expression of GSH and NQO1 mRNA. Results showed that the SOD and GSH levels in the serum of the observation group were lower than those of the control group (P<0.05). The protein expression levels of HO-1, Nrf2 and NQO1 in the observation group were higher than those in the control group (P<0.05). The GSH level of the HNE+ observation group was lower than that of the HNE+ control group before stimulation (P<0.05). 1.5 hours after the stimulation, the GSH levels of the two groups of cells were decreased. After 6 hours, the GSH levels of the two groups began to increase. The GSH level of HUVEC in the HNE+ observation group was lower than that of the HNE+ control group after 48 hours. The expression level of Bach1 protein in the HNE+ observation group was lower than that in the HNE+ control group (P<0.05). The expression level of Keap1 protein in the HNE+ observation group and HNE+ control group did not change (P>0.05). The expression levels of GSH and NQO1 mRNA in the HNE+Nrf2 silence group were lower than that in the Nrf2 silence group (P<0.05). The expression levels of GSH and NQO1 mRNA in the HNE+Nrf2 overexpression observation group were higher than those of the HNE+Nrf2 silence group (P<0.05). The apoptosis of trophoblast in the placenta of GDM patients was significantly decreased. The continuous lack of redox signals in fetal endothelial cells in patients with gestational diabetes can destroy the defense ability of cells in the uterus against oxidative stress. Nrf2 antioxidant defense pathway can provide therapeutic targets for reducing oxidative stress associated with diabetes and aging.

Effect of supercritical carbon dioxide fluid extract from Chrysanthemum indicum Linné on bleomycin-induced pulmonary fibrosis.

BACKGROUND: As a prevalent type of cryptogenic fibrotic disease with high mortality, idiopathic pulmonary fibrosis (IPF) still lacks effective therapeutic drugs. The compounds extracted from buds and flowers of Chrysanthemum indicum Linné with supercritical-carbon dioxide fluid (CISCFE) has been confirmed to have antioxidant, anti-inflammatory, and lung-protective effects. This paper aimed to clarify whether CISCFE could treat IPF induced by bleomycin (BLM) and elucidate the related mechanisms. METHODS: Rats (Sprague-Dawley, male) were separated into the following groups: normal, model, pirfenidone (50 mg/kg), CISCFE-L, -M, and -H (240, 360, and 480 mg/kg/d, i.g., respectively, for 4 weeks). Rats were given BLM (5 mg/kg) via intratracheal installation to establish the IPF model. A549 and MRC-5 cells were stimulated by Wnt-1 to establish a cell model and then treated with CISCFE. Haematoxylin-eosin (H&E) and Masson staining were employed to observe lesions in the lung tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) were performed to observe changes in genes and proteins connected with the Wnt/ß-catenin pathway. RESULTS: CISCFE inhibited the proliferation of MRC-5 cells (IC50: 2.723 ± 0.488 µg/mL) and A549 cells (IC50: 2.235 ± 0.229 µg/mL). In rats, A549 cells, and MRC-5 cells, BLM and Wnt-1 obviously induced the protein expression of α-smooth muscle actin (α-SMA), vimentin, type I collagen (collagen-I), and Nu-ß-catenin. The mRNA levels of matrix metalloproteinase-3 (MMP-3) and - 9 (MMP-9), two enzymes that degrade and reshape the extracellular matrix (ECM) were also increased while those of tissue inhibitor of metalloproteinase 1 (TIMP-1) were decreased. However, CISCFE reversed the effects of BLM and Wnt-1 on the expression pattern of these proteins and genes. CONCLUSION: These findings showed that CISCFE could inhibit IPF development by activating the Wnt/ß-catenin pathway and may serve as a treatment for IPF after further investigation.

Phenylethanoid Glycosides From Callicarpa kwangtungensis Chun Attenuate TNF-α-Induced Cell Damage by Inhibiting NF-κB Pathway and Enhancing Nrf2 Pathway in A549 Cells.

Background: Acute lung injury (ALI) is a complicated and severe lung disease, which is often characterized by acute inflammation. Poliumoside (POL), acteoside (ACT) and forsythiaside B (FTB) are phenylethanoid glycosides (PGs) with strong antioxidant, anti-inflammatory, and anti-apoptotic properties, which are extracted from Callicarpa kwangtungensis Chun (CK). The aim of this study was to investigate the protective effects of POL, ACT, and FTB against TNF-α-induced damage using an ALI cell model and explore their potential mechanisms. Methods and Results: MTT method was used to measure cell viability. Flow cytometry was used for detecting the apoptosis rate. Reactive oxygen species (ROS) activity was determined using fluorescence microscope. The expression of mRNA in apoptosis-related genes (Caspase 3, Caspase 8, and Caspase 9) were tested by qPCR. The effects of POL, ACT, FTB on the activities of nuclear factor erythroid-2 related factor 2 (Nrf2), nuclear factor kappa-B (NF-κB) and the expression of their downstream genes were assessed by western blotting and RT-PCR in A549 cells. In the current study, POL, ACT, and FTB dose-dependently attenuated TNF-α-induced IL-1ß, IL-6 and IL-8 production, cell apoptosis, the expression of apoptosis-related genes (Caspase 3, Caspase 8, and Caspase 9) and ROS activity. POL, ACT, and FTB not only increased in the mRNA levels of antioxidative enzymes NADPH quinone oxidoreductase (NQO1), glutamate cysteine ligase catalytic subunit (GCLC), heme oxygenase (HO-1), but also decreased the mRNA levels of IL-1ß, IL-6 and IL-8. Furthermore, they upregulated the expression of Keap1 and enhanced the activation of Nrf2, while decreased the expression of phosphor-IκBα (p-IκBα) and nuclear p65. In addition, no significant changes were observed in anti-inflammatory and antioxidant effects of POL, ACT, FTB following Nrf2 and NF-κB p65 knockdown. Conclusion: Our study revealed that POL, ACT, and FTB alleviated oxidative damage and lung inflammation of TNF-α-induced ALI cell model through regulating the Nrf2 and NF-κB pathways.

miR­29b suppresses proliferation and induces apoptosis of hepatocellular carcinoma ascites H22 cells via regulating TGF­ß1 and p53 signaling pathway.

MicroRNA (miR)­29b is a key tumor regulator. It can inhibit tumor cell proliferation, induce apoptosis, suppress tumor invasion and migration, thus delaying tumor progression. Our previous studies revealed an increased level of miR­29b in hepatoma 22 (H22) cells in ascites tumor­bearing mice. The present study investigated the effect of miR­29b on proliferation and apoptosis of hepatocellular carcinoma ascites H22 cells and its association with the transforming growth factor­ß1 (TGF­ß1) signaling pathway and p53­mediated apoptotic pathway. Briefly, H22 cells were transfected with miR­29b­3p (hereinafter referred to as miR­29b) mimic or miR­29b inhibitor. MTS cell proliferation assay and flow cytometry were used to analyze cell viability and apoptosis. The expression change of the TGF­ß1 signaling pathway and p53­mediated apoptotic pathway were detected by reverse transcription­quantitative PCR, western blotting and immunofluorescence. Furthermore, cells were treated with exogenous TGF­ß1 and TGF­ß1 small interfering RNA to evaluate the crosstalk between TGF­ß1 and p53 under miR­29b regulation. The overexpression of miR­29b decreased cell viability, increased cell apoptosis, activated the TGF­ß1 signaling pathway and p53­mediated apoptotic pathway. Conversely, these effects were reversed by the miR­29b inhibitor. Moreover, the effect of miR­29b mimic was further increased after treating cells with exogenous TGF­ß1. The activation of the TGF­ß1 signaling pathway and p53­mediated apoptotic pathway induced by miR­29b overexpression were reversed by TGF­ß1 inhibition. In summary, these data indicated that miR­29b has an important role in proliferation and apoptosis of H22 cells by regulating the TGF­ß1 signaling pathway, the p53­dependent apoptotic pathway, and the crosstalk between TGF­ß1 and p53.

Spatial pattern of the population casualty rate caused by super typhoon Lekima and quantification of the interactive effects of potential impact factors.

BACKGROUND: Typhoons greatly threaten human life and property, especially in China. Therefore, it is important to make effective policy decisions to minimize losses associated with typhoons. METHODS: In this study, the GeoDetector method was used to quantify the determinant powers of natural and socioeconomic factors, and their interactions, on the population casualty rate of super typhoon Lekima. The local indicator of spatial association (LISA) method was followed to explore the spatial pattern of the population casualty rate under the influence of the identified dominant factors. RESULTS: Both natural and socioeconomic factors were found to have significantly impacted the population casualty rate due to super typhoon Lekima. Among the selected factors, maximum precipitation was dominant factor (q = 0.56), followed by maximum wind speed (q = 0.45). In addition, number of health technicians (q = 0.35) and number of health beds (q = 0.27) have a strong influence on the population casualty rate. Among the interactive effects of 12 influencing factors, the combined effects of maximum precipitation and ratio of brick-wood houses, the maximum precipitation and ratio of steel-concrete houses, maximum precipitation and number of health technicians were highest (q = 0.72). Furthermore, high-risk areas with very high casualty rates were concentrated in the southeastern part of Zhejiang and northern Shandong Provinces, while lower-risk areas were mainly distributed in northern Liaoning and eastern Jiangsu provinces. CONCLUSIONS: These results contribute to the development of more specific policies aimed at safety and successful property protection according to the regional differences during typhoons.

The anti-hepatocellular carcinoma effect of Brucea javanica oil in ascitic tumor-bearing mice: The detection of brusatol and its role.

Brucea javanica oil (BJO), one of the main products of Brucea javanica, has been widely used in treating different kinds of malignant tumors. Quassinoids are the major category of anticancer phytochemicals of B. javanica. However, current researches on the anti-cancer effect of BJO mainly focused on oleic acid and linoleic acid, the common major components of dietary edible oils, essential and characteristic components of B. javanica like quassinoids potentially involved remained unexplored. In the current investigation, we developed an efficient HPLC method to detect brusatol, a characteristic quassinoid, and comparatively scrutinized the anti-hepatocellular carcinoma (anti-HCC) effect of BJO, brusatol-free BJO (BF-BJO), and brusatol-enriched BJO (BE-BJO) against hepatoma 22 (H22) in mice. High-performance liquid chromatography (HPLC) was utilized to identify the components in BJO. BE-BJO was extracted with 95 % ethanol. The anti-tumor effect of BJO, BF-BJO and BE-BJO was comparatively investigated, and the potential underlying mechanism was explored in H22 ascites tumor-bearing mice. The results indicated that BJO and BE-BJO significantly prolonged the survival time of H22 ascites tumor-bearing mice, while BF-BJO exhibited no obvious effect. BJO and BE-BJO exhibited pronounced anti-HCC activity by suppressing the growth of implanted hepatoma H22 in mice, including ascending weight, abdominal circumference, ascites volume and cancer cell viability, with a relatively wide margin of safety. BJO and BE-BJO significantly induced H22 cell apoptosis by upregulating the miRNA-29b gene level and p53 expression. Furthermore, BJO and BE-BJO treatment substantially downregulated Bcl-2 and mitochondrial Cytochrome C protein expression, and upregulated expression levels of Bax, Bad, cytosol Cytochrome C, caspase-3 (cleaved), caspase­9 (cleaved), PARP and PARP (cleaved) to induce H22 cells apoptosis. Brusatol was detected in BJO and found to be one of its major active anti-HCC components, rather than fatty acids including oleic acid and linoleic acid. The anti-HCC effect of BJO and BE-BJO was intimately associated with the activation of miRNA-29b, p53-associated apoptosis and mitochondrial-related pathways. Our study gained novel insight into the material basis of BJO in the treatment of HCC, and laid a foundation for a novel specific standard for the quality evaluation of BJO and its commercial products in terms of its anti-cancer application.