Hyperbaric oxygen therapy attenuates heatstroke-induced hippocampal injury by inhibiting microglial pyroptosis.

Background: Central nervous system (CNS) injury is the most prominent feature of heatstroke and the hippocampus is prone to damage. However, the mechanisms underlying the heatstroke-induced hippocampal injury remain unclear. Hyperbaric oxygen (HBO) therapy prevents CNS injury in heatstroke mice. However, the underlying mechanisms of HBO in heatstroke-induced hippocampal injury remain unclear. This study aimed to elucidate the protective effects of HBO against hippocampal injury and its potential role in microglial pyroptosis in heatstroke rats.Methods: A rat heatstroke model and a heat stress model with a mouse microglial cell line (BV2) were, respectively, used to illustrate the effect of HBO on heat-induced microglial pyroptosis in vivo and in vitro. We used a combination of molecular and histological methods to assess microglial pyroptosis and neuroinflammation both in vivo and in vitro.Results: The results revealed that HBO improved heatstroke-induced survival outcomes, hippocampal injury, and neurological dysfunction in rats. In addition, HBO mitigates microglial pyroptosis and reduces the expression of pro-inflammatory cytokines in the hippocampus of heatstroke rats. In vitro experiments showed that HBO attenuated BV2 cell injury under heat stress. Furthermore, HBO prevented heat-induced pyroptosis of BV2 cells, and the expression of pro-inflammatory cytokines IL-18 and IL-1ß was reduced. Mechanistically, HBO alleviates heatstroke-induced neuroinflammation and hippocampal injury by preventing microglial pyroptosis. Conclusions: In conclusion, HBO attenuates heatstroke-induced neuroinflammation and hippocampal injury by inhibiting microglial pyroptosis.

INFLUENCES OF HEAT STRESS ON GLUTAMATE TRANSMISSION-DEPENDENT EXPRESSION LEVELS OF IL-1ß and IL-18 IN BV-2 MICROGLIAL CELLS.

ABSTRACT: Objective: This study aimed to explore the impact of heat stress (HS) on glutamate transmission-dependent expression levels of interleukin-1ß (IL-1ß) and IL-18 in BV-2 microglial cells. Methods: BV-2 microglial cells were cultured in vitro , with cells maintained at 37°C serving as the control. The HS group experienced incubation at 40°C for 1 h, followed by further culturing at 37°C for 6 or 12 h. The experimental group was preincubated with glutamate, the glutamate antagonist riluzole, or the mGluR5 agonist, 2-chloro-5-hydroxyphenylglycine (CHPG), before HS. Glutamate content in BV-2 culture supernatant was assessed using colorimetric assay. Moreover, mRNA expression levels of EAAT3 and/or mGluR5 in BV-2 cells were determined via quantitative polymerase chain reaction. Interleukins (IL-1ß and IL-18) in cell culture supernatant were measured using enzyme-linked immunosorbent assay. Western blot analysis was employed to assess protein levels of IL-1ß and IL-18 in BV-2 cells. Results: HS induced a significant release of glutamate and increased the expression levels of mGluR5 and EAAT3 in BV-2 cells. It also triggered the expression levels and release of proinflammatory factors, such as IL-1ß and IL-18, synergizing with the effects of glutamate treatment. Preincubation with both riluzole and CHPG significantly reduced HS-induced glutamate release and mitigated the increased expression levels and release of IL-1ß and IL-18 induced by HS. Conclusion: The findings confirmed that microglia could be involved in HS primarily through glutamate metabolisms, influencing the expression levels and release of IL-1ß and IL-18.

Heat stroke alters hippocampal and cerebellar transmitter metabonomics.

BACKGROUND: The mechanisms underlying heat stroke (HS)-induced hippocampal injury remain unclear. This study aimed to evaluate the HS-induced metabonomics of hippocampal and cerebellar transmitters. METHODS: The HS model was established with male Sprague-Dawley rats subjected to heat exposure of up to 42 °C at a humidity of (55.0±5.0)%. The hippocampal and cerebellar transmitters and metabolites of rats were tested via ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). The primary transmitters and metabolites were identified by principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA). The major metabolic pathways for HS were selected after enrichment. The brain injury was evaluated by histological tests. RESULTS: HS induced hippocampal and cerebellar injuries in rats. HS upregulated the protein levels of hippocampal glutamate, glutamine, gamma-aminobutyric acid, L-tryptophan (Trp), 5-hydroxy-indoleacetic acid, and kynurenine; however, it downregulated asparagine, tryptamine, 5-hydroxytryptophan, melatonin, 3,4-dihydroxyphenylalanine (L-DOPA), and vanillylmandelic acid. HS also sharply elevated the protein levels of cerebellar methionine and Trp, and decreased the levels of serotonin, L-alanine, L-asparagine, L-aspartate, cysteine, norepinephrine, spermine, spermidine, and tyrosine. Hippocampal glutamate, monoamine transmitters, cerebellar aspartate acid, and catecholamine transmitters' metabolic pathways were identified as the main metablic pathways in HS. CONCLUSION: The hippocampus and cerebellum were injured in rats with HS, possibly induced the disorder of hippocampal glutamate and serotonin metabolism, cerebellar aspartate acid and catecholamine transmitter metabolism, and related metabolic pathways.

Physiological and transcriptomic evidence of antioxidative system and ion transport in chromium detoxification in germinating seedlings of soybean.

Chromium (Cr) toxicity impairs the productivity of crops and is a major threat to food security worldwide. However, the effect of Cr toxicity on seed germination and transcriptome of germinating seedlings of soybean crop has not been fully explored. In this study, two Cr-tolerant lines (J82, S125) and two Cr-sensitive ones (LD1, RL) were screened out of twenty-one soybean (Glycine max L.) genotypes based on seed germination rate, seed germinative energy, seed germination index, and growth of germinating seedlings under 50 mg L-1 Cr treatment. We found that Cr stress inhibits the growth of soybean seed germinating seedlings due to the Cr-induced overaccumulation of reactive oxygen species (ROS). Significantly different levels of element contents, antioxidant enzyme activities, malondialdehyde content were observed in the four soybean genotypes with contrasting Cr tolerance. Further, a total of 13,777 differentially expressed genes (DEGs) were identified in transcriptomic sequencing and 1298 DEGs in six gene modules were found highly correlated with the physiological traits by weighted correlation network analysis (WGCNA) analysis. The DEGs encoding antioxidant enzymes, transcription factors, and ion transporters are proposed to confer Cr tolerance in soybean germinating seedlings by reducing the uptake and translocation of Cr, decreasing the level of ROS, and keeping the osmotic balance in soybean germinating seedings. In conclusion, our study provided a molecular regulation network on soybean Cr tolerance at seed germinating stage and identified candidate genes for molecular breeding of low Cr accumulation soybean cultivars.

Pre-soaking treatment can improve cooking quality of high-amylose rice while maintaining its low digestibility.

Rice is a staple food for more than half of the world's population and it is regarded as a high glycemic index (GI) food. Breeders developed high amylose rice having low digestibility, but it also has inferior palatability. This study used high-amylose rice (HAR) produced by gamma irradiation and compared the digestion and physicochemical properties related to palatability with those of low-amylose rice (LAR). Pre-soaking and different-pH treatments were adopted to find a way to enhance the palatability of HAR while maintaining its low digestibility. After pre-soaking, HAR had a higher water uptake ratio (4.68 vs. 4.11 g g-1), proportion of leached starch (16.6 vs. 12.6%) and adhesiveness (77 vs. 39), but lower setback (0.092 vs. 0.107 Pa s), hardness (10.1 vs. 12.6 kg) and resilience (0.20 vs. 0.25). The results showed that pre-soaking was able to enhance the quality of the cooked rice mainly by modifying the starch amorphous region while maintaining the low digestibility of HAR. Pre-soaking can be adopted as a practical and effective household cooking method to prepare rice with relatively low digestibility and good palatability.

Quetiapine-related acute lung injury: A case report.

BACKGROUND: Quetiapine, known as a non-classical antipsychotic drug, is frequently used for the treatment of mental diseases, such as schizophrenia, bipolar disorder, and major depressive disorder. Acute lung injury, a rarely reported side effect of quetiapine, is described in this case report. CASE SUMMARY: Due to terminal delirium, a 66-year-old man took a large dose of quetiapine and then developed severe pulmonary disease. His symptoms were not resolved after routine treatment, such as antibiotics, diuretic, and supportive therapies. Quetiapine-related acute lung injury was therefore suspected and hormonal therapy was initiated. Subsequently, his symptoms were alleviated and the radiological results improved dramatically. CONCLUSION: Our findings in the present report highlight a potential adverse effect of quetiapine, drug-related acute lung injury, which deserves awareness in clinical practice.

Efficacy and Safety of Subcutaneous and Oral Semaglutide Administration in Patients With Type 2 Diabetes: A Meta-Analysis.

Background: This meta-analysis aimed to combine the data available from clinical trials to assess the effects of subcutaneous and oral semaglutide administration on glycemic control, weight management, and safety outcomes in patients with type 2 diabetes (T2D). Methods: We systematically searched for phase 3 randomized controlled trials (RCTs) that compared semaglutide with placebo or other anti-diabetic drugs in T2D patients. The primary outcome was the change from baseline in glycated hemoglobin (HbA1c) levels. Secondary efficacy endpoints included the change from baseline in body weight, achievement of HbA1c targets, and clinically significant weight loss. Key safety outcomes were also assessed. Results: In this meta-analysis, 24 trials with a total of 22185 patients were included. Subcutaneous semaglutide administration reduced HbA1c levels (weighted mean difference [WMD]: -1.14% and -1.37%, for 0.5 mg and 1 mg, respectively) and body weight (WMD: -2.73 kg and -4.09 kg, for 0.5 mg and 1 mg, respectively) when compared with placebo; its efficacy was also superior to other anti-diabetic drugs in reducing HbA1c levels (WMD: -0.71% and -0.86%, for 0.5 mg and 1 mg, respectively) and body weight (WMD: -2.65 kg and -3.78 kg, for 0.5 mg and 1 mg, respectively). Oral semaglutide administration was superior to placebo in decreasing HbA1c levels (WMD: -0.96% and -1.02%, for 7 mg and 14 mg, respectively). Moreover, oral administration of 14 mg of semaglutide also showed a significant reduction in HbA1c levels (WMD: -0.36%) compared with other anti-diabetic drugs. Furthermore, oral semaglutide administration resulted in substantial weight loss compared with other anti-diabetic drugs (WMD: -1.53 kg and -1.73 kg, for 7 mg and 14 mg, respectively). Notably, subcutaneous and oral semaglutide administration also resulted in higher numbers of patients achieving the targets of HbA1c levels and weight loss than placebo and other anti-diabetic drugs. Overall, we noted no clear evidence of detrimental effects on safety endpoints due to semaglutide treatment, except for some gastrointestinal adverse events. Conclusion: Both subcutaneous and oral semaglutide administration could enable the achievement of sufficient glycemic control and weight management without increasing the risk of hypoglycemia, which were effective and safe for the treatment of T2D.

Pooled analysis of Xpert Bladder Cancer based on the 5 mRNAs for rapid diagnosis of bladder carcinoma.

BACKGROUND: Xpert Bladder Cancer is a detection method developed in recent years, designed with the functions of integrating sample automatically, nucleic acid amplification, and target sequence detection. It is a urine assay targeting five mRNAs (CRH, IGF2, UPK1B, ANXA10, and ABL1). The purpose of this article is to review the accuracy of Xpert Bladder Cancer in the follow-up diagnosis of bladder cancer and evaluate the role of Xpert Bladder Cancer in detecting the recurrence of non-muscle-invasive bladder cancer in the round. METHODS: In the database of Embase, PubMed, Web of Science, and Cochrane Library, the articles published up to October 13, 2020, were searched and screened based on the exclusion and inclusion criteria, and data were extracted from the included studies. The sensitivity, specificity, negative likelihood ratio, positive likelihood ratio summary of receiver operating characteristic curves, and diagnostic odds ratio were combined by the Meta-DiSc 1.4 software. The Stata 12.0 software was used to obtain the assessment of publication bias. RESULTS: A total of 8 articles involving eight fourfold tables were finally identified. The pooled sensitivity and specificity of Xpert Bladder Cancer in the diagnosis of bladder cancer were 0.71 and 0.81, respectively. The positive likelihood ratio and negative likelihood ratio were 3.74 and 0.34, respectively. The area under the curve was 0.8407. The diagnostic odds ratio was 11.99. Deeks' funnel plot asymmetry test manifested no publication bias. CONCLUSIONS: In summary, Xpert Bladder Cancer presents high accuracy and specificity in monitoring bladder cancer compared with cystoscopy. More researches are still required to further confirm this conclusion.

Diagnosis of severe community-acquired pneumonia caused by Acinetobacter baumannii through next-generation sequencing: a case report.

BACKGROUND: Acinetobacter baumannii is a gram-negative aerobic bacillus that is commonly causes of hospital-acquired infections. Community-acquired pneumonia caused by Acinetobacter baumannii (CAP-Ab) is rare but fatal if diagnosis and treatment are delayed. Conventional culture of clinical specimens is the main method for clinical diagnosis of A. baumannii infections which may suffer from limited positive rate and is time consuming. Timely and precise diagnosis of CAP-Ab remains challenging. CASE PRESENTATION: A 66-year-old man with 24 h history of acute fever and dyspnea was admitted to our hospital. He was diagnosed as severe community acquired pneumonia (CAP), septic shock, respiratory failure and acute kidney injury. Next-generation sequencing (NGS) was performed on the patient's sputum and blood, which identified numerous A. baumannii nucleotide sequences in the sample of sputum and led to the rapid diagnosis and treatment of community acquired pneumonia caused by A. baumannii. This result was confirmed by subsequent sputum culture. CONCLUSIONS: This case described that the successful application of the next generation sequencing assisting the speedy diagnosis of A. baumannii infection provides a new idea for the timely diagnosis of CAP-Ab and highlights that NGS is a promising tool in rapid etiological diagnosis of acute and severe infectious diseases.

Anti-diabetic agents for prevention of type 2 diabetes mellitus in people with pre-diabetes: a systematic review and network meta-analysis protocol.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a substantial health problem worldwide. Pre-diabetic state is associated with increased risk for the development of diabetes. There are various pharmacological therapies with glucose-lowering activity for diabetes prevention. Of those, most are being compared with placebo instead of active agents. The relative effects and safety of different glucose-lowering drugs still remain uncertain. To address this gap, we will conduct a systematic review and network meta-analysis (NMA) to evaluate comparative efficacy and safety of glucose-lowering agents for T2DM prevention in patients with pre-diabetes. METHODS AND ANALYSIS: PubMed, the Cochrane library and Embase will be searched from inception to December 2019 for relevant randomised controlled trials (RCTs) that examined anti-diabetic drugs for diabetes prevention in patients with pre-diabetes. Two reviewers working independently will screen titles, abstracts and full papers. Data extraction will also be completed by two independent authors. The primary outcome will be the incidence of T2DM in patients with pre-diabetes at baseline. Secondary outcomes will include the achievement of normoglycaemia, all-cause mortality, cardiovascular mortality and hypoglycaemic event. Pairwise meta-analysis and NMA will be conducted for each outcome using a frequentist random-effects model. Additionally, subgroup analyses will also be performed. The comparison-adjusted funnel plot will be used to assess publication bias. The overall quality of evidence will be rated with the Grading of Recommendations Assessment, Development and Evaluation framework. Data analysis will be conducted using Stata V.14.0. ETHICS AND DISSEMINATION: Ethics approval is not required. We plan to submit the results of this study to a peer-review journal. PROSPERO REGISTRATION NUMBER: CRD42019119157.

Lorcaserin for prevention and remission of type 2 diabetes mellitus in people with overweight or obesity: protocol for a systematic review and meta-analysis.

INTRODUCTION: High body mass index (BMI) is associated with risk of diabetes. Lorcaserin is a selective 5-hydroxytryptamine 2C agonist which exerts robust benefits on long-term weight loss by suppressing appetite among adults with overweight or obesity. The magnitude of efficacy of lorcaserin for preventing and remitting type 2 diabetes mellitus (T2DM) among those people remains undefined. Therefore, we plan to conduct this systematic review and meta-analysis to aggregate data from all published studies with regard to the issue to acquire reliable evidence. METHODS AND ANALYSIS: We will search various databases for relevant trials published up to June 2019. Randomised controlled trials investigating the efficacy of lorcaserin for preventing and remitting T2DM among overweight and obese population will be included. A standardised data form will be used to complete data search and extraction in duplicate. All discrepancies will be resolved by consensus. The primary outcome will be incidence of T2DM in patients with pre-diabetes. Secondary outcomes will include achievement of normoglycaemia in people with pre-diabetes, remission of hyperglycaemia in patients with diabetes, the proportion of patients with weight loss of at least 5% or 10% and hypoglycaemia incident. Data synthesis and statistical analysis will be performed for each outcome with Stata V.14.0. ETHICS AND DISSEMINATION: Ethics approval is not required. Results of our study will be submitted to a peer-review journal. PROSPERO REGISTRATION NUMBER: CRD42019119136.

Rat bite fever caused by Streptobacillus moniliformis infection in a Chinese patient.

BACKGROUND: Rat bite fever (RBF), a severe infectious disease, can result from transmission of the pathogen Streptobacillus moniliformis (S. moniliformis) by rat bite. RBF diagnosis can be overlooked. CASE PRESENTATION: We present a case of RBF in a Chinese patient who was infected with S. moniliformis in mainland China. Meta-next generation sequencing (mNGS) was used to identify potential pathogens and detected S. moniliformis genome sequences in the pustular sample in less than 72 h. Then the diagnosis was validated by polymerase chain reaction analysis. Despite having severe RBF with complications, this 54-year-old male patient was successfully cured with penicillin as a result of timely pathogen-based diagnosis. CONCLUSIONS: Physicians should inquire about recent rat exposure and consider the possibility of RBF when a patient develops unexplained fever and rashes. mNGS is a new diagnostic technology and may identify RBF pathogens even when blood culture results are negative.

Pharmacologic interventions for preventing delirium in adult patients after cardiac surgery: Protocol of a systematic review and network meta-analysis.

BACKGROUND: Delirium is common in adult patients undergoing cardiac surgery and related to a high morbidity and mortality. Although a variety of pharmacologic interventions have been applied in delirium prevention, there is still uncertainty concerning which drug is optimal. Thus, we plan to conduct a systematic review and network meta-analysis (NMA) of published studies to assess the efficacy and safety of pharmacologic interventions for preventing delirium among those patients. METHODS: A systematic literature search will be conducted in Embase, PubMed, and the Cochrane Library. The primary outcome will be the incidence of postoperative delirium. Secondary outcomes will include all-cause mortality and length of hospital or intensive care unit stay. A frequentist NMA will be conducted using Stata version 14.0. The inconsistency between direct and indirect comparisons will be evaluated using a node splitting method. In addition, surface under the cumulative ranking area will be used to evaluate superiority of different treatments. RESULTS: The findings of our review will be submitted to a peer-reviewed publication. CONCLUSION: Our study will generate convincing evidence regarding the effectiveness and safety of different pharmacologic interventions for delirium prevention in cardiac surgery patients.

Use of statins and the risk of delirium in critically ill and surgical patients: Protocol of a systematic review and meta-analysis.

BACKGROUND: The critically ill and surgical patients are at significant risk of delirium, which is associated with a high morbidity and mortality. The association between statin use and the incidence of delirium is still controversial. In this article, we will perform a systematic review and meta-analysis of published studies to evaluate the effectiveness of statins for the prophylaxis of delirium among critically ill and surgical patients. METHODS: We will conduct a systematic literature search in EMBASE, PubMed, and the Cochrane Library from inception date to October 2018 for randomized controlled trials (RCTs) and observational studies (either cohort or case-control studies) investigating the association between use of statins and delirium risk. The Cochrane Collaboration's tool for evaluating the risk of bias and Newcastle-Ottawa scale (NOS) will be used to assess the methodological quality of RCTs and observational studies, separately. The primary outcome will be the risk of incident delirium associated with statin use. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) will be calculated by a random-effects or fixed-effects model according to heterogeneity among included studies. Subgroup analyses, meta-regression method, and assessment of publication bias will be also performed. Statistical analyses will be conducted with RevMan (version 5.3.5) and Stata (version 14.0) software. In addition, the grading of recommendations assessment, development and evaluation (GRADE) approach will be applied to evaluate the quality of evidence. RESULTS: The study will provide a high-quality synthesis and evaluate the effectiveness of statins for delirium prevention among critically ill and surgical patients. CONCLUSIONS: The systematic review and meta-analysis will provide convincing evidence concerning the effect of statins against delirium in critically ill and surgical patients.

[An experimental study on acute poisoning by fipronil in mice and its pharmaceutical therapy].

OBJECTIVE: To investigate the toxicity of fipronil in mice and the therapeutic effects of diazepam and phenobarbital sodium. METHODS: Mice were administered by gastric tube with fipronil at six doses and their behavioral changes, pathological changes in their major viscera under light and electron microscopy and deaths were observed after acute poisoning. Distribution and quantity of nerve cells positive in glutamic acid (Glu) or gamma-aminobutyric acid (gamma-GABA) in the brain of mice were detected by immunohistochemical methods and micro-image analysis. The time of death time and survival rate were observed and compared between the varied groups of mice injected intraperitoneally with diazepam and phenobarbital sodium, respectively, 0.5 h after poisoning by fipronil at dose of 90 mg/kg. RESULTS: All the mice acutely poisoned by fipronil at varied doses showed some exciting symptoms in the central nervous system (CNS), including convulsion. Nuclear membrane space slightly expanded, neuroglia cells vacuolized and nerve fiber demyelinated under electron microscopy. The number and area of cells positive in Glu in the cerebral cortex of mice acutely poisoned by fipronil increased significantly, as compared to those in control mice. There was no significant difference in the number and area of cells positive in gamma-GABA in the hippocampal CA(1) region between poisoned and normal control groups. Survival rate of mice treated with diazepam or phenobarbital sodium was 58 percent. CONCLUSION: Mice with acute poisoning by fipronil appeared exciting symptoms in CNS, leading to damage in its nerve cells. Immunohistochemical techniques showed the damage could be related with the over-expression of glutamate transmitter in CNS. Early use of diazepam or phenobarbital sodium in treatment for acutely poisoned mice by fipronil could get better therapeutic efficacy.