A 11-year-old boy with Blastocystis hominis infection, presents as immune thrombocytopenia.

BACKGROUND: Some causes of first-line treatment failure for ITP are often closely related to infections. But parasitic infections are rarely mentioned and easily overlooked. The case is the first to describe a boy with immune thrombocytopenia associated with blastocystis hominis. CASE PRESENTATION: The case involved a boy presenting with bleeding skin spots and ecchymosis and accompanied by intermittent epigastric pain and constipation. After a series of complete examinations, the platelet count was found to be decreased to 13 × 109/L and immune thrombocytopenia was diagnosed. After first-line treatment with gamma globulin and prednisolone, the thrombocytopenia remained unchanged. Blastocystis hominis was subsequently found in the patient's stool and then the treatment of metronidazole was provided. One week later, the patient's thrombocytopenia was completely relieved. He was followed up for six months and was found to have recovered well. CONCLUSIONS: The screening for potential predisposing factors is very important for immune thrombocytopenia patients with poor response to first-line treatment, and the best treatment strategy should include the management of potential diseases.

Effect of delayed antibiotic use on mortality outcomes in patients with sepsis or septic shock: A systematic review and meta-analysis.

BACKGROUND: The use of antibiotics is essential in the treatment of sepsis and septic shock, and delaying their administration may impact patient mortality outcomes. However, there is currently a controversial debate surrounding this issue. In this meta-analysis, we aimed to explore the association between delayed antibiotic use and mortality in patients with sepsis and septic shock. METHODS: A systematic search was conducted on PubMed, EMBASE, Web of Science, and Cochrane Library to identify relevant studies published from 2013 to 2023. These studies focused on patients with sepsis or septic shock and provided information on various antibiotic administration times and mortality rates. Two independent reviewers screened and extracted the data. The quality of each study was assessed using the Newcastle-Ottawa Scale, and the collected data were analyzed using STATA 15.1 software. RESULTS: A total of 29 studies were included, consisting of 17 prospective cohort studies and 12 retrospective cohort studies. The meta-analysis showed that compared to administration of antibiotics within 1 h, each hour of delay in antibiotic administration increased the in-hospital mortality (IHM) (OR = 1.041, 95 % CI: 1.021-1.062), and ministration of antibiotics after 1 h increased the IHM (OR = 1.205, 95 % CI: 1.123-1.293). There was no significant change in the 28-day mortality (OR = 1.297, 95 % CI: 0.882-1.906), 90-day mortality (OR = 1.172, 95 % CI: 0.846-1.622), and 1-year mortality (OR = 0.986, 95 % CI: 0.422-2.303). Administration of antibiotics within 3 h may reduce the IHM (OR = 1.297, 95 % CI: 1.011-1.664, p = 0.041), while administration of antibiotics within 6 h showed no significant association with the IHM. CONCLUSION: The administration of antibiotics beyond 1 h after emergency triage or disease identification is strongly associated with an increased IHM in patients with sepsis or septic shock, and each hour of delay in antibiotic administration may be associated with an increase in the IHM. Furthermore, the use of antibiotics identification beyond 3 h after emergency triage / sepsis or septic shock may also increase the IHM.

The role of RIM in neurotransmitter release: promotion of synaptic vesicle docking, priming, and fusion.

There are many special sites at the end of a synapse called active zones (AZs). Synaptic vesicles (SVs) fuse with presynaptic membranes at these sites, and this fusion is an important step in neurotransmitter release. The cytomatrix in the active zone (CAZ) is made up of proteins such as the regulating synaptic membrane exocytosis protein (RIM), RIM-binding proteins (RIM-BPs), ELKS/CAST, Bassoon/Piccolo, Liprin-α, and Munc13-1. RIM is a scaffold protein that interacts with CAZ proteins and presynaptic functional components to affect the docking, priming, and fusion of SVs. RIM is believed to play an important role in regulating the release of neurotransmitters (NTs). In addition, abnormal expression of RIM has been detected in many diseases, such as retinal diseases, Asperger's syndrome (AS), and degenerative scoliosis. Therefore, we believe that studying the molecular structure of RIM and its role in neurotransmitter release will help to clarify the molecular mechanism of neurotransmitter release and identify targets for the diagnosis and treatment of the aforementioned diseases.

Predictive value of neutrophil gelatinase-associated lipocalin in children with acute kidney injury: A systematic review and meta-analysis.

Purpose: Neutrophil gelatin lipase carrier protein (NGAL) has been used as an early biomarker to predict acute kidney injury (AKI). However, the predictive value of NGAL in urine and blood in children with acute kidney injury in different backgrounds remains unclear. Therefore, we conducted this systematic review and meta-analysis to explore the clinical value of NGAL in predicting AKI in children. Methods: Computerized databases were searched for relevant the studies published through August 4th, 2022, which included PUBMED, EMBASE, COCHRANE and Web of science. The risk of bias of the original included studies was assessed by using the Quality Assessment of Studies for Diagnostic Accuracy (QUADA-2). At the same time, subgroup analysis of these data was carried out. Results: Fifty-three studies were included in this meta-analysis, involving 5,049 patients, 1,861 of whom were AKI patients. The sensitivity and specificity of blood NGAL for predicting AKI were 0.79 (95% CI: 0.69-0.86) and 0.85 (95% CI: 0.75-0.91), respectively, and SROC was 0.89 (95% CI: 0.86-0.91). The sensitivity and specificity of urine NGAL for predicting AKI were 0.83 (95% CI: 0.78-0.87) and 0.81 (95% CI: 0.77-0.85), respectively, and SROC was 0.89 (95% CI: 0.86-0.91). Meanwhile, the sensitivity and specificity of overall NGAL (urine and blood NGAL) for predicting AKI in children were 0.82 (95% CI: 0.77-0.86) and 0.82 (95% CI: 0.78-0.86), respectively, and SROC was 0.89 (95% CI: 0.86-0.91). Conclusion: NGAL is a valuable predictor for AKI in children under different backgrounds. There is no significant difference in the prediction accuracy between urine NGAL and blood NGAL, and there is also no significant difference in different measurement methods of NGAL. Hence, NGAL is a non-invasive option in clinical practice. Based on the current evidence, the accuracy of NGAL measurement is the best at 2 h after cardiopulmonary bypass (CPB) and 24 h after birth in asphyxiated newborns. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022360157.

Munc18-1 Contributes to Hippocampal Injury in Septic Rats Through Regulation of Syntanxin1A and Synaptophysin and Glutamate Levels.

Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction closely associated with mortality in the acute phase of sepsis. Abnormal neurotransmitters release, such as glutamate, plays a crucial role in the pathological mechanism of SAE. Munc18-1 is a key protein regulating neurotransmission. However, whether Munc18-1 plays a role in SAE by regulating glutamate transmission is still unclear. In this study, a septic rat model was established by the cecal ligation and perforation. We found an increase in the content of glutamate in the hippocampus of septic rat, the number of synaptic vesicles in the synaptic active area and the expression of the glutamate receptor NMDAR1. Meanwhile, it was found that the expressions of Munc18-1, Syntaxin1A and Synaptophysin increased, which are involved in neurotransmission. The expression levels of Syntaxin1A and Synaptophysin in hippocampus of septic rats decreased after interference using Munc18-1siRNA. We observed a decrease in the content of glutamate in the hippocampus of septic rats, the number of synaptic vesicles in the synaptic activity area and the expression of NMDAR1. Interestingly, it was also found that the down-regulation of Munc18-1 improved the vital signs of septic rats. This study shows that CLP induced the increased levels of glutamate in rat hippocampus, and Munc18-1 may participate in the process of hippocampal injury in septic rats by affecting the levels of glutamate via regulating Syntaxin1A and Synaptophysin. Munc18-1 may serve as a potential target for SAE therapy.

Knockdown of lncRNA MEG3 protects against sepsis-induced acute lung injury in mice through miR-93-5p-dependent inhibition of NF­κB signaling pathway.

Excessive inflammatory response is a prominent pathogenic hallmark of acute lung injury (ALI). Long noncoding RNA (lncRNA) has been recently reported to play a key role in the pathophysiology of many inflammatory disorders, including ALI. Herein, we attempted to explore the role and underlying mechanism of lncRNA MEG3 in the inflammation in ALI. Firstly, an ALI mouse model was generated via intra-tracheal instillation of lipopolysaccharide (LPS), and then, the impact of lncRNA MEG3 on lung tissue damage, pulmonary edema, lung microvascular permeability and pulmonary inflammatory response, as well as the ALI mice survival rate was investigated. LncRNA MEG3 was upregulated in lung tissues, and knockdown of lncRNA MEG3 protected mice from LPS-induced ALI, with significantly reduced lung pathological changes, decreased lung wet/dry (W/D) ratio and lung microvascular permeability, attenuated inflammatory response, along with increased ALI mice survival. Moreover, lncRNA MEG3 could sponge miR-93, negatively regulated its expression, and lncRNA MEG3 overexpression liberated the suppression of TLR4 expression caused by miR-93. Further, functional studies demonstrated that the protective effects of lncRNA MEG3 on excessive inflammatory response may be related to miR-93-mediated modulation of TLR4/MyD88/NF-κB pathway. Collectively, lncRNA MEG3 inhibition blocked TLR4/MyD88/NF-κB pathway to repress the progression of sepsis-induced lung injury via upregulating miR-93, implying that lncRNA MEG3 might be a viable therapeutic target for ALI.

The Role of Vti1a in Biological Functions and Its Possible Role in Nervous System Disorders.

Vesicle transport through interaction with t-SNAREs 1A (Vti1a), a member of the N-ethylmaleimide-sensitive factor attachment protein receptor protein family, is involved in cell signaling as a vesicular protein and mediates vesicle trafficking. Vti1a appears to have specific roles in neurons, primarily by regulating upstream neurosecretory events that mediate exocytotic proteins and the availability of secretory organelles, as well as regulating spontaneous synaptic transmission and postsynaptic efficacy to control neurosecretion. Vti1a also has essential roles in neural development, autophagy, and unconventional extracellular transport of neurons. Studies have shown that Vti1a dysfunction plays critical roles in pathological mechanisms of Hepatic encephalopathy by influencing spontaneous neurotransmission. It also may have an unknown role in amyotrophic lateral sclerosis. A VTI1A variant is associated with the risk of glioma, and the fusion product of the VTI1A gene and the adjacent TCF7L2 gene is involved in glioma development. This review summarizes Vti1a functions in neurons and highlights the role of Vti1a in the several nervous system disorders.

m6A: An Emerging Role in Programmed Cell Death.

Programmed cell death is an active extinction process, including autophagy, ferroptosis, pyroptosis, apoptosis, and necroptosis. m6A is a reversible RNA modification which undergoes methylation under the action of methylases (writers), and is demethylated under the action of demethylases (erasers). The RNA base site at which m6A is modified is recognized by specialized enzymes (readers) which regulate downstream RNA translation, decay, and stability. m6A affects many aspects of mRNA metabolism, and also plays an important role in promoting the maturation of miRNA, the translation and degradation of circRNA, and the stability of lncRNA. The regulatory factors including writers, erasers and readers promote or inhibit programmed cell death via up-regulating or down-regulating downstream targets in a m6A-dependent manner to participate in the process of disease. In this review, we summarize the functions of m6A with particular reference to its role in programmed cell death.

CAPN3: A muscle­specific calpain with an important role in the pathogenesis of diseases (Review).

Calpains are a family of Ca2+­dependent cysteine proteases that participate in various cellular processes. Calpain 3 (CAPN3) is a classical calpain with unique N­terminus and insertion sequence 1 and 2 domains that confer characteristics such as rapid autolysis, Ca2+­independent activation and Na+ activation of the protease. CAPN3 is the only muscle­specific calpain that has important roles in the promotion of calcium release from skeletal muscle fibers, calcium uptake of sarcoplasmic reticulum, muscle formation and muscle remodeling. Studies have indicated that recessive mutations in CAPN3 cause limb­girdle muscular dystrophy (MD) type 2A and other types of MD; eosinophilic myositis, melanoma and epilepsy are also closely related to CAPN3. In the present review, the characteristics of CAPN3, its biological functions and roles in the pathogenesis of a number of disorders are discussed.

Role of Munc18-1 in the biological functions and pathogenesis of neurological disorders (Review).

The release of neurotransmitters following the fusion of synaptic vesicles and the presynaptic membrane is an important process in the transmission of neuronal information. Syntaxin-binding protein 1 (Munc18-1) is a synaptic fusion protein binding protein, which mainly regulates synaptic vesicle fusion and neurotransmitter release by interacting with soluble N-ethylmaleimide sensitive factor attachment protein receptor. In addition to affecting neurotransmitter transmission, Munc18-1 is also involved in regulating neurosynaptic plasticity, neurodevelopment and neuroendocrine cell release functions (including thyroxine and insulin release). A number of previous studies have demonstrated that Munc18-1 has diverse and vital biological functions, and that its abnormal expression serves an important role in the pathogenesis of a variety of neurological diseases, including epileptic encephalopathy, schizophrenia, autism, Parkinson's disease, Alzheimer's disease, multiple sclerosis, Duchenne's muscular dystrophy and neuronal ceroid lipofuscinosis. The present review summarizes the function of Munc18-1 and its possible relationship to the pathogenesis of various neurological diseases.

The pannexin-1 channel regulates pyroptosis through autophagy in a mouse model of sepsis-associated encephalopathy.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction caused by sepsis. Pyroptosis and autophagy are important mechanisms in the pathogenesis of sepsis, and also pannexin-1 is involved in the occurrence of sepsis. However, role of pannexin-1 in SAE and its relationship with pyroptosis and autophagy are unclear. This study examined the relationship between pannexin-1 and pyroptosis, and further explore the relationship between pyroptosis and autophagy in SAE mice. METHODS: A SAE mouse model was established by cecal ligation and puncture (CLP). Different groups of mice were administrated probenecid (PRB), 3-methyladenine (3-MA), or a vehicle control and the survival rates were monitored at different time points. Cortical pathological changes were examined by hematoxylin and eosin (HE) staining. The expression of cortical pannexin-1 and adenosine monophosphate-activated protein kinase (AMPK), as well as pyroptosis and autophagy related proteins, was detected by Western blotting and immunofluorescence analysis. The ultrastructure of neurons was observed by transmission electron microscopy. RESULTS: Septic mice showed significantly higher rates of mortality and cortical pathological change compared to control mice. In addition, the pannexin-1 and AMPK signaling pathway were activated in the cerebral cortex of the septic mice, coupled with the activation of pyroptosis and incomplete activation of autophagy. Inhibition of pannexin-1 expression reduce the rates of mortality and the cortical pathological changes in the mice, further activated the AMPK signaling pathway, inhibited pyroptosis, and completely activated autophagy. The inhibition of autophagy may cause pyroptosis to reactivate. CONCLUSIONS: The present findings suggested that in SAE mice, pannexin-1 may regulate neuronal pyroptosis through autophagy. Moreover, the regulation of autophagy may be related to the AMPK signaling pathway. Inhibiting pannexin-1 expression in SAE mice may have a neuroprotective effect.

Cumulative Evidence for the Association of Thrombosis and the Prognosis of COVID-19: Systematic Review and Meta-Analysis.

BACKGROUND: Although thrombosis events have been reported in patients with coronavirus disease 2019 (COVID-19), the association between thrombosis and COVID-19-related critical status or risk of mortality in COVID-19 has been inconsistent. OBJECTIVE: We conducted a meta-analysis of reports assessing the association between thrombosis and the prognosis of COVID-19. METHODS: The EMBASE, Ovid-MEDLINE, and Web of Science databases were searched up to December 9, 2021, and additional studies were retrieved via manual searching. Studies were included if they reported the risk of COVID-19-related critical status or COVID-19-related mortality in relation to thrombosis. The related data were extracted by two authors independently, and a random effects model was conducted to pool the odds ratios (ORs). In addition, stratified analyses were conducted to evaluate the association. RESULTS: Among 6,686 initially identified studies, we included 25 studies published in 2020 and 2021, with a total of 332,915 patients according to predefined inclusion criteria. The associations between thrombosis and COVID-19-related mortality and COVID-19-related critical status were significant, with ORs of 2.61 (95% CI, 1.91-3.55, p < 0.05) and 2.9 (95% CI, 1.6-5.24, p < 0.05), respectively. The results were statistically significant and consistent in stratified analyses. CONCLUSIONS: Thrombosis is associated with an increased risk of mortality and critical status induced by COVID-19. Further prospective studies with large sample sizes are required to establish whether these associations are causal by considering more confounders and to clarify their mechanisms.Observational studies cannot prove causality. However, autopsy studies show thrombosis events preceding COVID-19-related deaths. The results of this meta-analysis reported that thrombosis was associated with a 161% increased risk of mortality from COVID-19 and a 190% increased risk of COVID-19-related critical status. The type of thrombosis included in the original studies also seemed to be related to the results.

Research progress of diabetic ketoacidosis complicated withcerebral edema in children / 预防医学

Abstract@#Diabetic ketoacidosis (DKA) is a serious complication of diabetes in children. A small number of children with DKA can be complicated by cerebral edema, leading to acute brain dysfunction, which is the main cause of death in children with diabetes. Because of unclear pathogenesis and non-specific clinical manifestations, DKA complicated with brain edema is easy to be missed or misdiagnosed. The identification and management of risk factors of DKA complicated with brain edema and early identification of brain edema are of great importance for improving the prognosis. This article reviewed the literature about the pathogenesis, clinical manifestations, risk factors, treatment and prevention of DKA complicated with brain edema, so as to provide reference for its early clinical identification and intervention.

CAPN6 in disease: An emerging therapeutic target (Review).

As a member of the calpain protein family, calpain6 (CAPN6) is highly expressed mainly in the placenta and embryos. It plays a number of important roles in cellular processes, such as the stabilization of microtubules, the maintenance of cell stability, the control of cell movement and the inhibition of apoptosis. In recent years, various studies have found that CAPN6 is one of the contributing factors associated with the tumorigenesis of uterine tumors and osteosarcoma, and that CAPN6 participates in the development of tumors by promoting cell proliferation and angiogenesis, and by inhibiting apoptosis, which is mainly regulated by the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) pathway. Due to its abnormal cellular expression, CAPN6 has also been found to be associated with a number of diseases, such as white matter damage and muscular dystrophy. Therefore, CAPN6 may be a novel therapeutic target for these diseases. In the present review, the role of CAPN6 in disease and its possible use as a target in various therapies are discussed.

The association between vitamin D status and tuberculosis in children: A meta-analysis.

BACKGROUND: Vitamin D deficiency (VDD) has been implicated in the pathogenesis of tuberculosis (TB), but most studies have not reported a significant association. We conducted a meta-analysis to explore the association between vitamin D status and TB in children. METHODS: Web of Science, Ovid Medline, and EMBASE were searched for studies in English that discussed vitamin D status and TB in children before January 22, 2018. RESULTS: From the 585 initially identified studies, we selected those that addressed an association between vitamin D status and TB according to our preselected inclusion criteria. Our meta-analysis included 10 studies. According to the random effects model, TB was significantly associated with VDD (ORs, 1.70; 95% CI, 1.20-2.42; P < .05) in children. Vitamin D levels were significantly lower in TB patients than in controls, with a mean difference d = -5.49 nmol/L (95% CI, -10.42 to -0.55; P < .05), indicating that VDD was significantly associated with TB (OR, 1.78; 95% CI, 1.30-2.44; P < .05) in children. CONCLUSION: This study suggests that vitamin D levels are significantly lower in children with TB/latent TB infection than in controls. TB may contribute to VDD in children. Therefore, VDD may be associated with TB in children.