Association of obesity with cardiovascular disease in the absence of traditional risk factors.

BACKGROUND: The association between obesity and cardiovascular disease (CVD) in people without traditional CVD risk factors is unclear. This study aimed to investigate the association of obesity with CVD and its subtypes in people without traditional CVD risk factors. METHODS: Based on the Kailuan cohort study, the included participants were divided into different groups according to levels of body mass index (BMI) and waist height ratio (WHtR), respectively. Multivariate Cox proportional hazard models were used to evaluate the associations. RESULTS: This study included 31,955 participants [men 63.99%; mean age (48.14 ± 3.33) years]. During a median follow-up period of 12.97 (interquartile range: 12.68-13.17) years, 1298 cases of CVD were observed. Compared with the normal BMI group, the hazard ratios (HRs) for CVD, stroke, and myocardial infarction (MI) in the BMI obese group were 1.31 (95% confidence interval [CI] 1.11-1.55), 1.21 (95%CI 1.01-1.46), 1.62 (95%CI 1.13-2.33), respectively. Compared with the WHtR non-obese group, the HRs for CVD, stroke, and MI in the obese group were 1.25(95%CI 1.11-1.41), 1.18 (95%CI 1.03-1.34), 1.57 (95%CI 1.18-2.09), respectively. There was an interaction between age and WHtR (P for interaction was 0.043). The association between WHtR and CVD was stronger in people under 60 years old, with a HR of 1.44 (95%CI 1.24-1.67). CONCLUSION: We found that obesity increased the risk of CVD in people without traditional CVD risk factors. The association of WHtR with CVD was stronger in people under 60 years old.

Bioactive compounds and biological functions of medicinal plant-derived extracellular vesicles.

Extracellular vesicles (EVs) are tiny lipid bilayer-enclosed membrane particles released from a variety of cell types into the surrounding environment. These EVs have massive participated in cell-to-cell communication and interspecies communication. In recent years, plant-derived extracellular vesicles (PDEVs) and "exosome-like" EVs populations found in distinct plants have attracted widespread attention. Especially, research on medicinal plant-derived extracellular vesicles (MPDEVs) are increasing, which are considered a kind of promising natural compound. This review summarizes current knowledge on MPDEVs in terms of bioactive compounds, including small RNA, protein, lipid, and metabolite, have been found on the surface and/or in the lumen of MPDEVs. Moreover, both in vitro and in vivo experiments have shown that MPDEVs exert broad biomedical functions, such as anti-inflammatory, anticancer, antioxidant, modulate microbiota, etc. MPDEVs may be a better substitute than animal-derived extracellular vesicles (ADEVs) because of safety and biocompatibility in the future.

Adoption of the cardiopulmonary exercise test in the exercise ability and cardiopulmonary function rehabilitation of coronary artery disease (CAD) patients.

BACKGROUND: This study aimed to explore the application of cardiopulmonary exercise testing in coronary artery disease (CAD) patients, evaluate its impact on exercise ability and cardiopulmonary function in patients with coronary heart disease (CHD), and promote the application of cardiopulmonary exercise testing in CAD management. METHODS: Fifty CHD patients after percutaneous coronary intervention (PCI) were recruited and randomly enrolled into the control (Ctrl) group and intervention (Int) group. Routine health education and health education combined with RT training were carried out for the two groups. Blood lipid levels and lung function were compared between the two groups after intervention. Cardiac function was evaluated by Doppler ultrasonography, and cardiopulmonary fitness and exercise ability were evaluated by a cardiopulmonary exercise test (CPET). The self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were employed to evaluate negative emotions. The 36-item short-form (SF-36) was adopted to evaluate quality of life. RESULT: Compared with those in the Ctrl group, the levels of serum total cholesterol (TC), triglycerides (TGs), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) decreased in the Int group, while the levels of high-density lipoprotein increased (P < 0.05). The quantitative load results showed that compared with the Ctrl group, the heart rate (HR) and self-perceived fatigue degree of the Int group decreased, and the ST segment increased (P < 0.05). Compared with the Ctrl group, the left ventricular ejection fraction (LVEF), forced expiratory volume at 1 s (FEV1), ratio of forced expiratory volume to forced vital volume (FEV1/FVC%), and maximum chase volume (MVV) increased in the Int group, while the left ventricular end diastolic diameter and left ventricular end contractile diameter decreased (P < 0.05). The results of the CPET showed that compared with the Ctrl group, minute ventilation/carbon dioxide production slope, VE/VCO2 - Peak, anaerobic threshold (AT), peak oxygen pulse (VO2/HR peak), oxygen uptake efficiency platform (OUEP), increasing power exercise time (IPEt), HR recovery 1 min after exercise, peak load power (Watt peak), and value metabolic equivalent (Watt peak) increased in the Int group (P < 0.05). Compared with the Ctrl group, the SAS and SDS scores in the Int group decreased (P < 0.05). The results of the quality of life evaluation showed that compared with the Ctrl group, the score of the SF-36 dimensions increased in the Int group (P < 0.05). CONCLUSION: RT training can reduce postoperative blood lipid and quantitative load levels in CAD patients and improve adverse mood. Furthermore, it can improve patients' cardiopulmonary function, cardiopulmonary fitness, exercise ability, and quality of life.

Incomplete Kawasaki disease with muscular weakness and bladder retention: a case report.

BACKGROUND: Kawasaki disease (KD) is an acute systemic immune vasculitis affecting multiple organs and systems in children, and is prevalent in children under 5 years of age. Muscular weakness is a rare manifestation of KD, and only 11 pediatric patients with KD combined with muscular weakness have been reported, of which evidence of myositis was found in 2/3 of the patients, and 1/3 could not be explained by myositis, the mechanism of which is still unclear. Cases of KD combined with bladder retention are even more rare, and there has been only 1 case report of KD combined with bladder retention in a child with no previous underlying disease. CASE PRESENTATION: We report a 22-month-old Asian child with incomplete Kawasaki disease (IKD) who initially presented with fever and progressive muscular weakness in the lower extremities, followed by the bladder and bowel retention abnormalities and rapid onset of heart failure, respiratory failure and shock. The child developed coronary artery ectasia (CAA) without the main clinical features of KD such as rash, conjunctival congestion, desquamation of the extremity endings, orofacial changes and enlarged lymph nodes in the neck. Creatine kinase and electromyography were normal. Temperature gradually normalized and muscle strength recovered slightly after intravenous immunoglobulin. The child could be helped to walk after 1 week of aspirin combined with steroid therapy. CONCLUSIONS: We present the case of a 22-month-old child with IKD. The child began with progressive muscular weakness in the extremities, followed by the bladder and bowel retention abnormalities, and rapidly developed heart failure, respiratory failure, and shock. Despite early failure to detect the disease, the child recovered rapidly and had a favorable prognosis. KD comorbidities with muscular weakness as the main manifestation are uncommon. This is the first case report of IKD combined with both muscular weakness and bladder and bowel retention, which may provide clinicians with diagnostic and therapeutic ideas, as well as a basis for future exploration of the mechanisms of KD combined with muscular weakness or bladder and bowel retention abnormalities.

[Association between exposure to PM_(2.5) and chronic kidney disease in a population with metabolic syndrome].

OBJECTIVE: To investigate the association between long-term fine particulate matter(PM_(2.5)) exposure and the risk of chronic kidney disease(CKD) in people with abnormal metabolism syndrome(MS) components. METHODS: Based on health checkup data from a hospital in Beijing, a retrospective cohort study was used to collect annual checkup data from 2013-2019. A questionnaire was used to obtain information on demographic characteristics and lifestyle habits. We measured blood pressure, height, weight, waist circumference, concentrations of triglycerides(TG), fasting glucose, and high-density lipoprotein cholesterol(HDL-C). Longitude and latitude were also extracted from the addresses of the study subjects for pollutant exposure data estimation. Logistic regression models were used to explore the estimated effect of long-term PM_(2.5) exposure on the risk of CKD prevalence in people with abnormal MS components. Two-pollutant and multi-pollutant models were developed to test the stability of these result. Subgroup analysis was conducted based on age, the presence of MS, individual MS component abnormalities, and dual-component MS abnormalities. RESULTS: The study included 1540 study subjects with abnormal MS components at baseline, 206 with CKD during the study period. The association between long-term PM_(2.5) exposure and increased risk of CKD in people with abnormal MS fractions was statistically significant, with a 2.26-fold increase in risk of CKD for every 10 µg/m~3 increase in PM_(2.5) exposure(OR=3.26, 95% CI 2.72-3.90). The result in the dual-pollutant models and multi-pollutant models suggested that the association between long-term PM_(2.5) exposure and increased risk of CKD in people with abnormal MS fractions remained stable after controlling for contemporaneous confounding by other air pollutants. The result of subgroup analysis revealed that individuals aged 45 or older, without MS, with TG<1.7 mmol/L, HDL-C≥1.04 mmol/L, without hypertension, and with central obesity and high blood sugar had a stronger association between PM_(2.5) exposure and CKD-related health effects. CONCLUSION: Long-term exposure to PM_(2.5) may increase the risk of CKD in people with abnormal MS components. More attention should be paid to middle-aged and elderly people aged ≥45 years, people with central obesity and hyperglycemia.

Co-expression of transcription factors ZmC1 and ZmR2 establishes an efficient and accurate haploid embryo identification system in maize.

Because of their high efficiency during chromosome doubling, immature haploid maize (Zea mays L.) embryos are useful for doubled haploid production. The R1-nj marker is commonly used in doubled haploid breeding and has improved the efficiency of haploid identification. However, its effectiveness is limited by genetic background and environmental factors. We addressed this technical challenge by developing an efficient and accurate haploid embryo identification marker through co-expression of two transcription factor genes (ZmC1 and ZmR2) driven by the embryo-aleurone-specific bidirectional promoter PZmBD1 ; these factors can activate anthocyanin biosynthesis in the embryo and aleurone layer during early seed development. We developed a new haploid inducer, Maize Anthocyanin Gene InduCer 1 (MAGIC1), by introducing the transgenes into the haploid inducer line CAU6. MAGIC1 could identify haploids at 12 days after pollination, which is nine days earlier than CAU6. Importantly, MAGIC1 increased haploid identification accuracy to 99.1%, compared with 88.3% for CAU6. In addition, MAGIC1 could effectively overcome the inhibition of anthocyanin synthesis in some germplasms. Furthermore, an upgraded anthocyanin marker was developed from ZmC1 and ZmR2 to generate MAGIC2, which could identify haploids from diploids due to differential anthocyanin accumulation in immature embryos, coleoptiles, sheaths, roots, leaves, and dry seeds. This haploid identification system is more efficient and accurate than the conventional R1-nj-based method, and it simplifies the haploid identification process. Therefore, this system provides technical support for large-scale doubled haploid line production.

Astrocytic connexin 43 deletion ameliorates SNI-induced neuropathic pain by reducing microglia activation.

Neuropathic pain (NP) is a chronic disease caused by damage to the peripheral or central nervous system. Connexin 43 (Cx43), the primary connexin expressed by astrocytes, has been reported to be significantly increased in NP. However, the roles and mechanisms of Cx43 in the development and maintenance of NP remain largely unknown, while microglia activation has been commonly regarded as a key factor of NP. In the present study, we found that Cx43 deletion significantly ameliorated spared nerve injury (SNI)-induced NP and suppressed SNI induced c-Fos expression in the spinal cord. Notably, Cx43 deletion led to much less SNI-induced microglia activation in the spinal cord. These results suggest that astrocyte Cx43 may play a significant role in regulating microglial activation and NP.

Efficacy of endoscopic ultrasound and endoscopic resection for esophageal schwannoma.

BACKGROUND: Esophageal schwannoma (ES) is a rare submucosal tumor, and its complete and safe resection is a topic that deserves special attention. AIM: This study aimed to investigate the clinical value of endoscopic ultrasound (EUS) in the diagnosis of ES and the clinical efficacy of endoscopic resection for ES. METHODS: The clinical data, endoscopic characteristics, endoscopic treatment, postoperative complications, immunohistochemical results, and follow-up records of patients with ES admitted to the Tianjin Medical University General Hospital from January 2012 to January 2022 were retrospectively analyzed. RESULTS: Under white-light endoscopy, 81.8% (9/11) of lesions were submucosal elevations, covering the normal esophageal epithelium. Two of the lesions with redness and erosive surface. Eight lesions (72.7%) appear on EUS originating from the muscularis propria were homogeneous or inhomogeneous hypoechoic signals. Two lesions were inhomogeneous hyperechoic originating from the submucosa or muscularis propria, respectively. One lesion was homogeneous hypoechoic originating from the submucosa. All lesions had no blood flow signals, cystic changes, or calcification, and were completely removed by submucosal tunnel endoscopic resection (STER) or endoscopic submucosal dissection (ESD). All patients did not experience serious adverse events as well as recurrence, metastasis, or cicatricial esophageal stenosis during the follow-up period. CONCLUSION: ES is a rare submucosal lesion, which endoscopic characteristics are difficult to distinguish from other esophageal submucosal tumors. Endoscopic resection can provide a minimally invasive and alternative treatment for ES.

Adiponectin receptor agonist AdipoRon modulates human and mouse platelet function.

Adiponectin, an adipokine secreted by adipocytes, has anti-atherosclerotic and antithrombotic activities. AdipoRon is synthetic small molecule adiponectin receptor agonist. In this study, we investigated the effect of AdipoRon on platelet activation and thrombus formation. Washed human platelets were prepared from the peripheral blood of healthy donors. In a series of in vitro platelet functional assays, pre-treatment with AdipoRon (10, 20, 40 µg/mL) dose-dependently inhibited the aggregation, granule secretion and spreading of washed human platelets. We showed that AdipoRon (20, 40 µg/mL) significantly inhibited AMPK, Syk, PLCγ2, PI3K, Akt, p38-MAPK and ERK1/2 signalling pathways in washed human platelets. In addition, we demonstrated that the phosphorylation of CKII at Tyr255 was an important mechanism of the integrin αIIbß3-mediated platelet activation. Meanwhile, AdipoR1 deficiency impaired the inhibitory effect of AdipoRon on mouse platelets. In ferric chloride-induced carotid injury model, injection of AdipoRon (5 or 12.5 mg/kg, iv) significantly attenuated arterial thrombosis. In conclusion, AdipoRon attenuates platelet function via the AdipoR1/AMPK/CKII/PI3K/AKT signalling pathways, while exerting a protective effect against arterial thrombosis. This study offers new insights into the fields of cardiovascular disease and antiplatelet drug discovery.Schematic model of AdipoRon regulating platelet activation. (BioRender.com).

Extracellular ATP and cAMP signaling promote Piezo2-dependent mechanical allodynia after trigeminal nerve compression injury.

Trigeminal neuralgia (TN) is a type of severe paroxysmal neuropathic pain commonly triggered by mild mechanical stimulation in the orofacial area. Piezo2, a mechanically gated ion channel that mediates tactile allodynia in neuropathic pain, can be potentiated by a cyclic adenosine monophosphate (cAMP)-dependent signaling pathway that involves the exchange protein directly activated by cAMP 1 (Epac1). To study whether Piezo2-mediated mechanotransduction contributes to peripheral sensitization in a rat model of TN after trigeminal nerve compression injury, the expression of Piezo2 and activation of cAMP signal-related molecules in the trigeminal ganglion (TG) were detected. Changes in purinergic P2 receptors in the TG were also studied by RNA-seq. The expression of Piezo2, cAMP, and Epac1 in the TG of the TN animals increased after chronic compression of the trigeminal nerve root (CCT) for 21 days, but Piezo2 knockdown by shRNA in the TG attenuated orofacial mechanical allodynia. Purinergic P2 receptors P2X4, P2X7, P2Y1, and P2Y2 were significantly up-regulated after CCT injury. In vitro, Piezo2 expression in TG neurons was significantly increased by exogenous adenosine 5'-triphosphate (ATP) and Ca2+ ionophore ionomycin. ATP pre-treated TG neurons displayed elevated [Ca2+ ]i and faster increase in responding to blockage of Na+ /Ca2+ exchanger by KB-R7943. Furthermore, mechanical stimulation of cultured TG neurons led to sustained elevation in [Ca2+ ]i in ATP pre-treated TG neurons, which is much less in naïve TG neurons, or is significantly reduced by Piezo2 inhibitor GsMTx4. These results indicated a pivotal role of Piezo2 in peripheral mechanical allodynia in the rat CCT model. Extracellular ATP, Ca2+ influx, and the cAMP-to-Epac1 signaling pathway synergistically contribute to the pathogenesis and the persistence of mechanical allodynia.

Role of endoscopic ultrasound and endoscopic resection in the diagnosis and treatment of esophageal granular cell tumors.

BACKGROUND AND AIM: Diagnosis and complete resection of esophageal granular cell tumors (GCTs) is an area of concern. However, articles on endoscopic ultrasound (EUS) and endoscopic resection of esophageal granular cell tumors are few. To evaluate the role of endoscopic ultrasound and endoscopic resection in the diagnosis and treatment of esophageal granular cell tumors. METHODS: A retrospective analysis of 15 patients with esophageal granular cell tumors who underwent endoscopic ultrasound examination and endoscopic resection in our hospital was conducted. The clinical data, endoscopic ultrasound images, endoscopic treatment, pathological characteristics, postoperative complications and follow-up status of all patients were evaluated. Ten board-certified endoscopists independently evaluated the white light endoscopic images of the 15 patients (Test 1) and the endoscopic ultrasound images together with white light endoscopic images of the same patient set (Test 2). RESULT: Female patients accounted for 53.4% of the participants. The average age at the time of diagnosis was 49.13 ± 9.31 years old. Ten lesions (66.67%) showed hypoechoic signal, four lesions (26.67%) showed hyperechoic signal and one lesion showed medium signal. The diagnostic accuracy was significantly higher with Test 2(65.3% vs. 92.0%, p < .001). Complete endoscopic resection was performed in all the patients. No complications occurred in any of the patients. No esophageal stenosis, recurrence, or metastases was found in all patients during the follow-up period. CONCLUSION: The endoscopic ultrasound images of esophageal granular cell tumors have certain characteristics that help diagnose esophageal granular cell tumors. Endoscopic resection of esophageal granular cell tumors is an effective, safe and feasible treatment method.

Cinnamic Acid Improved Lipopolysaccharide-Induced Depressive-Like Behaviors by Inhibiting Neuroinflammation and Oxidative Stress in Mice.

AIM: Recent evidence indicates that neuroinflammation and oxidative stress play vital roles in the pathological process of major depressive disorder (MDD). Cinnamic acid (CA), a naturally occurring organic acid, has been reported to ameliorate neuroinflammation and oxidative stress for treatment of diabetes-related memory deficits. Here, we explored whether CA pretreatment ameliorated lipopolysaccharide (LPS)-induced depressive-like behaviors in mice by suppressing neuroinflammation and by improving oxidative stress status. METHODS: The mice were treated with CA, vehicle, or fluoxetine as a positive control. After 14 days, LPS (1 mg/kg, i.p.) or saline was administered. The depression-like behaviors were examined by the sucrose preference test (SPT), the forced swimming test (FST), and the tail suspension test (TST). Furthermore, the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and brain-derived neurotrophic factor (BDNF) in the hippocampus and cortex of mice were assayed. RESULTS: Our results demonstrated that CA pretreatment at the doses of 100 and 200 mg/kg significantly attenuated depressive-like behaviors in the TST, FST, and SPT. In addition, not only the upregulation of pro-inflammatory cytokines (IL-6 and TNF-α) but also oxidative stress parameters including SOD, GSH, and MDA in the hippocampus and cortex of mice treated with LPS were dramatically improved by CA pretreatment. Finally, CA pretreatment strikingly ameliorated the downregulation of BDNF induced by LPS in the hippocampus and cortex of mice. CONCLUSION: Our results indicated that CA may have therapeutic potential for MDD treatment through attenuating the LPS-induced inflammation and oxidative stress along with significant improvement of BDNF impairment.

[Clinical Study on Early Extubation and Sequential Non-Invasive Respiratory Support for Children with Acute Respiratory Failure Receiving Invasive Mechanical Ventilation].

Objective: To explore the treatment outcome of the strategy of early extubation and then switching to non-invasive mechanical ventilation in children with acute respiratory failure, and the safety and feasibility of using the strategy to replace traditional methods. Methods: A total of 102 children, aged between 1 month to 14 years old, who had acute respiratory failure and were admitted to the pediatric ICU of West China Second University Hospital, Sichuan University between January 2019 and December 2020 were enrolled and randomly assigned to treatment group 1 (n=55) and treatment group 2 (n=47). In addition, 53 children who had the same condition in the 12 month prior to the beginning of the study were included in the control group. In the two treatment groups, the patients were extubated first, and then weaned off the ventilator. In group 1, when the patient met the invasive-non-invasive switching criteria, the tracheal tube was pulled out and non-invasive bi-level positive airway pressure (BiPAP) ventilation was used for respiratory support. In group 2, high-flow nasal cannula (HFNC) oxygen therapy was used for respiratory support. The traditional progressive weaning method was adopted for the control group (extubing and weaning were performed at the same time). The incidence of ventilator-associated pneumonia (VAP) during the period of tracheal intubation was compared and the mortality of the two groups was evaluated from the point when the patients were recruited. At the time of extubation in the treatment groups and extubation plus weaning in the control group, the pressure support levels, or PC above PEEP, intubation time, sequential time (between 2 treatment groups only), weaning failure rate, and the incidence of laryngeal edema and nasal pressure ulcer were compared. Results: The subjects of the study were predominantly infants (93 cases, 60%) and young children (31 cases, 20%). Among the 155 cases, 82 (53%) were male. There was no statistical difference in age distribution or gender among the groups. There was no significant difference in the clinical indicators among the three groups before tracheal intubation. At the time of extubation, the PC above PEEP in the two treatment groups was higher than that in the control group, and higher in group 1 than that of group 2, the difference being statistically significant (P<0.05). The intubation time of the two treatment groups was shorter than that of the control group, and shorter in group 1 than that of group 2 (P<0.05). The sequential time of group 2 was shorter than that of group 1 (P<0.05). The extubation failure rate and the incidence of VAP in the two treatment groups were lower than those in the control group, and there was no statistically significant difference between the two treatment groups. The incidence of nasal pressure ulcers in group 1 was higher than that in the other two groups (P<0.05). There was 1 death in treatment group 1, and no deaths in treatment group 2 or the control group. There was no significant difference in mortality or the incidence of laryngeal edema after extubation in the three groups. Conclusion: Early extubation and then switching to non-invasive mechanical ventilation can be well tolerated by the patients, and can be used in clinical practice as an effective weaning method for children with acute respiratory failure.

Metabolic engineering of astaxanthin-rich maize and its use in the production of biofortified eggs.

Production of the high-value carotenoid astaxanthin, which is widely used in food and feed due to its strong antioxidant activity and colour, is less efficient in cereals than in model plants. Here, we report a new strategy for expressing ß-carotene ketolase and hydroxylase genes from algae, yeasts and flowering plants in the whole seed using a seed-specific bidirectional promoter. Engineered maize events were backcrossed to inbred maize lines with yellow endosperm to generate progenies that accumulate astaxanthin from 47.76 to 111.82 mg/kg DW in seeds, and the maximum level is approximately sixfold higher than those in previous reports (16.2-16.8 mg/kg DW) in cereals. A feeding trial with laying hens indicated that they could take up astaxanthin from the maize and accumulate it in egg yolks (12.10-14.15 mg/kg) without affecting egg production and quality, as observed using astaxanthin from Haematococcus pluvialis. Storage stability evaluation analysis showed that the optimal conditions for long-term storage of astaxanthin-rich maize are at 4 °C in the dark. This study shows that co-expressing of functional genes driven by seed-specific bidirectional promoter could dramatically boost astaxanthin biosynthesis in every parts of kernel including embryo, aleurone layer and starch endosperm other than previous reports in the starch endosperm only. And the staple crop maize could serve as a cost-effective plant factory for reliably producing astaxanthin.

Maternal intake of caffeinated products and birth defects: a systematic review and meta-analysis of observational studies.

Caffeinated products are frequently consumed by women of childbearing age worldwide. It still unclear that whether maternal intake of caffeine associated with an increased risk of birth defects. We searched the databases of PubMed, Embase, the Cochrane Library, and Web of Science for eligible studies through July 2020. All studies examining the association between maternal consumption of caffeine or caffeinated products and birth defects were included. Twenty-nine studies were included in this meta-analysis. Among all the birth defects, maternal caffeine consumption was associated with a higher risk of cardiovascular defects, [odds ratio (OR) 1.17; 95% confidence interval (CI), 1.07-1.28], craniofacial defects (OR 1.09; 95% CI, 1.02-1.17), alimentary tract defects (OR 1.35; 95% CI, 1.16-1.56), and abdominal-wall defects and hernia (OR 1.13; 95% CI, 1.03-1.25). No association was found between maternal caffeine intake and musculoskeletal system defects, genitourinary system defects, nervous system defects, or chromosomal abnormalities. Meanwhile, all three of the caffeine consumption categories (low, moderate, and high) were associated with a higher risk of cardiovascular defects and alimentary tract defects.

Predictive value of coagulation profiles for both initial and repeated immunoglobulin resistance in Kawasaki disease: A prospective cohort study.

BACKGROUND: Intravenous immunoglobulin (IVIG) resistance prediction remains substantial in Kawasaki disease (KD), with limited data on the predictive value of coagulation profile for IVIG resistance, particularly for repeated IVIG resistance. Therefore, the aim of our study was to testify the predictive validity of coagulation profile for both initial IVIG resistance and repeated IVIG resistance in KD. METHODS: A total of 385 KD patients were prospectively recruited between April 2015 and May 2019. Coagulation and other profiles were evaluated between the IVIG-responsive and IVIG-resistant groups. Multivariate logistic regression analysis was applied to determine the association between coagulation profiles and IVIG resistance. ROC curves analysis was further performed to assess the validity of coagulation profiles in predicting both initial IVIG resistance and repeated IVIG resistance. RESULTS: Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), fibrinogen degradation products (FDPs), and D-dimer were significantly increased in the initial IVIG-resistant group with antithrombin III (ATIII) and thrombin time (TT) significantly reduced. Meanwhile, ATIII was declined markedly in repeated IVIG-resistant patients. Multivariate logistic regression analysis showed that PT, APTT, D-dimer, and ATIII were independent risk factors for predicting initial IVIG resistance and ATIII for predicting repeated IVIG-resistant patients with KD. PT, APTT, D-dimer, and ATIII cutoff values of 13.95 s, 41.15 s, 1.48 mg/L, and 89.5% yielded sensitivities of 73%, 32%, 71%, and 81%, and specificities of 55%, 88%, 62%, and 51% for predicting initial IVIG resistance, respectively. The cutoff value of ATIII for predicting repeated IVIG resistance was 68.5%, with sensitivity of 71% and specificity of 55%. CONCLUSIONS: KD patients who have hypercoagulation during the acute phase might be at higher risk of developing IVIG resistance.

Nitrogen flow characteristics of solid waste in China.

The surge in solid waste (SW) has become major issues in the fields of public health and ecological environment fuelled by the rapid development of social economy. The fate of nitrogen contained in SW (SWN) varies with different treatment methods, which will affect the environment to varying degrees. It is of great practical and guiding significance to comprehensively evaluate the sources, fate and its cascading effects of SWN. Here, a systematic SWN flow evaluation of the generation, treatment and emissions in China from 2008 to 2017 was established. During this period, the SWN flow and the N pollution emissions from SW treatment increased by 19.7% and 27.6% respectively, with the domestic garbage being the largest contributor. This shows that it is particularly important to reinforce the classified of domestic garbage and resource recycling in China. Landfill was the main treatment, accounting for 51.8% of the total SWN. Landfill and incineration were the main sources of pollution N emissions, while compost treatment has the lowest contribution rate. It highlights the urgency of changing the waste treatment methods in China. About 92.3% of the N pollution emissions was lost to the atmosphere and 7.7% to the groundwater. NH3 and NOx were the main pollutants to the atmosphere. Special attention is paid to the reduction and control of NH3 in landfill, dumping and compost processes, while NOx in incineration. This study provides scientific basis for management and disposal of SW, so as to reduce its impact on the ecological environment and develop more sustainable policies for China and other developing countries.

Sestrin 2 attenuates sepsis-associated encephalopathy through the promotion of autophagy in hippocampal neurons.

Sepsis-associated encephalopathy (SAE) has typically been associated with a poor prognosis. Although sestrin 2 (SESN2) plays a crucial role in metabolic regulation and the stress response, its expression and functional roles in SAE are still unclear. In the present study, SAE was established in mice through caecal ligation and puncture (CLP). The adeno-associated virus 2 (AAV2)-mediated SESN2 expression (ie overexpression and knockdown) system was injected into the hippocampi of mice with SAE, and subsequently followed by electron microscopic analysis, the Morris water maze task and pathological examination. Our results demonstrated an increase of SESN2 in the hippocampal neurons of mice with SAE, 2-16 hours following CLP. AAV2-mediated ectopic expression of SESN2 attenuated brain damage and loss of learning and memory functions in mice with SAE, and these effects were associated with lower pro-inflammatory cytokines in the hippocampus. Mechanistically, SESN2 promoted unc-51-like kinase 1 (ULK1)-dependent autophagy in hippocampal neurons through the activation of the AMPK/mTOR signalling pathway. Finally, AMPK inhibition by SBI-0206965 blocked SESN2-mediated attenuation of SAE in mice. In conclusion, our findings demonstrated that SESN2 might be a novel pharmacological intervention strategy for SAE treatment through promotion of ULK1-dependent autophagy in hippocampal neurons.

Fibrinogen levels are associated with bleeding in patients with primary immune thrombocytopenia.

Bleeding is the most common clinical symptom and the leading cause of death in patients with primary immune thrombocytopenia (ITP). Our research intends to verify the role of fibrinogen levels as independent determinants of bleeding. We retrospectively analyzed the relationship between fibrinogen levels and bleeding events in 463 patients. Additionally, we confirmed the impact of fibrinogen level on clot firmness in 25 patients via thrombelastography (TEG). Fibrinogen levels (median and inter-quartile range, IQR) were significantly different (p < .001) between bleeding and non-bleeding patients [258(207-314) mg/dL vs. 315(262-407) mg/dL, respectively]. Further analyzes in three subgroups based on platelet (PLT) count showed that non-bleeding patients still had higher fibrinogen levels than bleeding patients. The optimal discriminant threshold of fibrinogen in bleeding was 288.5 mg/dL according to receiver operating characteristic (ROC) curves. Patients were divided into low (LF, 230[193-258] mg/dL) and high (HF, 349[313-424] mg/dL) fibrinogen groups based on this threshold. Bleeding event rates were significantly different (LF: 84.6% vs. HF: 60.4%, P < .001) between the two groups. Multivariable analyses further confirmed these differences. Moreover, TEG parameters showed elevated clot firmness in the HF group. Our data suggest that high fibrinogen levels are associated with reduced bleeding events.

Spatial variation and health risk assessment of fluoride in drinking water in the Chongqing urban areas, China.

Fluoride is an essential trace element for humans, and its deficiency or excess in the environment could lead to disease. To investigate the spatial distribution and health risk assessment of fluoride (F-) in drinking water, 302 tap water samples from Chongqing urban areas, China, were collected to analyze F- using an ion chromatograph. The results showed that (1) F- concentration in drinking water ranged from 0.100 to 0.503 mg/L, with an average of 0.238 ± 0.045 mg/L. (2) The spatial autocorrelation analysis showed that high-low clusters were mostly located in Dadukou District and Beibei District, while low-low clusters were mainly in southern Banan District. (3) The fluoride average daily doses of children, teens and adults were 0.030, 0.029 and 0.031 mg/(kg day). (4) Hazard quotients of excessive fluoride (HQe) of children, teens and adults were 0.51 ± 09, 0.49 ± 0.09 and 0.52 ± 0.10, respectively (inferior to 1.00), whereas hazard quotients of inadequate fluoride (HQi) of those groups were 1.21 ± 0.26, 1.23 ± 0.26 and 1.15 ± 0.25, respectively (superior to 1.00). Therefore, average daily fluoride intake of residents with drinking water was inadequate. This could pose dental caries and osteoporosis threats for residents from Chongqing urban areas.