Cannabidiol is a behavioral modulator in BTBR mouse model of idiopathic autism.

Introduction: The prevalence of Autism Spectrum Disorder (ASD) has drastically risen over the last two decades and is currently estimated to affect 1 in 36 children in the U.S., according to the center for disease control (CDC). This heterogenous neurodevelopmental disorder is characterized by impaired social interactions, communication deficits, and repetitive behaviors plus restricted interest. Autistic individuals also commonly present with a myriad of comorbidities, such as attention deficit hyperactivity disorder, anxiety, and seizures. To date, a pharmacological intervention for the treatment of core autistic symptoms has not been identified. Cannabidiol (CBD), the major nonpsychoactive constituent of Cannabis sativa, is suggested to have multiple therapeutic applications, but its effect(s) on idiopathic autism is unknown. We hypothesized that CBD will effectively attenuate the autism-like behaviors and autism-associated comorbid behaviors in BTBR T+Itpr3tf/J (BTBR) mice, an established mouse model of idiopathic ASD. Methods: Male BTBR mice were injected intraperitoneally with either vehicle, 20 mg/kg CBD or 50 mg/kg CBD daily for two weeks beginning at postnatal day 21 ± 3. On the final treatment day, a battery of behavioral assays were used to evaluate the effects of CBD on the BTBR mice, as compared to age-matched, vehicle-treated C57BL/6 J mice. Results: High dose (50 mg/kg) CBD treatment attenuated the elevated repetitive self-grooming behavior and hyperlocomotion in BTBR mice. The social deficits exhibited by the control BTBR mice were rescued by the 20 mg/kg CBD treatment. Discussion: Our data indicate that different doses for CBD are needed for treating specific ASD-like behaviors. Together, our results suggest that CBD may be an effective drug to ameliorate repetitive/restricted behaviors, social deficits, and autism-associated hyperactivity.

Corrigendum: Comparative efficacy of non-electric cooling techniques to reduce nutrient solution temperature for the sustainable cultivation of summer vegetables in open-air hydroponics.

[This corrects the article DOI: 10.3389/fpls.2024.1340641.].

Comparative efficacy of non-electric cooling techniques to reduce nutrient solution temperature for the sustainable cultivation of summer vegetables in open-air hydroponics.

The cultivation of summer vegetables in open-air nutrient film technique (NFT) hydroponics is limited due to the elevated nutrient solution temperature (NST). In this regard, non-electric evaporative-cooling techniques were explored to maintain NST in open-air NFT hydroponics. Four cooling setups were employed by wrapping polyvinyl chloride (PVC) grow pipes with one and two layers of either wet or dry jute fabrics and attaching them with coiled aluminum pipe buried inside a) wet sand-filled brick tunnels (Cooling Setup I), b) two inverted and vertically stacked earthen pots (Cooling Setup II), c) two inverted and vertically stacked earthen pots externally wrapped with wet jute fabric (Wrapped Cooling Setup II), and d) an earthen pitcher wrapped with wet jute fabric (Cooling Setup III). Wrapping grow pipes with two layers of wet jute fabric reduced NST by 5°C as compared to exposed (naked) grow pipes. The double-layer jute fabric-wrapped grow pipes produced 182% more reduction in NST in comparison to single layer-wrapped grow pipes. Additionally, the installation of Wrapped Cooling Setup II and Cooling Setup III outperformed Cooling Setup I and Cooling Setup II through NST reduction of approximately 4°C in comparison to control. Interestingly, Cooling Setup III showed its effectiveness through NST reductions of 193%, 88%, and 23% during 11 a.m.-12 p.m. as compared to Cooling Setup I, Cooling Setup II, and Wrapped Cooling Setup II, respectively. In contrast, Wrapped Cooling Setup II caused NST reductions of 168%, 191%, and 18% during 2-3 p.m. in comparison to Cooling Setup I, Cooling Setup II, and Cooling Setup III, respectively. Thus, the double-layer jute fabric-wrapped grow pipes linked with Wrapped Cooling Setup II can ensure summer vegetable cultivation in open-air NFT hydroponics as indicated by the survival of five out of 12 vegetable plants till harvest by maintaining NST between 26°C and 28°C.

Comparison of clinical outcomes in patients with mixed angina and pure vasospastic angina.

OBJECTIVE: This study investigated differences in clinical outcomes between mixed angina (MA) and pure vasospastic angina (PVA). METHODS: A total of 524 vasospastic angina patients who did or did not have >50% coronary artery stenosis from January 2005 to January 2021 were divided into two groups (Group 1: PVA, N  = 399; Group 2: MA, N  = 125) and then three groups [Group 1: PVA, N  = 399; Group 2: MA without percutaneous coronary intervention (PCI), N  = 67; Group 3: MA with PCI, N  = 58] for assessment. We recorded the incidence of major adverse cardiac and cerebrovascular events (MACCE: the composite of death, myocardial infarction, nonfatal stroke or rehospitalization) during 3-year clinical follow-up. RESULTS: Compared to the PVA group, there were significant differences in MACCE (20.8% vs. 11.8%, P  = 0.011) and rehospitalization (20.0% vs. 9.8%, P  = 0.002) in the MA group. Kaplan-Meier analysis showed that patients in the MA with PCI group had the highest cumulative incidence rate of MACCE during the 3-year follow-up (log-rank P  < 0.001). CONCLUSION: Compared with the PVA patients, MA patients had significantly worse clinical outcomes during long-term follow-up.

Surgical Treatment of Brucellar Cervical Epidural Abscess.

OBJECTIVES: Brucellar cervical epidural abscess (CEA) is a rare condition with potentially permanent neurological damage if left untreated. This study aims to define the clinical presentation of brucellar CEA and evaluate the outcome of surgical treatment, specifically decompression and fusion surgery. The findings will contribute to understanding whether all patients with brucellar CEA could benefit from this surgical intervention. METHODS: A retrospective study on brucellar spondylitis was conducted at the First Hospital of Jilin University from August 2018 to August 2022. During this period, a total of 37 patients were diagnosed with brucellar spondylitis at the hospital. Out of the 37 cases, six patients (16.2%) were confirmed to have CEA through cervical magnetic resonance imaging examination and serology test results.. RESULTS: Six patients were diagnosed with brucellar CEA (16.2%), of whom 5 successfully underwent anterior cervical decompression and fusion surgery. One patient had a large prevertebral abscess that could only be drained. In combination with effective antibiotic therapy, the clinical performance of the 5 patients who underwent surgery improved after the surgery. The remaining one patient required delayed surgery due to instability of the cervical spine. The follow-up period of all the 6 patients was 6 months. CONCLUSIONS: Brucellosis should be considered as a potential cause of CEA, especially in endemic areas. Timely detection and effective management of this condition are crucial in order to minimize the associated morbidity and mortality. For patients with detectable brucellar CEA, we recommend decompression and fusion surgery.

Regio- and enantioselective CuH-catalyzed 1,2- and 1,4-hydrosilylation of 1,3-enynes.

We report a copper-catalyzed ligand-controlled selective 1,2- and 1,4-hydrosilylation of 1,3-enynes, which furnishes enantiomerically enriched propargyl- and 1,2-allenylsilane products in high yields with excellent enantioselectivities (up to 99% ee). This reaction proceeds under mild conditions, shows broad substrate scope for both 1,3-enynes and trihydrosilanes, and displays excellent regioselectivities. Mechanistic studies based on deuterium-labeling reactions and density functional theory (DFT) calculations suggest that allenylcopper is the dominant reactive intermediate under both 1,2- and 1,4-hydrosilylation conditions, and it undergoes metathesis with silanes via selective four-membered or six-membered transition state, depending on the nature of the ligand. The weak interactions between the ligands and the reacting partners are found to be the key controlling factor for the observed regioselectivity switch. The origin of high enantiocontrol in the 1,4-hydrosilylation is also revealed by high level DLPNO-CCSD(T) calculations.

Clinical Outcomes of Calcium-Channel Blocker vs Beta-Blocker: From the Korean Acute Myocardial Infarction Registry.

Background: Although current guidelines recommend beta-blockers (BBs) after acute myocardial infarction (AMI), the role of calcium-channel blockers (CCBs) has not been well investigated, especially nondihydropyridine. Objectives: This study aimed to compare the effects of CCBs on cardiovascular outcomes compared with BBs in AMI because patients from East Asia have a higher incidence of a vasospastic angina component compared with Western countries. Methods: Among 15,628 patients enrolled in the KAMIR-V (Korean Acute Myocardial Infarction Registry-V), we evaluated 10,650 in-hospital survivors who were treated with either CCBs or BBs. We applied a propensity score for 1:4 pair matching of baseline covariates and Cox regression to compare CCBs and BBs. The primary endpoint was all-cause death at 1 year. The secondary endpoints were 1-year major adverse cardiac and cerebrovascular events, which was the composite of cardiac death, myocardial infarction, revascularization, and readmission due to heart failure and stroke. Results: There was a significant interaction with the treatment arm with left ventricular ejection fraction (LVEF) (P for interaction = 0.011). CCB groups at discharge had higher 1-year cardiac death and major adverse cardiac and cerebrovascular events for patients with LVEF <50% (HR: 4.950; 95% CI: 1.329-18.435; P = 0.017; and HR: 1.810; 95% CI: 1.038-3.158; P = 0.037, respectively) but not for patients with LVEF ≥50% (HR: 0.699; 95% CI: 0.435-1.124; P = 0.140). Conclusions: CCB therapy did not increase adverse cardiovascular events for patients after AMI with preserved LVEF. CCBs can be considered as an alternative for BBs in East Asian patients after AMI with preserved LVEF.

Kinetics study of chloride-activated peracetic acid for purifying bisphenol A: Role of Cl2/HClO and carbon-centered radicals.

Peracetic acid is an emerging oxidant and disinfectant for wastewater purification. In this study, we first developed a comprehensive and accurate model to elucidate the reaction mechanisms and simulate reaction kinetics of peracetic acid (PAA, CH3C(=O)OOH) activated by chloride (Cl-) based on experimental results and literature. A diversity of experiments methods (e.g., quenching experiments, probe compounds degradation, electron paramagnetic resonance (EPR) measurements) and kinetic modeling were used to determine the reactive species. As a result, carbon-centered radicals and free chlorine reactive species (Cl2 and HClO) were devoted to BPA degradation in the PAA/Cl- system. The carbon-centered radicals CH3C(=O)OO•, CH3C(=O)O•, CH3OO•, and •CH3 greatly accelerated BPA degradation with their corresponding kinetics of kCH3C(=O)OO•, BPA = 2 × 108 M-1 s-1, kCH3C(=O)O•, BPA = 2 × 107 M-1 s-1, k•CH3, BPA = 2 × 106 M-1 s-1 and kCH3OO•, BPA = 2 × 104 M-1 s-1. Dissolved Cl2(l) species was also important for BPA degradation with kCl2, BPA of 2 × 107 M-1 s-1, much higher than HClO/ClO- of kHClO, BPA = 1.2 × 101 M-1 s-1 and kClO-, BPA = 9 × 10-3 M-1 s-1. While free chlorine tends to transform BPA to estrogenic chlorinated organic products, the primary degradation of BPA by carbon-centered radicals results in chlorine-free products, reducing the production of disinfection byproducts during the treatment of saline wastewater. This study improves the knowledge of reaction kinetics and mechanism and reactive species generation in the PAA/Cl- system.

Statin therapy reduces dementia risk in atrial fibrillation patients receiving oral anticoagulants.

AIMS: Atrial fibrillation (AF) is linked to an increased risk of dementia, even in stroke-free patients. The impact of statin therapy on dementia risk is unclear in AF patients receiving oral anticoagulant (OAC) (vitamin K antagonist and direct-acting OAC). We sought to investigate the impact of statin therapy on dementia risk in AF patients receiving OAC. METHODS AND RESULTS: Using the Korean National Health Insurance Service database, 91 018 non-valvular AF (NVAF) patients from January 2013 to December 2017 were included in the analysis. Of the total, 17 700 patients (19.4%) were in the statin therapy group, and 73 318 patients (80.6%) were in the non-statin therapy group. The primary endpoint was the occurrence of dementia. The median duration of follow-up was 2.1 years. Statin therapy was associated with a significantly lower dementia risk than non-statin therapy for CHA2DS2-VASc scores ≥2 (hazard ratio = 0.77, 95% confidence interval 0.64-0.90, P = 0.026) in NVAF patients receiving OAC. The statin therapy group had a significantly lower dementia risk in a dose-dependent relationship compared with the non-statin therapy group (P for trend <0.001). CONCLUSION: In NVAF patients who received OAC, statin therapy lowered the dementia risk compared with no statin therapy. Furthermore, statin therapy is associated with a dose-dependent reduction in dementia risk.

Effect of N-oleoyl dopamine on myofibroblast trans-differentiation of retinal pigment epithelial cells.

Retinal pigment epithelial (RPE) cells contribute to several clinical conditions resulting in retinal fibrotic scars. Myofibroblast trans-differentiation of RPE cells is a critical step in the process of retinal fibrosis. In this study, we investigated the effects of N-oleoyl dopamine (OLDA), a newer endocannabinoid with a structure distinct from classic endocannabinoids, on TGF-ß2-induced myofibroblast trans-differentiation of porcine RPE cells. Using an in vitro collagen matrix contraction assay, OLDA was found to inhibit TGF-ß2 induced contraction of collagen matrices by porcine RPE cells. This effect was concentration-dependent, with significant inhibition of contraction observed at 3 µM and 10 µM. OLDA did not affect the proliferation of porcine RPE cells. Immunocytochemistry showed that at 3 µM, OLDA decreased incorporation of α-SMA in the stress fibers of TGF-ß2-treated RPE cells. In addition, western blot analysis showed that 3 µM OLDA significantly downregulated TGF-ß2-induced α-SMA protein expression. Taken together these results demonstrate that OLDA inhibits TGF-ß induced myofibroblast trans-differentiation of RPE cells. It has been established that classic endocannabinoid such as anandamide, by activating the CB1 cannabinoid receptor, promote fibrosis in multiple organ systems. In contrast, this study demonstrates that OLDA, an endocannabinoid with a chemical structure distinct from classic endocannabinoids, inhibits myofibroblast trans-differentiation, an important step in fibrosis. Unlike classic endocannabinoids, OLDA has weak affinity for the CB1 receptor. Instead, OLDA acts on non-classic cannabinoid receptors such as GPR119, GPR6, and TRPV1. Therefore, our study indicates that the newer endocannabinoid OLDA and its non-classic cannabinoid receptors could potentially be novel therapeutic targets for treating ocular diseases involving retinal fibrosis and fibrotic pathologies in other organ systems.

Fine mapping and gene silencing pinpoint Capana10g002229 as a strong candidate gene regulating the deciduous character of ripe pepper fruit (Capsicum spp.).

KEY MESSAGE: The pepper S locus, which controls the deciduous character of ripe fruit, was first fine mapped into an interval with a physical length of ~ 38.03 kb on chromosome P10. Capana10g002229, encoding a polygalacturonase, was proposed as a strong candidate gene based on sequence comparison, expression pattern analysis and virus-induced gene silencing (VIGS). The deciduous character of ripe fruit, which is controlled by the dominant S locus, is a domesticated trait with potential value in the pepper processing industry (Capsicum spp.). However, the gene associated with the S locus has not been identified. Here, one major QTL designated S10.1 was detected by using the F2 population (n = 155) derived from BA3 (Capsicum annuum) × YNXML (Capsicum frutescens) and was further verified in an intraspecific backcross population (n = 254) derived from the cross between BB3 (C. annuum) and its wild relative Chiltepin (C. annuum var. glabriusculum) with BB3 as the recurrent parent. Then, a large BC1F2 population derived from the self-pollination of BB3 × (BB3 × Chiltepin) individuals and comprising 4217 individuals was used to screen the recombinants, and the S locus was ultimately delimited into a 38.03-kb region on chromosome P10 harbouring four annotated genes. Capana10g002229, encoding a polygalacturonase (PG), was proposed as the best candidate gene for S based on sequence comparison and expression pattern analyses. Downregulation of Capana10g002229 in fruits through VIGS significantly delayed fruit softening and abscission from the fruit-receptacle junction. Taken together, the results show that Capana10g002229 could be regarded as a strong candidate gene associated with the S locus in pepper. These findings not only lay a foundation for deciphering the molecular mechanisms underlying pepper domestication but also provide a strategy for genetic improvement of the deciduous character of ripe fruit using a marker-assisted selection approach.

EG-Unet: Edge-Guided cascaded networks for automated frontal brain segmentation in MR images.

Accurate segmentation of frontal lobe areas on magnetic resonance imaging (MRI) can assist in diagnosing and managing idiopathic normal-pressure hydrocephalus. However, frontal lobe segmentation is challenging due to the complexity of the degree and shape of damage and the ambiguity of the boundaries of frontal lobe sites. Therefore, to extract the rich edge information and feature representation of the frontal lobe, this paper designs an edge guidance (EG) module to enhance the representation of edge features. Accordingly, an edge-guided cascade network framework (EG-Net) is proposed to segment frontal lobe parts automatically. Two-dimensional MRI slice images are fed into the edge generation and segmentation networks. First, the edge generation network extracts the edge information from the input image. Then, the edge information is sent to the EG module to generate an edge attention map for feature representation enhancement. Meanwhile, multi-scale attentional convolution (MSA) is utilized in the feature coding stage of the segmentation network to obtain feature responses from different perceptual fields in the coding stage and enrich the spatial context information. Besides, the feature fusion module is employed to selectively aggregate the multi-scale features in the coding stage with the edge features output by the EG module. Finally, the two components are fused, and a decoder recovers the spatial information to generate the final prediction results. An extensive quantitative comparison is performed on a publicly available brain MRI dataset (MICCAI 2012) to evaluate the effectiveness of the proposed algorithm. The experimental results indicate that the proposed method achieves an average DICE score of 95.77% compared to some advanced methods, which is 4.96% better than the classical U-Net. The results demonstrate the potential of the proposed EG-Net in improving the accuracy of frontal edge pixel classification through edge guidance.

Overexpression of Krüppel-Like Factor 9 Enhances the Antitumor Properties of Paclitaxel in Malignant Melanoma-Derived Cell Lines.

Over the past decade, the treatment of metastatic melanoma has improved significantly due to the development of innovative therapies, such as drugs that target the BRAF/MAPK kinase pathway and the PD-1 pathway. However, these therapies do not work for all patients, highlighting the need for additional research on the pathophysiology of melanoma. Paclitaxel is a chemotherapeutic agent used when first-line treatments are unsuccessful; however, its efficacy is limited. Since Krüppel-like factor 9 (KLF9) (antioxidant repressor) is downregulated in melanoma, we propose that restoring KLF9 levels may sensitize malignant melanoma to chemotherapeutic agents, such as paclitaxel. We used adenovirus overexpression and siRNA technologies to assess the role of KLF9 in mediating the response of malignant melanoma-derived cell lines RPMI-7951 and A375 to paclitaxel treatment. We found that increasing KLF9 levels potentiates the effectiveness of paclitaxel, as shown by apoptotic parameters such as decreased cell viability, pro-caspase-3 activation, increased number of annexin V-positive cells, and reduction in nuclear proliferation marker (KI67). These results suggest that KLF9 may be a potential target for improving chemotherapeutic response in melanoma.

Efficacy and Safety of Coadministered Ezetimibe-Rosuvastatin plus Telmisartan in South Korean Patients with Dyslipidemia and Hypertension: A Multicenter, Randomized, Double-Blind, Active-Controlled, Phase III Trial.

BACKGROUND: The introduction of a fixed-dose combination (FDC) is expected to improve treatment compliance. METHODS: There were 181 subjects who were randomized to three groups: ezetimibe-rosuvastatin 10/20 mg + telmisartan 80 mg, ezetimibe-rosuvastatin 10/20 mg, and telmisartan 80 mg. The primary outcomes were change in mean sitting systolic blood pressure (MSSBP) and percentage change in low-density-lipoprotein cholesterol (LDL-C) compared to baseline at week 8. RESULTS: The least-square mean (SE) in MSSBP changes between the ezetimibe-rosuvastatin 10/20 mg + telmisartan 80 mg group and the ezetimibe-rosuvastatin 10/20 mg group were -25.81 (2.34) mmHg and -7.66 (2.45) mmHg. There was a significant difference between the two groups (-18.15 (2.83) mmHg, 95% CI -23.75 to -12.56, p < 0.0001). Changes in least-square mean (SE) in LDL-C between the ezetimibe-rosuvastatin 10/20 mg + telmisartan 80 mg group and the telmisartan 80 mg group were -63.82 (2.87)% and -2.48 (3.12)%. A significant difference was observed between the two groups (-61.34 (3.33)%, 95% CI -67.91 to -54.78, p < 0.0001). No serious adverse events were observed. CONCLUSIONS: Ezetimibe-rosuvastatin plus telmisartan treatment is effective and safe when compared to either ezetimibe-rosuvastatin or telmisartan.

LC-MS/MS quantitation of non-psychotropic cannabinoid cannabidiol in aqueous humor.

Cannabidiol (CBD) is the most abundant non-psychotropic phytocannabinoid isolated from Cannabis sativa. To support preclinical studies of ocular pharmacology of CBD, a bioanalytical method was developed and validated for quantification of CBD in aqueous humor using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Aqueous humor samples were subjected to protein precipitation by acetonitrile, followed by chromatographic separation using reversed phase LC on a Raptor ARC-18 column with mobile phase A: 0.1 % (v/v) formic acid in water (B) 0.1 % formic acid in acetonitrile (B) as eluents. Detection was carried out with a triple quadrupole mass spectrometer with electrospray ionization operated in positive ion mode. Stable-isotope labeled CBD (CBD-d3) was used as internal standard. The total run time was 8 min. Quantification was accomplished within the validated concentration range of 0.5-500 ng/mL for CBD using a 5 µL sample. The lower limit of quantitation was 0.5 ng/mL. Inter- and intra-day precision is 4.737-7.620 % and 3.426-5.830 %, respectively. Inter- and intra-day accuracy ranged between 99.01 % and 100.2 % and 99.85-101.4 % respectively. The extraction recoveries were found to be 66.06 ± 5.146 %. The established method was successfully applied to investigate ocular pharmacokinetics of CBD in mice. Following intraperitoneal (i.p.) administration of 50 mg/kg CBD, its concentration reaches a Cmax of 71.55 ± 36.64 ng/mL in aqueous humor, with a Tmax of 2 h and a half-life of 1.046 h. The AUC was 183.4 ± 49.17 ng * h/mL. The development and validation of this LC-MS/MS method is an important step toward the goal of assessing the aqueous humor concentrations of CBD and correlating the concentrations of this phytocannabinoid with its ocular pharmacologic effects.

Case report: A rare case of massive peripheral nerve melanotic schwannoma and review of the literature.

Melanotic schwannoma is a rare tumor with indeterminate biologic behavior and varying treatment recommendations. Just about 200 cases have been reported worldwide, in which occurred in peripheral nerves has even less reported. Due to the lack of cognition of melanotic schwannoma, it is easy to be misdiagnosed and mistreatment in primary hospitals. Herein, we presented a case of massive melanotic schwannoma growing in the brachial plexus of an elderly male patient. First, the patient underwent a left forearm tumor resection in the local primary hospital because a painless lump was found there in 2017, of which details remain unclear. After this operation, the patient developed the symptoms of left median nerve injury. Thus, he came to our hospital and underwent a second operation. During this operation, we found that a part of the median nerve was absent at the left forearm, and the remanent median nerve, from the broken end to the elbow, was totally turned black, which was accompanied by petroleum-like exudate. Losing the opportunity for nerve repair, the black nerve was removed extensively and thoroughly. Postoperative pathological diagnosis revealed that the tumor was melanotic schwannoma. Then 4 years later, the tumor recurrence again, which led to the paralysis of the whole left arm and severe nerve pain, and the pulmonary metastasis of the tumor was detected at the same time. The black nerve was resected again in our hospital, and the nerve pain was partially relieved after the operation. To the best of our knowledge, it is the first time to report a melanotic schwannoma case that happened in the peripheral nerve trunk and then spread to the whole brachial plexus. There were many questions that worthy of discussion could be invited from this case, and we analyzed and discussed them based on the relevant literature. In conclusion, we reported a rare case of melanotic schwannoma that happened in the brachial plexus and illustrated the problems of the diagnosis and treatment of it based on the analysis of the relevant literature, which is helpful for the cognition of this rare nerve tumor.

Sex differences between serum uric acid levels and cardiovascular outcomes in patients with coronary artery disease after stent implantation.

Background: The relationship between elevated serum uric acid (SUA) levels and cardiovascular outcomes after stent implantation remains uncertain. This study sought to evaluate the impact of SUA on 12-month cardiovascular outcomes after stent implantation. Methods: We performed a retrospective study of patients who successfully underwent stent implantation and enrolled 3,222 patients with coronary artery disease (CAD) from a single center. SUA levels were measured before stent implantation. The patients were divided into six groups (<4, 4-4.9, 5-5.9, 6-6.9, 7-7.9 and ≥ 8 mg/dL) at SUA intervals of 1.0 mg/dL. The incidence of cardiovascular outcomes in the six groups was monitored for 1 year after stent implantation and the hazard ratios were estimated. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for cardiovascular outcomes were estimated using a Cox proportional hazard regression analysis. The primary endpoint was all-cause death. The secondary endpoint was a composite of all-cause death, myocardial infarction, target vessel revascularization, stent thrombosis and stroke. The follow-up duration was 12 months. Results: Over the 12-month follow-up period, there were 101 all-cause deaths and 218 MACCE. After adjustment for several parameters, the group with SUA levels of more than or equal to 8 mg/dL had significantly higher hazard ratios in the incidence of all-cause death or MACCE. The group with <4.0 mg/dL had significantly higher hazard ratios in all-cause death only in male patients. In contrast, there were no significant differences observed for cardiovascular outcomes in female patients. Conclusions: Our study identified a U-shaped association between SUA levels and cardiovascular outcomes during 12-month follow-up for males, but not for females. Further studies are warranted to clarify the sex differences between SUA levels and clinical outcomes.

Elevated serum anti-Saccharomyces cerevisiae antibody accompanied by gut mycobiota dysbiosis as a biomarker of diagnosis in patients with de novo Parkinson disease.

BACKGROUND AND PURPOSE: Intestinal inflammation and gut microbiota dysbiosis contribute to Parkinson disease (PD) pathogenesis, and growing evidence suggests associations between inflammatory bowel diseases (IBD) and PD. Considered as markers of chronic gastrointestinal inflammation, elevated serum anti-Saccharomyces cerevisiae antibody (ASCA) levels, against certain gut fungal components, are related to IBD, but their effect on PD is yet to be investigated. METHODS: Serum ASCA IgG and IgA levels were measured using an enzyme-linked immunosorbent assay, and the gut mycobiota communities were investigated using ITS2 sequencing and analyzed using the Qiime pipeline. RESULTS: The study included 393 subjects (148 healthy controls [HCs], 140 with PD, and 105 with essential tremor [ET]). Both serum ASCA IgG and IgA levels were significantly higher in the PD group than in the ET and HC groups. Combining serum ASCA levels and the occurrence of constipation could discriminate patients with PD from controls (area under the curve [AUC] = 0.81, 95% confidence interval [CI] = 0.76-0.86) and from patients with ET (AUC = 0.85, 95% CI = 0.79-0.89). Furthermore, the composition of the gut fungal community differed between the PD and HC groups. The relative abundances of Saccharomyces cerevisiae, Aspergillus, Candida solani, Aspergillus flavus, ASV601_Fungi, ASV866_Fungi, and ASV755_Fungi were significantly higher in the PD group, and enriched Malassezia restricta was found in the HC group. CONCLUSIONS: Our study identified elevated serum ASCA levels and enriched gut Saccharomyces cerevisiae in de novo PD.

Protective effect of melatonin against oxygen-induced retinopathy: a study based on the HMGB1/NF-κB/NLRP3 axis / 中国当代儿科杂志

OBJECTIVES@#To study the protective effect of melatonin (Mel) against oxygen-induced retinopathy (OIR) in neonatal mice and the role of the HMGB1/NF-κB/NLRP3 axis.@*METHODS@#Neonatal C57BL/6J mice, aged 7 days, were randomly divided into a control group, a model group (OIR group), and a Mel treatment group (OIR+Mel group), with 9 mice in each group. The hyperoxia induction method was used to establish a model of OIR. Hematoxylin and eosin staining and retinal flat-mount preparation were used to observe retinal structure and neovascularization. Immunofluorescent staining was used to measure the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis and lymphocyte antigen 6G. Colorimetry was used to measure the activity of myeloperoxidase.@*RESULTS@#The OIR group had destruction of retinal structure with a large perfusion-free area and neovascularization, while the OIR+Mel group had improvement in destruction of retinal structure with reductions in neovascularization and perfusion-free area. Compared with the control group, the OIR group had significant increases in the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis, the expression of lymphocyte antigen 6G, and the activity of myeloperoxidase (P<0.05). Compared with the OIR group, the OIR+Mel group had significant reductions in the above indices (P<0.05). Compared with the control group, the OIR group had significant reductions in the expression of melatonin receptors in the retina (P<0.05). Compared with the OIR group, the OIR+Mel group had significant increases in the expression of melatonin receptors (P<0.05).@*CONCLUSIONS@#Mel can alleviate OIR-induced retinal damage in neonatal mice by inhibiting the HMGB1/NF-κB/NLRP3 axis and may exert an effect through the melatonin receptor pathway.

Establishment and evaluation of a method for extracting exogenous short DNA fragments of Schistosoma japonicum from urine samples / 中国血吸虫病防治杂志

Objective To establish the method for extracting exogenous short DNA fragments of Schistosoma japonicum from urine samples, and to evaluate the efficiency of this method for extraction from urine samples treated with various methods. Methods The S. japonicum SjG28 gene fragment was selected as a target sequence, and the 81 bp short DNA fragment was amplified on the target sequence using PCR assay. Following characterization using sequencing, the short DNA fragment was added into the urine samples as an exogenous short DNA fragment. Primers and probes were designed with SjG28 as a target gene, to establish the real-time fluorescent quantitative PCR (qPCR) assay. The sensitivity of this qPCR assay was evaluated with exogenous short DNA fragments that were diluted at a 1:10 dilution ratio as the DNA template, and the specificity of the qPCR assay was evaluated with the genomic DNA of S. mansoni, S. haematobium, Babesia, Ancyiostoma duodenaie, Cionorchis sinensis, and Paragonimus westermani as DNA templates. Exogenous short DNA fragments were added into artificial and healthy volunteers’ urine samples, followed by pH adjustment, centrifugation and concentration, and the efficiency of extracting exogenous short DNA fragments from urine samples was compared with the QIAmp Viral RNA Mini Kit (Qiagen kit) and BIOG cfDNA easy kit (BIOG kit). Results An 81 bp small DNA fragment of S. japonicum was successfully prepared, and the lowest detection limit of the established qPCR assay was 100 copies/μL of the 81 bp small DNA fragment of S. japonicum. If the genomic DNA of S. japonicum, S. mansoni, S. haematobium, Babesia, A. duodenaie, C. sinensis, and P. westermani served as DNA templates, the qPCR assay only detected fluorescent signals with S. japonicum genomic DNA as the DNA template. If the pH values of artificial urine samples were adjusted to 5, 6, 7 and 8, the recovery rates were (49.12 ± 2.09)%, (84.52 ± 4.96)%, (89.38 ± 3.32)% and (87.82 ± 3.90)% for extracting the exogenous short DNA fragment of S. japonicum with the Qiagen kit, and were (2.30 ± 0.07)%, (8.11% ± 0.26)%, (13.35 ± 0.61)% and (20.82 ± 0.68)% with the BIOG kit, respectively (t = 38.702, 26.955, 39.042 and 29.571; all P values < 0.01). If the Qiagen kit was used for extracting the exogenous short DNA fragment from artificial urine samples, the lowest recovery rate was seen from urine samples with a pH value of 5 (all P values < 0.05), and there were no significant differences in the recovery rate from urine samples with pH values of 6, 7 and 8 (all P values > 0.05). Following centrifugation of artificial [(64.30 ± 1.00)% vs. (58.87 ± 0.26)%; t = 12.033, P < 0.05] and healthy volunteers’ urine samples [(31 165 ± 1 017) copies/μL vs. (28 471 ± 818) copies/μL; t = 23.164, P < 0.05]. In addition, concentration of artificial urine samples with the 10 kDa Centrifugal Filter and concentration of healthy volunteers’ urine samples with the 100 kDa Centrifugal Filter were both effective to increase the recovery of the Qiagen kit for extracting the exogenous short DNA fragment of S. japonicum (both P values < 0.01). Conclusions A method for extracting exogenous short DNA fragments of S. japonicum from urine samples has been successfully established, and the Qiagen kit has a high extraction efficiency. Adjustment of urine pH to 6 to 8 and concentration of healthy volunteers’ urine samples with the 100 kDa Centrifugal Filter are both effective to increase the efficiency of extracting exogenous short DNA fragments of S. japonicum.