GWAS identifies two important genes involved in Chinese chestnut weight and leaf length regulation.

There are many factors that affect the yield of Chinese chestnut (Castanea mollissima), with single nut weight (SNW) being one of the most important. Leaf length is also related to Chinese chestnut yield. However, the genetic architecture and gene function associated with Chinese chestnut nut yield have not been fully explored. In this study, we performed genotyping by sequencing 151 Chinese chestnut cultivars, followed by a genome-wide association study (GWAS) on six horticultural traits. First, we analyzed the phylogeny of the Chinese chestnut and found that the Chinese chestnut cultivars divided into two ecotypes, a northern and southern cultivar group. Differences between the cultivated populations were found in the pathways of plant growth and adaptation to the environment. In the selected regions, we also found interesting tandemly arrayed genes that may influence Chinese chestnut traits and environmental adaptability. To further investigate which horticultural traits were selected, we performed a GWAS using six horticultural traits from 151 cultivars. Forty-five loci that strongly associated with horticultural traits were identified, and six genes highly associated with these traits were screened. In addition, a candidate gene associated with SNW, APETALA2 (CmAP2), and another candidate gene associated with leaf length (LL), CRYPTOCHROME INTERACTING BASIC HELIX-LOOP-HELIX 1 (CmCIB1), were verified in Chinese chestnut and Arabidopsis (Arabidopsis thaliana). Our results showed that CmAP2 affected SNW by negatively regulating cell size. CmCIB1 regulated the elongation of new shoots and leaves by inducing cell elongation, potentially affecting photosynthesis. This study provided valuable information and insights for Chinese chestnut breeding research.

Density-dependent species interactions modulate alpine treeline shifts.

Species interactions such as facilitation and competition play a crucial role in driving species range shifts. However, density dependence as a key feature of these processes has received little attention in both empirical and modelling studies. Herein, we used a novel, individual-based treeline model informed by rich in situ observations to quantify the contribution of density-dependent species interactions to alpine treeline dynamics, an iconic biome boundary recognized as an indicator of global warming. We found that competition and facilitation dominate in dense versus sparse vegetation scenarios respectively. The optimal balance between these two effects was identified at an intermediate vegetation thickness where the treeline elevation was the highest. Furthermore, treeline shift rates decreased sharply with vegetation thickness and the associated transition from positive to negative species interactions. We thus postulate that vegetation density must be considered when modelling species range dynamics to avoid inadequate predictions of its responses to climate warming.

Colorectal cancer harboring EGFR kinase domain duplication response to EGFR tyrosine kinase inhibitors.

Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare, recurrent oncogenic variant that constitutively activates EGFR in non-small-cell lung cancer. Herein, we report the case of a 70-year-old man with resectable colorectal adenocarcinoma who underwent surgery followed by adjuvant therapy. He relapsed with multiple liver metastases and received standard chemotherapy until his disease became refractory. Comprehensive genomic profiling of his postoperative colorectal cancer tissue revealed EGFR-KDD. He was treated with an EGFR tyrosine kinase inhibitor (TKI), afatinib and achieved a partial response (- 55%) after 8 weeks; however, he developed massive malignant ascites after 13 weeks. Osimertinib, another EGFR-TKI, controlled his tumors for 9 months. Patient-derived cancer organoids from his malignant ascites confirmed sensitivity to EGFR-TKIs. The findings suggest that EGFR-TKIs can be a potential treatment option for this molecular subgroup.

Electrochemical Lateral Flow Immunoassay with Built-In Electrodes for Ultrasensitive and Wireless Detection of Inflammatory Biomarkers.

Paper-based lateral flow immunoassays (LFIAs) are cost-effective, portable, and simple methods for detection of diverse analytes, which however only provide qualitative or semiquantitative results and lack sufficient sensitivity. A combination of LFIA and electrochemical detection, namely, electrochemical lateral flow immunoassay (eLFIA), enables quantitative detection of analytes with high sensitivity, but the integration of external electrodes makes the system relatively expensive and unstable. Herein, the working, counter, and reference electrodes were prepared directly on the nitrocellulose membrane using screen printing, which remarkably simplified the structure of eLFIA and decreased the cost. Moreover, a horseradish peroxidase (HRP)-based electrochemical signal amplification strategy was used for further increasing the analytical sensitivity. HRP captured on the working electrode can catalyze the oxidation of tetramethylbenzidine (TMB) to form the TMB-TMBox precipitate on the electrode surface, which as an electrochemically active product can output an amplified current for quantification. We demonstrated that the eLFIA could detect low-abundant inflammatory biomarkers in human plasma samples with limits of detection of 0.17 and 0.54 pg mL-1 for interleukin-6 and C-reactive protein, respectively. Finally, a fully portable system was fabricated by integrating eLFIA with a flexible and wireless electrochemical workstation, realizing the point-of-care detection of interleukin-6.

A comprehensive review of AAV-mediated strategies targeting microglia for therapeutic intervention of neurodegenerative diseases.

Neurodegenerative diseases pose a significant health burden globally, with limited treatment options available. Among the various cell types involved in the pathogenesis of these disorders, microglia, the resident immune cells of the central nervous system, play a pivotal role. Dysregulated microglial activation contributes to neuroinflammation and neuronal damage, making them an attractive target for therapeutic intervention. Adeno-associated virus (AAV) vectors have emerged as powerful tools for delivering therapeutic genes to specific cell types in the central nervous system with remarkable precision and safety. In the current review, we discuss the strategies employed to achieve selective transduction of microglia, including the use of cell-specific promoters, engineered capsids, and microRNA (miRNA) strategies. Additionally, we address the challenges and future directions in the development of AAV-based therapies targeting microglia. Overall, AAV-mediated targeting of microglia holds promise as a novel therapeutic approach for neurodegenerative diseases, offering the potential to modify disease progression and improve patient outcomes.

Specific metabolic and cellular mechanisms of the vegetative desiccation tolerance in resurrection plants for adaptation to extreme dryness.

MAIN CONCLUSION: Substantial advancements have been made in our comprehension of vegetative desiccation tolerance in resurrection plants, and further research is still warranted to elucidate the mechanisms governing distinct cellular adaptations. Resurrection plants are commonly referred to as a small group of extremophile vascular plants that exhibit vegetative desiccation tolerance (VDT), meaning that their vegetative tissues can survive extreme drought stress (> 90% water loss) and subsequently recover rapidly upon rehydration. In contrast to most vascular plants, which typically employ water-saving strategies to resist partial water loss and optimize water absorption and utilization to a limited extent under moderate drought stress, ultimately succumbing to cell death when confronted with severe and extreme drought conditions, resurrection plants have evolved unique mechanisms of VDT, enabling them to maintain viability even in the absence of water for extended periods, permitting them to rejuvenate without harm upon water contact. Understanding the mechanisms associated with VDT in resurrection plants holds the promise of expanding our understanding of how plants adapt to exceedingly arid environments, a phenomenon increasingly prevalent due to global warming. This review offers an updated and comprehensive overview of recent advances in VDT within resurrection plants, with particular emphasis on elucidating the metabolic and cellular adaptations during desiccation, including the intricate processes of cell wall folding and the prevention of cell death. Furthermore, this review highlights existing unanswered questions in the field, suggests potential avenues for further research to gain deeper insights into the remarkable VDT adaptations observed in resurrection plants, and highlights the potential application of VDT-derived techniques in crop breeding to enhance tolerance to extreme drought stress.

The role of the ER stress sensor IRE1 in cardiovascular diseases.

Despite enormous advances in the treatment of cardiovascular diseases, including I/R injury and heart failure, heart diseases remain a leading cause of mortality worldwide. Inositol-requiring enzyme 1 (IRE1) is an evolutionarily conserved sensor endoplasmic reticulum (ER) transmembrane protein that senses ER stress. It manages ER stress induced by the accumulation of unfolded/misfolded proteins via the unfolded protein response (UPR). However, if the stress still persists, the UPR pathways are activated and induce cell death. Emerging evidence shows that, beyond the UPR, IRE1 participates in the progression of cardiovascular diseases by regulating inflammation levels, immunity, and lipid metabolism. Here, we summarize the recent findings and discuss the potential therapeutic effects of IRE1 in the treatment of cardiovascular diseases.

FOXO1 reduces STAT3 activation and causes impaired mitochondrial quality control in diabetic cardiomyopathy.

AIMS: To investigate the role of FOXO1 in STAT3 activation and mitochondrial quality control in the diabetic heart. METHODS: Type 1 diabetes mellitus (T1DM) was induced in rats by a single intraperitoneal injection of 60 mg · kg-1 streptozotocin (STZ), while type 2 diabetes mellitus (T2DM) was induced in rats with a high-fat diet through intraperitoneal injection of 35 mg · kg-1 STZ. Primary neonatal mouse cardiomyocytes and H9c2 cells were exposed to low glucose (5.5 mM) or high glucose (HG; 30 mM) with or without treatment with the FOXO1 inhibitor AS1842856 (1 µM) for 24 hours. In addition, the diabetic db/db mice (aged 8 weeks) and sex- and age-matched non-diabetic db/+ mice were treated with vehicle or AS1842856 by oral gavage for 15 days at a dose of 5 mg · kg-1 · d-1 . RESULTS: Rats with T1DM or T2DM had excessive cardiac FOXO1 activation, accompanied by decreased STAT3 activation. Immunofluorescence and immunoprecipitation analysis showed colocalization and association of FOXO1 and STAT3 under basal conditions in isolated cardiomyocytes. Selective inhibition of FOXO1 activation by AS1842856 or FOXO1 siRNA transfection improved STAT3 activation, mitophagy and mitochondrial fusion, and decreased mitochondrial fission in isolated cardiomyocytes exposed to HG. Transfection with STAT3 siRNA further reduced mitophagy, mitochondrial fusion and increased mitochondrial fission in HG-treated cardiomyocytes. AS1842856 alleviated cardiac dysfunction, pathological damage and improved STAT3 activation, mitophagy and mitochondrial dynamics in diabetic db/db mice. Additionally, AS1842856 improved mitochondrial function indicated by increased mitochondrial membrane potential and adenosine triphosphate production and decreased mitochondrial reactive oxygen species production in isolated cardiomyocytes exposed to HG. CONCLUSIONS: Excessive FOXO1 activation during diabetes reduces STAT3 activation, with subsequent impairment of mitochondrial quality, ultimately promoting the development of diabetic cardiomyopathy.

Cathodic electrochemiluminescence of L012 and its application in antioxidant detection.

Cathodic electrochemiluminescence (ECL) of a luminol (or its analogues)-dissolved oxygen (O2) system is an ideal alternative to ECL of the traditional luminol-hydrogen peroxide (H2O2) system, which can efficiently avoid the self-decomposition of H2O2 at room temperature. However, the mechanism for the generation of cathodic ECL by the luminol (or its analogues)-O2 system is still ambiguous. Herein, we report the study of cathodic ECL generation by the L012-O2 system at a glassy carbon electrode (GCE). The types of reactive oxygen species (ROS) involved generated during ECL reactions were verified. A possible reaction mechanism for the system was proposed and the rate constants of related reactions were estimated. Furthermore, several intermediates of L012 involved in the proposed pathways were validated by electrochemistry-coupled mass spectrometry. Finally, the cathodic ECL system was successfully used for measuring the antioxidant capacity of commercial juice with Trolox as a standard.

Mitigating lead-induced osteoporosis: The role of butyrate in gut-bone axis restoration.

Lead (Pb) is an environmentally widespread bone toxic pollutant, contributes to the development of osteoporosis. Butyric acid, mainly produced by the fermentation of indigestible dietary fiber by gut microbiota, plays a pivotal role in the maintenance of bone homeostasis. However, the effects of butyric acids on the Pb induced osteoporosis have not yet been elucidated. In this study, our results showed that Pb exposure was negatively related to the abundance of butyric acid, in the Pb-exposed population and Pb-exposed mice. Pb exposure caused gut microbiota disorders, resulting in the decline of butyric acid-producing bacteria, such as Butyrivibrio_crossotus, Clostridium_sp._JN9, and the butyrate-producing enzymes through the acetyl-CoA pathway. Moreover, results from the NHANES data suggested that dietary intake of butyrate was associated with a reduced risk of osteoporosis in lead-burdened populations, particularly among men or participants aged 18-60 years. In addition, butyrate supplementation in mice with chronic Pb exposure improved the bone microarchitectures, repaired intestinal damage, upregulated the proportion of Treg cells. Taken together, these results demonstrated that chronic Pb exposure disturbs the gut-bone axis, which can be restored by butyric acid supplement. Our results suggest that butyrate supplementation is a possible therapeutic strategy for lead-induced bone toxicity.

Scalable synchronization cluster in networked chaotic oscillators.

Cluster synchronization in synthetic networks of coupled chaotic oscillators is investigated. It is found that despite the asymmetric nature of the network structure, a subset of the oscillators can be synchronized as a cluster while the other oscillators remain desynchronized. Interestingly, with the increase in the coupling strength, the cluster is expanding gradually by recruiting the desynchronized oscillators one by one. This new synchronization phenomenon, which is named "scalable synchronization cluster," is explored theoretically by the method of eigenvector-based analysis, and it is revealed that the scalability of the cluster is attributed to the unique feature of the eigenvectors of the network coupling matrix. The transient dynamics of the cluster in response to random perturbations are also studied, and it is shown that in restoring to the synchronization state, oscillators inside the cluster are stabilized in sequence, illustrating again the hierarchy of the oscillators. The findings shed new light on the collective behaviors of networked chaotic oscillators and are helpful for the design of real-world networks where scalable synchronization clusters are concerned.

Electrochemiluminescence Enhanced by a Non-Emissive Dual Redox Mediator.

A sulfonated tris(1-phenylpyrazolato)iridium(III) complex ([Ir(sppz)3]3-) serves as a proof-of-concept non-emissive enhancer of the widely used ECL detection system of tris(2,2'-bipyridine)ruthenium(II) ([Ru(bpy)3]2+) with tri-n-propylamine (TPrA) co-reactant, acting through electrocatalysis of TPrA oxidation and efficient chemi-excitation of the luminophore. Using self-interference ECL spectroscopy, we show that the enhancer extends diffusion of the required electrogenerated precursors from the electrode surface. Previously reported enhancement through these pathways has been confounded by the inherent ECL of the enhancer, but the increase in [Ru(bpy)3]2+ ECL intensity using [Ir(sppz)3]3- was obtained without its concomitant emission. The most prominent enhancement (11-fold) occurred at low potentials associated with the 'indirect' co-reactant ECL pathway, which translated to between 2- and 6-fold enhancement when the luminophore was immobilised on microbeads as a general model for enhanced ECL assays.

The promotion action of AURKA on post-ischemic angiogenesis in diabetes-related limb ischemia.

BACKGROUND: Diabetes-related limb ischemia is a challenge for lower extremity amputation. Aurora Kinase A (AURKA) is an essential serine/threonine kinase for mitosis, while its role in limb ischemia remains unclear. METHOD: Human microvascular endothelial cells (HMEC-1) were cultured in high glucose (HG, 25 mmol/L D-glucose) and no additional growth factors (ND) medium to mimic diabetes and low growth factors deprivation as in vitro model. Diabetic C57BL/6 mice were induced by streptozotocin (STZ) administration. After seven days, ischemia was surgically performed by left unilateral femoral artery ligation on diabetic mice. The vector of adenovirus was utilized to overexpress AURKA in vitro and in vivo. RESULTS: In our study, HG and ND-mediated downregulation of AURKA impaired the cell cycle progression, proliferation, migration, and tube formation ability of HMEC-1, which were rescued by overexpressed AURKA. Increased expression of vascular endothelial growth factor A (VEGFA) induced by overexpressed AURKA were likely regulatory molecules that coordinate these events. Mice with AURKA overexpression exhibited improved angiogenesis in response to VEGF in Matrigel plug assay, with increased capillary density and hemoglobin content. In diabetic limb ischemia mice, AURKA overexpression rescued blood perfusion and motor deficits, accompanied by the recovery of gastrocnemius muscles observed by H&E staining and positive Desmin staining. Moreover, AURKA overexpression rescued diabetes-related impairment of angiogenesis, arteriogenesis, and functional recovery in the ischemic limb. Signal pathway results revealed that VEGFR2/PI3K/AKT pathway might be involved in AURKA triggered angiogenesis procedure. In addition, AURKA overexpression impeded oxidative stress and subsequent following lipid peroxidation both in vitro and in vivo, indicating another protective mechanism of AURKA function in diabetic limb ischemia. The changes in lipid peroxidation biomarkers (lipid ROS, GPX4, SLC7A11, ALOX5, and ASLC4) in in vitro and in vivo were suggestive of the possible involvement of ferroptosis and interaction between AUKRA and ferroptosis in diabetic limb ischemia, which need further investigation. CONCLUSIONS: These results implicated a potent role of AURKA in diabetes-related impairment of ischemia-mediated angiogenesis and implied a potential therapeutic target for ischemic diseases of diabetes.

Prolonged anesthesia induces neuroinflammation and complement-mediated microglial synaptic elimination involved in neurocognitive dysfunction and anxiety-like behaviors.

BACKGROUND: Perioperative neurocognitive disorders (PND) with a high incidence frequently occur in elderly surgical patients closely associated with prolonged anesthesia-induced neurotoxicity. The neuromorphopathological underpinnings of anesthesia-induced neurotoxicity have remained elusive. METHODS: Prolonged anesthesia with sevoflurane was used to establish the sevoflurane-induced neurotoxicity (SIN) animal model. Morris water maze, elevated plus maze, and open field test were employed to track SIN rats' cognitive behavior and anxiety-like behaviors. We investigated the neuropathological basis of SIN through techniques such as transcriptomic, electrophysiology, molecular biology, scanning electron microscope, Golgi staining, TUNEL assay, and morphological analysis. Our work further clarifies the pathological mechanism of SIN by depleting microglia, inhibiting neuroinflammation, and C1q neutralization. RESULTS: This study shows that prolonged anesthesia triggers activation of the NF-κB inflammatory pathway, neuroinflammation, inhibition of neuronal excitability, cognitive dysfunction, and anxiety-like behaviors. RNA sequencing found that genes of different types of synapses were downregulated after prolonged anesthesia. Microglial migration, activation, and phagocytosis were enhanced. Microglial morphological alterations were also observed. C1qa, the initiator of the complement cascade, and C3 were increased, and C1qa tagging synapses were also elevated. Then, we found that the "Eat Me" complement pathway mediated microglial synaptic engulfment in the hippocampus after prolonged anesthesia. Afterward, synapses were remarkably lost in the hippocampus. Furthermore, dendritic spines were reduced, and their genes were also downregulated. Depleting microglia ameliorated the activation of neuroinflammation and complement and rescued synaptic loss, cognitive dysfunction, and anxiety-like behaviors. When neuroinflammatory inhibition or C1q neutralization occurred, complement was also decreased, and synaptic elimination was interrupted. CONCLUSIONS: These findings illustrated that prolonged anesthesia triggered neuroinflammation and complement-mediated microglial synaptic engulfment that pathologically caused synaptic elimination in SIN. We have demonstrated the neuromorphopathological underpinnings of SIN, which have direct therapeutic relevance for PND patients.

Fabrication of Flower-like Rhodium-Doped ß-Ni(OH)2 as an Efficient Electrocatalyst for Methanol Oxidation Reaction in Alkaline Media.

In this study, ß-Ni(OH)2 with a unique flower-like morphology was synthesized through a hydrothermal method. The doping of Rh in ß-Ni(OH)2 was achieved by a reduction method. The as-synthesized catalysts were characterized by X-ray diffraction, transmission electron microscopy, and X-ray photoelectron spectroscopy for the crystal structure, morphology, composition, and chemical state analysis. The electrochemical tests revealed that the doping of Rh can significantly increase the electrocatalytic performance of ß-Ni(OH)2 in 1.0 M KOH solution. The methanol oxidation peak current density of Rh-doped ß-Ni(OH)2 reached 95 mA cm-2 with a Tafel slope of 40 mV dec-1. The reason for these improvements is that Rh can suppress the phase transformation of NiOOH from ß to α. Meanwhile, the electronic structure change of nickel in ß-Ni(OH)2 and the defect ratio increase caused by Rh doping are beneficial to methanol oxidation reaction (MOR) catalytic activity. Furthermore, the synergistic effect between Rh and Ni(OH)2 improved the surface activity of ß-NiOOH. The doping of Rh in ß-Ni(OH)2 is initiative in this work, which provides a new strategy to design highly efficient and cost-effective MOR electrocatalysts for alkaline DMFCs.

Preventive effect of LCZ696 on hypoxic pulmonary hypertension in rats via regulating the PI3K/AKT signaling pathway.

Hypoxic pulmonary hypertension (HPH) is a devastating disease worldwide; however, effective therapeutic drugs are lacking. This study investigated the effects and underlying mechanisms of LCZ696 treatment on hypoxia-induced pulmonary hypertension. Male Sprague-Dawley (SD) rats were kept in a hypobaric chamber with an oxygen concentration of 5% for 4 weeks. Rats were treated with either LCZ696 (18 mg/kg, 36 mg/kg, and 72 mg/kg) or sildenafil. The mean pulmonary artery pressure (mPAP), right ventricle hypertrophy index (RVHI), and lung system index were measured. Hematoxylin-eosin (HE) staining, Masson staining, and immunofluorescence staining were used for histological analysis. Enzyme linked immunosorbent assay (ELISA) kits were used to determine the concentrations of inflammatory and hypoxia-related factors. Western blotting was used to examine the expression of apoptotic and PI3K/AKT signaling pathway proteins in rat lung tissue. Hypoxia increased mPAP, RVHI, and lung system index and induced pulmonary vascular remodeling, pulmonary arteriomyosis, and pulmonary artery fibrosis. LCZ696 treatment reduced the increase in mPAP, RVHI, and the lung system index and ameliorated the induced pathological changes. Hypoxia upregulated expression of NF-kB, TNF-α, IL-6, HIF-1α, and Vascular endothelial growth factor (VEGF), decreased the ratio of Bax/Bcl-2, and activated the PI3K/AKT signaling pathway in lung tissue, and these effects were partially reversed by treatment with LCZ696. These results demonstrated that LCZ696 can ameliorate hypoxia-induced HPH by suppressing apoptosis, inhibiting the inflammatory response, and inhibiting the PI3K/AKT signaling pathway. It provides a reference for clinical rational drug use and lays a foundation for the study of HPH therapeutic drugs.

STING-IFN-I pathway relieves incision induced acute postoperative pain via inhibiting the neuroinflammation in dorsal root ganglion of rats.

BACKGROUND: The purpose of this study was to study the effect of STING-IFN-I pathway on incision induced postoperative pain in rats and its possible mechanisms. METHODS: The pain thresholds were evaluated by measuring the mechanical withdrawal threshold and the thermal withdrawal latency. The satellite glial cell and macrophage of DRG were analyzed. The expression of STING, IFN-a, P-P65, iNOS, TNF-α, IL-1ß and IL-6 in DRG was evaluated. RESULTS: The activation of STING-IFN-I pathway can reduce the mechanical hyperalgesia, thermal hyperalgesia, down-regulate the expression of P-P65, iNOS, TNF-α, IL-1ß and IL-6, and inhibit the activation of satellite glial cell and macrophage in DRG. CONCLUSIONS: The activation of STING-IFN-I pathway can alleviate incision induced acute postoperative pain by inhibiting the activation of satellite glial cell and macrophage, which reducing the corresponding neuroinflammation in DRG.

Disability weight measurement for the severity of different diseases in Wuhan, China.

BACKGROUND: Measurement of the Chinese burden of disease with disability-adjusted life-years (DALYs) requires disability weight (DW) that quantify health losses for all non-fatal consequences of disease and injury. The Global Burden of Disease (GBD) 2013 DW study indicates that it is limited by lack of geographic variation in DW data and by the current measurement methodology. We aim to estimate DW for a set of health states from major diseases in the Wuhan population. METHODS: We conducted the DW measurement study for 206 health states through a household survey with computer-assisted face-to-face interviews and a web-based survey. Based on GBD 2013 DW study, paired comparison (PC) and Population health equivalence (PHE) method was used and different PC/PHE questions were randomly assigned to each respondent. In statistical analysis, the PC data was analyzed by probit regression. The probit regression results will be anchored by results from the PHE data analyzed by interval regression on the DW scale units between 0 (no loss of health) and 1 (loss equivalent to death). RESULTS: A total of 2610 and 3140 individuals were included in the household and web-based survey, respectively. The results from the total pooled data showed health state "mild anemia" (DW = 0.005, 95% UI 0.000-0.027) or "allergic rhinitis (hay fever)" (0.005, 95% UI 0.000-0.029) had the lowest DW and "heroin and other opioid dependence, severe" had the highest DW (0.699, 95% UI 0.579-0.827). A high correlation coefficient (Pearson's r = 0.876; P < 0.001) for DWs of same health states was observed between Wuhan's survey and GBD 2013 DW survey. Health states referred to mental symptom, fatigue, and the residual category of other physical symptoms were statistically significantly associated with a lower Wuhan's DWs than the GBD's DWs. Health states with disfigurement and substance use symptom had a higher DW in Wuhan population than the GBD 2013 study. CONCLUSIONS: This set of DWs could be used to calculate local diseases burden for health policy-decision in Wuhan population. The DW differences between the GBD's survey and Wuhan's survey suggest that there might be some contextual or culture factors influencing assessment on the severity of diseases.

The effect of anesthetic depth on postoperative delirium in older adults: a systematic review and meta-analysis.

BACKGROUND: Postoperative delirium (POD) is an important complication for older patients and recent randomised controlled trials have showed a conflicting result of the effect of deep and light anesthesia. METHODS: We included randomised controlled trials including older adults that evaluated the effect of anesthetic depth on postoperative delirium from PubMed, Embase, Web of Science and Cochrane Library. We considered deep anesthesia as observer's assessment of the alertness/ sedation scale (OAA/S) of 0-2 or targeted bispectral (BIS) < 45 and the light anesthesia was considered OAA/S 3-5 or targeted BIS > 50. The primary outcome was incidence of POD within 7 days after surgery. And the secondary outcomes were mortality and cognitive function 3 months or more after surgery. The quality of evidence was assessed via the grading of recommendations assessment, development, and evaluation approach. RESULTS: We included 6 studies represented 7736 patients aged 60 years and older. We observed that the deep anesthesia would not increase incidence of POD when compared with the light anesthesia when 4 related studies were pooled (OR, 1.40; 95% CI, 0.63-3.08, P = 0.41, I2 = 82%, low certainty). And no significant was found in mortality (OR, 1.12; 95% CI, 0.93-1.35, P = 0.23, I2 = 0%, high certainty) and cognitive function (OR, 1.13; 95% CI, 0.67-1.91, P = 0.64, I2 = 13%, high certainty) 3 months or more after surgery between deep anesthesia and light anesthesia. CONCLUSIONS: Low-quality evidence suggests that light general anesthesia was not associated with lower POD incidence than deep general anesthesia. And High-quality evidence showed that anesthetic depth did not affect the long-term mortality and cognitive function. SYSTEMATIC REVIEW REGISTRATION: CRD42022300829 (PROSPERO).

A de novo ANK1 mutation in a childhood hereditary spherocytosis: a case report.

BACKGROUND: Due to the heterogeneity of the phenotype of Hereditary spherocytosis (HS) patients, some patients may have rare clinical complications such as biliary obstruction and ultra-high bilirubinemia. CASE PRESENTATION: A 8-y-old boy presented to the emergency with complaints of anemia for 6 years and worsened abdominal pain and scleral yellowing of the skin for 2 days. Physical examination showed tenderness in the middle and upper abdomen and splenomegaly. Abdominal CT revealed biliary obstruction. Genetic analysis revealed a de novo mutation in the gene ANK1, HS with biliary obstruction was diagnosed. The surgery of bile duct exploration and T-tube drainage, and splenectomy were performed successively. This patient was followed up for 13 months after splenectomy, and his condition was stable. CONCLUSION: The diagnosis of HS is not clinically difficult, and once a patient with HS is diagnosed, regular follow-up management and standardized treatment are required. Genetic testing is also needed to screen for other genetic disorders that may co-exist in patients with HS who do not have a good efficacy or who have a long-term chronic onset of jaundice.