A new pressure-densified orthogonal hard superconducting phase of RhB4.

A new hard superconducting phase of RhB4 with the space group Cmca is predicted, and the phase transition and mechanical and superconducting properties of RhB4 under 300 GPa are studied using first principles. We predict a new high-pressure phase of RhB4 by substituting the most stable Cmca structure of OsB4, known for its excellent mechanical properties. The calculated enthalpy shows that above 112.6 GPa, Cmca is superior to Pmmn as was previously predicted by particle swarm optimization. The stability of the predicted phase is checked using formation enthalpy, elastic constant and phonon dispersion. Additionally, the convex hull of the Rh-B system confirms that the phase is expected to be synthesized experimentally. The Cmca phase is an incompressible hard material with a hardness of 23.75 GPa at 300 GPa attributed to strong intralayer covalent B-B bonds. Furthermore, the phase is a relatively pressure-insensitive superconductor, with a Tc of 8.6 K at 112.6 GPa and a pressure-dependent coefficient of -0.03 K GPa-1. The finding reveals a superconducting hard material that is well-suited for extreme high-pressure environments.

CYLD Maintains Retinal Homeostasis by Deubiquitinating ENKD1 and Promoting the Phagocytosis of Photoreceptor Outer Segments.

Phagocytosis of shed photoreceptor outer segments by the retinal pigment epithelium (RPE) is essential for retinal homeostasis. Dysregulation of the phagocytotic process is associated with irreversible retinal degenerative diseases. However, the molecular mechanisms underlying the phagocytic activity of RPE cells remain elusive. In an effort to uncover proteins orchestrating retinal function, the cylindromatosis (CYLD) deubiquitinase is identified as a critical regulator of photoreceptor outer segment phagocytosis. CYLD-deficient mice exhibit abnormal retinal structure and function. Mechanistically, CYLD interacts with enkurin domain containing protein 1 (ENKD1) and deubiquitinates ENKD1 at lysine residues K141 and K242. Deubiquitinated ENKD1 interacts with Ezrin, a membrane-cytoskeleton linker, and stimulates the microvillar localization of Ezrin, which is essential for the phagocytic activity of RPE cells. These findings thus reveal a crucial role for the CYLD-ENKD1-Ezrin axis in regulating retinal homeostasis and may have important implications for the prevention and treatment of retinal degenerative diseases.

Efficient unsymmetric disulfide formation by molecular-scale tailoring of ortho-polyquinone-based polymer photocatalyst.

Disulfide bonds, especially unsymmetric disulfide bonds, have important applications in bioactivity and drug molecules, but the synthesis of unsymmetric disulfide bonds remains challenging due to efficiency and selectivity issues. Herein, this work utilizes anthraquinone (AQ) and cyclictriphosphonononitrile through a nucleophilic substitution reaction to synthesize an organic polymer (ANTH-AMI) that incorporates an ortho-polyquinone (o-polyquinone) redox center. The anthraquinone molecule functions as a redox center, capable of accepting photoinduced electrons and subsequently transferring them to initiate an electron-coupled hydrogenation reaction (AQ to AQH). Moreover, the proximity of the o-polyquinone redox sites facilitates the catalysis of unsymmetric disulfide bond formation. Consequently, the ANTH-AMI photocatalysts demonstrate exceptional yields (up to 82 %), substrate versatility, cycling stability, and scalable preparation in promoting unsymmetric coupling reactions of thiol. This work offers a solution for designing organic polymer photocatalysts with adjacent multiple redox centers for cross-coupling reactions.

Deciphering the Role of LncRNAs in Osteoarthritis: Inflammatory Pathways Unveiled.

Long non-coding RNA (LncRNA), with transcripts over 200 nucleotides in length, play critical roles in numerous biological functions and have emerged as significant players in the pathogenesis of osteoarthritis (OA), an inflammatory condition traditionally viewed as a degenerative joint disease. This review comprehensively examines the influence of LncRNA on the inflammatory processes driving OA progression, focusing on their role in regulating gene expression, cellular activities, and inflammatory pathways. Notably, LncRNAs such as MALAT1, H19, and HOTAIR are upregulated in OA and exacerbate the inflammatory milieu by modulating key signaling pathways like NF-κB, TGF-ß/SMAD, and Wnt/ß-catenin. Conversely, LncRNA like MEG3 and GAS5, which are downregulated in OA, show potential in dampening inflammatory responses and protecting against cartilage degradation by influencing miRNA interactions and cytokine production. By enhancing our understanding of LncRNA' roles in OA inflammation, we can better leverage them as potential biomarkers for the disease and develop innovative therapeutic strategies for OA management. This paper aims to delineate the mechanisms by which LncRNA influence inflammatory responses in OA and propose them as novel targets for therapeutic intervention.

1,25-D3 ameliorates ischemic brain injury by alleviating endoplasmic reticulum stress and ferroptosis: Involvement of vitamin D receptor and p53 signaling.

Endoplasmic reticulum stress (ERS) and ferroptosis are linked to cerebral ischemia reperfusion injury (CIRI). The neuroprotective properties of 1α, 25-dihydroxyvitamin D3 (VitD3 or 1,25-D3) have been well established; however, the mechanism by which VitD3 treats CIRI through ERS and ferroptosis has not been examined. Hence, we developed middle cerebral artery occlusion/reperfusion (MCAO/R) model in SD rats to ascertain if VitD3 preconditioning mediates ERS and ferroptosis involving of p53 signaling. In this study, we observed that VitD3 can reduce infarction volume and cerebral edema, which leads to the improvement of nerve function. HE, Nissl and Tunel staining showed that VitD3 treatment significantly improved the morphology of neuronal cells and reduced their death. The expression and activation of Vitamin D receptor (VDR), PKR-like ER kinase (PERK), C/EBP-homologous protein (CHOP), p53, nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4) and reactive oxygen species (ROS) in the ischemic penumbral area were detected by real-time qPCR, Western-blotting and Elisa. The results showed that after VitD3 treatment, VDR increased, ERS-related indices (PERK, CHOP) significantly decreased and ferroptosis-related indices (Nrf2, GPX4) increased. As a VDRs antagonist, pyridoxal-5-phosphate (P5P) can partially block the neuroprotective effects of VitD3. Therefore, CIRI can induce ERS and ferroptosis in the ischemic penumbra area and VitD3 may ameliorate nerve damage in CIRI rats by up-regulating VDR, alleviating p53-associated ERS and ferroptosis.

Successful treatment of juvenile polyposis of infancy with sirolimus: a case report.

BACKGROUND: Infantile Juvenile polyposis of infantile (JPI) is a rare and aggressive form of juvenile polyposis syndrome (JPS) typically diagnosed in the first year of life. It often carries a poor prognosis due to chronic gastrointestinal bleeding, protein-losing enteropathy, malnutrition and immune deficiency. CASE PRESENTATION: We report a case of a girl initially presented with pallor at 7 months of age, which progressed to gastrointestinal bleeding and protein-losing enteropathy. Endoscopic examination, which included both upper gastrointestinal endoscopy and enteroscopy, showed diffuse polyposis. Histopathology results indicated the presence of juvenile polyps with no dysplasia in all removed polyps. Genetic testing identified a 2.1 Mb deletion on chromosome 10q23.2q23.31 involving the phosphatase and tensin homolog (PTEN) and bone morphogenetic protein receptor type IA (BMPR1A) genes. Treatment with sirolimus initiated at 10 months of age led to a reduction in the need for blood and albumin infusions, improved patient growth, and quality of life. While the frequency of endoscopic evaluations decreased with sirolimus, regular endoscopic polypectomy every 5 months remained necessary. However, discontinuation of sirolimus resulted in polyp recurrence after 2 months due to pneumonia. CONCLUSION: This case highlights sirolimus treatment can alleviate many complications of JPI, it does not eliminate the need for aggressive polypectomy.

Gender-specific factors of suicidal ideation among high school students in Yunnan province, China: A machine learning approach.

BACKGROUND: Suicidal ideation (SI) assumes a pivotal role in predicting suicidal behaviors. The incidence of SI among high (junior and senior) school students is significantly higher than that of other age groups. The aim of this study is to explore the gender differences in SI among high school students in Yunnan Province. METHOD: A total of 6180 students in grades 7-12 in Yunnan province, China from May 2021 to May 2022 participated in this survey. Univariate analysis was employed to describe the influencing factors of male and female students' SI. Subsequently, data were stratified by gender. Adopting machine learning technique, including Least Absolute Shrinkage and Selection Operator (Lasso) and Boruta algorithm, and logistic regression model to estimate the direction and effect magnitude of the influencing factors. RESULTS: The prevalence of SI was significantly higher for females (31.34 %) than males (16.73 %). The logistic regression model was established using the variables screened by Boruta algorithm, indicated that anxiety, depression, suffering emotion abuse or emotion neglect in childhood, non-suicidal self-injury, evening chronotype are common risk factors for SI in male and female students. Notably, female students who exhibited aggressive behavior, have experienced bullying, and were in the junior high school learning stage were more likely to report SI than their male counterparts. CONCLUSIONS: Females showed more vulnerability to SI than males especially among females in junior high school, reporting aggressive behavior and bullying experiences. Tailored prevention strategies, informed by these gender-related distinctions, should be developed and implemented.

Discovery of Biphenyl Derivatives to Target Hsp70-Bim Protein-Protein Interaction in Chronic Myeloid Leukemia by Scaffold Hopping Strategy.

Hsp70-Bim protein-protein interaction (PPI) is the most recently identified specific target in chronic myeloid leukemia (CML) therapy. Herein, we developed a new class of Hsp70-Bim PPI inhibitors via scaffold hopping of S1g-10, the most potent Hsp70-Bim PPI inhibitor thus far. Through structure-activity relationship (SAR) study, we obtained a biphenyl scaffold compound JL-15 with a 5.6-fold improvement in Hsp70-Bim PPI suppression (Kd = 123 vs 688 nM) and a 4-fold improvement in water solubility (29.42 vs 7.19 µg/mL) compared to S1g-10. It maintains comparable apoptosis induction capability with S1g-10 against both TKI-sensitive and TKI-resistant CML cell lines in an Hsp70-Bim-dependent manner. Additionally, through SAR, 1H-15N TRSOY-NMR, and molecular docking, we revealed that Lys319 is a "hot spot" in the Hsp70-Bim PPI interface. Collectively, these results provide a novel chemical scaffold and structural insights for the rational design of Hsp70-Bim PPI inhibitors.

Appendicectomy pathway: Insights from electronic medical records of a local health district in Australia.

BACKGROUND: This study aims to identify the common pathways of appendicectomy, the most common emergency surgery in Australia's public hospitals and any variations within a regional public health district in New South Wales, Australia. METHODS: We analyzed the electronic medical records of 3,943 patients who underwent appendicectomy between January 2014 and July 2020 at 2 hospitals in the Illawarra Shoalhaven Local Health District, New South Wales, Australia, using the PM2 approach for surgical pathway identification and subsequent statistical analyses. RESULTS: Among 3,943 patients, 3,606 (91.5%) followed an 11-step main pathway: (1) emergency department admission, (2) surgery booking, (3) anesthesia start, (4) operating room entry, (5) surgery start, (6) surgery end, (7) anesthesia end, (8) operating room discharge, (9) postanesthesia care unit admission, (10) postanesthesia care unit discharge, and (11) hospital discharge. The median length of stay was 48.13 hours (interquartile range 32.74). The main pathway differed from either variation 1 (n = 246, 6.2%) or variation 2 (n = 30, 0.8%) only in the timing and location of anesthesia administration or conclusion. Variation 3 (n = 26, 0.7%) included patients who underwent appendicectomy twice, whereas variation 4 (n = 25, 0.6%) included patients booked for surgery before emergency department admission through community doctor referrals. Thirteen exceptional cases experienced combinations of the aforementioned pathways. The length of stay and phase durations varied between the main pathway and these variations. CONCLUSION: The appendicectomy pathway was largely standardized across the studied hospitals, with the location of anesthesia administration or conclusion affecting specific stages but not the overall length of stay. Only a complex 2-surgery pathway increased length of stay.

Distinct signatures of gut microbiota and metabolites in primary biliary cholangitis with poor biochemical response after ursodeoxycholic acid treatment.

BACKGROUND: About 1/3 of primary biliary cholangitis (PBC) patients suffered from poor response worldwide. And these patients present intestinal disturbances. We aimed to identify signatures of microbiota and metabolites in PBC patients with poor response, comparing to patients with response. METHODS: This study enrolled 25 subjects (14 PBC patients with response and 11 PBC patients with poor response). Metatranscriptomics and metabolomics analysis were carried out on their fecal. RESULTS: PBC patients with poor response had significant differences in the composition of bacteria, characterized by decreased Gemmiger etc. and increased Ruminococcus etc. The differential microbiota functions characterized by decreased abundance of elongation factor Tu and elongation factor G base on the KO database, as well as decreased abundance of Replicase large subunit etc. based on the SWISS-PROT database. PBC with poor response also had significant differences in 17 kinds of bacterial metabolites, characterized by decreased level of metabolites vital in bile acids metabolism pathway (L-Cysteine etc.) and the all-trans-Retinoic acid, a kind of immune related metabolite. The altered microbiota was associated with the differential expressed metabolites and clinical liver function indicators. 1 bacterial genera, 2 bacterial species and 9 metabolites simultaneously discriminated PBC with poor response from PBC with response with high accuracy. CONCLUSION: PBC patients with poor response exhibit unique changes in microbiota and metabolite. Gut microbiota and metabolite-based algorithms could be used as additional tools for differential prediction of PBC with poor prognosis.

Cyanobacterial blooms in Lake Taihu: Temporal trends and potential drivers.

Lake Taihu, an inland lake, frequently experiences Cyanobacterial blooms that have historically posed severe threats to its aquatic ecosystem. Combining field observations and satellite remote-sensed data, factors that influence algal bloom intensity in Lake Taihu over an eight-year period, from 2016 to 2023, are examined, and changes in phytoplankton community composition, climate, water quality, economic activities, and food web dynamics are reported. Sentinel-2 MSI data analysis reveals a dramatic decrease in Cyanobacterial blooms in 2023, with a reduction in the annual maximum bloom area of 76.90 % from 2016 values. From 2016 to 2022, the ratio of Cyanobacteria to other phytoplankton ranged 82.09 %-98.29 %, but in 2023, this dropped to 60.98 %. Concurrently, Cyanobacteria density dropped to an historic low of 2.29 × 107 cells/L (16.4 % of 2021 peak values). Redundancy and random forest analyses indicated that nitrogen has a greater influence on phytoplankton than phosphorus, with temperature and permanganate index being the important parameters to affect phytoplankton community structure. We attribute the decrease in Cyanobacterial blooms in Lake Taihu in 2023 to be largely caused by shifts in phytoplankton community structure, particularly the sharp decline in Microcystis sp. density, a genus often linked to bloom formation. Meteorological conditions such as reduced rainfall and wind speed during the winter and spring of 2023 also contributed to diminishing Cyanobacterial blooms. Ongoing improvements in water quality, reduced economic activities because of pandemic restrictions, and implementation of a fishing ban since 2020 have likely further contributed to reductions in bloom frequency. These results improve our understanding of the processes that affect algal blooms in Lake Taihu, and potentially other eutrophic inland lakes.

Photoselectively modulating main products by changing the wavelength of visible light over D-π-A-D conjugated polymers.

The diversity of catalytic products determines the difficulty of selective product modulation, which usually relies on adjusting the catalyst and reaction conditions to obtain different main products selectively. Herein, we synthesized D-π-A-D conjugated organic polymers (TH-COP) using cyclotriphosphonitrile, alkyne, 2H-benzimidazole, and sulfur units as electron donors, π bridges, electron acceptors, and electron donors, respectively. TH-COP exhibited excellent photoinduced carrier separation and redox ability under different visible light wavelengths, and the main products of its CO2 reduction are CH4 (1000.0 µmol g-1) and CO (837.0 µmol g-1) under 400-420 nm and 420-560 nm, respectively. In addition, TH-COP could completely convert phenylmethyl sulfide to methyl phenyl sulfone at 400-420 nm and diphenyl disulfide at 480-485 nm in yields up to 95 %. This study presents a novel strategy for the targeted fabrication of various main products using conjugated polymers by simply changing the wavelength range of visible light.

Minimalistic approach to left atrial appendage occlusion guided by cardiac computed tomography angiography.

OBJECTIVE: To assess the feasibility and safety of the minimalistic approach to left atrial appendage occlusion (LAAO) guided by cardiac computed tomography angiography (CCTA). METHODS: Ninety consecutive patients who underwent LAAO, with or without CCTA-guided, were matched (1:2). Each step of the LAAO procedure in the computed tomography (CT) guidance group (CT group) was directed by preprocedural CT planning. In the control group, LAAO was performed using the standard method. All patients were followed up for 12 months, and device surveillance was conducted using CCTA. RESULTS: A total of 90 patients were included in the analysis, with 30 patients in the CT group and 60 matched patients in the control group. All patients were successfully implanted with Watchman devices. The mean ages for the CT group and the control group were 70.0 ± 9.4 years and 68.4 ± 11.9 years (P = 0.52), respectively. The procedure duration (45.6 ± 10.7 min vs. 58.8 ± 13.0 min, P < 0.001) and hospital stay (7.5 ± 2.4 day vs. 9.6 ± 2.8 day, P = 0.001) in the CT group was significantly shorter compared to the control group. However, the total radiation dose was higher in the CT group compared to the control group (904.9 ± 348.0 mGy vs. 711.9 ± 211.2 mGy, P = 0.002). There were no significant differences in periprocedural pericardial effusion (3.3% vs. 6.3%, P = 0.8) between the two groups. The rate of postprocedural adverse events (13.3% vs. 18.3%, P = 0.55) were comparable between both groups at 12 months follow-up. CONCLUSIONS: CCTA is capable of detailed LAAO procedure planning. Minimalistic LAAO with preprocedural CCTA planning was feasible and safe, with shortened procedure time and acceptable increased radiation and contras consumption. For patients with contraindications to general anesthesia and/or transesophageal echocardiography, this promising method may be an alternative to conventional LAAO.

Application of 3D-PCASL combined with t-ASL and MRA in the diagnosis of patients with isolated vertigo induced by posterior circulation ischemia.

OBJECTIVES: Isolated vertigo induced by posterior circulation ischemia (PCIV) can further progress into posterior circulation infarction. This study aimed to explore the diagnostic values of three-dimensional pseudo-continuous arterial spin labeling (3D-PCASL) combined with territorial arterial spin labeling (t-ASL) and magnetic resonance angiography (MRA) in visualizing and evaluating PCIV, seeking improved diagnostic tools for clinical guidance. METHODS: 28 PCIVs (11 males, 17 females, aged from 55 to 83 years, mean age: 69.68 ± 9.01 years) and 28 healthy controls (HCs, 12 male, 16 female, aged from 56 to 87 years, mean age: 66.75 ± 9.86 years) underwent conventional magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), MRA, 3D-PCASL, and t-ASL. We compared the incidence of anatomic variants of the posterior circle of Willis in MRA, cerebral blood flow (CBF) and anterior collateral blood flow on postprocessing maps obtained from 3D-PCASL and t-ASL sequence between PCIVs and HCs. Chi-square test and paired t-test were analyzed statistically with SPSS 24.0 software. RESULTS: 7 PCIVs (7/28, 25%) and 6 HCs (6/28, 21%) showed fetal posterior cerebral artery (FPCA) on MRA, including 1 HC, and 6 PCIVs with FPCA appeared hypoperfusion. 18 PCIVs (64%) and 2 HCs (7%) showed hypoperfusion in the posterior circulation (PC), including 1 HC and 7 PCIVs displayed anterior circulation collateral flow. Chi-square analyses demonstrated a difference in PC hypoperfusion between PCIVs and HCs, whether in the whole or FPCA-positive group assessment (P < 0.05). Paired t-test showed that the CBF values were significant difference for the bilateral PC asymmetrical perfusion in the PCIVs (P < 0.01). When compared to the bilateral PC symmetrical non-hypoperfusion area in the PCIVs and HCs, the CBF values were not significant (P > 0.05). The CBF values of the PC in PCIVs were lower than in HCs (P < 0.05). The reduction rate in the hypoperfusion side of the bilateral PC asymmetrical perfusion of the PCIVs ranged from 4% to 37%, while the HCs reduction rate was 7.7%. The average PC symmetrical perfusion average reduction rate of the PCIVs was 52.25%, while the HCs reduction rate was 42.75%. CONCLUSION: 3D-PCASL is a non-invasive and susceptible method for detecting hypoperfusion in PC, serving as a potential biomarker of PCIV. The suspected hypoperfusion in PC may be attributed to the emergence of FPCA and the manifestation of anterior collateral flow when combining t-ASL and MRA sequences. These findings demonstrated that 3D-PCASL combined with t-ASL and MRA sequences are the potential method to identify PCIV, leading to early diagnosis of PCIV and reducing the risk of progressing into infarction.

Yeast Bxi1/Ybh3 mediates conserved mitophagy and apoptosis in yeast and mammalian cells: convergence in Bcl-2 family.

The process of degrading unwanted or damaged mitochondria by autophagy, called mitophagy, is essential for mitochondrial quality control together with mitochondrial apoptosis. In mammalian cells, pan-Bcl-2 family members including conical Bcl-2 members and non-conical ones are involved in and govern the two processes. We have illustrated recently the BH3 receptor Hsp70 interacts with Bim to mediate both apoptosis and mitophagy. However, whether similar pathways exist in lower eukaryotes where conical Bcl-2 members are absent remained unclear. Here, a specific inhibitor of the Hsp70-Bim PPI, S1g-10 and its analogs were used as chemical tools to explore the role of yeast Bxi1/Ybh3 in regulating mitophagy and apoptosis. Using Om45-GFP processing assay, we illustrated that yeast Ybh3 mediates a ubiquitin-related mitophagy pathway in both yeast and mammalian cells through association with Hsp70, which is in the same manner with Bim. Moreover, by using Bax/Bak double knockout MEF cells, Ybh3 was identified to induce apoptosis through forming oligomerization to trigger mitochondrial outer membrane permeabilization (MOMP) like Bax. We not only illustrated a conserved ubiquitin-related mitophagy pathway in yeast but also revealed the multi-function of Ybh3 which combines the function of BH3-only protein and multi-domain Bax protein as one.

Automatic IMRT treatment planning through fluence prediction and plan fine-tuning for nasopharyngeal carcinoma.

BACKGROUND: At present, the implementation of intensity-modulated radiation therapy (IMRT) treatment planning for geometrically complex nasopharyngeal carcinoma (NPC) through manual trial-and-error fashion presents challenges to the improvement of planning efficiency and the obtaining of high-consistency plan quality. This paper aims to propose an automatic IMRT plan generation method through fluence prediction and further plan fine-tuning for patients with NPC and evaluates the planning efficiency and plan quality. METHODS: A total of 38 patients with NPC treated with nine-beam IMRT were enrolled in this study and automatically re-planned with the proposed method. A trained deep learning model was employed to generate static field fluence maps for each patient with 3D computed tomography images and structure contours as input. Automatic IMRT treatment planning was achieved by using its generated dose with slight tightening for further plan fine-tuning. Lastly, the plan quality was compared between automatic plans and clinical plans. RESULTS: The average time for automatic plan generation was less than 4 min, including fluence maps prediction with a python script and automated plan tuning with a C# script. Compared with clinical plans, automatic plans showed better conformity and homogeneity for planning target volumes (PTVs) except for the conformity of PTV-1. Meanwhile, the dosimetric metrics for most organs at risk (OARs) were ameliorated in the automatic plan, especially Dmax of the brainstem and spinal cord, and Dmean of the left and right parotid glands significantly decreased (P < 0.05). CONCLUSION: We have successfully implemented an automatic IMRT plan generation method for patients with NPC. This method shows high planning efficiency and comparable or superior plan quality than clinical plans. The qualitative results before and after the plan fine-tuning indicates that further optimization using dose objectives generated by predicted fluence maps is crucial to obtain high-quality automatic plans.

The candidate proteins associated with keratoconus: A meta-analysis and bioinformatic analysis.

PURPOSE: Keratoconus (KC) is a multifactorial disorder. This study aimed to conduct a systematic meta-analysis to exclusively explore the candidate proteins associated with KC pathogenesis. METHODS: Relevant literature published in the last ten years in Pubmed, Web of Science, Cochrane, and Embase databases were searched. Protein expression data were presented as the standard mean difference (SMD) and 95% confidence intervals (CI). The meta-analysis is registered on PROSPERO, registration number CRD42022332442 and was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement (PRISMA). GO and KEGG enrichment analysis were performed, as well as the miRNAs and chemicals targeting the candidate proteins were predicted. PPI was analyzed to screen the hub proteins, and their expression was verified by RT-qPCR. RESULTS: A total of 21 studies were included in the meta-analysis, involving 346 normal eyes and 493 KC eyes. 18 deregulated proteins with significant SMD values were subjected to further analysis. In which, 7 proteins were up-regulated in KC compared with normal controls, including IL6 (SMD 1.54, 95%CI [0.85, 2.24]), IL1B (SMD 2.07, 95%CI [0.98, 3.16]), TNF (SMD 2.1, 95%CI [0.24, 3.96]), and MMP9 (SMD 1.96, 95%CI [0.68, 3.24]). While 11 proteins were down-regulated in KC including LOX (SMD 2.54, 95%CI [-4.51, -0.57]). GO and KEGG analysis showed that the deregulated proteins were involved in inflammation, extracellular matrix (ECM) remodeling, and apoptosis. MMP9, IL6, LOX, TNF, and IL1B were regarded as hub proteins according to the PPI analysis, and their transcription changes in stromal fibroblasts of KC were consistent with the results of the meta-analysis. Moreover, 10 miRNAs and two natural polyphenols interacting with hub proteins were identified. CONCLUSION: This study obtained 18 candidate proteins and demonstrated altered cytokine profiles, ECM remodeling, and apoptosis in KC patients through meta-analysis and bioinformatic analysis. It will provide biomarkers for further understanding of KC pathogenesis, and potential therapeutic targets for the drug treatment of KC.

Region fine-grained attention network for accurate bone age assessment.

Bone age assessment plays a vital role in monitoring the growth and development of adolescents. However, it is still challenging to obtain precise bone age from hand radiography due to these problems: 1) Hand bone varies greatly and is always masked by the background; 2) the hand bone radiographs with successive ages offer high similarity. To solve such issues, a region fine-grained attention network (RFGA-Net) was proposed for bone age assessment, where the region aware attention (RAA) module was developed to distinguish the skeletal regions from the background by modeling global spatial dependency; then the fine-grained feature attention (FFA) module was devised to identify similar bone radiographs by recognizing critical fine-grained feature regions. The experimental results demonstrate that the proposed RFGA-Net shows the best performance on the Radiological Society of North America (RSNA) pediatric bone dataset, achieving the mean absolute error (MAE) of 3.34 and the root mean square error (RMSE) of 4.02, respectively.

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OBJECTIVES: To investigate the clinical characteristics and prognosis of pneumococcal meningitis (PM), and drug sensitivity of Streptococcus pneumoniae (SP) isolates in Chinese children. METHODS: A retrospective analysis was conducted on clinical information, laboratory data, and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country. RESULTS: Among the 160 children with PM, there were 103 males and 57 females. The age ranged from 15 days to 15 years, with 109 cases (68.1%) aged 3 months to under 3 years. SP strains were isolated from 95 cases (59.4%) in cerebrospinal fluid cultures and from 57 cases (35.6%) in blood cultures. The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87) and 27% (21/78), respectively. Fifty-five cases (34.4%) had one or more risk factors for purulent meningitis, 113 cases (70.6%) had one or more extra-cranial infectious foci, and 18 cases (11.3%) had underlying diseases. The most common clinical symptoms were fever (147 cases, 91.9%), followed by lethargy (98 cases, 61.3%) and vomiting (61 cases, 38.1%). Sixty-nine cases (43.1%) experienced intracranial complications during hospitalization, with subdural effusion and/or empyema being the most common complication [43 cases (26.9%)], followed by hydrocephalus in 24 cases (15.0%), brain abscess in 23 cases (14.4%), and cerebral hemorrhage in 8 cases (5.0%). Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old, with rates of 91% (39/43) and 83% (20/24), respectively. SP strains exhibited complete sensitivity to vancomycin (100%, 75/75), linezolid (100%, 56/56), and meropenem (100%, 6/6). High sensitivity rates were also observed for levofloxacin (81%, 22/27), moxifloxacin (82%, 14/17), rifampicin (96%, 25/26), and chloramphenicol (91%, 21/23). However, low sensitivity rates were found for penicillin (16%, 11/68) and clindamycin (6%, 1/17), and SP strains were completely resistant to erythromycin (100%, 31/31). The rates of discharge with cure and improvement were 22.5% (36/160) and 66.2% (106/160), respectively, while 18 cases (11.3%) had adverse outcomes. CONCLUSIONS: Pediatric PM is more common in children aged 3 months to under 3 years. Intracranial complications are more frequently observed in children under 1 year old. Fever is the most common clinical manifestation of PM, and subdural effusion/emphysema and hydrocephalus are the most frequent complications. Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates. Adverse outcomes can be noted in more than 10% of PM cases. SP strains are high sensitivity to vancomycin, linezolid, meropenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.

Effect of Dexmedetomidine on Intraoperative Hemodynamics and Blood Loss in Patients Undergoing Spine Surgery: A Systematic Review and Meta-Analysis.

Objective Dexmedetomidine (Dex) is a highly selective α2 adrenoceptor agonist that reduces blood pressure and heart rate. However, its ability to provide stable hemodynamics and a clinically significant reduction in blood loss in spine surgery is still a matter of debate. This study aimed to investigate the effects of Dex on intraoperative hemodynamics and blood loss in patients undergoing spine surgery.Methods The Web of Science, MEDLINE, EMBASE, and the Cochrane Library were searched up to February 2023 for randomized controlled trials (RCTs) including patients undergoing spine surgeries under general anaesthesia and comparing Dex and saline. A fixed- or random-effect model was used depending on heterogeneity.Results Twenty-one RCTs, including 1388 patients, were identified. Dex added the overall risk of intraoperative hypotension (odds ratio [OR]: 2.11; 95% confidence interval [CI]: 1.24 - 3.58; P=0.006) and bradycardia (OR: 2.48; 95%CI: 1.57 - 3.93; P=0.0001). The use of a loading dose of Dex led to significantly increased risks of intraoperative hypotension (OR: 2.00; 95%CI: 1.06 - 3.79; P=0.03) and bradycardia (OR: 2.28; 95%CI: 1.42 - 3.66; P=0.0007). For patients receiving total intravenous anesthesia, there was an increased risk of hypotension (OR: 2.90; 95%CI: 1.24 - 6.82; P=0.01) and bradycardia (OR: 2.66; 95%CI: 1.53 - 4.61; P=0. 0005). For patients in the inhalation anesthesia group, only an increased risk of bradycardia (OR: 4.95; 95%CI: 1.41 - 17.37; P=0.01) was observed. No significant increase in the risk of hypotension and bradycardia was found in the combined intravenous-inhalation anesthesia group. The incidence of severe hypotension (OR: 2.57; 95%CI: 1.05 - 6.32; P=0.04), but not mild hypotension, was increased. Both mild (OR: 2.55; 95%CI: 1.06 - 6.15; P=0.04) and severe (OR: 2.45; 95%CI: 1.43 - 4.20; P=0.001) bradycardia were associated with a higher risk. The overall analyses did not reveal significant reduction in intraoperative blood loss. However, a significant decrease in blood loss was observed in total inhalation anesthesia subgroup (mean difference [MD]: -82.97; 95%CI: -109.04 - -56.90; P<0.001).Conclusions Dex increases the risks of intraoperative hypotension and bradycardia in major spine surgery. The administration of a loading dose of Dex and the utilization of various anesthesia maintenance methods may potentially impact hemodynamic stability and intraoperative blood loss.