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Guan-Qiao Liu,1,2,&ast; Peng Chen,1,3,&ast; Mou-Zhang Huang,1,4 Ming-Rui Song,2 Chen-Sheng Song,1 Run-Jiu Zhu,1 Jun Xiong,3 Nan Jiang,1,2 Bin Yu1,2 1Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 3Department of Orthopaedics, Hainan General Hospital, Hainan Hospital affiliated to Hainan Medical University, Haikou, People’s Republic of China; 4Department of Orthopaedics and Traumatology, Ganzhou Hospital Affiliated to Nanfang Hospital, Southern Medical University, Ganzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nan Jiang; Bin Yu, Division of Orthopaedics & Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou Avenue North, Baiyun District, Guangzhou, 510515, People’s Republic of China, Email hnxyjn@smu.edu.cn; yubin@smu.edu.cnBackground: Current information were still limited regarding clinical characteristics, diagnosis, and treatment efficacy of calcaneal osteomyelitis (CO). The present study summarized similarities and differences between diabetes-related CO (DRCO) and trauma-related CO (TRCO) based on synthesis analysis of literature-reported cases.Methods: We searched the PubMed, Embase, and Cochrane Library databases to find English studies reporting DRCO and TRCO published between January 2000 and December 2021. Effective data were extracted and synthesized for comparisons.Results: Altogether 108 studies with 278 DRCO and 403 TRCO patients were analyzed. The ratio of females among the DRCO patients was significantly higher than that of the TRCO patients (37.4% vs 24.3%, P < 0.001). The median age at diagnosis of the DRCO patients was statistically older than the TRCO patients (56 vs 44 years, P < 0.001). The median symptom duration of the DRCO patients was longer than the TRCO patients (4 vs 2 months, P = 0.136), with ulcer and sinus as the top symptoms for the DRCO and TRCO patients, respectively. The positive rate of pathogen culture for the DRCO patients was significantly higher than that for the TRCO patients (94.8% vs 69.5%, P < 0.001). The DRCO patients had higher risks of infection relapse (32.3% vs 16.3%, P < 0.001) and amputation (24.8% vs 1.4%, P < 0.001), and a higher all-cause mortality (4.9% vs 1.3%, P = 0.03) than the TRCO patients.Conclusion: DRCO and TRCO shared similar and different clinical features and diagnostic issues. However, compared with TRCO, the clinical efficacy and prognosis of DRCO were worse.Keywords: calcaneal osteomyelitis, diabetic foot, post-traumatic osteomyelitis, fracture-related infection, synthesis analysis

Contents Immunocastration is an alternative method to replace surgical castration that is commonly performed in domestic and pet animals. In this study, a new immunocastration vaccine was developed, and its efficacy was evaluated in male rats. Six tandem copies of gonadotrophin-releasing hormone (GnRH) peptide were genetically fused to Salmonella typhimurium flagellin fljB (STF2) that is a ligand of toll-like receptor 5 (TLR5). The recombinant STF2-GnRH protein expressed in Escherichia coli was used as the immunocastration vaccine. Sixteen male rats were equally assigned to four groups. Excluding the control rats, three groups were immunized with 100, 200 and 400 μg of the STF2-GnRH vaccine, respectively. All of the immunized rats developed significantly higher titres of antibodies to GnRH than the control rats. The size and weight of both testes and epididymides from the immunized rats were significantly smaller than those of the control rats. Testicular tissues in the immunized rats demonstrated atrophy of seminiferous tubules and decreased numbers of both spermatogonia and spermatocytes. These data indicate that the newly developed STF2-GnRH vaccine has a potent immunogenicity to GnRH and efficiently suppresses the development of testes in rats. [ABSTRACT FROM AUTHOR]

BACKGROUND: Endoscopic stone removal is difficult in patients with a Billroth II gastrectomy. OBJECTIVE: To evaluate the usefulness of a rotatable papillotome and large-balloon dilation for removing bile-duct stones in patients with a Billroth II gastrectomy. DESIGN: A case series. SETTING: A large tertiary-referral center. PATIENTS AND INTERVENTION: Nine patients with bile-duct stones and a previous Billroth II gastrectomy were included. An endoscopic sphincterotomy (EST) was performed with a rotatable papillotome that could correct the axis of the cut toward the 5-o'clock direction; a large-balloon dilation (LBD) was then performed. MAIN OUTCOME MEASUREMENTS: The ability to perform an EST in the desired direction, successful stone removal, and complications. RESULTS: Rotation of the papillotome toward the 5-o'clock direction and an EST were achieved in 8 patients (89%). Stones were removed by EST and LBD in all 8 patients. There were no complications. LIMITATION: A small sample size. CONCLUSIONS: Limited EST by using a rotatable papillotome plus large-balloon dilation seemed to be safe, easy, and effective for removing bile-duct stones in patients with a Billroth II gastrectomy. [ABSTRACT FROM AUTHOR]

The involvement of protein intrinsic disorder in essential biological processes, it is well known in structural biology. However, experimental methods for detecting intrinsic structural disorder and directly measuring highly dynamic behavior of protein structure are limited. To address this issue, several computational methods to predict intrinsic disorder from protein sequences were developed and their performance is evaluated by the Critical Assessment of protein Intrinsic Disorder (CAID). In this paper, we describe a new computational method, PredIDR, which provides accurate prediction of intrinsically disordered regions in proteins, mimicking experimental X-ray missing residues. Indeed, missing residues in Protein Data Bank (PDB) were used as positive examples to train a deep convolutional neural network which produces two types of output for short and long regions. PredIDR took part in the second round of CAID and was as accurate as the top state-of-the-art IDR prediction methods. PredIDR can be freely used through the CAID Prediction Portal available at https://caid.idpcentral.org/portal or downloaded as a Singularity container from https://biocomputingup.it/shared/caid-predictors/., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Background: Clinically relevant postoperative pancreatic fistula (CR-POPF) is the major complication of pancreatoduodenectomy, and the pancreatic texture is one of the potential affecting factors. Multi-frequency Magnetic Resonance Elastography (MRE) is a novel technique for measuring stiffness of tissue, while its value in predicting CR-POPF preoperatively has not been well-documented., Method: Seventy patients who underwent multi-frequency MRE before pancreatoduodenectomy between July 2021 and April 2024 were retrospectively recruited into the study. The parameter of MRE, shear wave speed (c) and phase angle (φ), and clinical data were collected. Logistic regression and the receiver operating characteristic curve (ROC) analyses were used to assess the performance of multi-frequency MRE in predicting CR-POPF., Results: CR-POPF was developed in 14 out of 70 patients (20%), all categorized as Grade B. CR-POPF group had significantly lower c (1.339±0.210m/s) and longer hospital stays (21±22days) than no CR-POPF group. The MRE parameters, c and φ were moderately correlated with pancreas stiffness (eta 2 for φ =0.189, eta 2 for c =0.106). Dilated major pancreatic duct (MPD) (≥3mm) and higher c were independently associated with lower risk of CR-POPF in univariant and multivariant analysis (odds ratio for c = 0.041, 95%CI: 0.002~0.879, odds ratio for dilated MPD: 0.129, 95%CI: 0.022~0.768). The AUC of the predictive model based on c and MPD diameter was 0.786, which was better than Fistula Risk Score (FRS) (AUC=0.587) and alternative Fistula Risk Score (a-FRS) (AUC=0.556) in our center, with DeLong's test p= 0.028 and p=0.002 respectively., Conclusion: The MRE parameters were associated with pancreatic stiffness, and c was an independent predictor for CR-POPF after pancreatoduodenectomy., (Copyright © 2024. Published by Elsevier Inc.)

Competing Interests: DS was employed by Birdflu Veterinarian LLC, a private poultry veterinary practice. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with a dismal prognosis. Gemcitabine-based chemotherapy has emerged as a first-line treatment for PDAC. However, the development of gemcitabine resistance often results in therapeutic failure. In order to uncover the underlying mechanisms of gemcitabine resistance, gemcitabine-resistant PDAC cell lines and patient-derived xenograft (PDX) models are established and subjected to RNA sequencing. It is found that CMTM6 is closely related to gemcitabine resistance in PDAC. Multi-omics analysis revealed that EP300-mediated H3K27ac modification is involved in the transcriptional activation of CMTM6, which maintains IGF2BP1 expression by preventing its ubiquitination. The m 6 A reader IGF2BP1 stabilizes the EP300 and MYC mRNAs by recognizing m 6 A modifications, forming a positive feedback loop that enhances tumor stemness and ultimately contributes to PDAC resistance. The combined application of the EP300 inhibitor inobrodib and gemcitabine exerts a synergistic effect on PDAC. Overall, these findings reveal that the EP300-CMTM6-IGF2BP1 positive feedback loop facilitates gemcitabine resistance via epigenetic reprogramming and the combined use of inobrodib and gemcitabine represents a promising strategy for overcoming chemoresistance in PDAC, warranting further investigation in clinical trials., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Co-occurring mutations in KEAP1 in STK11/LKB1-mutant NSCLC activate NFE2L2/NRF2 to compensate for the loss of STK11-AMPK activity during metabolic adaptation. Characterizing the regulatory crosstalk between the STK11-AMPK and KEAP1-NFE2L2 pathways during metabolic stress is crucial for understanding the implications of co-occurring mutations. Here, we found that metabolic stress increased the expression and phosphorylation of SQSTM1/p62, which is essential for the activation of NFE2L2 and AMPK, synergizing antioxidant defense and tumor growth. The SQSTM1-driven dual activation of NFE2L2 and AMPK was achieved by inducing macroautophagic/autophagic degradation of KEAP1 and facilitating the AXIN-STK11-AMPK complex formation on the lysosomal membrane, respectively. In contrast, the STK11-AMPK activity was also required for metabolic stress-induced expression and phosphorylation of SQSTM1, suggesting a double-positive feedback loop between AMPK and SQSTM1. Mechanistically, SQSTM1 expression was increased by the PPP2/PP2A-dependent dephosphorylation of TFEB and TFE3, which was induced by the lysosomal deacidification caused by low glucose metabolism and AMPK-dependent proton reduction. Furthermore, SQSTM1 phosphorylation was increased by MAP3K7/TAK1, which was activated by ROS and pH-dependent secretion of lysosomal Ca 2+ . Importantly, phosphorylation of SQSTM1 at S24 and S226 was critical for the activation of AMPK and NFE2L2. Notably, the effects caused by metabolic stress were abrogated by the protons provided by lactic acid. Collectively, our data reveal a novel double-positive feedback loop between AMPK and SQSTM1 leading to the dual activation of AMPK and NFE2L2, potentially explaining why co-occurring mutations in STK11 and KEAP1 happen and providing promising therapeutic strategies for lung cancer. Abbreviations : AMPK: AMP-activated protein kinase; BAF1: bafilomycin A 1 ; ConA: concanamycin A; DOX: doxycycline; IP: immunoprecipitation; KEAP1: kelch like ECH associated protein 1; LN: low nutrient; MAP3K7/TAK1: mitogen-activated protein kinase kinase kinase 7; MCOLN1/TRPML1: mucolipin TRP cation channel 1; MEFs: mouse embryonic fibroblasts; MTORC1: mechanistic target of rapamycin kinase complex 1; NAC: N-acetylcysteine; NFE2L2/NRF2: NFE2 like bZIP transcription factor 2; NSCLC: non-small cell lung cancer; PRKAA/AMPKα: protein kinase AMP-activated catalytic subunit alpha; PPP2/PP2A: protein phosphatase 2; ROS: reactive oxygen species; PPP3/calcineurin: protein phosphatase 3; RPS6KB1/p70S6K: ribosomal protein S6 kinase B1; SQSTM1/p62: sequestosome 1; STK11/LKB1: serine/threonine kinase 11; TCL: total cell lysate; TFEB: transcription factor EB; TFE3: transcription factor binding to IGHM enhancer 3; V-ATPase: vacuolar-type H + -translocating ATPase.

Dual cognitive-walking treadmill training (DTT), designed to replicate real-life walking conditions, has shown promise effect in individuals with Parkinson's disease (PD). This study aims to compare the effects of DTT versus single treadmill training (STT) on cognitive and walking performance under both single and dual task conditions, as well as on fall, patients' subjective feeling, and quality of life. Sixteen individuals with PD were randomly assigned to DTT or STT group and underwent 8 weeks of training. The DTT group received treadmill training with cognitive loads, while the STT group received treadmill training without cognitive load. Outcome measures included gait parameters (speed, step length) and cognitive performance (reaction time, accuracy, composite score) under both single and dual task conditions. Unified Parkinson's Disease Rating Scale-part III (UPDRS-III), Falls Efficacy Scale (FES), Patient Global Impression of Change (PGIC), and Parkinson's Disease Questionnaire (PDQ-39) were also measured. Both DTT and STT groups showed increased comfortable walking speed and step length. Only the DTT group demonstrated significant improvements in cognitive composite score under both single and dual task conditions, as well as UPDRS-III, FES, and PDQ-39(p < 0.05). DTT can enhance cognitive function without compromising walking ability and also have real-world transferability., (© 2024. The Author(s).)

Background: Rheumatoid arthritis (RA) is an autoimmune condition characterized by inflammation and the deterioration of joints. Current treatments often have side effects, highlighting the need for safer options. This study investigates the therapeutic effects of Kunduan Yimu Decoction (KDYMD) on RA, focusing on the role of miR-124 in regulating Th17/Treg differentiation., Methods: PBMCs from RA patients were analyzed before and after KDYMD treatment. RT-qPCR was used to measure the miR-124 expressions. Flow cytometry was used to assess the ratios of Th17 to Treg cells. ELISA was used to quantify the cytokine concentrations. The effects of KDYMD on JAK2/STAT3 signaling were evaluated by western blot analysis. A CIA mouse model was used to validate the in vivo effects of KDYMD., Results: MiR-124 expression was significantly upregulated in PBMCs of RA patients after KDYMD treatment. This upregulation was associated with increased Tip60 and Foxp3 expression and decreased RORγt expression. In the cytokine analysis, IL-1, IL-6, and IL-17A were decreased, and IL-10 and TGF- were increased after treatment. Flow cytometry showed a restoration of the Th17/Treg balance, with a decrease in Th17 and an increase in Treg cells. In vivo, KDYMD treatment ameliorated ankle swelling and arthritis index in CIA mice, comparable to methotrexate (MTX). In addition, KDYMD modulated JAK2/STAT3 signaling and enhanced anti-inflammatory responses., Conclusions: KDYMD exerts significant anti-inflammatory effects in RA by upregulating miR-124, which in turn regulates Th17/Treg differentiation and modulates JAK2/STAT3 signaling. A novel mechanism involving miR-124 and immune cell balance suggests KDYMD could be a promising therapeutic agent for RA., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Qiang Xu reports financial support was provided by Guangzhou University of Chinese Medicine. Qiang Xu reports financial support was provided by the Natural Science Foundation of the Department of Education of Guangdong Province. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Introduction: The robotic-assisted surgical system has been widely used in hepatectomy. However, the effectiveness and feasibility of robotic-assisted hemi-hepatectomy (RH) has not been well-documented., Methods: Patients who underwent RH or open hemi-hepatectomy (OH) performed by a single surgeon at our hospital between January 2010 and August 2023 were included in this study. A stabilized inverse probability of treatment weighting adjusted analysis was performed., Results: Of the 163 consecutive patients identified, 60 underwent RH, and 103 underwent OH. After stabilized inverse probability of treatment weighting adjustment, RH demonstrated less blood loss than OH. In subgroup analyses, robotic-assisted left hemi-hepatectomy was associated with a shorter postoperative stay, a lower postoperative complication rate, and less blood loss compared with open left hemi-hepatectomy. While robotic-assisted right hemi-hepatectomy (RRH) was associated with less blood loss and a lower intraoperative blood transfusion rate, but a longer operation time compared with open right hemi-hepatectomy., Conclusions: RH is a safe and effective technique. In addition to less blood loss, robotic-assisted left hemi-hepatectomy had advantages in postoperative complications and postoperative stay, while RRH had advantages in intraoperative blood transfusions. However, operation time was longer for RRH than for open right hemi-hepatectomy., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Axis inhibition protein 1 (AXIN1), a scaffold protein interacting with various critical molecules, plays a vital role in determining cell fate. However, its impact on the antiviral innate immune response remains largely unknown. Here, we identify that AXIN1 acts as an effective regulator of antiviral innate immunity against both DNA and RNA virus infections. In the resting state, AXIN1 maintains the stability of the transcription factor interferon regulatory factor 3 (IRF3) by preventing p62-mediated autophagic degradation of IRF3. This is achieved by recruiting ubiquitin-specific peptidase 35 (USP35), which removes lysine (K) 48-linked ubiquitination at IRF3 K366. Upon virus infection, AXIN1 undergoes a phase separation triggered by phosphorylated TANK-binding kinase 1 (TBK1). This leads to increased phosphorylation of IRF3 and a boost in IFN-I production. Moreover, KYA1797K, a small molecule that binds to the AXIN1 RGS domain, enhances the AXIN1-IRF3 interaction and promotes the elimination of various highly pathogenic viruses. Clinically, patients with HBV-associated hepatocellular carcinoma (HCC) who show reduced AXIN1 expression in pericarcinoma tissues have low overall and disease-free survival rates, as well as higher HBV levels in their blood. Overall, our findings reveal how AXIN1 regulates IRF3 signaling and phase separation-mediated antiviral immune responses, underscoring the potential of the AXIN1 agonist KYA1797K as an effective antiviral agent., (© 2024. The Author(s).)

Aberrant A-to-I RNA editing, mediated by ADAR1 has been found to be associated with increased tumourigenesis and the development of chemotherapy resistance in various types of cancer. Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive malignancy with a poor prognosis, and overcoming chemotherapy resistance poses a significant clinical challenge. This study aimed to clarify the roles of ADAR1 in tumour resistance to cisplatin in iCCA. We discovered that ADAR1 expression is elevated in iCCA patients, particularly in those resistant to cisplatin, and associated with poor clinical outcomes. Downregulation of ADAR1 can increase the sensitivity of iCCA cells to cisplatin treatment, whereas its overexpression has the inverse effect. By integrating RNA sequencing and Sanger sequencing, we identified BRCA2, a critical DNA damage repair gene, as a downstream target of ADAR1 in iCCA. ADAR1 mediates the A-to-I editing in BRCA2 3'UTR, inhibiting miR-3157-5p binding, consequently increasing BRCA2 mRNA and protein levels. Furthermore, ADAR1 enhances cellular DNA damage repair ability and facilitates cisplatin resistance in iCCA cells. Combining ADAR1 targeting with cisplatin treatment markedly enhances the anticancer efficacy of cisplatin. In conclusion, ADAR1 promotes tumour progression and cisplatin resistance of iCCA. ADAR1 targeting could inform the development of innovative combination therapies for iCCA., (© 2024 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

The shift of carbon utilization from primarily glucose to other nutrients is a fundamental metabolic adaptation to cope with decreased blood glucose levels and the consequent decline in glucose oxidation. AMP-activated protein kinase (AMPK) plays crucial roles in this metabolic adaptation. However, the underlying mechanism is not fully understood. Here, we show that PDZ domain containing 8 (PDZD8), which we identify as a new substrate of AMPK activated in low glucose, is required for the low glucose-promoted glutaminolysis. AMPK phosphorylates PDZD8 at threonine 527 (T527) and promotes the interaction of PDZD8 with and activation of glutaminase 1 (GLS1), a rate-limiting enzyme of glutaminolysis. In vivo, the AMPK-PDZD8-GLS1 axis is required for the enhancement of glutaminolysis as tested in the skeletal muscle tissues, which occurs earlier than the increase in fatty acid utilization during fasting. The enhanced glutaminolysis is also observed in macrophages in low glucose or under acute lipopolysaccharide (LPS) treatment. Consistent with a requirement of heightened glutaminolysis, the PDZD8-T527A mutation dampens the secretion of pro-inflammatory cytokines in macrophages in mice treated with LPS. Together, we have revealed an AMPK-PDZD8-GLS1 axis that promotes glutaminolysis ahead of increased fatty acid utilization under glucose shortage., (© 2024. The Author(s).)

Autoimmune attack toward pancreatic β cells causes permanent loss of glucose homeostasis in type 1 diabetes (T1D). Insulin secretory granules store and secrete insulin but are also thought to be tissue messengers for T1D. Here, we show that the crinophagic granules (crinosome), a minor set of vesicles formed by fusing lysosomes with the conventional insulin dense-core granules (DCG), are pathogenic in T1D development in mouse models. Pharmacological inhibition of crinosome formation in β cells delays T1D progression without affecting the dominant DCGs. Mechanistically, crinophagy inhibition diminishes the epitope repertoire in pancreatic islets, including cryptic, modified and disease-relevant epitopes derived from insulin. These unconventional insulin epitopes are largely undetectable in the MHC-II epitope repertoire of the thymus, where only canonical insulin epitopes are presented. CD4 + T cells targeting unconventional insulin epitopes display autoreactive phenotypes, unlike tolerized T cells recognizing epitopes presented in the thymus. Thus, the crinophagic pathway emerges as a tissue-intrinsic mechanism that transforms insulin from a signature thymic self-protein to a critical autoantigen by creating a peripheral-thymic mismatch in the epitope repertoire., (© 2024. The Author(s).)

The aim of this study was to identify independent risk factors for preoperative lower extremity deep vein thrombosis (DVT) in elderly hip fracture patients and to construct a nomogram prediction model based on them. We collected clinical data from elderly hip fracture patients from Ya'an Hospital of Traditional Chinese Medicine (2021-2023), and used univariate and multivariate logistic regression analyses to identify independent risk factors for preoperative DVT. In this way, a nomogram prediction model was established. In addition, external validation of the model was performed by patient data from Ya'an Mingshan District Hospital of Traditional Chinese Medicine. Receiver operating characteristic curve analysis was used to calculate the area under the curve, and calibration and decision curves were plotted to assess the predictive performance of the model. Of the 223 elderly hip fracture patients, 23 (10.31%) developed DVT of the lower extremities before surgery. A total of 6 variables were identified as independent risk factors for preoperative lower extremity DVT in elderly hip fracture patients by logistic regression analysis: age > 75 years (OR = 1.932; 95% CI: 1.230-3.941), diabetes mellitus (OR = 2.139; 95% CI: 1.149-4.342), and prolonged duration of disease (OR. 2.535; 95% CI: 1.378-4.844), surgical treatment (OR = 1.564; 95% CI: 1.389-3.278), D-dimer > 0.5 mg/L (OR = 3.365; 95% CI: 1.229-7.715) fibrinogen > 4 g/L (OR = 3.473; 95% CI: 1.702-7.078). The constructed nomogram model has high accuracy in predicting the risk of preoperative DVT in elderly hip fracture patients, providing an effective tool for clinicians to identify high-risk patients and implement early intervention., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: The translocation of intestinal flora has been linked to the colonization of diverse and heavy lower respiratory flora in patients with septic ARDS, and is considered a critical prognostic factor for patients., Methods: On the first and third days of ICU admission, BALF, throat swab, and anal swab were collected, resulting in a total of 288 samples. These samples were analyzed using 16S rRNA analysis and the traceability analysis of new generation technology., Results: On the first day, among the top five microbiota species in abundance, four species were found to be identical in BALF and throat samples. Similarly, on the third day, three microbiota species were found to be identical in abundance in both BALF and throat samples. On the first day, 85.16% of microorganisms originated from the throat, 5.79% from the intestines, and 9.05% were unknown. On the third day, 83.52% of microorganisms came from the throat, 4.67% from the intestines, and 11.81% were unknown. Additionally, when regrouping the 46 patients, the results revealed a significant predominance of throat microorganisms in BALF on both the first and third day. Furthermore, as the disease progressed, the proportion of intestinal flora in BALF increased in patients with enterogenic ARDS., Conclusions: In patients with septic ARDS, the main source of lung microbiota is primarily from the throat. Furthermore, the dynamic trend of the microbiota on the first and third day is essentially consistent.It is important to note that the origin of the intestinal flora does not exclude the possibility of its origin from the throat.

Cyanthillium cinereum, which belongs to the family of Asteraceae, is an annual or perennial herbaceous plant with significant medicinal uses for treating colds and fever. During September to November of 2020, C. cinereum showing symptoms of witches'-broom were found in economic forests distributed in Ding'an, Hainan Province of China, with 20% incidence. The symptoms of the plant were consistent with infections by 'Candidatus Phytoplasma' species. To identify the pathogen, five symptomatic and three asymptomatic C. cinereum samples were collected. Total DNAs were extracted using 0.10 g fresh leaf tissues of symptomatic and asymptomatic C. cinereum through a CTAB DNA extraction method according to Doyle and Doyle (1990). PCR amplification were performed employing the primer pairs of R16mF2/R16mR1 (Gundersen and Lee, 1996) and secAfor1/secArev3 (Hodgetts et al., 2008) specific for the conserved gene fragments of 16S rRNA and secA from phytoplasma. The PCR products were purified and sequenced through Biotechnology (Shanghai) Co., Ltd. (Guangzhou, China), and the obtained sequences were deposited in GenBank. The phytoplasmal 16S rRNA and secA gene fragments obtained in the study were all identical with the length of 1325 bp (GenBank accession: PP098738) and 741 bp (PP072217), respectively. The phytoplasma strain was described as CcWB-hnda. A BLAST search based on 16S rRNA genes indicated that CcWB-hnda strain was identical to phytoplasmas belonging to 16SrII group like peanut witches'-broom phytoplasma strain T48 (OR239773) and 'Ca. Phytoplasma aurantifolia' strain TB2022 (CP120449). Virtual RFLP profiles based on 16S rRNA gene fragments obtained by iPhyClassifier (Zhao et al., 2009) showed that CcWB-hnda strain was a member of 16SrII-A subgroup with 1.00 similarity coefficient to the reference phytoplasma strain (L33765). A BLAST search based on secA genes indicated that CcWB-hnda had 100% sequence identity with phytoplasmas belonging to 16SrII group such as 'Ca. Phytoplasma aurantifolia' isolate TB2022 (CP120449), Vigna unguiculata witches'-broom phytoplasma (OR661282) and Emilia sonchifolia witches'-broom phytoplasma (MW353710). Phylogenetic analysis based on 16S rRNA and secA genes by MEGA 7.0 employing Neighbor-Joining method with 1000 bootstrap value (Kumar et al., 2016; Felsenstein, 1985) demonstrated that CcWB-hnda was clustered into one clade with the phytoplasmas belonging to 16SrII group, with 98% and 100% bootstrap value respectively. To our knowledge, this is the first report of C. cinereum infected by phytoplasmas belonging to 16SrII-A subgroup in China. Identification of the vector insects of the pathogens is necessary in future, revealing the epidemiology of the related diseases. Phytoplasmas belonging to same 16Sr group or subgroup can infect different plants and spread through them in nature. The finding in this study will be beneficial to epidemic monitoring and early warning of C. cinereum witches'-broom disease and the related plant diseases caused by the phytoplasmas belonging to 16SrII group.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), emerged as a global outbreak in 2019, profoundly affecting both human health and the global economy. Various vaccine modalities were developed and commercialized to overcome this challenge, including inactivated vaccines, mRNA vaccines, adenovirus vector-based vaccines, and subunit vaccines. While intramuscular vaccines induce high IgG levels, they often fail to stimulate significant mucosal immunity in the respiratory system. We employed the Newcastle disease virus (NDV) vector expressing the spike protein of the SARS-CoV-2 Beta variant (rK148/beta-S), and evaluated the efficacy of intranasal vaccination with rK148/beta-S in K18-hACE2 transgenic mice. Intranasal vaccination with a low dose (10 6.0 EID 50 ) resulted in an 86% survival rate after challenge with the SARS-CoV-2 Beta variant. Administration at a high dose (10 7.0 EID 50 ) led to a reduction in lung viral load and 100% survival against the SARS-CoV-2 Beta and Delta variants. A high level of the SARS-CoV-2 spike-specific IgA was also induced in vaccinated mice lungs following the SARS-CoV-2 challenge. Our findings suggest that rK148/beta-S holds promise as an intranasal vaccine candidate that effectively induces mucosal immunity against SARS-CoV-2.

Brain swelling after cardiac arrest may affect brain ventricular volume. This study aimed to investigate the prognostic implications of ventricular volume on early thin-slice brain computed tomography (CT) after cardiac arrest. We measured the gray-to-white matter ratio (GWR) and the characteristics and volumes of the lateral, third, and fourth ventricles. The primary outcome was a poor 6-month neurological outcome. Of the 166 patients, 115 had a poor outcome. The fourth ventricle was significantly smaller in the poor outcome group (0.58 cm 3 [95% CI, 0.43-0.80]) than in the good outcome group (0.74 cm 3 [95% CI, 0.68-0.99], p < 0.001). Ventricular characteristics and other ventricular volumes did not differ between outcome groups. The area under the curve for the fourth ventricular volume was 0.68, comparable to 0.69 for GWR. Lower GWR (<1.09) and lower fourth ventricular volume (<0.41 cm 3 ) predicted poor outcomes with 100% specificity and sensitivities of 8.7% (95% CI, 4.2-15.4) and 20.9% (95% CI, 13.9-29.4), respectively. Combining these measures improved the sensitivity to 25.2% (95% CI, 17.6-34.2). After adjusting for covariates, the fourth ventricular volume was independently associated with neurologic outcome. A marked decrease in fourth ventricular volume, with concomitant hypoattenuation on CT scans, more accurately predicted outcomes.

Before the COVID-19 pandemic, Mycoplasma pneumoniae infections emerged during spring to summer yearly in Taiwan, but infections were few during the pandemic. M. pneumoniae macrolide resistance soared to 85.7% in 2020 but declined to 0% during 2022-2023. Continued molecular surveillance is necessary to monitor trends in macrolide-resistant M. pneumoniae.

Peony ( Paeonia suffruticosa Andr.), belonging to family Paeoniaceae, is an important medicinal and ornamental plant. During August of each year from 2016 to 2023, peony plants at Heze city were found to exhibit leaf yellows symptoms. The incidence rate of the symptomatic plant was recorded from 10% to 30% in four peony gardens with about 200 acres. Total DNA was extracted from 0.10 g fresh plant leaf tissues from 24 symptomatic and 8 asymptomatic samples using rapid plant genomic DNA isolation kit (Aidlab Biotechnology, Beijing, China). The extracted DNA was amplified by nested polymerase chain reaction using universal primers R16mF2/R16mR1 followed by R16F2/R16R2 (Lee et al., 1993; Gundersen and Lee, 1996) specific for the 16S rRNA gene and new designed tuf gene specific primers JWB-tuforfF1 (5'-ATGGCTGAAATATTTTCAAGAG-3') and JWB-tuforfR1 (5'-TTATTCTATGATTTTAATAACAG-3') followed by JWB-tuforfF2 (5'-ATGTAAACGTAGGAACTATTGG-3') and JWB-tuforfR2 (5'- TCCGATAGTTCTTCCACCTTCAC-3'). Amplicons of about 1.25 kb and 1.02 kb (16S rRNA gene and tuf gene, respectively) were obtained in 8 symptomatic samples from four peony gardens. However, no amplification was obtained in any of the asymptomatic samples. The representative amplicons of 16S rRNA and tuf genes of three positive samples (Heze-9, -18 and -27) were cloned into a zero background pLB-simple vector (Tiangen Biotechnology, Beijing, China) and sequenced by Taihe Biotechnology, Beijing, China. Sequences obtained in the study were deposited in NCBI GenBank with accession numbers PP504882, PP504883 and PP504884 for the 16S rRNA gene as well as PP530237, PP530238 and PP530239 for the tuf gene. The phytoplasma strain under the study was described as peony yellows (PeY) phytoplasma, PeY-Heze strain. Alignment analysis by DNAMAN software showed that three 16S rRNA gene sequences obtained in the study shared 99.36% to 99.60% sequence identity and three tuf gene sequences obtained in the study were identical. BLAST analysis of the 16S rRNA gene sequences of the PeY-Heze phytoplasma strains showed 99.60%-99.84% sequence identity with ' Candidatus Phytoplasma ziziphi' (GenBank accession: CP025121). And tuf sequences of the strains showed 100% similarity with ' Ca . P. ziziphi' (CP025121). Interestingly, the virtual RFLP patterns derived from three 16Sr RNA gene sequences obtained in the study by iPhyClassifier (Zhao et al., 2009) were different from the reference patterns of all previously established 16Sr groups/subgroups. The most similar are the reference pattern of the 16Sr group VII, subgroup E (AY741531), with a similarity coefficient of 0.72, which is less than 0.85. These phytoplasma strains may represent a new 16Sr group. Phylogenetic analysis based on 16S rRNA genes using MEGA 7.0 by neighbor-joining (NJ) method with 1000 bootstrap value indicated that PeY-Heze strains clustered into one clade with the phytoplasma strains of ' Ca . P. ziziphi' with 68% bootstrap value. Although there are several reports available on ' Ca . P. solani' infecting peony in Shandong Province, China (Gao et al., 2013). To our knowledge, this is the first report of ' Ca . P. ziziphi'-related strains infecting peony in China. The findings in this study will be beneficial to the detection, quarantine, and prevention of peony yellows phytoplasmas in China.

Objective: Previous studies have reported that the inappropriate use of allopurinol may increase the risk of cerebrovascular accidents, but some studies have also confirmed that allopurinol is a protective factor against stroke. To clarify whether there is a relevant causal relationship between allopurinol and cerebral infarction, we conducted a two-sample Mendelian randomization (MR) study., Methods: Data on single nucleotide polymorphisms (SNPs) associated with allopurinol and genome-wide association studies of cerebral infarction were obtained from the genome-wide association study (GWAS) web site. Five basic MR analyses were performed using MR-Egger regression, weighted median (WM1), inverse variance weighting (IVW), weighted mode (WM2), and simple mode. Sensitivity analysis was subsequently performed to detect horizontal pleiotropy, heterogeneity, and potential outliers. The final analysis results were mainly based on the IVW estimates., Results: A total of 10 SNPs were used as instrumental variables (IVs). MR analysis [(IVW: odds ratio (OR) = 1.053, 95% confidence interval (CI): 1.019-1.088, P = 0.002), (WM1: OR = 1.053, 95% CI: 1.009-1.098, P = 0.017), (WM2: OR = 1.050, 95% CI: 1.008-1.095, P = 0.044), (MR Egger: Q = 4.285, P = 0.830)] showed a positive causal association between allopurinol and the risk of cerebral infarction. Sensitivity analysis such as horizontal pleiotropy and heterogeneity increased the reliability of this result., Conclusion: The results of this study provide direct evidence that there is a causal relationship between allopurinol and cerebral infarction and that allopurinol may increase the risk of cerebral infarction., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

A Newcastle disease virus (NDV)-vectored vaccine expressing clade 2.3.4.4b H5 Hemagglutinin was developed and assessed for efficacy against H5N1 highly pathogenic avian influenza (HPAI) in specific pathogen-free (SPF) chickens, broilers, and domestic ducks. In SPF chickens, the live recombinant NDV-vectored vaccine, rK148/22-H5, achieved complete survival against HPAI and NDV challenges and significantly reduced viral shedding. Notably, the live rK148/22-H5 vaccine conferred good clinical protection in broilers despite the presence of maternally derived antibodies. Good clinical protection was observed in domestic ducks, with decreased viral shedding. It demonstrated complete survival and reduced cloacal viral shedding when used as an inactivated vaccine from SPF chickens. The rK148/22-H5 vaccine is potentially a viable and supportive option for biosecurity measure, effectively protecting in chickens against the deadly clade 2.3.4.4b H5 HPAI and NDV infections. Furthermore, it aligns with the strategy of Differentiating Infected from Vaccinated Animals (DIVA)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

To explore the role of YAP, a key effector of the Hippo pathway, in temporomandibular joint (TMJ) ankylosis. The temporal and spatial expression of YAP was detected via immunohistochemistry and multiplex immunohistochemistry on postoperative Days 1, 4, 7, 9, 11, 14 and 28 in a sheep model. Isolated mesenchymal stem cells (MSCs) from samples of the Day 14. The relative mRNA expression of YAP was examined before and after the osteogenic induction of MSCs. A YAP-silenced MSC model was constructed, and the effect of YAP knockdown on MSC function was examined. YAP is expressed in the nucleus of the key sites that determine the ankylosis formation, indicating that YAP is activated in a physiological state. The expression of YAP increased gradually over time. Moreover, the number of cells coexpressing of RUNX2 and YAP-with the osteogenic active zone labelled by RUNX2-tended to increase after Day 9. After the osteogenic induction of MSCs, the expression of YAP increased. After silencing YAP, the osteogenic, proliferative and migratory abilities of the MSCs were inhibited. YAP is involved in the early development of TMJ bony ankylosis. Inhibition of YAP using shRNA might be a promising way to prevent or treat TMJ ankylosis., (© 2024. The Author(s).)

Phytophthora root and stem rot (PRR), caused by Phytophthora sojae, can occur at any growth stage under poorly drained and humid conditions. The expansion of soybean cultivation in South Korean paddy fields has increased the frequency of PRR outbreaks. This study aimed to identify four P. sojae isolates newly collected from domestic fields and evaluate race-specific resistance using the hypocotyl inoculation technique. The four isolates exhibited various pathotypes, with GJ3053 exhibiting the highest virulence complexity. Two isolates, GJ3053 and AD3617, were screened from 205 soybeans, and 182 and 190 genotypes (88.8 and 92.7%, respectively) were susceptible to each isolate. Among these accessions, five genotypes resistant to both isolates were selected. These promising genotypes are candidates for the development of resistant soybean cultivars that can effectively control PRR through gene stacking.

Background: Previous studies have reported low serum 25-hydroxyvitamin D [25(OH)D] levels in dermatomyositis (DM) patients, but the exact causal relationship between them remains elusive. Our aim is to confirm the causal relationship between 25(OH)D and DM risk through a Mendelian randomization study., Methods: Retrieve genome-wide association study (GWAS) data on 25(OH)D (n = 441 291) and DM (n cases = 201, n controls = 172 834) from the GWAS database (https://gwas.mrcieu.ac.uk/). Select single-nucleotide polymorphisms (SNPs) strongly correlated with 25(OH)D as instrumental variables (IVs). The primary analytical approach involves the use of the inverse-variance weighted method (IVW), supplemented by MR-Egger regression and weighted median methods to enhance the reliability of the results. Heterogeneity and sensitivity analyses were conducted using Cochran's Q and leave-one-out approaches, respectively., Results: The IVW analysis confirmed a positive causal relationship between genetic variation in 25(OH)D levels and DM (OR = 2.36, 95% CI = 1.01-5.52, p = .048). Although not statistically significant (all p > .05), the other methods also suggested a protective effect of 25(OH)D on DM. Based on MR-Egger intercepts and Cochran's Q analysis, the selected SNPs showed no horizontal pleiotropy and heterogeneity. Sensitivity analysis demonstrated the robustness of the results against individual SNPs., Conclusion: We provide the first evidence of a causal relationship between 25(OH)D levels and DM. Our findings support the importance of measuring serum 25(OH)D levels and considering vitamin D supplementation in clinical practice for patients with DM., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

We report the first North American origin class I avian orthoavulavirus 1 (AOAV-1) isolated from a faecal dropping of wild Eurasian teal ( Anas crecca ) in South Korea. Whole genome sequencing and comparative phylogenetic analysis revealed that the AOAV-1/Eurasian teal/South Korea/KU1405-3/2017 virus belongs to the sub-genotype 1.2 of class I AOAV-1. Phylogenetic analysis suggested multiple introductions of the North American sub-genotype 1.2 viruses into Asia and its establishment in the wild bird population in East Asia since May 2011. These results provide information on the epidemiology of AOAV-1, particularly the role of migratory wild birds in exchanging viruses between the Eurasian and North American continents. Enhanced genomic surveillance is required to improve our understanding on the evolution and transmission dynamics of AOAV-1 in wild birds.

We isolated novel reassortant avian influenza A(H5N6) viruses containing genes from clade 2.3.4.4b H5N1 virus and low pathogenicity avian influenza viruses in carcasses of whooper swans and bean geese in South Korea during December 2023. Neuraminidase gene was from a clade 2.3.4.4b H5N6 virus infecting poultry and humans in China.

Astrocyte aerobic glycolysis provides vital trophic support for central nervous system neurons. However, whether and how astrocytic metabolic dysregulation contributes to neuronal dysfunction in intellectual disability (ID) remain unclear. Here, we demonstrate a causal role for an ID-associated SNX27 mutation (R198W) in cognitive deficits involving reshaping astrocytic metabolism. We generated SNX27 R196W (equivalent to human R198W) knock-in mice and found that they displayed deficits in synaptic function and learning behaviors. SNX27 R196W resulted in attenuated astrocytic glucose uptake via GLUT1, leading to reduced lactate production and a switch from homeostatic to reactive astrocytes. Importantly, lactate supplementation or a ketogenic diet restored neuronal oxidative phosphorylation and reversed cognitive deficits in SNX27 R196W mice. In summary, we illustrate a key role for astrocytic SNX27 in maintaining glucose supply and glycolysis and reveal that altered astrocytic metabolism disrupts the astrocyte-neuron interaction, which contributes to ID. Our work also suggests a feasible strategy for treating ID by restoring astrocytic metabolic function., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Aim: To assess the ability of clinical examination, biomarkers, electrophysiology and brain imaging, individually or in combination to predict good neurological outcomes at 6 months after CA., Methods: This was a retrospective analysis of the Korean Hypothermia Network Prospective Registry 1.0, which included adult out-of-hospital cardiac arrest (OHCA) patients (≥18 years). Good outcome predictors were defined as both pupillary light reflex (PLR) and corneal reflex (CR) at admission, Glasgow Coma Scale Motor score (GCS-M) >3 at admission, neuron-specific enolase (NSE) <17 µg/L at 24-72 h, a median nerve somatosensory evoked potential (SSEP) N20/P25 amplitude >4 µV, continuous background without discharges on electroencephalogram (EEG), and absence of anoxic injury on brain CT and diffusion-weighted imaging (DWI)., Results: A total of 1327 subjects were included in the final analysis, and their median age was 59 years; among them, 412 subjects had a good neurological outcome at 6 months. GCS-M >3 at admission had the highest specificity of 96.7% (95% CI 95.3-97.8), and normal brain DWI had the highest sensitivity of 96.3% (95% CI 92.9-98.4). When the two predictors were combined, the sensitivities tended to decrease (ranging from 2.7-81.1%), and the specificities tended to increase, ranging from81.3-100%. Through the explorative variation of the 2021 European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) prognostication strategy algorithms, good outcomes were predicted, with a specificity of 83.2% and a sensitivity of 83.5% in patients by the algorithm., Conclusions: Clinical examination, biomarker, electrophysiology, and brain imaging predicted good outcomes at 6 months after CA. When the two predictors were combined, the specificity further improved. With the 2021 ERC/ESICM guidelines, the number of indeterminate patients and the uncertainty of prognostication can be reduced by using a good outcome prediction algorithm., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Recent studies have suggested a potential association between methotrexate use and an increased risk of dementia. However, the causal relationship between methotrexate and dementia remains unclear. This study aims to investigate the potential causal effect of methotrexate use on the risk of dementia using a two-sample Mendelian randomization (TSMR) approach., Methods: We conducted a TSMR study using summary statistics from genome-wide association studies (GWAS) of methotrexate use and dementia. We obtained genetic instruments for methotrexate use from a large-scale GWAS meta-analysis and genetic instruments for dementia from a separate GWAS meta-analysis. We performed several statistical analyses, including inverse-variance weighted (IVW), weighted median (WM1), weighted mode (WM2), and MR-Egger regression methods, to estimate the causal effect of methotrexate on dementia risk., Results: Our TSMR analysis showed a significant positive association between genetic predisposition to methotrexate use and dementia risk. The IVW method estimated a causal odds ratio (OR) of 0.476 [95% confidence interval (CI) 0.362-0.626] per unit increase in the log odds ratio of methotrexate use. WM1, WM2, and MR-Egger methods provided consistent results., Conclusion: The findings of this mendelian randomization (MR) study suggest a potential causal effect of methotrexate use on the risk of dementia. However, further research is needed to validate these findings and explore the underlying mechanisms. Since methotrexate is widely prescribed for various autoimmune diseases, a better understanding of its potential impact on dementia risk is crucial for optimizing treatment strategies and addressing potential adverse effects., (© 2024. The Author(s).)

Objective: To compare the effects of tofacitinib and adalimumab on the risk of adverse lipidaemia outcomes in patients with newly diagnosed rheumatoid arthritis (RA)., Methods: Data of adult patients newly diagnosed with RA who were treated with tofacitinib or adalimumab at least twice during a 3-year period from 1 January 2018 to 31 December 2020, were enrolled in the TriNetX US Collaborative Network. Patient demographics, comorbidities, medications, and laboratory data were matched by propensity score at baseline. Outcome measurements include incidental risk of dyslipidemia, major adverse cardiac events (MACE) and all-cause mortality., Results: A total of 7,580 newly diagnosed patients with RA (1998 receiving tofacitinib, 5,582 receiving adalimumab) were screened. After propensity score matching, the risk of dyslipidaemia outcomes were higher in the tofacitinib cohort, compared with adalimumab cohort (hazard ratio [HR] with 95% confidence interval [CI], 1.250 [1.076-1.453]). However, there is no statistically significant differences between two cohorts on MACE (HR, 0.995 [0.760-1.303]) and all-cause mortality (HR, 1.402 [0.887-2.215])., Conclusion: Tofacitinib use in patients with RA may increase the risk of dyslipidaemia to some extent compared to adalimumab. However, there is no differences on MACE and all-cause mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ma, Shi, Wang, Feng, Chen, Zhong, Liu, Cheng-Chung Wei, Lin and Xu.)

Background: In stroke rehabilitation, the selection of appropriate assistive devices is of paramount importance for patients. Specifically, the choice of device can significantly influence the functional recovery of the upper limb, impacting their overall activities or functional tasks., Objectives: This review aimed to comprehensively analyze and summarize the clinical evidence from randomized controlled trials (RCTs) regarding the therapeutic effects of commonly used assistive devices on upper extremity function in patients with stroke., Methods: To evaluate assistive devices for patients with stroke, we summarized qualitatively throughout synthesis of results, such as therapeutic intervention, intensity, outcome, and summary of results, and examined risk of bias, heterogeneity, mean difference, 95% confidence interval, and I-squared value. To analyze, we used RoB 2 and RevMan 5.4., Results: The qualitative synthesis included 31 RCTs. The randomization process and the reporting of results showed minimal bias, but there were issues with bias from intended interventions, and missing outcome data presented some concerns. The quantitative synthesis included 16 RCTs. There was a significant difference in the Fugl-Meyer assessment-upper extremity functioning (FMA-UE) scores between the groups, with a total mean difference (95% confidence interval) of 2.40 (0.21, 4.60), heterogeneity values were Tau 2 = 0.32, chi-square = 8.22, degrees of freedom = 8 (p = 0.41), and I 2 = 3% for FMA-UE and the test for the overall effect produced Z = 2.14 (p = 0.03) in patients with chronic stroke. However, there was no significant difference in all other outcome measures., Conclusions: Upper-limb robots did not demonstrate significant superiority over conventional treatments in improving function of upper limbs, with the exception of FMA-UE scores for patients with chronic stroke. The mean difference of FMA-UE was also lower than minimally important difference. Nonetheless, the usage of upper-limb robots may contribute to enhanced function for patients with stroke, as those devices support clinicians and enable a greater number of movement repetitions within specific time frames., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Myosin Va (Myo Va) is one of three protein complexes involved in melanosome transport. In this study, we identified BMP-2 as an up-regulator of Myo Va expression using 2-methyl-naphtho[1,2,3-de]quinolin-8-one (MNQO). Our results showed that MNQO reduced the mRNA and protein expression of Myo Va and BMP-2 in melanocytes. Knockdown of BMP-2 by siRNA also affected Myo Va mRNA and protein expression, confirming that MNQO regulates Myo Va through BMP-2. Furthermore, phosphorylation of Smad1/5/8 by BMP2 treatment confirmed that the BMP-2/Smad signaling pathway regulates Myo Va expression in Melan-a melanocytes. Smad-binding elements were found in the Myo Va promoter and phosphorylated Smad1/5/8 bind directly to the Myo Va promoter to activate Myo Va transcription and BMP-2 enhances this binding. These findings provide insight into a new role for BMP-2 in Melan-a melanocytes and a mechanism of regulation of Myo Va expression that may be beneficial in the treatment of albinism or hyperpigmentation disorders., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Spondylitis caused by Brucella infection is a rare but challenging condition, and its successful management depends on timely diagnosis and appropriate treatment. This study reports two typical cases of thoracic and lumbar brucellosis spondylitis, highlighting the pivotal roles of real-time polymerase chain reaction (real-time PCR) detection and surgical intervention., Case Presentation: Case 1 involved a 49-year-old male shepherd who presented with a 6-month history of fever (40°C), severe chest and back pain, and 2-week limited lower limb movement with night-time exacerbation. Physical examination revealed tenderness and percussion pain over the T9 and T10 spinous processes, with grade 2 muscle strength in the lower limbs. CT showed bone destruction of the T9 and T10 vertebrae with narrowing of the intervertebral space, whereas MRI demonstrated abnormal signals in the T9-T10 vertebrae, a spinal canal abscess, and spinal cord compression. The Rose Bengal plate agglutination test was positive. Case 2 was a 59-year-old man who complained of severe thoracolumbar back pain with fever (39.0°C) and limited walking for 2 months. He had a 2.5 kg weight loss and a history of close contact with sheep. The Rose Bengal test was positive, and the MRI showed inflammatory changes in the L1 and L2 vertebrae. Diagnosis and treatment: real-time PCR confirmed Brucella infection in both cases. Preoperative antimicrobial therapy with doxycycline, rifampicin, and ceftazidime-sulbactam was administered for at least 2 weeks. Surgical management involved intervertebral foraminotomy-assisted debridement, decompression, internal fixation, and bone grafting under general anesthesia. Postoperative histopathological examination with HE and Gram staining further substantiated the diagnosis. Outcomes: both patients experienced significant pain relief and restored normal lower limb movement at the last follow-up (4-12 weeks) after the intervention., Conclusion: Real-time PCR detection offers valuable diagnostic insights for suspected cases of brucellosis spondylitis. Surgical treatment helps in infection control, decompression of the spinal cord, and restoration of stability, constituting a necessary and effective therapeutic approach. Prompt diagnosis and comprehensive management are crucial for favorable outcomes in such cases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Ji, Zhao and Zhang.)

Background: Esophageal cancer (EC) metastasized to the kidney is extremely rare clinically. Here, we present a case of metachronous renal metastasis of esophageal squamous cell carcinoma (ESCC) through epithelial-mesenchymal transition (EMT)., Case Presentation: A 60-year-old patient, male, complained of left waist pain for 5 days, 11 months after radical esophagectomy. Laboratory tests revealed haematuria. Both CT and PET-CT scan showed retroperitoneal lymph nodes and left renal masses. Subsequently the patient received a left nephrectomy and lymph nodes resection, and squamous cell carcinoma of kidney and renal hilar lymph nodes was diagnosed, combined with morphology, medical history and immunophenotype, it was presumed to be metastasis of ESCC through the EMT pathway., Conclusions: The renal metastasis of squamous cell carcinoma should be considered in patients with history of EC, although this is very rare. Histopathological examination combined with immunochemical detection is helpful in differential diagnosis., Competing Interests: None., (AJTR Copyright © 2024.)

Background: Progressive supranuclear palsy (PSP) is a tauopathy that involves subcortical regions but also extends to cortical areas. The clinical impact of different tau protein sites and their influence on glymphatic dysfunction have not been investigated., Patients and Methods: Participants (n = 55; 65.6 ± 7.1 years; 29 women) with PSP (n = 32) and age-matched normal controls (NCs; n = 23) underwent 18 F-Florzolotau tau PET, MRI, PSP Rating Scale (PSPRS), and Mini-Mental State Examination. Cerebellar gray matter (GM) and parametric estimation of reference signal intensity were used as references for tau burden measured by SUV ratios. Glymphatic activity was measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS)., Results: Parametric estimation of reference signal intensity is a better reference than cerebellar GM to distinguish tau burden between PSP and NCs. PSP patients showed higher cortical and subcortical tau SUV ratios than NCs ( P < 0.001 and <0.001). Cortical and subcortical tau deposition correlated with PSPRS, UPDRS, and Mini-Mental State Examination scores (all P 's < 0.05). Cortical tau deposition was further associated with the DTI-ALPS index and frontal-temporal-parietal GM atrophy. The DTI-ALPS indexes showed a significantly negative correlation with the PSPRS total scores ( P < 0.01). Finally, parietal and occipital lobe tau depositions showed mediating effects between the DTI-ALPS index and PSPRS score., Conclusions: Cortical tau deposition is associated with glymphatic dysfunction and plays a role in mediating glymphatic dysfunction and clinical severity. Our results provide a possible explanation for the worsening of clinical severity in patients with PSP., Competing Interests: Conflicts of interest sources of funding: T.C.Y. owns equity in APRINOIA Therapeutics. The other authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: The objective of this study is to provide a description of a group of retrospective cohort outcomes in patients with systemic lupus erythematosus (SLE) complicated with immune thrombocytopenia (ITP) receiving belimumab., Methods: This study reports on the treatment of 10 female patients (mean age 34.3 ± 14.0 years, mean weight 58.7 ± 18.2 kg) with both SLE and ITP who received belimumab in addition to basic drug therapy. The belimumab treatment regimen consisted of a dosage of 10 mg/kg, with an initial infusion every 2 weeks for the first 3 doses, followed by an infusion every 4 weeks., Results: Ten patients were included in the study. The overall response rate of thrombocytopenia was 90% after treatment. The parameters such as platelet count, lymphocyte count, erythrocyte count, hemoglobin, dsDNA, C3, and C4 were significantly improved ( p < .05). The SLE Disease Activity Index (SLEDAI), British Islet lupus Assessment Group 2004 (BILAG-2004), and Physician Global assessment (PGA) scores were significantly decreased ( p < .05). There were no significant differences in glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST), and serum creatinine (Scr) before and after treatment ( p > .05)., Conclusion: Belimumab shows promising clinical outcomes in the treatment on patients with both SLE and ITP. Further studies are needed to validate these findings in larger patient populations and compare the efficacy of belimumab with other treatments for SLE complicated with ITP. Long-term response rates and adverse events associated with belimumab treatment also warrant further investigation., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: This study aims to analyze the safety and clinical efficacy of using double posterolateral coaxial portals for endoscopic treatment of posterior ankle impingement syndrome (PAIS), a procedure that has gained popularity in recent times., Methods: Six fresh foot samples were randomly selected to measure the distances of two posterolateral portals to the sural nerve in different positions (plantar flexion 10°, dorsiflexion 30°, and plantar flexion 30°) for safety evaluation. A prospective analysis was conducted on the clinical efficacy of the operative approach for endoscopic management of posterior ankle impingement syndrome, including evaluation of effectiveness and complications., Results: In this study, the mean distances of the first and second portals to the sural nerve were measured in different ankle positions. The distances were found to be 2.26 ± 0.22 cm and 1.59 ± 0.12 cm in the plantar flexion 10° position, 2.21 ± 0.21 cm and 1.55 ± 0.12 cm in the dorsiflexion 30° position, and 2.46 ± 0.29 cm and 1.73 ± 0.19 cm in the plantar flexion 30° position, demonstrating a significant safety margin from the nerve. A total of 38 patients underwent endoscopic treatment for posterior ankle impingement syndrome using double posterolateral coaxial portals between January 2012 and December 2017. This surgical approach provided access to the subtalar joint and posterior ankle region. The patients were followed up for an average of 38.2 months (24-72 months), with a satisfaction rate of 94.7%. There were no reported complications, and significant improvements were observed in both visual analogue scale (VAS) and The American Orthopedic Foot and Ankle Society Score (AOFAS) scores postoperatively. The VAS score decreased from 5.68 to 0.51 (P < 0.001), while the AOFAS score increased from 71.68 to 92.34 (P < 0.001), resulting in an excellent/good rate of 97.3%., Conclusion: The use of double posterolateral coaxial portals in the treatment of posterior ankle impingement syndrome offers several advantages, including improved safety, reduced risk of nerve injury, enhanced visualization of the posterior ankle and subtalar joint, favorable clinical outcomes, and minimal complications., Competing Interests: All surgical procedures were carried out by Rui Li, Yuan-qiang Li,Cheng-song Yuan, Wan Chen and Fang-yuan Wei in this study. The Data measurement of cadaver specimens was performed by Kun-gao He and Xiao-li Gou participated in the patient selection, investigation on the outpatient clinic and radiographic assessments, literature search, and data monitoring. Chen-ke Zhang completed the statistical analysis and manuscript writing. All authors have read and approved the final manuscript. All authors declared that they have no conflict of interest., (© 2024 Asia Pacific Knee, Arthroscopy and Sports Medicine Society. Published by Elsevier (Singapore) Pte Ltd.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Excellent hip joint function facilitates limb recovery and improves the quality of survival. This study aimed to investigate the potential risk factors affecting postoperative joint functional activity and outcomes in elderly hip fractures patients and to provide evidence for patient rehabilitation and clinical management., Aim: To explore the relationship between inflammatory factors and hip function and the interaction between inflammation and health after hip fracture in elderly patients., Methods: The elderly patients who had hip fracture surgery at our hospital between January 1, 2021, and December 31, 2022 were chosen for this retrospective clinical investigation. Patients with excellent and fair postoperative hip function had their clinical information and characteristics gathered and compared. Age, gender, fracture site, surgical technique, laboratory indices, and other variables that could have an impact on postoperative joint function were all included in a univariate study. To further identify independent risk factors affecting postoperative joint function in hip fractures, risk factors that showed statistical significance in the univariate analysis were then included in a multiple logistic regression analysis. In addition to this, we also compared other outcome variables such as visual analogue scale and length of hospital stay between the two groups., Results: A total of 119 elderly patients with hip fractures were included in this study, of whom 37 were male and 82 were female. The results of univariate logistic regression analysis after excluding the interaction of various factors showed that there was a statistically significant difference in interleukin (IL)-6, IL-8, IL-10, C-reactive protein (CRP), and complement C1q (C1q) between the fair and excellent joint function groups ( P < 0.05). The results of multiple logistic regression analysis showed that IL-6 > 20 pg/mL [(Odds ratio (OR) 3.070, 95%CI: 1.243-7.579], IL-8 > 21.4 pg/ mL (OR 3.827, 95%CI: 1.498-9.773), CRP > 10 mg/L (OR 2.142, 95%CI: 1.020-4.498) and C1q > 233 mg/L (OR 2.339, 95%CI: 1.094-5.004) were independent risk factors for poor joint function after hip fracture surgery (all P < 0.05)., Conclusion: After hip fractures in older patients, inflammatory variables are risk factors for fair joint function; therefore, early intervention to address these markers is essential to enhance joint function and avoid consequences., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

From the perspective of lncRNA MALAT1 regulating cholesterol metabolism in chondrocytes, this paper explores the effect and mechanism of Tougu Xiaotong Capsules(TGXTC) in delaying the degeneration of osteoarthritis. After one week of adaptive feeding, 48(8-week-old) C57BL/6 mice were randomly divided into a blank group(12 mice) and a model group(36 mice) by random number table method. The mice in the model group were anesthetized by inhalation of 5% isoflurane, and the OA model was induced by Hulth method. The experiment randomly divided the mice into a model group(12 mice), a drug-positive group(taururso-deoxycholic acid)(12 mice), and a TGXTC group(12 mice). The drug-positive group was given 500 mg·kg~(-1) taurodeoxycholic acid by intragastric administration. TGXTC group was given TGXTC 368 mg·kg~(-1) by gavage. The blank group and model group were given the same amount of normal saline for four weeks. After the intervention, the mice in each group were killed under anesthesia, and the knee cartilage tissue was separated and collected. The morphologic changes of knee cartilage were observed. The level of lncRNA MALAT1 in the cartilage tissue was detected by real-time PCR. The protein expressions of ABCA1, ApoA1, LXRβ, CHOP, and caspase-3 in mouse articular cartilage were detected by Western blot. Lentivirus-coated plasmid was used to transfect mouse chondrocytes with sh-MALAT1. The gene levels of lncRNA MALAT1 in mouse chondrocytes transfected with sh-MALAT1 were detected by real-time PCR. Western blot was used to detect the effect of TGXTC on the protein content of ABCA1, ApoA1, LXRβ, CHOP, and caspase-3 in thapsigargin(TG)-induced mouse chondrocytes after lncRNA MALAT1 knockdown. Flow cytometry was used to detect the effect of TGXTC on apoptosis of TG-induced mouse chondrocytes after lncRNA MALAT1 knockdown. The results of HE and saffranine O staining showed that compared with the model group, the structure of the cartilage layer was basically intact; the damage degree of joint structure was significantly improved, and the cartilage matrix was significantly enhanced by saffranine O staining in the TGXTC group and drug-positive group. Compared with the model group, the lncRNA MALAT1 level was significantly decreased in the TGXTC group and drug-positive group. Compared with the model group, the protein content of ABCA1, ApoA1, and LXRβ was significantly increased, while that of CHOP and caspase-3 in the TGXTC group and drug-positive group significantly decreased. Compared with the TG group, the lncRNA MALAT1 level in the TG+sh-MALAT1 group was decreased. The lncRNA MALAT1 level in the TG+sh-MA-LAT1+TGXTC group was increased compared with the TG+TGXTC group. Western blot results showed that compared with the model group, protein expressions of ABCA1, ApoA1, LXRβ, CHOP, and caspase-3 in the TGXTC group were significantly decreased, after lncRNA MALAT1 knockdown, the regulation and apoptosis of ABCA1, ApoA1, LXRβ, CHOP, and caspase-3 in TG-induced mouse chondrocytes were weakened by TGXTC. TGXTC can improve the disorder of cholesterol metabolism in OA chondrocytes and delay OA degeneration, which is closely related to the regulation of lncRNA MALAT1.

Introduction: The role of lactate measurement in out-of-hospital cardiac arrest (OHCA) survivors remains controversial. We assessed the association between early lactate-related variables, OHCA characteristics, and long-term neurological outcome., Methods: In OHCA patients who received targeted temperature management, lactate levels were measured at 0, 12, and 24 h after the return of spontaneous circulation. We calculated lactate clearance and time-weighted cumulative lactate (TWCL), which represent the area under the time-lactate curve. The area under the receiver operating characteristic curve (AUC) and the adjusted odds ratios (AORs) of lactate-related variables for predicting 6-month poor outcome (Cerebral Performance Category 3-5) were evaluated. Interactions between lactate variables and characteristics of OHCA were evaluated by a multivariable logistic model with interaction terms and subgroup analysis., Results: A total of 347 OHCA patients were included. After adjustment, higher lactate levels at the three time points were associated with a poor outcome (AOR 1.10 [95% CI, 1.03-1.18], AOR 1.15 [95% CI, 1.02-1.29], and AOR 1.36 [95% CI, 1.15-1.60], respectively), while TWCL was the only lactate kinetics variable associated with a poor outcome (AOR 1.29 [95% CI, 1.12-1.49]). We identified several interactions between lactate-related variables and OHCA characteristics. In particular, the AUC of TWCL was excellent in cases of noncardiac etiology (AUC 0.92 [95% CI, 0.86-0.96] but only moderate in cardiac etiology (AUC 0.69 [95% CI, 0.62-0.75])., Conclusions: Early lactate levels, especially at 24 h, and TWCL were independent predictors of neurologic outcome in these patients, whereas lactate clearance was not. The prognostic ability of lactate-related variables varied depending on the OHCA characteristics., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)