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Skeletal muscle atrophy is a common complication of chronic kidney disease (CKD) that affects the quality of life and prognosis of patients. We aimed to investigate the effects and mechanisms of caffeic acid (CA), a natural phenolic compound, on skeletal muscle atrophy in CKD rats. Male Sprague-Dawley rats underwent 5/6 nephrectomy (NPM) and were treated with CA (20, 40, or 80 mg/kg/day) for 10 weeks. The body and muscle weights, renal function, hemoglobin, and albumin were measured. The histological, molecular, and biochemical changes in skeletal muscles were evaluated using hematoxylin-eosin staining, quantitative real-time PCR, malondialdehyde/catalase/superoxide dismutase/glutathione level detection, and enzyme-linked immunosorbent assay. Western blotting and network pharmacology were applied to identify the potential targets and pathways of CA, CKD, and muscle atrophy. The results showed that CA significantly improved NPM-induced muscle-catabolic effects, reduced the expression of muscle atrophy-related proteins (muscle atrophy F-box and muscle RING finger 1) and proinflammatory cytokines (interleukin [IL]-6, tumor necrosis factor-alpha, and IL-1β), and attenuated muscle oxidative stress. Network pharmacology revealed that CA modulated the response to oxidative stress and nuclear factor kappa B (NF-κB) signaling pathway and that Toll-like receptor 4 (TLR4) was a key target. In vivo experiment confirmed that CA inhibited the TLR4/myeloid differentiation primary response 88 (MYD88)/NF-kB signaling pathway, reduced muscle iron levels, and restored glutathione peroxidase 4 activity, thereby alleviating ferroptosis and inflammation in skeletal muscles. Thus, CA might be a promising therapeutic agent for preventing and treating skeletal muscle atrophy in CKD by modulating the TLR4/MYD88/NF-κB pathway and ferroptosis., 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 Masson SAS.. All rights reserved.)

Background: Avian influenza viruses (AIVs) constitute significant zoonotic pathogens encompassing a broad spectrum of subtypes. Notably, the H4 subtype of AIVs has a pronounced ability to shift hosts. The escalating prevalence of the H4 subtype heightens the concern for its zoonotic potential, signaling an urgent need for vigilance., Methods: During the period from December 2021 to November 2023, we collected AIV-related environmental samples and assessed them using a comprehensive protocol that included nucleic acid testing, gene sequencing, isolation culture, and resequencing., Results: In this study, a total of 934 environmental samples were assessed, revealing a remarkably high detection rate (43.66%, 289/662) of AIV in the live poultry market. Notably, the H4N1 subtype AIV (cs2301) was isolated from the live poultry market and its complete genome sequence was successfully determined. Subsequent analysis revealed that cs2301, resulting from a reassortment event between wild and domesticated waterfowl, exhibits multiple mutations and demonstrates potential for host transfer., Conclusions: Our research once again demonstrates the significant role of wild and domesticated waterfowl in the reassortment process of avian influenza virus, enriching the research on the H4 subtype of AIV, and emphasizing the importance of proactive monitoring the environment related to avian influenza virus., (© 2024. The Author(s).)

Background: Diabetic kidney disease (DKD) represents a microvascular complication of diabetes mellitus. Shenkang Pills (SKP), a traditional Chinese medicine formula, has been widely used in the treatment of DKD and has obvious antioxidant effect. Ferroptosis, a novel mode of cell death due to iron overload, has been shown to be associated with DKD. Nevertheless, the precise effects and underlying mechanisms of SKP on ferroptosis in diabetic kidney disease remain unclear., Methods: The active components of SKP were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Protein-protein interaction (PPI) network and Herb-ingredient-targets gene network were constructed using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted utilizing the Metascape system database. Additionally, an in vivo model of DKD induced by Streptozotocin (STZ) was established to further investigate and validate the possible mechanisms underlying the effectiveness of SKP., Results: We retrieved 56 compounds and identified 223 targets of SKP through the TCMSP database. Key targets were ascertained using PPI network analysis. By constructing a Herb-Ingredient-Targets gene network, we isolated the primary active components in SKP that potentially counteract ferroptosis in diabetic kidney disease. KEGG pathway enrichment analysis suggested that SKP has the potential to alleviate ferroptosis through HIF signaling pathway, thereby mitigating renal injury in DKD. In animal experiments, fasting blood glucose, 24 h urine protein, urea nitrogen and serum creatine were measured. The results showed that SKP could improve DKD. Results from animal experiments were also confirmed the efficacy of SKP in alleviating renal fibrosis, oxidative stress and ferroptosis in DKD mice. These effects were accompanied by the significant reductions in renal tissue expression of HIF-1α and HO-1 proteins. The mRNA and immunohistochemistry results were the same as above., Conclusions: SKP potentially mitigating renal injury in DKD by subduing ferroptosis through the intricacies of the HIF-1α/HO-1 signaling pathway., (© 2024. The Author(s).)

Diabetic kidney disease (DKD) stands as a pressing health challenge, with mesangial cell fibrosis identified as a pivotal hallmark leading to glomerular sclerosis. Gaining a deeper grasp on the molecular dynamics behind this can potentially introduce groundbreaking therapeutic avenues. Recent revelations from studies on ROCK1-deficient mice, which displayed resilience against high-fat diet (HFD)-induced glomerulosclerosis and mitochondrial fragmentation, spurred our hypothesis regarding ROCK1's potential role in mesangial cell fibrosis. Subsequent rigorous experiments corroborated our theory, highlighting the critical role of ROCK1 in orchestrating mesangial cell proliferation and fibrosis, especially in high-glucose settings. Mechanistically, ROCK1 inhibition led to a notable hindrance in the high-glucose-triggered MAPK signaling pathway, particularly emphasizing the ROCK1/ERK/P38 axis. To translate this understanding into potential therapeutic interventions, we embarked on a comprehensive drug screening journey. Leveraging molecular modeling techniques, Myricetin surfaced as an efficacious inhibitor of ROCK1. Dose-dependent in vitro assays substantiated Myricetin's prowess in curtailing mesangial cell proliferation and fibrosis via ROCK1/ERK/P38 pathway. In vivo verifications paralleled these findings, with Myricetin treatment resulting in significant renal function enhancements and diminished DKD pathological markers, all pivoted around the ROCK1/ERK/P38 nexus. These findings not only deepen our comprehension of DKD molecular underpinnings but also elevate ROCK1 to the pedestal of a promising therapeutic beacon. Concurrently, Myricetin is spotlighted as a potent natural contender, heralding a new era in DKD therapeutic design., 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 Masson SAS.. All rights reserved.)

Objective: To investigate the value of Hounsfield units (HUs) as an independent predictor of failed percutaneous drainage of spinal tuberculosis paraspinal abscess under computed tomography (CT) guidance., Methods: A retrospective analysis was conducted on 61 patients who underwent CT-guided percutaneous drainage for spinal tuberculosis paraspinal abscess between October 2017 and October 2020. Preoperative CT scans were used to measure the HUs of the abscess. Patients were categorized into successful drainage (n = 49) and failed drainage (n = 12) groups. Statistical analysis involved independent sample t-tests and chi-square tests to compare between the 2 groups. Binary logistic regression was performed to identify independent predictive factors for drainage failure. Receiver operating characteristic (ROC) curves were employed to ascertain risk factor thresholds and diagnostic performance., Results: Among the patients, 49 experienced successful drainage while 12 faced drainage failure. The mean HUs of abscesses in the failed drainage group were significantly higher than those in the successful drainage group (p < 0.001). ROC analysis revealed an area under the curve of 0.897 (95% confidence interval, 0.808-0.986) for predicting drainage failure based on HUs. The optimal HU cutoff value for predicting drainage failure was 22.3, with a sensitivity of 91.7% and specificity of 69.4%., Conclusion: HUs are an independent predictor of failed percutaneous drainage of spinal tuberculosis paraspinal abscess under CT guidance. The HU value of 22.3 can be used as an initial screening threshold for predicting the success or failure of drainage.

Objective: Cage subsidence is a common morbidity after oblique lumbar interbody fusion (OLIF), with risk of compromising clinical and radiographic outcomes. The study aims to describe an innovative reverse lumbar pedicle screw (RLPS) technique in OLIF and compare its effect on restricting cage subsidence with classical lateral fixation (LF) in radiological and clinical evaluation., Method: Consecutive patients having undergone single-level OLIF-LF/RLPS from 2018 to 2020 were retrospectively reviewed. In OLIF-RLPS, the upper entry point was determined at the intersection between one horizontal line (1 cm above inferior endplate) and one vertical line (dissecting anterior and middle thirds of the vertebra) while the inferior entry point between one horizontal line (5 mm below superior endplate) and the same vertical line. Trajectories were from vertebrae reverse into contralateral pedicle. Radiological evaluation included disc height (DH) and segmental lordosis (SL); cage subsidence was evaluated by DH loss. Clinical assessment included visual analogue scale (VAS) and Oswestry disability index (ODI). Student t or Mann-Whitney U test was used for continuous variation according to normality analysis while Chi-square test for category variation., Results: A total of 29 patients had been enrolled in the study including 14 cases in the RLPS group and 15 cases in the LF group. The DH in the OLIF-RLPS group had increased from the preoperative 9.07 ± 1.73 mm to 13.73 ± 1.83 mm postoperatively, without significant difference compared with the OLIF-LF group during the perioperative, but decreased to 12.53 ± 1.74 mm in 3 months and maintained at 12.00 ± 1.45 mm in 12 months, significantly higher than the OLIF-LF group (p < 0.05). At the last follow-up, 7.1% (1/14) cases in the OLIF-RLPS group had shown subsidence of grade I, significantly less than 46.7% (7/15) cases in the OLIF-LF group. Pain and disability had improved similarly in two groups, without significant difference detected between two groups at the last follow-up., Conclusion: RLPS technique with modified entry points and prolonged trajectory could effectively restrict cage subsidence in OLIF postoperatively compared with traditional lateral fixation., (© 2023 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Objective: To illustrate a simultaneous single-position oblique lateral interbody fusion (SPOLIF) combined with unilateral percutaneous pedicle screw fixation in treating single-level lumbar tuberculosis, compared with posterior-only approach in clinical and radiographic evaluations., Methods: Consecutive patients who had undergone surgeries for single-level lumbar tuberculosis from January 2018 to December 2020 were retrospectively reviewed. The patients included were divided into SP-OLIF and posterior-only groups according to surgical methods applied, with follow-up for at least 36 months. Outcomes included estimated blood loss, operative time, and complications for safety evaluation; visual analogue scale (VAS), Oswestry Disability Index (ODI) for efficacy evaluation; erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) for evaluating tuberculosis activity; x-ray and computed tomography scan were used for radiographic evaluation., Results: A total of 136 patients had been enrolled in the study (60 for SP-OLIF and 76 for Posterior-only). The median operative time, blood loss, and hospital stay in SP-OLIF group were significantly less, with a lower complication rate. Meanwhile, the SP-OLIF group showed substantially lower VAS in 1 and 7 days and decreased ODI in the first month postoperatively, without significant difference afterward. Similarly, the median CRP and ESR in SP-OLIF group were significantly lower in 3 and 7 days postoperatively. All indicators had reduced to normal after 3 months. No recurrence had been reported throughout the whole follow-up., Conclusion: SP-OLIF was an efficient minimally invasive protocol for single-level lumbar tuberculosis, facilitating earlier clinical improvement, with decreased blood loss, operative time and hospital stay compared with posterior-only approach.

Purpose: To advance a modified oblique lumbar interbody fusion (M-OLIF) achieving anterior debridement and posterior freehand instrumentation simultaneously in circumferential approach via dynamic position and compare with traditional combined anterior-posterior surgery (CAPS) in clinical and radiological evaluation., Patients and Methods: Innovative freehand instrumentation in floating position was described. Consecutive patients having undergone surgeries for lumbar tuberculosis from 2017 January to 2019 December had been retrospectively reviewed. Patients with follow-ups for at least 36 months were included and divided into M-OLIF or CAPS group according to surgical methods applied. Outcomes included operation time, estimated blood loss, complication profile for safety evaluation; Vascular Analogue Scale (VAS) and Oswestry Disability Index (ODI) for efficacy evaluation; C-reactive protein and Erythrocyte Sedimentation Rate for tuberculosis activity and recurrence evaluation; X-ray and CT scan for radiological evaluation., Results: Totally 56 patients had been enrolled in the study (26 for M-OLIF and 30 for CAPS). Compared with CAPS group, M-OLIF group illustrated significantly decreased estimated blood loss, operation time, hospital stay, and less postoperative morbidities. Meanwhile, M-OLIF group showed earlier improvement in VAS in 3 days and ODI in the first month postoperatively, without obvious discrepancy in further follow-ups. The overall screw accuracy in M-OLIF and CAPS group was 93.8% and 92.3% respectively, without significant difference in perforation distribution., Conclusion: M-OLIF was efficient for lumbar tuberculosis requiring multilevel fixation, with reduced operation time and iatrogenic trauma, earlier clinical improvement compared with traditional combined surgery., (© 2023. The Author(s).)

Chronic kidney disease (CKD) affects approximately 10% of the global population. Muscle atrophy occurs in patients with almost all types of CKD, and the gut microbiome is closely related to protein consumption during chronic renal failure (CRF). This study investigated the effects of Bacteroides plebeius on protein energy consumption in rats with CKD, and our results suggest that Bacteroides plebeius may combat muscle atrophy through the Mystn/ActRIIB/SMAD2 pathway. A total of 5/6 Nx rats were used as a model of muscle wasting in CKD. The rats with muscle wasting were administered Bacteroides plebeius (2 × 10 8  cfu/0.2 ml) for 8 weeks. The results showed that Bacteroides plebeius administration significantly inhibited muscle wasting in CKD. High-throughput 16 S rRNA pyrosequencing revealed that supplementation with Bacteroides plebeius rescued disturbances in the gut microbiota. Bacteroides plebeius could also enhance the barrier function of the intestinal mucosa. Bacteroides plebeius may modulate the gut microbiome and reduce protein consumption by increasing the abundance of probiotics and reducing damage to the intestinal mucosal barrier. Our findings suggest that Bacteroides plebeius may combat muscle atrophy through the Mystn/ActRIIB/SMAD2 pathway., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Objective: Existing freehand techniques of screw placement mainly emphasized on various entry points and complex trajectory reference. The aim of this study is to illustrate a standardized and reliable freehand technique of pedicle screw insertion for open pedicle screw fixation with a universal entry point and a stereoscopic trajectory reference system and report the results from a single surgeon's clinical experience with the technique., Method: In this study, the author respectively reviewed a total of 200 consecutive patients who had undergone open freehand pedicle screw fixation with Superior Articular Process (SAP) technique from January 2019 to May 2020. For accuracy and safety, all 200 cases had undergone postoperative X-ray while 33 cases including spinal deformity, infection, and tumor had received additional CT-scan. Screw accuracy was analyzed via a CT-based classification system with Student's t test., Results: A total of 1126 screws had been placed from T1-S1 with SAP-guided freehand technique and the majority had been confirmed safe in X-ray without the need of CT scan. A total of 316 screws in deformity or infectious or tumor cases had undergone additional CT scan with 95.5% (189 of 198 screws) accuracy in thoracic group and 94.9% (112 of 118 screws) in lumbar group. The accuracy had been 90.5% (114 of 126 screws) in deformity group and 95.8% (182 of 190 screws) in non-deformity group. All perforation cases had been rated Grade B (<2 mm) without significant difference between the medial and the lateral (p < 0.05). No cases had been detected with significant neurological deficiencies. The mean intraoperative X-ray shots were 0.73 per screw., Conclusion: SAP-guidance is a reliable freehand technique for thoracic and lumbar pedicle screw instrument. It allows accurate and safe screw insertion in both non-deformity and deformity cases with less radiation exposure., (© 2022 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Clinically, bone destruction caused by Mycobacterium tuberculosis was serious especially in patients with vitamin D (VD) deficiency. However, the role of VD in M. tuberculosis-induced bone destruction remains clear. In this context, we investigate the role of VD and vitamin D receptor (VDR) in the M. tuberculosis-induced bone destruction. First, we infected RAW264.7 and bone marrow-derived macrophages (BMMs) with Mycobacterium bovis Bacillus Calmette-Guérin (M. bovis BCG) in vitro. Then, we activated VDR through VD administration. TRAP and FAK staining, bone resorption assays, immunofluorescence staining, qPCR, and western blot were carried out. In vivo, the M. tuberculosis-induced osteolytic model on the murine skull was established and the μCT and histological analyses were performed. We found that VDR and TRAP were upregulated in bone tuberculosis tissue and proved that M. tuberculosis infection promoted osteoclastogenesis in RAW264.7 and BMMs. VD could inhibit osteoclasts differentiation, fusion, and bone resorption dose-dependently. However, when VDR was knocked down, the inhibitory effect of VD on osteoclasts disappeared. In mechanism, activation of VDR inhibits the phosphorylation of IκB α, thereby inhibiting NFκB signaling pathway and alleviating osteoclastogenesis. Furthermore, in the skull osteolysis model, VD administration reduced osteolysis, but not in VDR -/- mice. Our study, for the first time, demonstrates that activation of VDR by VD administration inhibits M. tuberculosis-induced bone destruction. Our results reveal that VD and VDR are potential therapeutic targets for M. tuberculosis-induced bone destruction, and are of great clinical significance for the development of new therapeutic strategies., (© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Intervertebral disc degeneration (IDD), which is caused by multiple factors, affects the health of individuals and contributes to low back pain. The pathology of IDD is complicated, and changes in the extracellular microenvironment play an important role in promoting the process of degeneration. Cartilage intermediate layer protein (CILP) is a matrix protein that resides in the middle of human articular cartilage and is involved in numerous diseases that affect cartilage. However, there is no detailed review of the relationship between CILP and degenerative disc disease. Growing evidence has revealed the presence of CILP in the extracellular microenvironment of intervertebral discs (IVDs) and has suggested that there is a gradual increase in CILP in degenerative discs. Specifically, CILP plays an important role in regulating the metabolism of the extracellular matrix (ECM), an important component of the extracellular microenvironment. CILP can combine with transforming growth factor‑β or insulin‑like growth factor‑1 to regulate the ECM synthesis of IVDs and influence the balance of ECM metabolism, which leads to changes in the extracellular microenvironment to promote the process of IDD. It may be possible to show the correlation of CILP with IDD and to target CILP to interfere with IDD. For this purpose, in the present study, the current knowledge on CILP was summarized and a detailed description of CILP in discs was provided.

Lumbar disc disease (LDD) is common in aged populations, and it is primarily caused by intervertebral disc degeneration (IDD). Cartilage intermediate layer protein (CILP), which is specifically expressed in intervertebral discs (IVDs), is suspected to be associated with IDD. However, it remains unclear whether CILP contributes to IDD in humans. Furthermore, the regulation of CILP in human IVDs is poorly understood, especially by mechanical stimuli, which are regarded as primary factors promoting IDD. To address these issues, the present study collected nucleus pulposus (NP) cells from patients undergoing lumbar spinal surgery for degenerative disc disease (DDD). Subsequently, CILP expression was measured in human NP cells in response to mechanical stimuli, including cyclic compressive stress and cyclic tensile strain (CTS), by reverse transcription‑quantitative polymerase chain reaction and western blotting. Aggrecan and collagen II, which are the main components of the extracellular matrix (ECM) and traditional degenerative markers for IDD, were detected following the treatment with CILP small interfering (si)RNA or recombinant human CILP (rhCILP) at various concentrations to determine whether CILP contributes to IDD by negatively regulating expression of the ECM. The results revealed that CILP expression in loaded NP cells was significantly increased compared with that in non‑loaded cells under compressive loading, and that it was markedly decreased in cells under tensile loading, in contrast with the expression of aggrecan and collagen II in response to the same stimuli. Furthermore, CILP siRNA effectively inhibited CILP expression and significantly increased the expression of aggrecan and collagen II. In addition, treatment of NP cells with a high concentration of rhCILP resulted in significantly decreased expression of aggrecan and collagen II. In conclusion, these results demonstrated for the first time, to the best of our knowledge, that in human NP cells, CILP is regulated by mechanical stress and that its expression affects ECM synthesis. Therefore, CILP represents a promising therapeutic target for preventing loss of the matrix during IDD as a novel treatment strategy.

N-acetylated proline-glycine-proline (N-Ac-PGP) is a chemokine involved in inflammatory diseases and is found to accumulate in degenerative discs. N-Ac-PGP has been demonstrated to have a pro-inflammatory effect on human cartilage endplate stem cells. However, the effect of N-Ac-PGP on human intervertebral disc cells, especially nucleus pulposus (NP) cells, remains unknown. The purpose of this study was to investigate the effect of N-Ac-PGP on the expression of pro-inflammatory factors and extracellular matrix (ECM) proteases in NP cells and the molecular mechanism underlying this effect. Therefore, Milliplex assays were used to detect the levels of various inflammatory cytokines in conditioned culture medium of NP cells treated with N-Ac-PGP, including interleukin-1β (IL-1β), IL-6, IL-17, tumor necrosis factor-α (TNF-α) and C-C motif ligand 2 (CCL2). RT-qPCR was also used to determine the expression of pro-inflammatory cytokines and ECM proteases in the NP cells treated with N-Ac-PGP. Moreover, the role of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in mediating the effect of N-Ac-PGP on the phenotype of NP cells was investigated using specific signaling inhibitors. Milliplex assays showed that NP cells treated with N-Ac-PGP (10 and 100 µg/ml) secreted higher levels of IL-1β, IL-6, IL-17, TNF-α and CCL2 compared with the control. RT-qPCR assays showed that NP cells treated with N-Ac-PGP (100 µg/ml) had markedly upregulated expression of matrix metalloproteinase 3 (MMP3), MMP13, a disintegrin and metalloproteinase with thrombospondin motif 4 (ADAMTS4), ADAMTS5, IL-6, CCL-2, CCL-5 and C-X-C motif chemokine ligand 10 (CXCL10). Moreover, N-Ac-PGP was shown to activate the MAPK and NF-κB signaling pathways in NP cells. MAPK and NF-κB signaling inhibitors suppressed the upregulation of proteases and pro-inflammatory cytokines in NP cells treated with N-Ac-PGP. In conclusion, N-Ac-PGP induces the expression of pro-inflammatory cytokines and matrix catabolic enzymes in NP cells via the NF-κB and MAPK signaling pathways. N-Ac-PGP is a novel therapeutic target for intervertebral disc degeneration.

Objective: To assess the reliability and validity of the scale RYDM, as well as the resilience status and its impact factors., Methods: 964 students were investigated. The participants were chosen through the stratified cluster sampling. The software of SPSS 17.0 was used for the analysis., Results: (1) RYDM: The Cronbach alpha coefficient of the RYDM was 0.945. The split-half reliability was 0.865. The re-test reliability was 0.838. The correlations between total scale and 2 factor scales were 0.896 and 0.9743 respectively. The correlation between the 2 factor scales was 0.776. (2) The scores on family closeness, family high expectations, community expectation of left-behind children were lower than that of the no-left-behind children (P < 0.05). The protective factors of mental resilience in left-behind children were age, frequency of conflict with the guardian, worry degree about out-working parent(s) (P < 0.05)., Conclusion: Reliability and validity of the RYDM scale are psychometrically qualified. The resilience of the left-behind children is worse in some aspects than that of the no-left-behind children, which is influenced most by family factors.