Integrating genomic profiling to clinical data: assessing the impact of CD147 expression on plaque stability.

Background: Acute Coronary Syndrome (ACS) continues to be a leading cause of death and illness worldwide. Differentiating stable from unstable coronary plaques is essential for enhancing patient outcomes. This research investigates the role of CD147 as a biomarker for plaque stability among coronary artery disease patients. Methods: The study began with high-throughput sequencing of blood samples from six patients, divided equally between those with Stable Angina (SA) and Unstable Angina (UA), followed by bioinformatics analysis. Expanding upon these findings, the study included 31 SA patients and 30 patients with ACS, using flow cytometry to examine CD147 expression on platelets and monocytes. Additionally, logistic regression was utilized to integrate traditional risk factors and evaluate the predictive value of CD147 expression for plaque stability. Results: Initial sequencing displayed a notable difference in CD147 expression between SA and UA groups, with a significant increase in UA patients. Further analysis confirmed that elevated platelet CD147 expression was strongly associated with unstable plaques (OR = 277.81, P < .001), after adjusting for conventional risk factors, whereas monocyte CD147 levels did not show a significant difference. Conclusion: Elevated CD147 expression on platelets is a crucial biomarker for identifying unstable coronary artery plaques, offering insights into patient risk stratification and the development of targeted treatment strategies. This underscores the pivotal role of molecular research in understanding and managing coronary artery disease, paving the way for improved clinical outcomes.

PHD2 shRNA-Modified Bone Marrow Mesenchymal Stem Cells Facilitate Periodontal Bone Repair in Response to Inflammatory Condition.

OBJECTIVE: To investigate whether bone marrow mesenchymal stem cells (BMMSCs) modulate periodontal bone repair through the hydroxylase domain-containing protein 2 (PHD2)/hypoxia- inducible factor-1 (HIF-1) signalling pathway in response to inflammatory conditions. METHODS: Osteogenic differentiation of PHD2 shRNA-modified BMMSCs and the possible mechanism were explored in an inflammatory microenvironment stimulated by porphyromonas gingivalis lipopolysaccharide (Pg-LPS) in vitro. The effect of PHD2 gene-modified BMMSCs on periodontal bone loss was evaluated with experimental periodontitis. RESULTS: Pg-LPS stimulation greatly impaired the osteogenic differentiation of BMMSCs, whereas the silence of PHD2 significantly enhanced the osteogenesis of BMMSCs. More importantly, increased level of vascular endothelial growth factor (VEGF) was detected under Pg-LPS stimulation, which was verified to be associated with the augmented osteogenesis. In experimental periodontitis, PHD2-modified BMMSCs transplantation elevated osteogenic parameters and the expression of VEGF in periodontal tissue. CONCLUSION: This study highlighted that PHD2 gene silencing could be a feasible approach to combat inflammatory bone loss by rescuing the dysfunction of seed cells.

Integration of high-resolution mass spectrometry technology with molecular network analysis and systems biology techniques to elucidate the active ingredients and mechanisms of Shiduqing capsules.

RATIONALE: Shiduqing Capsules, a well-known Chinese patent medicine, are widely used clinically for the treatment of pruritus. However, to date, there is a lack of research on its pharmacological substances and mechanisms of action. METHODS: In the current study, the chemical components of Shiduqing Capsules were identified using UHPLC-QE-Orbitrap-MS technology. Molecular network analysis was employed to identify structurally similar compounds to the known chemical components. The potential molecular targets of the active ingredients were predicted using the SwissTargetPrediction website. The identified targets were further analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis through the DAVID database. Molecular docking was used to validate the network pharmacology results. RESULTS: Ultimately, A total of 51 chemical components of Shiduqing Capsules were identified. Molecular network analysis identified 21 flavonoids and 13 terpenoids. The core targets of these ingredients include TP53, AKT1, and STAT3. GO and KEGG enrichment analysis revealed 1,371 different biological functions and 177 signaling pathways. Molecular docking confirmed the high affinity between multiple core active ingredients of Shiduqing Capsules and pruritus targets. CONCLUSION: In conclusion, the effective ingredients of Shiduqing Capsules exert a multifaceted therapeutic effect on pruritus through multiple targets and pathways.

Improved Unsupervised Stitching Algorithm for Multiple Environments SuperUDIS.

Large field-of-view images are increasingly used in various environments today, and image stitching technology can make up for the limited field of view caused by hardware design. However, previous methods are constrained in various environments. In this paper, we propose a method that combines the powerful feature extraction capabilities of the Superpoint algorithm and the exact feature matching capabilities of the Lightglue algorithm with the image fusion algorithm of Unsupervised Deep Image Stitching (UDIS). Our proposed method effectively improves the situation where the linear structure is distorted and the resolution is low in the stitching results of the UDIS algorithm. On this basis, we make up for the shortcomings of the UDIS fusion algorithm. For stitching fractures of UDIS in some complex situations, we optimize the loss function of UDIS. We use a second-order differential Laplacian operator to replace the difference in the horizontal and vertical directions to emphasize the continuity of the structural edges during training. Combined with the above improvements, the Super Unsupervised Deep Image Stitching (SuperUDIS) algorithm is finally formed. SuperUDIS has better performance in both qualitative and quantitative evaluations compared to the UDIS algorithm, with the PSNR index increasing by 0.5 on average and the SSIM index increasing by 0.02 on average. Moreover, the proposed method is more robust in complex environments with large color differences or multi-linear structures.

Identification of active ingredients in Naomaitai capsules using high-resolution mass spectrometry unite molecular network analysis and prediction of their action mechanisms.

RATIONALE: Although Naomaitai capsule (NMC) is widely used in clinical practice and has a good curative effect for cerebral infarction, its material basis and mechanism of action remain unclear. METHODS: In this study, ultra-high-performance liquid chromatography (UHPLC) coupled with quadrupole Orbitrap MS technology was used to analyse the in vivo and in vitro components of NMC, and the Global Natural Products Social Molecular Networking website was used to further analyse the components of NMC. Next, systems biology approaches were employed to investigate the mechanism of action of NMC. Finally, molecular docking technology was used to verify the network pharmacological results. RESULTS: In total, 177 compounds were identified in vitro, including 65 terpenoids, 62 flavonoids, 25 organic acids and 11 quinones. 64 compounds were identified in the blood of mice, and the main active components included ginkgolide C, ginkgolide A, ligustilide, tanshinone IIB, olmelin, emodin and puerarin. The main targets in vivo included TP53, SRC, STAT3, PIK3CA and PIK3R1. CONCLUSIONS: In conclusion, this study has revealed that NMC acts on multiple targets in the body through various active components, exerting synergistic effects in the treatment of CI. Its mechanism of action may involve inhibiting neuronal apoptosis, oxidative stress and inflammatory responses as well as reducing cerebral vascular permeability and promoting cerebral vascular regeneration.

AtSRT1 regulates flowering by regulating flowering integrators and energy signals in Arabidopsis.

Epigenetic modifications, such as histone alterations, play crucial roles in regulating the flowering process in Arabidopsis, a typical long-day model plant. Histone modifications are notably involved in the intricate regulation of FLC, a key inhibitor of flowering. Although sirtuin-like protein and NAD+-dependent deacetylases play an important role in regulating energy metabolism, plant stress responses, and hormonal signal transduction, the mechanisms underlying their developmental transitions remain unclear. Thus, this study aimed to reveal how Arabidopsis NAD + -dependent deacetylase AtSRT1 affects flowering by regulating the expression of flowering integrators. Genetic and molecular evidence demonstrated that AtSRT1 mediates histone deacetylation by directly binding near the transcriptional start sites (TSS) of the flowering integrator genes FT and SOC1 and negatively regulating their expression by modulating the expression of the downstream gene LFY to inhibit flowering. Additionally, AtSRT1 directly down-regulates the expression of TOR, a glucose-driven central hub of energy signaling, which controls cell metabolism and growth in response to nutritional and environmental factors. This down-regulation occurs through binding near the TSS of TOR, facilitating the addition of H3K27me3 marks on FLC via the TOR-FIE-PRC2 pathway, further repressing flowering. These results uncover a multi-pathway regulatory network involving deacetylase AtSRT1 during the flowering process, highlighting its interaction with TOR as a hub for the coordinated regulation of energy metabolism and flowering initiation. These findings significantly enhance understanding of the complexity of histone modifications in the regulation of flowering.

Ultrahigh-performance liquid chromatography Q-Exactive-Orbitrap mass spectrometry and molecular network analysis alongside network pharmacology to elucidate the active constituents and mechanism of action of Huahong tablet in treating pelvic inflammatory disease.

RATIONALE: Huahong tablet, a commonly used clinical Chinese patent medicine, shows good efficacy in treating pelvic inflammation and other gynaecological infectious diseases. However, the specific composition of Huahong tablets, which are complex herbal formulations, remains unclear. Therefore, this study aims to identify the active compounds and targets of Huahong tablets and investigate their mechanism of action in pelvic inflammatory diseases. METHODS: We utilised ultrahigh-performance liquid chromatography Q-Exactive-Orbitrap mass spectrometry and the relevant literature to identify the chemical components of Huahong tablets. The GNPS database was employed to further analyse and speculate on the components. Potential molecular targets of the active ingredients were predicted using the SwissTargetPrediction website. Protein-protein interaction analysis was conducted using the STRING database, with visualisation in Cytoscape 3.9.1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID database. Additionally, a traditional Chinese medicine-ingredient-target-pathway network was constructed using Cytoscape 3.10.1. Molecular docking validation was carried out to investigate the interaction between core target and specific active ingredient. RESULTS: A total of 66 chemical components were identified, and 41 compounds were selected as potential active components based on the literature and the TCMSP database. Moreover, 38 core targets were identified as key targets in the treatment of pelvic inflammatory diseases with Huahong tablets. GO and KEGG enrichment analysis revealed 986 different biological functions and 167 signalling pathways. CONCLUSION: The active ingredients in Huahong tablets exert therapeutic effects on pelvic inflammatory diseases by acting on multiple targets and utilising different pathways. Molecular docking confirmed the high affinity between the specific active ingredients and disease targets.

[Analysis and prospect of correlation between relative molecular weight and efficacy of polysaccharides from medicinal plant resources].

Polysaccharides from medicinal plant resources are a kind of polymers extracted from medicinal plants. They are complex long chains formed by different monosaccharides connected via glucosidic bonds. These polysaccharides usually have straight chain and branched chain structures, and their relative molecular weight changes greatly. Modern studies have shown that the biological activi-ty of polysaccharides from medicinal plant resources is closely related to their relative molecular weight. This paper first reviewed the preparation and detection methods of polysaccharides from medicinal plant resources with different relative molecular weights. Then, the paper summarized and analyzed the general experience of the correlation between efficacy and relative molecular weight of polysaccharides from medicinal plant resources with different molecular weights. It was considered that polysaccharides with large relative molecular weights(>100 kDa) play a leading role in immune regulation. Polysaccharides with medium relative molecular weights(10-100 kDa) play a leading role in immune regulation and the protection of the liver. Polysaccharides with small relative molecular weights(<10 kDa) play a leading role in anti-oxidation, regulation of intestinal flora, regulation of blood glucose and lipids, anti-fatigue, and the protection of nerves. Therefore, precise development of polysaccharides from medicinal plant resources based on relative molecular weight is expected to improve their biological activity and application value.

Specific molecular weight of Lycium barbarum polysaccharide for robust breast cancer regression by repolarizing tumor-associated macrophages.

The pro-tumorigenic M2-type tumor-associated macrophages (TAMs) in the immunosuppressive tumor microenvironment (TME) promote the progression, angiogenesis, and metastasis of breast cancer. The repolarization of TAMs from an M2-type toward an M1-type holds great potential for the inhibition of breast cancer. Here, we report that Lycium barbarum polysaccharides (LBPs) can significantly reconstruct the TME by modulating the function of TAMs. Specifically, we separated four distinct molecular weight segments of LBPs and compared their repolarization effects on TAMs in TME. The results showed that LBP segments within 50-100 kDa molecular weight range exhibited the prime effect on the macrophage repolarization, augmented phagocytosis effect of the repolarized macrophages on breast cancer cells, and regression of breast tumor in a tumor-bearing mouse model. In addition, RNA-sequencing confirms that this segment of LBP displays an enhanced anti-breast cancer effect through innate immune responses. This study highlights the therapeutic potential of LBP segments within the 50-100 kDa molecular weight range for macrophage repolarization, paving ways to offer new strategies for the treatment of breast cancer.

Acupuncture and moxibustion for irritable bowel syndrome: An umbrella systematic review.

BACKGROUND: Irritable bowel syndrome (IBS) is a functional bowel disease characterized by abdominal pain or discomfort associated with altered bowel habits. Several clinical studies have demonstrated the effectiveness of acupuncture and moxibustion for IBS. Many systematic reviews of acupuncture and moxibustion for IBS have been published in recent years, but their results are not entirely consistent. OBJECTIVE: To evaluate the methodological, reporting, and evidence quality of systematic reviews of acupuncture and moxibustion for IBS. SEARCH STRATEGY: Systematic reviews of acupuncture and moxibustion for IBS published before February 20, 2023 were searched in eight databases: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Data, VIP Database for Chinese Technical Periodicals, and China Biology Medicine. The keywords used for literature search were acupuncture, moxibustion, systematic review, meta-analysis, and irritable bowel syndrome. INCLUSION CRITERIA: Systematic reviews and meta-analyses of randomized controlled trials of acupuncture and moxibustion for IBS were included. DATA EXTRACTION AND ANALYSIS: Relevant information was independently extracted by two investigators. The A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020), and Grading of Recommendations Assessment, Development and Evaluation (GRADE) were used to evaluate the methodological quality, reporting quality and evidence quality, respectively. RESULTS: A total of 342 studies were retrieved and 15 systematic reviews were included. The results of AMSTAR 2 showed low methodological quality in 2 studies and very low methodological quality in the remaining 13 studies, with main issues being failure to register a protocol, incomplete search strategy, not providing a list of excluded studies, incomplete consideration of the risk of bias in the included studies, and a failure to assess the publication bias. The results of PRISMA 2020 showed seriously deficient reporting quality of 2 studies, somewhat deficient reporting quality of 12 studies, and relatively complete reporting quality of 1 study, with the main problems being lack of a complete search strategy, non-availability of a list of excluded studies with justification for their exclusion, not conducting heterogeneity and sensitivity analyses, not evaluating the credibility of the evidence, and not registering the protocol. The results of GRADE showed that the quality of the evidence is low or very low. CONCLUSION: Most included systematic reviews interpreted findings to suggest that acupuncture and moxibustion have benefits for IBS. However, there is a need to improve the methodological, reporting and evidence quality of the systematic reviews. Larger, multicenter, rigorously designed randomized controlled trials and high-quality systematic reviews are required to obtain more robust evidence. PLEASE CITE THIS ARTICLE AS: Ma YY, Hao Z, Chen ZY, Shen YX, Liu HR, Wu HG, Bao CH. Acupuncture and moxibustion for irritable bowel syndrome: An umbrella systematic review. J Integr Med. 2024; 22(1): 22-31.

Cytochrome P450 26A1 Contributes to the Maintenance of Neuropathic Pain.

The cytochrome P450 proteins (CYP450s) have been implicated in catalyzing numerous important biological reactions and contribute to a variety of diseases. CYP26A1, a member of the CYP450 family, carries out the oxidative metabolism of retinoic acid (RA), the active metabolite of vitamin A. Here we report that CYP26A1 was dramatically upregulated in the spinal cord after spinal nerve ligation (SNL). CYP26A1 was mainly expressed in spinal neurons and astrocytes. HPLC analysis displayed that the content of all-trans-RA (at-RA), the substrate of CYP26A1, was reduced in the spinal cord on day 7 after SNL. Inhibition of CYP26A1 by siRNA or inhibition of CYP26A1-mediated at-RA catabolism by talarozole relieved the SNL-induced mechanical allodynia during the maintenance phase of neuropathic pain. Talarozole also reduced SNL-induced glial activation and proinflammatory cytokine production but increased anti-inflammatory cytokine (IL-10) production. The RA receptors RARα, RXRß, and RXRγ were expressed in spinal neurons and glial cells. The promoter of Il-10 has several binding sites for RA receptors, and at-RA directly increased Il-10 mRNA expression in vitro. Finally, intrathecal IL-10 attenuated SNL-induced neuropathic pain and reduced the activation of astrocytes and microglia. Collectively, the inhibition of CYP26A1-mediated at-RA catabolism alleviates SNL-induced neuropathic pain by promoting the expression of IL-10 and suppressing glial activation. CYP26A1 may be a potential therapeutic target for the treatment of neuropathic pain.

Overcoming biological barriers by virus-like drug particles for drug delivery.

Virus-like particles (VLPs) have natural structural antigens similar to those found in viruses, making them valuable in vaccine immunization. Furthermore, VLPs have demonstrated significant potential in drug delivery, and emerged as promising vectors for transporting chemical drug, genetic drug, peptide/protein, and even nanoparticle drug. With virus-like permeability and strong retention, they can effectively target specific organs, tissues or cells, facilitating efficient intracellular drug release. Further modifications allow VLPs to transfer across various physiological barriers, thus acting the purpose of efficient drug delivery and accurate therapy. This article provides an overview of VLPs, covering their structural classifications, deliverable drugs, potential physiological barriers in drug delivery, strategies for overcoming these barriers, and future prospects.

Clinical features, microbial spectrum, and antibiotic susceptibility patterns of spontaneous bacterial peritonitis in cirrhotic patients.

BACKGROUND AND AIMS: The microbial spectrum and antimicrobial resistance patterns change over time and vary across regions in patients with spontaneous bacterial peritonitis (SBP). There is an urgent need to clarify the factors associated with in-hospital mortality in these patients. METHODS: In this study, 377 patients with SBP and 794 patients with bacterascites were analyzed for the microbial spectrum, antimicrobial resistance profiles, and laboratory findings. RESULTS: The most common pathogens were Escherichia coli (96, 25.5%), Staphylococcus epidermidis (55, 14.6%), and Enterococcus faecium (42, 11.1%). Multidrug-resistant (MDR) bacteria comprised 49.7% of gram-positive bacteria (GPB) and 48.8% of gram-negative bacteria (GNB). The most sensitive antibiotics were amikacin (91.5%), meropenem (89.8%) and piperacillin/tazobactam (87.6%). Extensively drug-resistant (XDR) (OR=51.457, p < 0.001), neutrophil count (OR=1.088, p < 0.001), and the model for end-stage liver disease (MELD) score (OR=1.124, p < 0.001) were independent predictive factors of in-hospital mortality in patients with SBP. CONCLUSION: MDR represented nearly half of the bacteria isolated from patients with SBP, of which the high prevalence of extended-spectrum ß-lactamase-producing and Carbapenem-resistant bacteria is concerning. The presence of XDR, higher MELD score, and neutrophil count were independent predictive factors associated with higher in-hospital mortality in patients with SBP, indicating that intensive care should be provided to these patients.

A preliminary study for the clinical effect of one combinational physiotherapy and its potential influence on gut microbial composition in children with Tourette syndrome.

Introduction: Tourette syndrome (TS) is a chronic neuropsychiatric disorder with unknown causes and inadequate therapies. Inspired by the important roles of gut microbiota in some mental illnesses, the interactions between gut microbiota and TS via the gut-brain axis have gained more and more attention. This study aimed to characterize the gut microbial profiles in children with TS, and explore the clinical effects of one combinational physiotherapy and its potential influence on gut microbial composition. Methods: The gut microbial profiles were depicted based on the sequence data of 32 patients and 29 matched health children by 16S rDNA amplicon pyrosequencing. Thirty of thirty-two patients underwent uninterrupted two 10-day courses of combinational physiotherapy, which included a 60-minute cranial electrotherapy stimulation (CES) training followed by a 30-minute biofeedback training per session, 2 sessions a day. Results: Our results indicated that the gut microbial composition in children with TS was different from that in healthy controls. Multiple GBM neurotransmitter modules obtained through Picrust2 functional predictive analysis were significantly increased in patients, including Histamine degradation, Dopamine degradation, and DOPAC synthesis. Moreover, this combinational physiotherapy could significantly diminish tic activity, whose positive effects were first reported in children with TS. Lastly, different gut microbial compositions and predictive metabolic pathways were also observed between patients before and after this treatment, with lower abundances of the genera (e.g., Dorea) and significant decreases of GBM neurotransmitter modules (e.g. dopamine degradation) in patients after this treatment, indicating that improved clinical symptoms might be accompanied by an improvement of intestinal microenvironment. Discussion: Children with TS showed a cognizable gut microbial profile, and certain enriched bacteria with pro-inflammatory potential might induce neuroinflammatory responses. This combinational physiotherapy could significantly diminish tic activity, and the gut microbial compositions in patients after this treatment were different from those without any treatment, indicating the existence of bidirectional communication of the gut-brain axis in TS. But studies on the gut microbial characteristics in TS patients, the influences of gut microbiota on tic severity, the efficacy and safety of this treatment, and the bidirectional regulatory mechanism between brain signals and gut microbiota in TS still need to be explored.

Bioorthogonal Engineered Virus-Like Nanoparticles for Efficient Gene Therapy.

Gene therapy offers potentially transformative strategies for major human diseases. However, one of the key challenges in gene therapy is developing an effective strategy that could deliver genes into the specific tissue. Here, we report a novel virus-like nanoparticle, the bioorthgonal engineered virus-like recombinant biosome (reBiosome), for efficient gene therapies of cancer and inflammatory diseases. The mutant virus-like biosome (mBiosome) is first prepared by site-specific codon mutation for displaying 4-azido-L-phenylalanine on vesicular stomatitis virus glycoprotein of eBiosome at a rational site, and the reBiosome is then prepared by clicking weak acid-responsive hydrophilic polymer onto the mBiosome via bioorthogonal chemistry. The results show that the reBiosome exhibits reduced virus-like immunogenicity, prolonged blood circulation time and enhanced gene delivery efficiency to weakly acidic foci (like tumor and arthritic tissue). Furthermore, reBiosome demonstrates robust therapeutic efficacy in breast cancer and arthritis by delivering gene editing and silencing systems, respectively. In conclusion, this study develops a universal, safe and efficient platform for gene therapies for cancer and inflammatory diseases.

Factors Related to the Deterioration of Postoperative Lower Back Pain in Hemilaminectomy Approach for Lumbar Spinal Schwannoma Resection.

Objective: This study aimed to explore the related risk factors in patients who underwent hemilaminectomy for lumbar spinal schwannoma resection and who experienced deterioration of postoperative lower back pain in comparison to preoperative pain levels. Methods: This retrospective study recruited 61 patients from the First Affiliated Hospital of An Hui Medical University between January 2018 and June 2019. All data were collected from clinical records and analyzed at 1-month and at 1-year follow-up. The visual analog scale (VAS) was used to evaluate pain, and neurologic function was assessed using the Modified McCormick Scale. Intraoperative neurophysiological monitoring was used to assess neuronal integrity and mitigate injury. Statistical analysis of the data was performed using the SPSS version 19 software. Results: Preoperative pain improved dramatically in the 1-year follow-up (VAS: preoperative, 3.84±2.19; 1-year follow-up, 2.13±2.26; P<0.001). The pain-improved group and worsened group showed a significant difference at 1-month (VAS: 1.76±1.56; 5.54±1.26; P<0.05) and at 1-year (VAS: 0.83±1.09; 4.80±1.58; P<0.05) follow-up. The pain-improved and worsened groups had a significant difference in tumor size and hemilaminectomy removal segments at 1-month and 1-year follow-up, but A-train occurrence on electromyography could only be seen as a statistical difference in the 1-month follow-up. Logistic regression analysis revealed that tumor size was an independent risk factor for postoperative lower back pain deterioration. Conclusion: The hemilaminectomy approach is a safe and effective method that can dramatically relieve pain in spinal lumbar schwannoma resection. Tumor size is an independent risk factor for postoperative lower back pain. A-train on spontaneous electromyography has been shown to be a reliable predictive factor for the evaluation of postoperative lower back pain. However, further detailed analysis of A-train characteristics can provide a more accurate warning during surgery.

Spinal CBX2 contributes to neuropathic pain by activating ERK signaling pathway in male mice.

The deregulated spinal cord proteins induced by nerve injury are the key to neuropathic pain. Integrated transcriptome and translatome analyses can screen out deregulated proteins controlled by only post-transcriptional regulation. By comparing RNA sequencing (RNA-seq) and ribosome profiling sequencing (Ribo-seq) data, we identified an upregulated protein, chromobox 2 (CBX2), with its mRNA level unchanged in the spinal cord after peripheral nerve injury. CBX2 was mainly distributed in the spinal cord neurons. Blocking the SNL-induced increase of spinal CBX2 attenuated the neuronal and astrocytes hyperactivities and pain hypersensitivities in both the development and maintenance phases. Conversely, mimicking the upregulation of CBX2 in the spinal cord facilitated the activities of neurons and astrocytes and produced evoked nociceptive hypersensitivity and spontaneous pain. Our results also revealed that activating the ERK pathway, upregulating CXCL13 in neurons, and CXCL13 further inducing astrocyte activation were possible downstream signaling mechanisms of CBX2 in pain processing. In conclusion, upregulation of CBX2 after nerve injury leads to nociceptive hyperalgesia by promoting neuronal and astrocyte hyperactivities through the ERK pathway. Inhibiting CBX2 upregulation may be therapeutically beneficial.

Factors associated with subgroups of fatigue in maintenance hemodialysis patients: a cross-sectional study.

OBJECTIVE: This study aimed to investigate affected factors for subgroups of fatigue and the degree of fatigue in maintenance hemodialysis (MHD) patients. METHODS: This study included 120 MHD patients. Questionnaires, pre- and post-dialysis clinical data, bioimpedance spectroscopy, and ultrasound assessment were involved. RESULTS: The prevalence of fatigue in participants was 83%, including 54% of patients with fatigue worsened by dialysis, 13% with fatigue lessened by dialysis, and 16% with undifferentiated fatigue. Based on multi-nominal logistic regression analysis, age was associated with worsened fatigue by dialysis (odds ratio (OR) = 1.06, 95% confidence interval (CI) 1.01-1.11, p = 0.019), lower post-dialysis phosphorus was associated with lessened fatigue by dialysis (OR = 0.03, 95% CI 0.001-0.981, p = 0.049), and there was an increasing trend of patients experiencing undifferentiated fatigue as the extracellular water / intracellular water (E/I) level increased (p for trend = 0.020). Based on multi-ordinal logistic regression analysis, age was also a significant predictor for more severe fatigue (OR = 1.042, 95% CI 1.008-1.059, p = 0.015). CONCLUSIONS: Different subgroups of fatigue in MHD patients have different affecting factors. Older patients were prone to worsened fatigue by dialysis, patients with lower post-dialysis phosphorus were prone to lessened fatigue by dialysis, and patients with higher E/I levels were prone to undifferentiated fatigue. Meanwhile, older patients are prone to suffer from more severe fatigue. However, more in-depth studies are needed to clarify the pathogenesis of fatigue in MHD patients.

Nerve Injury-Induced γH2AX Reduction in Primary Sensory Neurons Is Involved in Neuropathic Pain Processing.

Phosphorylation of the serine 139 of the histone variant H2AX (γH2AX) is a DNA damage marker that regulates DNA damage response and various diseases. However, whether γH2AX is involved in neuropathic pain is still unclear. We found the expression of γH2AX and H2AX decreased in mice dorsal root ganglion (DRG) after spared nerve injury (SNI). Ataxia telangiectasia mutated (ATM), which promotes γH2AX, was also down-regulated in DRG after peripheral nerve injury. ATM inhibitor KU55933 decreased the level of γH2AX in ND7/23 cells. The intrathecal injection of KU55933 down-regulated DRG γH2AX expression and significantly induced mechanical allodynia and thermal hyperalgesia in a dose-dependent manner. The inhibition of ATM by siRNA could also decrease the pain threshold. The inhibition of dephosphorylation of γH2AX by protein phosphatase 2A (PP2A) siRNA partially suppressed the down-regulation of γH2AX after SNI and relieved pain behavior. Further exploration of the mechanism revealed that inhibiting ATM by KU55933 up-regulated extracellular-signal regulated kinase (ERK) phosphorylation and down-regulated potassium ion channel genes, such as potassium voltage-gated channel subfamily Q member 2 (Kcnq2) and potassium voltage-gated channel subfamily D member 2 (Kcnd2) in vivo, and KU559333 enhanced sensory neuron excitability in vitro. These preliminary findings imply that the down-regulation of γH2AX may contribute to neuropathic pain.

Troglonectes canlinensis sp. nov. (Teleostei: Nemacheilidae), a New Troglomorphic Loach from Guangxi, China.

A new species of the genus Troglonectes is described based on specimens from a karst cave in Andong Town, Xincheng County, Liuzhou City, Guangxi, China. Troglonectes canlinensis sp. nov. can be distinguished from its congener species by the following combination of characteristics: eye degenerated into a black spot; whole body covered by scales, except for the head, throat, and abdomen; incomplete lateral line; forked caudal fin; 8-10 gill rakers on the first gill arch; 13-14 branched caudal fin rays; 8-9 branched dorsal fin rays; 5-6 anal fin rays; 9-10 pectoral fin rays; upper adipose keel depth mostly 1/2 of the caudal peduncle depth; and caudal fin forked.