ZNF521 promotes acute myeloid leukemogenesis by suppressing the expression and acetylation of SMC3.

Zinc finger protein 521 (ZNF521) participates in the self-renewal of hematopoietic stem cells, and its abnormal expression has been implicated to promote leukemia. However, the specific role of ZNF521 in leukemia has not been fully understood. In this study, we aimed to further elucidate its role. Using acute leukemia cell line THP-1, we demonstrated that knocking down ZNF521 inhibited leukemia cell proliferation, promoted apoptosis, and induced cell arrest in G2/M phase. Interestingly, we also observed the upregulation of SMC3 expression and acetylation, as well as the downregulation of histone deacetylases 8 (HDAC8), CDK2, and CDK6. The proliferation inhibition was reversed by knocking down SMC3, suggesting the key role of SMC3 reduction in ZNF521 elevated proliferation. Conversely, ZNF521 overexpression in HL-60 cells resulted in enhanced proliferation and inhibited apoptosis. Furthermore, we discovered that ZNF521 can interact with HDAC8, which deacetylates SMC3, and the interaction promotes proliferation and suppresses apoptosis. Notably, when HDAC8 was knocked down or its activity was inhibited by a HDAC8 inhibitor, the previous observed trend was reversed. Consequently, ZNF521 plays a critical role in acute myeloid leukemogenesis by reducing the expression and acetylation of SMC3. Overall, this study sheds light on the potential for targeted treatment in highly ZNF521 expressed acute myeloid leukemia, providing a valuable clue for precise and effective therapeutic approaches.

Anemia, blood cell indices, genetic correlations, and brain structures: A comprehensive analysis of roles in Parkinson's disease risk.

INTRODUCTION: Anemia may contribute significantly to the onset of Parkinson's disease (PD). Current research on the association between anemia and PD risk is inconclusive, and the relationships between anemia-related blood cell indices and PD incidence require further clarification. This study aims to investigate the relationships between anemia, blood cell indicators, and PD risk using a thorough prospective cohort study. METHODS: We used data from the UK Biobank, a prospective cohort study of 502,649 participants, and ultimately, 365,982 participants were included in the analysis. Cox proportional hazards models were utilized to adjust for confounding factors, aiming to thoroughly explore the associations between anemia and blood cell indices with the risk of incident PD. The interaction between anemia and Polygenic Risk Score (PRS) for PD was also examined. Linear regression and mediation analyses assessed potential mechanisms driven by brain structures, including grey matter volume. RESULTS: During a median follow-up of 14.24 years, 2513 participants were diagnosed with PD. Anemia considerably increased PD risk (hazard ratio [HR] 1.98, 95 % confidence interval [CI]: 1.81-2.18, P < 0.001) after adjustments. Those with high PRS for anemia had an 83 % higher PD incidence compared to low PRS participants. Sensitivity analyses confirmed result robustness. Linear regression showed that anemia correlated with grey matter volumes and most white matter tracts. Furthermore, mediation analyses identified that the volume of grey matter in Thalamus mediates the relationship between anemia and PD risk. CONCLUSION: In summary, we consider there to be a substantial correlation between anemia and increased PD risk.

Taraxasterol attenuates zearalenone-induced kidney damage in mice by modulating oxidative stress and endoplasmic reticulum stress.

Taraxasterol is one of the bioactive ingredients from traditional Chinese herb Taraxacum, which exhibits multiple pharmacological activities and protective effects. However, the underlying influence and mechanism of its use against kidney damage caused from zearalenone (ZEA) remain unexplored. The ZEA-induced kidney damage model of mice was established by feeding diets containing ZEA (2 mg/kg), and taraxasterol (5 and 10 mg/kg) was administered by gavage for 28 days. Results demonstrated taraxasterol increased average daily gain (ADG) and average daily feed intake (ADFI), reduced feed-to-gain ratio (F/G) and kidney index of mice induced by ZEA. Taraxasterol alleviated histopathological changes of kidney, reduced ZEA residue and the levels of blood urea nitrogen (BUN), uric acid (UA), and creatinine (CRE). Concurrently, taraxasterol reduced the contents of oxidative stress indicator reactive oxygen species (ROS) and malondialdehyde (MDA), and increased the activities of antioxidant enzymes catalase (CAT), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px). Further, taraxasterol up-regulated the mRNA and protein expression of nuclear factor erythroid-2-related factor 2 (Nrf2), GSH-Px, NAD(P)H quinone oxidoreductase 1 (NQO1), and heme oxygenase-1 (HO-1), and down-regulated the mRNA and protein expression of KELCH like ECH associated protein (Keap1) in Nrf2/Keap1 pathway. Taraxasterol down-regulated the mRNA and protein expression of immunoglobulin binding protein (Bip), C/EBP homologous protein (CHOP), Bcl-2 associated X (Bax), cysteine protease (Caspase)-12, and Caspase-3, and up-regulated B-cell lymphoma 2 (Bcl-2) expression in endoplasmic reticulum stress pathway. This study suggests that taraxasterol attenuates ZEA-induced mouse kidney damage through the modulation of Nrf2/Keapl pathway to play antioxidant role and endoplasmic reticulum stress pathway to enhance anti-apoptotic ability. It will provide a basis for taraxasterol as a potential drug to prevent and treat ZEA-induced kidney damage.

The role of dietary modification in the prevention and management of metabolic dysfunction-associated fatty liver disease: An international multidisciplinary expert consensus.

Metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD), has become the leading cause of chronic liver disease worldwide. Optimal dietary intervention strategies for MAFLD are not standardized. This study aimed to achieve consensus on prevention of MAFLD through dietary modification. A multidisciplinary panel of 55 international experts, including specialists in hepatology, gastroenterology, dietetics, endocrinology and other medical specialties from six continents collaborated in a Delphi-based consensus development process. The consensus statements covered aspects ranging from epidemiology to mechanisms, management, and dietary recommendations for MAFLD. The recommended dietary strategies emphasize adherence to a balanced diet with controlled energy intake and personalized nutritional interventions, such as calorie restriction, high-protein, or low-carbohydrate diets. Specific dietary advice encouraged increasing the consumption of whole grains, plant-based proteins, fish, seafood, low-fat or fat-free dairy products, liquid plant oils, and deeply colored fruits and vegetables. Concurrently, it advised reducing the intake of red and processed meats, saturated and trans fats, ultra-processed foods, added sugars, and alcohol. Additionally, maintaining the Mediterranean or DASH diet, minimizing sedentary behavior, and engaging in regular physical activity are recommended. These consensus statements lay the foundation for customized dietary guidelines and proposing avenues for further research on nutrition and MAFLD.

Unraveling the rapid progression of non-target lesions: risk factors and the therapeutic potential of PCSK9 inhibitors in post-PCI patients.

BACKGROUND: Rapid progression of non-target lesions (NTLs) leads to a high incidence of NTL related cardiac events post-PCI, which accounting half of the recurrent cardiac events. It is important to identify the risk factors and establish an accurate clinical prediction model for the rapid progression of NTLs post-PCI. PCSK9 inhibitors lower LDL-c levels significantly, also show the anti-inflammation effect, and may have the potential to reduce the rapid progression of NTLs post-PCI. We tried to test this hypothesis and explore the potential mechanisms. METHODS: This retrospective study included 1250 patients who underwent the first PCI and underwent repeat coronary angiography for recurrence of chest pain within 24 months. General characteristics, laboratory tests and inflammatory factors(IL-10, IL-6, IL-8, IL-1ß, sIL-2R, and TNF-α) were collected. Machine learning (LASSO regression) was mainly employed to select the important characteristic risk factors for the rapid progression of NTLs post-PCI and build prediction models. Finally, mediator analysis was employed to explore the potential mechanisms by which PCSK9 inhibitors reduce the rapid progression of NTLs post-PCI. RESULTS: There were more diabetes, less beta-blockers and PCSK9 inhibitors application, higher HbA1c, LDL-c, ApoB, TG, TC, uric acid, hs-CRP, TNF-α, IL-6, IL-8, and sIL-2R in NTL progressed group. LDL-c, hs-CRP, IL-8, and sIL-2R were characteristic risk factors for the rapid progression of NTLs post-PCI, combining LDL-c, hs-CRP, IL-8, and sIL-2R builds the optimal model for predicting the rapid progression of NTLs post-PCI (AUC = 0.632). LDL-c had a clear and incomplete mediating effect (95% CI, mediating effect: 51.56%) in the reduction of the progression of NTLs by PCSK9 inhibitors, and there was a possible mediating effect of IL-8 (90% CI), and sIL-2R (90% CI). CONCLUSIONS: LDL-c, hs-CRP, IL-8, and sIL-2R may be the key characteristic risk factors for the rapid progression of NTLs post-PCI, and combining these parameters might predict the rapid progression of NTLs post-PCI. The application of PCSK9 inhibitors had a negative correlation with the rapid progression of NTLs. In addition to the significant LDL-c-lowering, PCSK9 inhibitors may reduce the rapid progression of NTLs by reducing local inflammation of plaque. TRIAL REGISTRATION: ChiCTR2200058529; Date of registration: 2022-04-10.

Clinical value of ACR O-RADS combined with CA125 in the risk stratification of adnexal masses.

Purpose: To develop a combined diagnostic model integrating the subclassification of the 2022 version of the American College of Radiology (ACR) Ovarian-Adnexal Reporting and Data System (O-RADS) with carbohydrate antigen 125 (CA125) and to validate whether the combined model can offer superior diagnostic efficacy than O-RADS alone in assessing adnexal malignancy risk. Methods: A retrospective analysis was performed on 593 patients with adnexal masses (AMs), and the pathological and clinical data were included. According to the large differences in malignancy risk indices for different image features in O-RADS category 4, the lesions were categorized into groups A and B. A new diagnostic criterion was developed. Lesions identified as category 1, 2, 3, or 4A with a CA125 level below 35 U/ml were classified as benign. Lesions identified as category 4A with a CA125 level more than or equal to 35 U/ml and lesions with a category of 4B and 5 were classified as malignant. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the curve (AUC) of O-RADS (v2022), CA125, and the combined model in the diagnosis of AMs were calculated and compared. Results: The sensitivity, specificity, PPV, NPV, accuracy, and AUCs of the combined model were 92.4%, 96.5%, 80.2%, 98.8%, 94.1%, and 0.945, respectively. The specificity, PPV, accuracy, and AUC of the combined model were significantly higher than those of O-RADS alone (all P < 0.01). In addition, both models had acceptable sensitivity and NPV, but there were no significant differences among them (P > 0.05). Conclusion: The combined model integrating O-RADS subclassification with CA125 could improve the specificity and PPV in diagnosing malignant AMs. It could be a valuable tool in the clinical application of risk stratification of AMs.

Risk factors and clinical significance of posterior slip of the proximal vertebral body after lower lumbar fusion.

BACKGROUND: Adjacent segment disease (ASD) after fusion surgery is frequently manifests as a cranial segment instability, disc herniation, spinal canal stenosis, spondylolisthesis or retrolisthesis. The risk factors and mechanisms of ASD have been widely discussed but never clearly defined. AIM: To investigate the risk factors and clinical significance of retrograde movement of the proximal vertebral body after lower lumbar fusion. METHODS: This was a retrospective analysis of the clinical data of patients who underwent transforaminal lumbar interbody fusion surgery between September 2015 and July 2021 and who were followed up for more than 2 years. Ninety-one patients with degenerative lumbar diseases were included (22 males and 69 females), with an average age of 52.3 years (40-73 years). According to whether there was retrograde movement of the adjacent vertebral body on postoperative X-rays, the patients were divided into retrograde and nonretrograde groups. The sagittal parameters of the spine and pelvis were evaluated before surgery, after surgery, and at the final follow-up. At the same time, the Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS) were used to evaluate the patients' quality of life. RESULTS: Nineteen patients (20.9%) who experienced retrograde movement of proximal adjacent segments were included in this study. The pelvic incidence (PI) of the patients in the retrograde group were significantly higher than those of the patients in the nonretrograde group before surgery, after surgery and at the final follow-up (P < 0.05). There was no significant difference in lumbar lordosis (LL) between the two groups before the operation, but LL in the retrograde group was significantly greater than that in the nonretrograde group postoperatively and at the final follow-up. No significant differences were detected in terms of the |PI-LL|, and there was no significant difference in the preoperative lordosis distribution index (LDI) between the two groups. The LDIs of the retrograde group were 68.1% ± 11.5% and 67.2% ± 11.9%, respectively, which were significantly lower than those of the nonretrograde group (75.7% ± 10.4% and 74.3% ± 9.4%, respectively) (P < 0.05). Moreover, the patients in the retrograde group had a greater incidence of a LDI < 50% than those in the nonretrograde group (P < 0.05). There were no significant differences in the ODI or VAS scores between the two groups before the operation, but the ODI and VAS scores in the retrograde group were significantly worse than those in the nonretrograde group after the operation and at the last follow-up, (P < 0.05). CONCLUSION: The incidence of posterior slippage after lower lumbar fusion was approximately 20.9%. The risk factors are related to a higher PI and distribution of lumbar lordosis. When a patient has a high PI and insufficient reconstruction of the lower lumbar spine, adjacent segment compensation via posterior vertebral body slippage is one of the factors that significantly affects surgical outcomes.

Effect of Temperature-Induced Aging on the Gas Permeation Behavior of Thin Film Composite Membranes of PIM-1 and Carboxylated PIM-1.

Polymers of intrinsic microporosity (PIMs) are a class of promising gas separation materials due to their high membrane permeabilities and reasonable selectivities. When processed into thin film composite (TFC) membranes, their high gas throughput aligns closely with industrial requirements, but they are prone to physical aging and plasticization effects. TFC membranes based on the prototypical PIM-1 and its carboxylated derivative cPIM-1 exhibit temperature-dependent gas permeation behavior, which has not been extensively studied before. In single CO2 permeation tests, measurable physical aging occurred when the temperature was raised to 55 °C within a period of 90 min, and the aging rate accelerated as temperature was raised further. TFC membranes prepared from cPIM-1 exhibited a faster aging rate compared to PIM-1 at the same temperature. The decreased permeance could be at least partially recovered through a 5 day methanol vapor treatment. In mixed gas experiments, all membranes showed decreased permselectivities at elevated temperatures. The plasticization pressure of TFC membranes occurred at around 1 bar of CO2 partial pressure, independent of temperature. Significant plasticization was particularly evident for cPIM-1 TFC membranes under CO2/CH4 conditions with increasing temperature, which resulted in increased gas permeance for both components.

MRI Indices of Glymphatic Function Correlate With Disease Duration in Idiopathic Intracranial Hypertension.

BACKGROUND: The glymphatic system represents an extravascular network of astrocytic channels responsible for interstitial fluid and solute transit through the brain parenchyma. Its dysfunction has been considered as a possible cause of idiopathic intracranial hypertension (IIH). METHODS: We enrolled participants with active IIH, treated or cured IIH, and controls. The active IIH group was divided into untreated participants with recently developed (<6 mo) and chronic (6+ mo) disease. Glymphatic function was assessed using diffusion tensor imaging along the paravascular space (DTI-ALPS) to generate an ALPS-index, hypothesized to measure glymphatic function. Participants were imaged before lumbar puncture (LP) if IIH was suspected and following LP when possible. RESULTS: ALPS indices were higher in participants with chronically present, active IIH than in those either with recently developed IIH or control participants. ALPS-indices correlated with papilledema but did not correlate significantly with age, BMI, or intracranial pressure (ICP). CONCLUSIONS: Our findings suggest that DTI-ALPS-indices of glymphatic function may be influenced by the chronicity of intracranial hypertension but do not support the hypothesis that glymphatic dysfunction causes IIH. Though these findings are preliminary, glymphatic imaging may be a useful radiographic biomarker in IIH.

Clinical Utility of Ultrasonographic Guidance for Arterial Catheterization in Patients with Obesity: A Randomized Controlled Trial.

OBJECTIVES: To compare the success and complication rates of radial artery catheterization using ultrasound guidance versus the conventional palpation technique in obese patients by anesthesia residents with similar levels of experience in both methods, and to measure the skin-to-artery distance of radial, brachial, and dorsalis pedis arteries using ultrasound with standardized anatomic landmarks. DESIGN: Prospective, randomized controlled trial SETTING: Single tertiary center PARTICIPANTS: Eighty adults with a body mass index (BMI) ≥30 kg/m2 INTERVENTIONS: Ultrasound guidance or conventional palpation method MEASUREMENTS AND MAIN RESULTS: The primary outcome was the first-attempt success rate of arterial catheterization. The skin-to-artery distance of the radial artery was significantly greater in the BMI groups of 40 to 49 kg/m2 and ≥50 kg/m2 compared to the BMI group of 30 to 39 kg/m2 (mean difference, 1.0 mm; 95% confidence interval [CI], 0.4-1.7; p = 0.0029) for BMI 40-49 kg/m2 vs 30-39 kg/m2 and 1.5 mm (95% CI, 0.6-2.4 mm; p = 0.0015) for ≥50 kg/m2 vs 30-39 kg/m2. Similar findings were observed for the brachial artery. BMI was inversely associated with first-attempt success rates (p = 0.0145) and positively with time to successful catheterization (p = 0.0271). The first-attempt success and vascular complication rates of catheterization did not differ significantly between the ultrasound guidance group (65.0% and 52.5%, respectively) and the conventional palpation group (70.0% [p = 0.6331] and 57.5% [p = 0.6531], respectively). CONCLUSION: The results of this study do not support the routine use of ultrasonography during radial arterial catheterizations for obese adults when junior practitioners perform the procedure.

Identification of novel natural compounds against CFTR p.Gly628Arg pathogenic variant.

Cystic fibrosis transmembrane conductance regulator (CFTR) protein is an ion channel found in numerous epithelia and controls the flow of water and salt across the epithelium. The aim of our study to find natural compounds that can improve lung function for people with cystic fibrosis (CF) caused by the p.Gly628Arg (rs397508316) mutation of CFTR protein. The sequence of CFTR protein as a target structure was retrieved from UniProt and PDB database. The ligands that included Armepavine, Osthole, Curcumin, Plumbagine, Quercetin, and one Trikafta (R*) reference drug were screened out from PubChem database. Autodock vina software carried out docking, and binding energies between the drug and the target were included using docking-score. The following tools examined binding energy, interaction, stability, toxicity, and visualize protein-ligand complexes. The compounds having binding energies of -6.4, -5.1, -6.6, -5.1, and - 6.5 kcal/mol for Armepavine, Osthole, Curcumin, Plumbagine, Quercetin, and R*-drug, respectively with mutated CFTR (Gly628Arg) structure were chosen as the most promising ligands. The ligands bind to the mutated CFTR protein structure active sites in hydrophobic bonds, hydrogen bonds, and electrostatic interactions. According to ADMET analyses, the ligands Armepavine and Quercetin also displayed good pharmacokinetic and toxicity characteristics. An MD simulation for 200 ns was also established to ensure that Armepavine and Quercetin ligands attached to the target protein favorably and dynamically, and that protein-ligand complex stability was maintained. It is concluded that Armepavine and Quercetin have stronger capacity to inhibit the effect of mutated CFTR protein through improved trafficking and restoration of original function.

Causal Relationship Between Autoimmune Arthritis and Temporomandibular Disorders.

OBJECTIVE: Accumulating evidence has indicated a close interrelation between autoimmune arthritis (AA) and temporomandibular disorders (TMD), but the causality is still unclear. The study aimed to explore the causal inference between AA and TMD using a bidirectional Mendelian randomization analysis. METHODS: Online genome-wide association study data on rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis, and TMD were obtained from the FinnGen and IEU databases. Causality was using the inverse variance-weighted method as the primary analysis and supplemented by other methods. Sensitivity analyses, including heterogeneity tests, horizontal pleiotropy tests, and leave-one-out methods, were conducted to investigate the stability and reliability of the results. RESULTS: The inverse variance-weighted test indicated that several AA types could causally increase the TMD risk, including overall RA (odds ratio [OR] = 1.348, 95% confidence interval [CI] = 1.1232-1.618, P = .001), subtype nRA (OR = 1.118, 95% CI = 1.044-1.197, P = .001), and AS (OR = 1.060, 95% CI = 1.024-1.097, P = .001). Moreover, the causal association of the above combinations has been proven to be stable and reliable using sensitivity and other tests. CONCLUSION: These findings suggest that RA and AS might be causally associated with an increased risk of TMD. However, more studies are needed to check the causal effects of AA on TMD and analyse the potential mechanisms further.

metaExpertPro: a computational workflow for metaproteomics spectral library construction and data-independent acquisition mass spectrometry data analysis.

Analysis of large-scale data-independent acquisition mass spectrometry (DIA-MS) metaproteomics data remains a computational challenge. Here, we present a computational pipeline called metaExpertPro for metaproteomics data analysis. This pipeline encompasses spectral library generation using data-dependent acquisition MS (DDA-MS), protein identification and quantification using DIA-MS, functional and taxonomic annotation, as well as quantitative matrix generation for both microbiota and hosts. By integrating FragPipe and DIA-NN, metaExpertPro offers compatibility with both Orbitrap and timsTOF MS instruments. To evaluate the depth and accuracy of identification and quantification, we conducted extensive assessments using human fecal samples and benchmark tests. Performance tests conducted on human fecal samples indicated that metaExpertPro quantified an average of 45,000 peptides in a 60-minute diaPASEF injection. Notably, metaExpertPro outperformed three existing software tools by characterizing a higher number of peptides and proteins. Importantly, metaExpertPro maintained a low factual false discovery rate (FDR) of approximately 5% for protein groups across four benchmark tests. Applying a filter of five peptides per genus, metaExpertPro achieved relatively high accuracy (F-score = 0.67-0.90) in genus diversity and showed a high correlation (rSpearman = 0.73-0.82) between the measured and true genus relative abundance in benchmark tests. Additionally, the quantitative results at the protein, taxonomy, and function levels exhibited high reproducibility and consistency across the commonly adopted public human gut microbial protein databases IGC and UHGP. In a metaproteomic analysis of dyslipidemia (DLP) patients, metaExpertPro revealed characteristic alterations in microbial functions and potential interactions between the microbiota and the host.

Efficacy and safety of microwave ablation for treatment of follicular thyroid neoplasms: a preliminary study.

OBJECTIVE: To assess the feasibility, efficacy, and safety of microwave ablation in treating follicular thyroid neoplasms and suspicious follicular thyroid neoplasms. METHODS: In this retrospective study, the data of patients treated with microwave ablation for follicular neoplasms from December 2016 to January 2024 were summarized. The changes in nodule size, volume, technical success rate, disease progression, complete tumor resolution, thyroid function, and complications post-ablation were evaluated. RESULTS: Seventy-four patients (15 men, 59 women; mean age 46.3 ± 15.2 years) with follicular neoplasms were included. Over a median follow-up of 13 months, complete ablation was achieved, giving a 100% technical success rate. At the first month post-ablation, the maximum diameter of nodules showed no significant change (p = 0.287). From the third month, both maximum diameter and volume significantly decreased (p < 0.005 for all). Volume reduction rates remained stable at one and three months (p = 0.389 and 0.06, respectively) but increased significantly thereafter (p < 0.005 for all). By 24 months, the median maximum diameter had reduced from 2.3 cm to 0 cm, achieving a median volume reduction rate of 100%. Nodules disappeared completely in 20.3% (15/74). Local recurrence was noted in 2.7% of cases (2/74), with no metastasis or neoplasm-related deaths reported. Thyroid function remained unchanged post-treatment (p > 0.05). The complication and side effect rates were 8.1% and 4.1%, respectively. CONCLUSIONS: Initial findings suggest microwave ablation is an effective and safe treatment for follicular neoplasms, with low incidences of disease progression and complications, while maintaining thyroid function.

A novel homozygous mutation of CFAP300 identified in a Chinese patient with primary ciliary dyskinesia and infertility.

Primary ciliary dyskinesia (PCD) is a clinically rare, genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections, male infertility, tympanitis, and laterality abnormalities. PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia. Here, we identified a novel nonsense mutation, c.466G>T, in cilia- and flagella-associated protein 300 (CFAP300) resulting in a stop codon (p.Glu156 *) through whole-exome sequencing (WES). The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm (IDA) and outer dynein arm (ODA). Bioinformatic programs predicted that the mutation is deleterious. Successful pregnancy was achieved through intracytoplasmic sperm injection (ICSI). Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.

Relationship between gut microbiota and multiple sclerosis: a scientometric visual analysis from 2010 to 2023.

Background: Numerous studies have investigated the relationship between gut microbiota (GM) and multiple sclerosis(MS), highlighting the significant role of GM in MS. However, there is a lack of systematic Scientometric analyses published in this specific research area to provide an overall understanding of the current research status. Methods: Perform a scientometric analysis on research conducted between 2010 and 2023 concerning the link between GM and MS using quantitative and visual analysis software (CiteSpace and VOSviewer.). Results: From January 1, 2010, and December 31, 2023, a total of 1019 records about GM and MS were retrieved. The number of publications exhibited a consistent upward trend annually. The United States led in publications, showed the strongest level of collaboration among countries. The University of California, San Francisco stands as the top institution in terms of output, and the most prolific and cited authors were Lloyd H. Kasper and Javier Ochoa-Reparaz from the USA. The research in this field primarily centers on investigating the alterations and associations of GM in MS or EAE, the molecular immunological mechanisms, and the potential of GM-based interventions to provide beneficial effects in MS or EAE. The Keywords co-occurrence network reveals five primary research directions in this field. The most frequently occurring keywords are inflammation, probiotics, diet, dysbiosis, and tryptophan. In recent years, neurodegeneration and neuropsychiatric disorders have been prominent, indicating that the investigation of the mechanisms and practical applications of GM in MS has emerged as a current research focus. Moreover, GM research is progressively extending into the realm of neurodegenerative and psychiatric diseases, potentially becoming future research hotspots. Conclusions: This study revealed a data-driven systematic comprehension of research in the field of GM in MS over the past 13 years, highlighted noteworthy research within the field, provided us with a clear understanding of the current research status and future trends, providing a valuable reference for researchers venturing into this domain.

Aldehyde dehydrogenase 2 preserves kidney function by countering acrolein-induced metabolic and mitochondrial dysfunction.

The prevalence of chronic kidney diseases (CKD) varies by race due to genetic and environmental factors. The Glu504Lys polymorphism in aldehyde dehydrogenase 2 (ALDH2), commonly observed among East Asians, alters the enzyme's function in detoxifying alcohol-derived aldehydes, impacting kidney function. This study investigated the association between variations in ALDH2 levels within the kidney and the progression of kidney fibrosis. Our clinical data indicates that diminished ALDH2 levels are linked to worse CKD outcomes, with correlations between ALDH2 expression, estimated glomerular filtration rate, urinary levels of acrolein, an aldehyde metabolized by ALDH2, and fibrosis severity. In mouse models of unilateral ureteral obstruction and folic acid nephropathy, reduced ALDH2 levels and elevated acrolein were observed in kidneys, especially in ALDH2 Glu504Lys knock-in mice. Mechanistically, acrolein modifies pyruvate kinase M2, leading to its nuclear translocation and co-activation of HIF-1α, shifting cellular metabolism to glycolysis, disrupting mitochondrial function, contributing to tubular damage and the progression of kidney fibrosis. Enhancing ALDH2 expression through adeno-associated virus vectors reduces acrolein and mitigates fibrosis in both wild-type and Glu504Lys knock-in mice. These findings underscore the potential therapeutic significance of targeting the dynamic interaction between ALDH2 and acrolein in CKD.

Gouty Tophus Erodes Nasal Bone But Presents as Painless Hump.

A 32-year-old male presented with a painless swelling on his nasal dorsum, persisting for over 3 months. He reported a gradual increase in the size of the mass, with no identifiable triggers except occasional skin redness. He denied nosebleeds, rhinorrhea, nasal obstruction, trauma, prior surgery, or spontaneous pain. His medical history revealed gout, managed with colchicine and diclofenac. Despite dietary and pharmaceutical interventions, he continued to have bouts of hyperuricemia, with blood uric acid levels measuring 739 µmol/L. Multiple tophi were evident, especially on the left first metatarsophalangeal joint (Figure 1A). Examination revealed an irregularly shaped, immobile, hard swelling at the nasal radix, measuring 3 cm×2 cm. Computerized tomography (CT) imaging of the nose showed bilateral nasal bone destruction from the lesion. Given its impact on the patient's appearance and his history of gout, the mass was initially diagnosed as unusual gouty tophus. The patient requested surgical removal of the lesion, and the dissection revealed a mass partly encased by a capsule-like connective tissue adherent to the nasal bone. As the lesion damaged the nasal bone, removal of the lesion led to defect of nasal bone. After an extensive rinse of the surgery site, the incision was sutured.

Quantitative diagnosis of early acute compartment syndrome using two-dimensional shear wave elastography in a rabbit model.

PURPOSE: This study explored the association of the elasticity modulus and shear wave velocity (SWV) of the tibialis anterior muscle, as measured by two-dimensional shear wave elastography (2D-SWE), with the intracompartmental pressure (ICP) determined using the Whitesides method in a New Zealand rabbit model of acute compartment syndrome (ACS). Additionally, it evaluated the viability of 2D-SWE as a noninvasive, quantitative tool for the early detection of ACS. METHODS: An ACS model was established through direct external compression by applying pressure bandaging to the lower legs of 15 New Zealand rabbits using neonatal blood pressure cuffs. Another five animals represented a non-modeled control group. To measure the elasticity modulus and SWV of the tibialis anterior muscles, 2D-SWE was employed. Blood oxygen saturation, serum creatine kinase (CK), and myoglobin levels were monitored. Subsequently, the anterior tibial compartment was dissected, and the tibialis anterior was removed for hematoxylin and eosin staining to assess muscle injury. RESULTS: The elasticity modulus and SWV of the tibialis anterior muscle increased with compression duration, as did serum CK and myoglobin levels. ICP was strongly positively correlated with these parameters, particularly mean velocity (r=0.942, P<0.001) and CK (r=0.942, P<0.001). Blood oxygen saturation was negatively correlated with ICP (r=-0.887, P<0.001). Histological analysis indicated progressive muscle cell swelling over time, with damage transitioning from reversible to irreversible and culminating in necrosis. CONCLUSION: In a rabbit ACS model, ICP was strongly positively correlated with muscle elasticity modulus/SWV. Consequently, 2D-SWE may represent a novel tool for assessing early-phase ACS.