OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

Methods: Cervical radiographs were analyzed. EOP hyperplasia was classified into three subtypes with standardized length measurements. Variables encompassed demographics, ONL-related indices, and sagittal parameters. Subtype comparisons and multivariate regression analyses (with EOP length as dependent variable) were conducted. Results: Analysis of 187 CSM patients (64.2% male) identified gender-specific patterns: males exhibited greater EOP length (9.4±6.8 mm vs. 4.6±3.4 mm, p<0.001). Type III EOP demonstrated male predominance (82.4% vs. type I 31.8%, type II 51.4%; p<0.001), with associated longer hyperplasia length (11.6±6.6 mm vs. type II 5.1±1.9 mm, p<0.001). Type III EOP was associated with higher ONL prevalence (type III 64.8% vs. type I 45.5%, type II 41.9%; p=0.010) and longer ONL osteophyte length (type III 18.8±9.8 mm vs. type I 14.2±8.1 mm, type II 14.2±9.4 mm; p=0.046). Multivariate regression confirmed male sex (β=–3.82, p=0.009), ONL osteophyte length (β=0.16, p=0.017), T1 slope (β=0.27, p=0.041), and spino-cranial angle (β=–0.19, p=0.009) as factors independently associated with EOP length (adjusted R²=0.382). Conclusions Severe EOP hyperplasia exhibits a male-predominant distribution pattern and demonstrates significant radiological associations with ONL and cervical sagittal imbalance in CSM patients. These findings advocate for EOP evaluation in clinical evaluations to identify high-risk biomechanical profiles.

Although global brain science research has progressed rapidly in recent decades, several fundamental questions in neuroscience remain unresolved. In particular, the physical mechanism underlying neural signal transmission remains controversial, and the carriers responsible for neural information storage and retrieval have not yet been fully clarified. These unresolved issues motivate us to re-examine the processes of neural information generation, transmission, integration, storage, and retrieval from multiple perspectives. A key observation is that neural electromagnetic activities are closely associated with time. Their duration, temporal structure, and dynamic evolution play crucial roles in neural information processing. In this work, we analyze neural electromagnetic activities from the perspective of temporal scales (referred to here as the “time course”). By reviewing and integrating findings from previous studies, we examine the characteristic time requirements and dynamic features of neural processes occurring at different stages of information processing. These stages include neural signal generation, signal transmission along axons, synaptic integration, synaptic plasticity, and memory formation and retrieval. Based on this temporal analysis, we outline a framework describing neural electromagnetic activities across a wide range of time scales, spanning from microseconds to minutes, hours, or even longer periods associated with long-term memory, which suggests that neural information processing involves multiple physical processes operating at different time levels. Rapid electromagnetic events may occur on microsecond scales, whereas electrophysiological phenomena such as action potentials typically last on the order of milliseconds. Longer time scales are associated with synaptic plasticity and memory-related processes. From this perspective, we propose that the physical carrier of neural information may be transient electromagnetic pulses with durations on the microsecond scale. In this framework, action potentials can be interpreted as the macroscopic electrophysiological manifestation of underlying electromagnetic processes triggered by ionic currents across neuronal membranes. Rather than being the fundamental neural signal itself, the action potential may represent a measurable membrane-level response associated with the successful activation of these electromagnetic events. Moreover, we discuss a possible mechanism for long-term memory storage. Considering the apparent temporal contradiction between the millisecond-scale excitation of neurons and the long-term persistence of memories, we believe that long-term memory information may be stored within neural network topologies formed by electrical synapse coupling. Such structures, referred to as electrically coupled memory networks (ECMNs), may enable neurons within the same network to respond rapidly and synchronously to stimuli, thereby facilitating efficient memory retrieval. Overall, this study emphasizes the importance of considering the temporal organization of neural electromagnetic activities when interpreting neural signaling mechanisms. It may provide new insights into the physical nature of neural information carriers and the mechanisms of memory storage and retrieval. Furthermore, highlighting the potential role of electromagnetic interactions in neural activity may contribute to the development of new theoretical frameworks and experimental approaches in neuroscience. Such perspectives may also offer valuable references for future research on neural coding, brain function mechanisms, and neuromodulation technologies.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

Objective Radial artery occlusion(RAO)is one of the common complications following coronary intervention via the traditional radial artery approach.This study aims to evaluate the clinical effectiveness of retrograde recanalization of occluded radial arteries through the distal transradial approach(dTRA)approach.Methods A total of 35 patients with RAO admitted to the cardiovascular department of the Anhui Chest hospital between December 2022 and April 2024,who were scheduled to undergo coronary intervention and had attempted recanalization of RAO via dTRA approach were selected.The primary result was the success rate of recanalizing RAO via dTRA.The secondary results included factors influencing the failure of recanalization via dTRA,postoperative puncture complications,and the patency rate at the 3-month follow-up.Results This study divided the patients into a successful group(29 cases,82.9％)and a failed group(6 cases,17.1％)based on whether the distal radial artery was successfully opened and occluded.The proportion of smoking(100.00％vs.17.24％,P=0.040),history of diabetes(100.00％vs.10.34％,P=0.025),and chronic total occlusion of coronary artery(83.33％vs.17.24％,P=0.030)in the failure group were higher than those in the success group,and the difference was statistically significant.The application rate of balloon tracking assisted technology in the failed group(16.67％vs.58.62％,P=0.045),and the diameter of the radial artery at 3 days after surgery[(1.63±0.13)mm vs.(2.13±0.32)mm,P=0.021]and the peak radial artery blood flow velocity at 3 days postoperatively[(0.10±0.78)m/s vs.(0.50±0.13)m/s,P＜0.001]were all lower in the successful group,and the differences were statistically significant.Logistic regression analysis 3 days after surgery showed that chronic complete occlusion of the coronary artery was an independent risk factor for surgical opening failure(OR 0.042,95％CI 0.004-0.438,P=0.008).After 3 months of follow-up,the patency rate of the successful group was 55.2％.Conclusions Retrograde recanalization of RAO via dTRA is safe and feasible,but its long-term patency rate is not high.

Objective:An in vivo mammalian hepatocyte Unscheduled DNA Synthesis(UDS)test was used to evaluate the genotoxicity of Cross-linked Sodium Hyaluronate Gel and Bone Repair Materials,providing experimental evidence for establishing a UDS testing method for medical devices and materials.Methods:0.9％sodium chloride injection and cottonseed oil were used as the solvent for test materials and negative control,respectively.N-dimethylnitrosamine(NDMA)was used as the positive control for the early sampling times,and 2-acetylaminofluorene(2-AAF)was used as the positive control for the late sampling times.SD rats were administered a single dose for toxic exposure,and liver tissues were collected at 4 h and 16 h,respectively.Hepatocytes were isolated using collagenase perfusion.After labeling with 5-ethynyl-2'-deoxyuridine(EdU),and the net average fluorescence intensity(NAFI)of cell nuclei and nucleoplasm was measured by fluorescence microscope.Data from 50 cells were used to analyze the DNA repair level.Results:Compared with the negative control groups,the positive control groups(NDMA and 2-AAF)showed highly statistically significant differences in NAFI(P＜0.01),indicating successful induction of DNA damage.There was no statistically significant differences between the cross-linked sodium hyaluronate gel groups,bone repair material groups and the negative control group(P＞0.05),suggesting that these materials did not significantly induce DNA damage under the experimental conditions.Conclusion:This study first applied EdU labeling technology to the in vivo hepatic UDS assay,achieving non-radioactive labeling through click chemistry reactions.Under the conditions of this study,cross-linked sodium hyaluronate gel and bone repair materials did not exhibit genotoxicity.In the follow-up,the sample range can be expanded and the observation period can be prolonged to further improve the genotoxicity evaluation system of medical devices.

Objective:To explore the effect of kidney-strengthening and blood stasis-eliminating formula on nutritional status and quality of life in patients with osteoporosis combined with hemodialysis.Methods:From January 2024 to January 2025,60 patients with liver and kidney yin deficiency and blood stasis obstruction were selected from the Pizhou City Traditional Chinese Medicine Hospital's Hemodialysis Center.60 patients were randomly divided into two groups,30 in each group.The matched group received general treatment plus paricalcitol,while the treatment group received the same treatment plus Yishen Zhuyu Fang(a traditional Chinese medicine formula for kidney and blood stasis).The treatment course lasted 12 weeks.Changes in TCM syndrome scores,the Modified Subjective Global Assessment(MQSGA),the Kidney and Life Quality(KDQOLTM-36)scale,lipid levels,and nutritional indicators were compared before and after treatment.Results:After treatment,the TCM syndrome scores in both groups decreased(P＜0.05),with a more pronounced decrease in the treatment group(P＜0.05).The KDQOLTM-36 score in the treatment group increased(P＜0.05),while the increase was not significant in the matched group(P＞0.05),indicating that the treatment group performed better than the matched group(P＜0.05).Both groups experienced a decrease in the MQSGA score(P＜0.05),although the difference was not statistically significant(P＞0.05),the treatment group showed a more noticeable decline.The TC,TG,LDL,and TG/HDL levels in the treatment group all decreased significantly,while HDL levels increased(P＜0.05).In contrast,the TC and HDL levels in the matched group did not change(P＞0.05),while the TG,LDL,and TG/HDL levels increased(P＜0.05).The treatment group performed significantly better than the matched group(P＜0.05).The TRF,Hb,and ALB levels in the treatment group increased(P＜0.05),while the increase was not significant in the matched group(P＞0.05).The total effective rate of the treatment group was 90％,higher than the matched group(23.3％)(P＜0.05).Conclusion:The formula of tonifying the kidney and removing stasis can improve the nutritional status and quality of life of patients with liver and kidney yin deficiency and blood stasis obstruction in hemodialysis combined with osteoporosis.

Objective To explore the correlation between serum homocysteine(Hcy),25-hydroxyvitamin D[25(OH)D]and frailty with type 2 diabites mellitus(T2DM)complicated with sarcopenia.Methods From September 2021 to March 2023,210 elderly T2DM patients were selected from the Department of Geriatrics of The First People's Hospital of Yunnan Province,and divided into simple T2DM(n=99)group,mild sarcopenia(M-Sar,n=59)group and severe sarcopenia(S-Sar,n=52)group.The"Elderly Comprehensive Assessment System"was used to evaluate subjects.The influencing factors of T2DM complicated with sarcopenia were analyzed by Logistic regression.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of Hcy,25(OH)D combined with frailty in evaluating T2DM with sarcopenia.Results In T2DM,M-Sar and S-Sar groups,the age,Hcy,the risk rate of balance gait work falling and the rate of weakness increased in turn(P<0.05),while BMI,hemoglobin,25(OH)D,the rate of good nutrition,the normal rate of basic daily living,the low risk rate of falling,the rate of good balance gait function and the rate of no weakness decreased in turn(P<0.05).Logistic regression analysis showed that serum Hcy,frailty and 25(OH)D were the influencing factors of senile T2DM complicated with sarcopenia.Hcy,25(OH)D and frailty combined to predict T2DM with sarcopenia had an area under ROC carve of 0.815,with a sensitivity of 0.811 and a specificity of 0.717.Conclusions Serum Hcy,25(OH)D and frailty are closely related to T2DM combined with sarcopenia.Detection of Hcy and 25(OH)D combined with frailty score is helpful for early diagnosis of sarcopenia in primary hospitals.

Rheumatoid arthritis(RA)is a chronic autoimmune disease of unknown etiology that can cause joint destruction and deformity.As a small molecule cytokine,the chemokine C-X-C motif chemokine ligand 12(CXCL12)regulates the pathogenesis of rheumatoid arthritis by binding to the specific receptor CXC chemokine receptor 4(CXCR4).Therefore,based on the bio-logical characteristics of CXCL12 and CXCR4,this paper intro-duces the pathogenesis of CXCL12/CXCR4 in RA and summari-zes the progress in RA-related research,with the aim of providing clinical value for understanding the pathogenesis of RA and de-veloping novel therapeutic targets.

Objective To develop a carriage-type field operating unit with advantages in mobility and rapid deployment to solve the problems of the traditional field operating equipment in flexibility and environmental adaptability.Methods The carriage-type field operating unit was made based on a BEIBEN TRUCK transport vehicle platform with external and internal modifications.The external modification involved a hydraulic loading platform with a capacity of 2 t and electric lifting function at the rear of the carriage and an external equipment compartment at the bottom.The internal modification included area renovation,tarp modification,facility remodeling and equipment configuration.Results The carriage-type field operating unit behaved better than the traditional field operating vehicle and operating shelter in deployment time,infection control,mobility,temperature control,etc.Conclusion The carriage-type field operating unit gains advantages in mobility,rapid deployment and complete supporting facilities,and can be used as a relatively independent field surgical unit.[Chinese Medical Equipment Journal,2025,46(8):113-117]