Parkinson’s disease (PD) is a common neurodegenerative disorder with profound impact on patients’ quality of life and long-term health, and early detection and intervention are particularly critical. In recent years, the search for precise and reliable biomarkers has become one of the key strategies to effectively address the clinical challenges of PD. In this paper, we systematically evaluated potential biomarkers, including proteins, metabolites, epigenetic markers, and exosomes, in the peripheral blood of PD patients. Protein markers are one of the main directions of biomarker research in PD. In particular, α‑synuclein and its phosphorylated form play a key role in the pathological process of PD. It has been shown that aggregation of α-synuclein may be associated with pathologic protein deposition in PD and may be a potential marker for early diagnosis of PD. In terms of metabolites, uric acid, as a metabolite, plays an important role in oxidative stress and neuroprotection in PD. It has been found that changes in uric acid levels may be associated with the onset and progression of PD, showing its potential as an early diagnostic marker. Epigenetic markers, such as DNA methylation modifications and miRNAs, have also attracted much attention in Parkinson’s disease research. Changes in these markers may affect the expression of PD-related genes and have an important impact on the onset and progression of the disease, providing new research perspectives for the early diagnosis of PD. In addition, exosomes, as a potential biomarker carrier for PD, are able to carry a variety of biomolecules involved in intercellular communication and pathological regulation. Studies have shown that exosomes may play an important role in the pathogenesis of PD, and their detection in blood may provide a new breakthrough for early diagnosis. It has been shown that exosomes may play an important role in the pathogenesis of PD, and their detection in blood may provide new breakthroughs in early diagnosis. In summary, through in-depth evaluation of biomarkers in the peripheral blood of PD patients, this paper demonstrates the important potential of these markers in the early diagnosis of PD and in the study of pathological mechanisms. Future studies will continue to explore the clinical application value of these biomarkers to promote the early detection of PD and individualized treatment strategies.

BACKGROUND: The American Heart Association (AHA) introduced the concept of cardiovascular-kidney-metabolic (CKM) health and stage, reflecting the interaction among metabolism, chronic kidney disease (CKD), and the cardiovascular system. However, the association between CKM stage and the long-term risk of cardiovascular disease (CVD) has not been validated. This study aimed to evaluate the long-term CVD risk associated with CKM health metrics and CKM stage using data from a population-based cohort study. METHODS: In total, 5293 CVD-free participants were followed up to around 13 years in the Chinese Multi-provincial Cohort Study (CMCS). Considering the pathophysiologic progression of CKM health metrics abnormalities (comprising obesity, central adiposity, prediabetes, diabetes, hypertriglyceridemia, CKD, and metabolic syndrome), participants were divided into CKM stages 0, 1, and 2. The time-dependent Cox regression models were used to estimate the cardiovascular risk associated with CKM health metrics and stage. Additionally, broader CVD outcomes were examined, with a specific assessment of the impact of stage 3 in 2581 participants from the CMCS-Beijing subcohort. RESULTS: Among participants, 91.2% (4825/5293) had at least one abnormal CKM health metric, 8.8% (468/5293), 13.3% (704/5293), and 77.9% (4121/5293) were in CKM stages 0, 1, and 2, respectively; and 710 incident CVD cases occurred during a median follow-up time of 13.3 years (interquartile range: 12.1 to 13.6 years). Participants with each poor CKM health metric exhibited significantly higher CVD risk. Compared with stage 0, the hazard ratio (HR) (95% confidence interval [CI]) for CVD incidence was 1.31 (0.84-2.04) in stage 1 and 2.27 (1.57-3.28) in stage 2. Significant interactive impacts existed between CKM stage and age or sex, with higher CVD risk related to increased CKM stages in participants aged <60 years or females. CONCLUSION These findings highlight the contribution of CKM health metrics and CKM stage to the long-term risk of CVD, suggesting the importance of multi-component recognition and management of poor CKM health in CVD prevention.
Humans ; Female ; Male ; Cardiovascular Diseases/etiology* ; Middle Aged ; Adult ; Cohort Studies ; Renal Insufficiency, Chronic/metabolism* ; Aged ; Risk Factors ; Metabolic Syndrome/metabolism* ; China ; East Asian People

The purpose of this study was to clarify the effect of Huotan Jiedu Tongluo Decoction on atherosclerosis(AS) injury in ApoE~(-/-) mice by regulating the ferroptosis pathway. Seventy-five ApoE~(-/-) mice were randomly divided into model group, low-, medium-, and high-dose of Huotan Jiedu Tongluo Decoction groups, and evolocumab group(n=15), and 15 C57BL/6J mice were selected as the blank group. Mice in the blank group were fed with a normal diet, and those in the other groups were fed with a high-fat diet to induce AS. From the 9th week, mice in Huotan Jiedu Tongluo Decoction groups were administrated with Huotan Jiedu Tongluo Decoction at corresponding doses by gavage, and those in the blank group and the model group were given an equal volume of distilled water. Mice in the evolocumab group were treated with evolocumab 18.2 mg·kg~(-1 )by subcutaneous injection every 2 weeks. After 8 weeks of continuous intervention, oil red O staining and hematoxylin-eosin(HE) staining were employed to observe the lipid deposition and plaque formation in the aortic root. Masson staining was used to evaluate the collagen content in the aortic root. The serum levels of total cholesterol(TC), triglycerides(TG), high-density lipoprotein cholesterol(HDL-C), and low-density lipoprotein cholesterol(LDL-C) were determined by biochemical kits. The levels of Fe~(2+), superoxide dismutase(SOD), malondialdehyde(MDA), and glutathione(GSH) in the aorta were measured by colorimetry. The protein and mRNA levels of nuclear factor erythroid 2-related factor 2(Nrf2), glutathione peroxidase 4(GPX4), solute carrier family 7 member 11(SLC7A11), and acyl-CoA synthetase long chain family member 4(ACSL4) in the aorta were detected by Western blot and RT-qPCR, respectively. The expression of Nrf2, GPX4, and SLC7A11 was localized by immunofluorescence. The results showed that low-, medium-, and high-dose Huotan Jiedu Tongluo Decoction reduced the plaque formation of aortic root and increased the collagen content in AS mice. At the same time, Huotan Jiedu Tongluo Decoction improved the lipid metabolism by lowering the levels of TC, LDL-C, and TG and elevating the level of HDL-C in the serum. Huotan Jiedu Tongluo Decoction enhanced the antioxidant capacity by elevating the levels of GSH and SOD and lowering the level of MDA in the aorta and inhibiting the accumulation of Fe~(2+) in the aorta. In addition, Huotan Jiedu Tongluo Decoction up-regulated the protein and mRNA levels of Nrf2, GPX4, and SLC7A11, while down-regulating the protein and mRNA levels of ACSL4. In summary, Huotan Jiedu Tongluo Decoction can effectively alleviate AS lesions in ApoE~(-/-) mice by activating the Nrf2/GPX4 pathway, reducing lipid peroxidation, and inhibiting ferroptosis.
Animals ; Ferroptosis/drug effects* ; Atherosclerosis/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; NF-E2-Related Factor 2/genetics* ; Mice ; Mice, Inbred C57BL ; Apolipoproteins E/metabolism* ; Male ; Phospholipid Hydroperoxide Glutathione Peroxidase/genetics* ; Signal Transduction/drug effects* ; Humans ; Mice, Knockout

The evaluation of blood compatibility of biomaterials is crucial for ensuring the clinical safety of implantable medical devices. To address the limitations of traditional testing methods in real-time monitoring and electrical property analysis, this study developed a portable electrical impedance tomography (EIT) system. The system uses a 16-electrode design, operates within a frequency range of 1 to 500 kHz, achieves a signal to noise ratio (SNR) of 69.54 dB at 50 kHz, and has a data collection speed of 20 frames per second. Experimental results show that the EIT system developed in this study is highly consistent with a microplate reader ( R ²=0.97) in detecting the hemolytic behavior of industrial-grade titanium (TA3) and titanium alloy-titanium 6 aluminum 4 vanadium (TC4) in anticoagulated bovine blood. Additionally, with the support of a multimodal image fusion Gauss-Newton one-step iterative algorithm, the system can accurately locate and monitor in real-time the dynamic changes in blood permeation and coagulation caused by TC4 in vivo. In conclusion, the EIT system developed in this study provides a new and effective method for evaluating the blood compatibility of biomaterials.
Electric Impedance ; Animals ; Tomography/instrumentation* ; Biocompatible Materials ; Materials Testing/instrumentation* ; Cattle ; Titanium ; Alloys ; Prostheses and Implants

OBJECTIVES: To study the clinical characteristics, efficacy, and prognosis of pediatric Langerhans cell histiocytosis (LCH). METHODS: A retrospective analysis was conducted on 72 children with newly diagnosed LCH. RESULTS: The median age of the 72 children was 5 years (range: 0-14 years), with skull involvement being the most common (56 cases, 77.8%). The BRAF-V600E mutation was not associated with clinical characteristics, efficacy, or prognosis (P>0.05). The 5-year overall survival rate was 91.6%±4.2%, and the 5-year event-free survival (EFS) rate was 67.5%±5.8%. The 6-week chemotherapy response rate and 5-year EFS rate were lower in the risk organ involvement group compared to the no risk organ involvement group (P<0.05). The five-year overall survival rates for the group with multi-system involvement and the group with platelet count ≥450×10⁹/L were respectively lower than those for the single-system involvement group and the group with platelet count <450×10⁹/L (P<0.05). Risk organ involvement is an independent risk factor for 5-year EFS (P<0.05). CONCLUSIONS Skull is the most commonly affected site in pediatric LCH. The BRAF-V600E mutation is not related to clinical characteristics, efficacy, or prognosis. Elevated platelet count, risk organ involvement, and multisystem involvement are associated with poor prognosis, with risk organ involvement being an independent risk factor for 5-year EFS.
Humans ; Histiocytosis, Langerhans-Cell/therapy* ; Child, Preschool ; Child ; Male ; Infant ; Female ; Adolescent ; Retrospective Studies ; Proto-Oncogene Proteins B-raf/genetics* ; Prognosis ; Infant, Newborn ; Mutation

OBJECTIVE: To investigate the molecular mechanism and explore blood transfusion strategies for a proband exhibiting the JK (a-b-) phenotype and anti-JK³ high frequency antigen antibody and her eight family members. METHODS: The Kidd blood phenotype and irregular antibodies in a family were identified by serologic tests. Exon 4-11 and intron region of SLC14A1 gene were sequenced by Sanger method. RESULTS: The combination of the gene JK*B (c.499A>G,c.512G>A,c.588A>G) and gene JK*B (c.342-1G>A,588A>G) in this family were considered to result in the JK (a-b-) phenotype in two members. The members carrying gene JK*A(c.130G>A,588A>G) all present serological JK^a+W. Members carrying gene JK*B (c.499A>G,c.588A>G) all present serological JK^b+W, which has not been previously reported to cause antigenic weakening. The proband with JK (a-b-) phenotype produced anti-JK³ antibodies, the hospital formulated a number of blood preparation strategies for the patient and she was discharged after recovery. CONCLUSION In this study, the molecular mechanism of JK (a-b-) in this family was identified, the transfusion strategy of rare blood group was established in our institution preliminary, and the necessity of establishing a rare blood group bank was revealed in this region. It is suggested that JK*B (c.499A>G,c.588A>G) may be a new genetic pattern leading to the weakening of Kidd antigenicity, which lays a foundation for the study of population genetics.
Humans ; Blood Transfusion ; Female ; Kidd Blood-Group System/genetics* ; Phenotype ; Pedigree

Objective:To compare the clinical efficacy of robot-assisted balloon tibioplasty and traditional open reduction and internal fixation in the treatment of AO/OTA type 41B2 tibial plateau fracture.Methods:A retrospective cohort study was conducted to analyze the clinical data of 70 patients with AO/OTA type 41B2 tibial plateau fracture who were admitted to Wuhan Fourth Hospital from September 2019 to October 2022, including 35 males and 35 females, aged 24-62 years [(44.9±9.5)years]. Among them, 41 patients underwent traditional open reduction and internal fixation (open reduction group), while 29 patients underwent robot-assisted balloon tibioplasty (balloon group). The following parameters were compared between the two groups: incision length, operative blood loss, number of intraoperative fluoroscopies, operation duration, and length of hospital stay; Rasmussen radiological scores at 3 days, 3 months postoperatively, and at the last follow-up and the fracture healing time; pain visual analogue scale (VAS) scores preoperatively, and at 2 days and 3 months postoperatively; knee joint range of motion at 5 days, 3 months postoperatively, and at the last follow-up; Hospital for Special Surgery (HSS) knee function scores at 3, 6 months postoperatively, and at the last follow-up; incidence rate of complications at 15 days postoperatively.Results:All the patients were followed for 12-24 months [18(17, 20)months]. The incision length, operative blood loss and length of hospital stay in the balloon group were 1.6(1.5, 3.0)cm, 5.0(5.0, 5.0)ml and 11.0(9.0, 14.0)days, less than those in the open reduction group [12.0(11.0, 12.0)cm, 100.0(50.0, 120.0)ml and 15.0(13.0, 20.0)days] ( P<0.01). The number of intraoperative fluoroscopies and operation duration in the open reduction group were 9.0(7.0, 10.0)times and 75.0(60.0, 90.0)minutes, less than those in the balloon group [336.0(335.0, 340.0)times and [90.0(70.0, 105.0)minutes] ( P<0.05). There were no significant differences in the Rasmussen radiological scores between the two groups at 3 days, 3 months postoperatively, or at the last follow-up ( P>0.05). The fracture healing time in the balloon group was 3.0(3.0, 3.0)months, shorter than 3.0(3.0, 3.5)months in the open reduction group ( P<0.05). No significant differences were observed between the two groups in VAS scores before operation or at 3 months postoperatively ( P>0.05). However, the VAS score was 2.0(2.0, 3.0)points at 2 days postoperatively in the balloon group, lower than 5.0(5.0, 6.0)points in the open reduction group ( P<0.01). The knee joint range of motion at 5 days, 3 months postoperatively and at the last follow-up were 90.0(85.0, 90.0)°, 135.0(130.0, 135.0)° and 140.0(135.0, 140.0)° in the balloon group, better than 65.0(60.0, 70.0)°, 125.0(120.0, 130.0)°, 130.0(130.0, 140.0)° in the open reduction group ( P<0.01). Similarly, the HSS knee function scores at 3, 6 months postoperatively and at the last follow-up were 80.0(80.0, 81.0)points, 91.0(90.0, 92.0)points, and 95.0(93.0, 96.0)points in the balloon group, better than 71.0(70.0, 72.0)points, 83.0(81.0, 84.0)points, and 86.0(84.0, 88.0)points in the open reduction group ( P<0.01). The incidence rate of complications in the balloon group was 0, comparable to 12% (5/41) in the open reduction group ( P>0.05). Conclusion:Compared with traditional open reduction and internal fixation surgery, robot-assisted balloon tibioplasty in the treatment of AO/OTA type 41B2 tibial plateau fracture significantly reduces surgical trauma, alleviates postoperative pain, promotes fracture healing, and accelerates functional recovery of the affected limbs.

Objective:To explore the clinical phenotype and genetic characteristics of four patients with Phelan-McDermid syndrome (PMS) due to variants of SHANK3 gene. Methods:Four patients diagnosed with PMS at Guangzhou Women and Children′s Medical Center Liuzhou Hospital from January 2020 to January 2025 were selected as the study subjects. Clinical data of the patients were collected. Peripheral venous blood samples were collected from each patient for the extraction of genomic DNA, followed by whole-exome sequencing (WES) and validation by Sanger sequencing. Pathogenicity of candidate variants was rated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), and multiple bioinformatic tools were used to assess the pathogenic effects of the variants. The study was approved by the Ethics Committee of the Guangzhou Women′s and Children′s Medical Center Liuzhou Hospital (Ethics No. 2025-007).Results:All four patients had exhibited language delay and intellectual disability (IQ 35 ~ 65). Some also presented with autism spectrum disorder and schizophrenia, albeit with significant phenotypic heterogeneity. All patients were found to harbor deletions of 22q13.33 region, ranging from 55.46 kb to 112.64 kb, primarily involving the SHANK3 gene. Conclusion:PMS is typically caused by deletions or mutations of the SHANK3 gene. The clinical manifestations are diverse, with developmental delay and intellectual disability being the most common. Accurate diagnosis requires integration of genetic testing and standardized clinical assessment. Genetic screening for suspected patients and at-risk pregnant women is recommended to facilitate their genetic counseling.

Objective:To understand the prevalence and related factors of three common chronic diseases, hyperlipidemia, hypertension and diabetes in HIV-infected persons.Methods:As of December 2023, HIV-infected persons >15 years old who are receiving antiviral therapy (ART) and follow-up in Henan Province were selected as the study objects. Questionnaires, physical examinations, and blood samples were collected to collect demographic information, ART, body weight, blood lipids, blood pressure, and blood sugar of HIV-infected persons. The logistic regression model was used to analyze the related factors of hyperlipidemia, hypertension and diabetes.Results:Among 4 023 HIV-infected patients, the prevalence rates of hyperlipidemia, hypertension, and diabetes were 64.47% (2 594/4 023), 16.80% (676/4 023), and 10.54% (424/4 023), respectively. Multivariate analysis showed that hyperlipidemia was positively associated with ≥40 years of age, overweight and obesity, two nucleoside reverse transcriptase inhibitors (NRTIs) + proteasome inhibitors (PIs) regimen and two NRTIs+ integrase inhibitor regimen, and negatively associated with low body weight. Hypertension was positively correlated with the age group ≥40 years old, family history of cardiovascular and cerebrovascular diseases, overweight and obesity, ART time ≥0.5 years, and negatively correlated with low body weight. Diabetes was positively associated with age group ≥40 years, family history of cardiovascular and cerebrovascular disease, overweight and obesity, and negatively associated with the use of two NRTIs+PIs treatment regimens.Conclusions:In 2023, the prevalence of hyperlipidemia, hypertension, and diabetes among HIV-infected people in Henan Province was relatively high, and the risk of common chronic diseases among those ≥40 years old, overweight and obese, and those with a family history of cardiovascular and cerebrovascular diseases was also relatively high. It is recommended to strengthen the prevention and management of common chronic diseases among HIV-infected people.

OBJECTIVES: Keloids are fibrotic skin disorders characterized by excessive collagen deposition and a high recurrence rate, closely associated with inflammatory mediators. However, existing epidemiological studies are limited by confounding factors and reverse causality, making it difficult to establish causation. This study aims to investigate the causal relationship between circulating cytokines and keloids using Mendelian randomization analysis. METHODS: Significant single nucleotide polymorphisms (SNPs) associated with circulating cytokines (exposures) and keloids (outcomes) were extracted from genome-wide association study (GWAS) summary datasets. Eligible SNPs were selected as instrumental variables (IVs). Exposure data were derived from a cytokine GWAS including 8 293 Finnish participants, and outcome data from a keloid GWAS based on the UK Biobank. The inverse-variance weighted (IVW) method served as the primary analytical approach to estimate causal effects, supplemented by weighted median (WME), MR-Egger regression, and other sensitivity analyses. Horizontal pleiotropy was assessed using MR-Egger regression and the MR pleiotropy residual sum and outlier (MR-PRESSO) test, while Cochran's Q test evaluated heterogeneity. Leave-one-out analysis was used to verify robustness and consistency. A reverse MR analysis was also conducted, with keloid as the exposure and cytokines as outcomes, to rule out reverse causation. RESULTS: IVW analysis identified significant positive causal associations between two cytokines and keloids-macrophage migration inhibitory factor (MIF) [odds ratio (OR)=2.081, 95% confidence interval (CI) 1.219 to 3.552, P=0.007] and monocyte chemoattractant protein-1 (MCP-1) (OR=1.673, 95% CI 1.036 to 2.701, P=0.035). Conversely, stem cell factor (SCF) showed a negative causal relationship with keloids (OR=0.518, 95% CI 0.269 to 0.998, P=0.049). Results from the MR-Egger and weighted median analyses were consistent with IVW findings. No evidence of horizontal pleiotropy was observed (P>0.05). Except for interleukin-6 (P=0.014), no heterogeneity was detected in other cytokines. Leave-one-out analysis further confirmed the robustness of the causal associations. In reverse MR analysis, keloids were causally related only to β-nerve growth factor (beta-NGF) (OR=1.048, 95% CI 1.002 to 1.095, P=0.039), with no heterogeneity or pleiotropy detected in most cytokines (P>0.05). CONCLUSIONS MIF and MCP-1 exhibit positive causal associations with keloid formation, while SCF shows a negative causal relationship. These findings provide new evidence for the causal involvement of inflammatory cytokines in keloid pathogenesis and offer potential molecular targets for developing novel keloid therapies.
Humans ; Keloid/blood* ; Mendelian Randomization Analysis ; Cytokines/genetics* ; Polymorphism, Single Nucleotide ; Genome-Wide Association Study ; Chemokine CCL2/genetics* ; Interleukin-6/genetics* ; Macrophage Migration-Inhibitory Factors/genetics* ; Male ; Stem Cell Factor/blood* ; Female ; Intramolecular Oxidoreductases