ObjectiveTo compare the differences between the ultrafiltration method and the dextran gel filtration method during the purification of Tfn-modified PCL micelles by using purification efficiency and micelle purity as indicators. MethodsCoumarin-6 （C6） was used as a fluorescent probe and was loaded into HOOC-PEG-PCL to form PCL micelles by the film-dispersion method. Tfn was then conjugated to the surface of PCL micelles via an amidation reaction， resulting in two types of micelles： Tfn/PCL_H and Tfn/PCL_L. The pharmaceutical properties of the two types of micelles were characterized. The micelles were then purified through ultrafiltration method and dextran gel method respectively， and the efficiency of the two methods， along with the purity of the final micelles， was compared. The density of Tfn on the surface of PCL micelles was also calculated. ResultsThe hydrated diameter of PCL micelles was approximately 73 nm， and the C6 loading efficiency was around 0.046%. The size increased to 134 nm and 158 nm for Tfn/PCL_L and Tfn/PCL_H， respectively. The micelle population was monodisperse. The purification results showed that， for the ultrafiltration method， after two and one rounds of purification， the Tfn/C6 ratio stabilized at 23.6 and 3.4 for Tfn/PCL_H and Tfn/PCL_L， respectively. For the dextran gel filtration method， the Tfn/C6 ratio reached 23.7 for the Tfn/PCL_H group after two rounds of purification. However， for the Tfn/PCL_L group， the Tfn/C6 ratio increased during four rounds of dextran gel purification， and a significant difference （P = 0.042 4） was observed between the first and last filtrations. The density of Tfn in the final micelles were calculated. For the ultrafiltration method， the Tfn density of Tfn/PCL_H and Tfn/PCL_L were 94.9% and 13.8%， respectively. For the dextran gel filtration method， the density of the two micelles were 95.6% and 14.4%， respectively. For Tfn/PCL_L group， the density results revealing a statistically significant difference （P=0.000 2）. ConclusionThe purification efficiency of the two methods is comparable. However， the purity of the final micelles shows a significant difference， with the dextran gel filtration method resulting in higher purity， particularly for the Tfn/PCL_L micelles.

By systematically analyzing the bottlenecks in current traditional Chinese medicine （TCM） efficacy evaluation， this study addresses the limitations of TCM efficacy assessment methods in terms of individualization， holism， and complexity representation. Drawing on the concepts and methodologies of evidence-based medicine and systems biology， this paper proposes a new evaluation path by integrating multidisciplinary technologies such as big data， artificial intelligence （AI）， omics techniques， and bioinformatics， and encompassing from foundational data， individualized evaluation， and mechanistic analysis to evidence translation. The path first integrates real-world data， multi-omics profiling， and dynamic monitoring via smart devices to construct a high-dimensional dynamic data foundation. Subsequently， leveraging this foundation， it combines digital twins， dynamic symptom networks， and reinforcement learning to develop a dynamic efficacy evaluation method based on individual self-reference， enabling a shift from group mean comparisons to individual potential outcome comparisons. Furthermore， adopting the systems biology paradigm， it employs dynamic omics monitoring and deep learning models to dissect the synergistic mechanisms of TCM compound prescriptions from network regulation， emergent effects， and dynamic evolution dimensions. Finally， it enhances real-world evidence strength through target trial emulation and causal inference， achieving model iteration via incremental learning. This path aims to advance efficacy evaluation from "point validation" to "systematic characterization" and from "outcome assessment" to "process mechanism elucidation，" providing methodological support for the modernization of TCM.

OBJECTIVES: This study aimed to investigate the association between temporomandibular disorder (TMD) and insomnia using a two-sample Mendelian randomization (MR) approach. METHODS: Bidirectional MR analyses of two samples, TMD (n=377 277) and insomnia (n=375 359), were performed using genome-wide association study statistics published in the FinnGen database. Instrumental variables were first screened, and then inverse variance weighting (IVW) and MR-Egger were used as the main-effect assessment methods. Weighted median, weighted mode, and simple mode served as supplementary methods. We used IVW and MR-Egger to test for heterogeneity, as well as MR-Egger intercepts to assess the single nucleotide polymorphism (SNP) potential level of multiplicity effects. Sensitivity analyses were conducted based on leave-one-out to identify potentially influential SNPs. All analyses were conducted by using the two-sample MR R package and were considered statistically significant when P<0.05. RESULTS: MR analysis showed the presence of TMD on insomnia (OR=1.089, 95%CI: 1.017-1.166, P=0.014). Meanwhile, no effect of insomnia on TMD (OR=0.996, 95%CI: 0.964-1.029, P=0.816) was found. The sensitivity-analysis showed that no heterogeneity existed (P>0.05), and the presence of horizontal pleiotropy was not detected (P>0.05). Leave-one-out sensitivity analysis showed no single SNP, which may affect the causal relation. All findings indicated that the causal relationship between TMD and insomnia was not significantly affected by any individual SNP and that IV did not bias the results. CONCLUSIONS Results of MR analyses showed that TMD is a risk factor for insomnia, whereas insomnia is not a risk factor for TMD.
Humans ; Sleep Initiation and Maintenance Disorders/genetics* ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; Temporomandibular Joint Disorders/complications* ; Genome-Wide Association Study

Autism spectrum disorder(ASD) is a neurodevelopmental disorder, and social impairment was one of the core symptoms of ASD, which can seriously affects the social life of patients.The pathogenesis of social impairment in ASD is unclear and it may involves many brain abnormalities.The related theories and hypotheses are numerous and there is no unified conclusion. Studies have shown that the cerebellum has extensive connections with brain networks and is involved in the regulation of social cognition, but its role in ASD has not been fully emphasized.The structural and functional abnormalities of the cerebellar-cortex (CC) loop in ASD patients can lead to language communication disorders, empathy disorders, difficulties in interpreting social cues, abnormal social reward processing and emotional regulation disorders, which are closely related to ASD social impairment. Noninvasive brain stimulation of the superficial cerebellum can improve the abnormal CC circuit in ASD patients, and the cerebellum can be considered as a target for the treatment of social disorders in ASD in the future.Based on the clinical and basic researches on social impairment in ASD in recent years, this article reviews the relevant manifestations of disorders which cerebellar and CC circuit involved, aiming to promote the development of related research in the future.

Objective::To report a fetus with ARCN1-related syndrome caused by a novel de novo heterozygous variant, highlighting the importance of early genetic diagnosis in prenatal care. Methods::The clinical and genetic data of a fetus with a complex combination of clinical signs and a novel de novo heterozygous variant were collected and have been summarized in this study. The potential pathogenic variant was identified throughout the whole exome sequencing and the effects of candidate variants were further validated by a minigene splicing assay. Results::Prenatal systematic ultrasound detected fetal growth restriction. Genetic analysis identified a novel de novo heterozygous variant within the ARCN1 gene—c.1241 +5G>A-located in intron 8. In vitro minigene splicing assays demonstrated that the variant led to two abnormal transcripts. The longer transcript retained 189 base pairs of intron 8, resulting in a truncated protein of 414 amino acids (p.Ser415*). The shorter transcript involved exon 8 skippings, producing a truncated protein of 407 amino acids (p.Ile378Serfs*31). Conclusion::A novel de novo heterozygous variant of the ARCN1 gene, namely NM_001655.5: c.1241 +5G>A, was discovered and identified in a fetus with rhizomelic short stature, microretrognathia, and developmental delays.

Objective::To evaluate the diagnostic efficacy and clinical application of the Obstetrical Chinese Disseminated Intravascular Coagulation (DIC) Scoring System (OCDSS).Methods::This study is a retrospective study that collected 1063 cases from Wuhan Union Hospital, Yichang Central People’s Hospital, and the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture between July 2017 and June 2024. These cases were divided into DIC and non-DIC groups based on score standard. Diagnosis of DIC, the rate of hysterectomy, neonatal mortality, and severe asphyxia are the main outcome measures. All the laboratory indicators are all determined by clinical laboratory department of the hospital. Data were expressed as mean ± standard deviation or median (interquartile range) and frequencies. Independent sample t-test or non-parametric test were used to compare measurement data, while the chi-square test was used for count data. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to test the predictive accuracy. Using univariate and multivariate logistic regression analysis to study the high-risk factors. P < 0.050 indicates a statistical significance. Results::Of 1063 participants in this study, 29 participants (2.73%) were diagnosed with obstetrical DIC by OCDSS score standard, and all the participants were diagnosed as DIC with underlying disease. When the Takao, Clark, and Erez score standard is the "gold standard", the OCDSS score standard always shows good sensitivity and specificity, with all the AUC over 0.75. OCDSS score standard also has better predictive of hysterectomy (68.18%, 91.07%, 0.872), severe neonatal asphyxia and death (79.17%, 75.07%, 0.842) than the other three score standards. All the indicators included in the OCDSS score standard contributed to the DIC diagnosis (all the P < 0.001). The indicators in the DIC group were more abnormal than the non-DIC group (all the P < 0.001). Conclusion::OCDSS is a first score standard, especially for pregnancies, it considers the underlying disease, clinical symptoms, and laboratory results. This score system shared a good diagnosis performance for DIC in the Chinese population and may help clinicians make timely decisions.

The pathogenesis of painful diabetic peripheral neuropathy(PDPN)is very complicated and tricky treat,which seriously affects the physical and mental health of patients.TCM has certain advantages in treating PDPN,but lacks theoretical guidance centered on pathogenesis.The dynamic evolution of the pathogenesis of PDPN fits the theory of"deficient-qi induced stagnation".PDPN is mainly characterized by pain,with prolonged pain entering the collaterals.This article discussed the pathogenesis of PDPN from the theory of"deficient-qi induced stagnation"based on collateral disease.Among them,the"deficient qi"is mainly responsible for the deficiency of qi,blood,yin and yang,and the collaterals are not be nourished;"stagnation"includes the pathological state of qi stagnation,phlegm and stasis caused by the abnormal movement of qi,blood and body fluid,and the obstruction of collaterals."Deficient qi"and"stagnation"interact with each other to promote the progress of PDPN.The article concluded that the key point of treatment is to regulate the deficiency qi(tonify deficiency)and remove stagnation and clear collaterals(smooth the stagnation),which could provide a new diagnosis and treatment idea and theoretical basis for the clinical differentiation and treatment of PDPN.

Objective:To explore the value of three-dimensional automatic right ventricular quantitive analysis（3D Auto RVQ）technology in predicting the improvement of left ventricular ejection fraction（LVEF）in patients with heart failure with reduced ejection fraction（HFrEF）.Methods:A retrospective analysis was conducted on 89 HFrEF patients admitted to the Cardiology Department of Central China Fuwai Hospital of Zhengzhou University from April 2022 to June 2024. All patients received medication treatment and were further divided into heart failure with improved ejection fraction（HFimpEF）group and non HFimpEF group based on changes detected by echocardiography in LVEF after treatment. The clinical data，biological indicators，and medication treatment status of patients were collected，routine echocardiographic parameters and right ventricular strain parameters were measured，3D right ventricular ejection fraction（3D-RVEF），3D right ventricular stroke volume index（3D-RVSVI），3D right ventricular end-diastolic volume index（3D-RVEDVI），3D right ventricular end-systolic volume index（3D-RVESVI），3D tricuspid annular plane systolic excursion（3D-TAPSE），and 3D right ventricular fractional area change（3D-RVFAC）were measured using 3D Auto RVQ technology. The differences of the above parameters between the two groups were compared. The ROC curve was used to analyze the predictive efficiency of right ventricular parameters for HFimpEF，and the area under ROC curve（AUC）was calculated and compared. Logistic regression models were used to analyze the predictive value of right ventricular parameters for HFimpEF.Results:Compared with the non HFimpEF group，the HFimpEF group had a younger age，shorter heart failure course，a smaller proportion of males，New York Heart Association（NYHA）functional class ≥Ⅲ，and patients with concomitant coronary heart disease. The baseline LVEF，absolute value of two dimensional right ventricular global longitudinal strain（2D-RVGLS），3D-RVEF，3D-TAPSE，and 3D-RVSVI were higher in the HFimpEF group（all P<0.05）. ROC curve analysis showed that the AUC of 3D-RVEF for predicting HFimpEF was 0.858，and the predictive efficiency was higher than other right ventricular parameters. According to the Yoden index，the optimal cutoff value for predicting HFimpEF based on 3D-RVEF was 36.2%，with a corresponding sensitivity of 84.0% and specificity of 75.0%. After adjusting for clinical and other echocardiographic parameters，the logistic regression model showed that 3D-RVEF was an independent predictor of HFimpEF（ OR=1.435，95% CI=1.145-1.800， P<0.05）. Conclusions:The 3D-RVEF evaluated by 3D Auto RVQ technology has high predictive value for HFimpEF，which can provide a reference for clinical treatment，thereby improving the prognosis of HFrEF patients.

Objective: To investigate the self-monitoring blood pressure behavior and its influencing factors among residents in Jiangsu Province, so as to provide the basis for strengthening proactive blood pressure monitoring among residents. Methods: Permanent residents aged 35-75 years in six counties (cities, districts), Jiangsu Province, were selected using the stratified cluster sampling method in 2023. Data on basic information, disease history, and self-monitoring blood pressure behavior were collected, height and weight were measured to calculate the body mass index (BMI); and blood glucose and lipid levels were measured. Self-monitoring blood pressure behavior was defined as having measured blood pressure at least once in the past three months. Factors affecting self-monitoring blood pressure behavior were identified using a multivariable logistic regression model. Results: A total of 12 475 residents were surveyed, including 5 748 males and 6 727 females, with a male-to-female ratio of 1∶1.17. There were 3 855 residents aged 45-<55 years (30.90%) and 5 511 residents who had self-monitoring blood pressure behaviors (44.18%). Multivariable logistic regression analysis showed that the residents who were males (OR=1.167, 95%CI: 1.081-1.261), lived in rural areas (OR=1.430, 95%CI: 1.321-1.547), aged 45-75 years (45-<55 years, OR=1.384, 95%CI: 1.241-1.543; 55-<65 years, OR=1.397, 95%CI: 1.243-1.570; 65-75 years, OR=1.196, 95%CI: 1.049-1.363), had an annual household income ≥30 000 yuan (30 000-<60 000 yuan, OR=1.190, 95%CI: 1.072-1.321; 60 000-<110 000 yuan, OR=1.330, 95%CI: 1.191-1.485; ≥110 000 yuan, OR=1.746, 95%CI: 1.536-1.984), were overweight (OR=1.170, 95%CI: 1.070-1.280) or obese (OR=1.248, 95%CI: 1.120-1.391), were unaware (OR=1.221, 95%CI: 1.103-1.353) or aware (OR=3.937, 95%CI: 3.575-4.335) of having hypertension, were aware of having diabetes (OR=1.538, 95%CI: 1.354-1.749), and aware of having dyslipidemia (OR=1.265, 95%CI: 1.106-1.447) were more likely to have self-monitoring blood pressure behaviors. Conclusions Among the residents aged 35-75 years in Jiangsu Province, 44.18% had self-monitoring blood pressure behavior. Gender, place of residence, age, annual household income, BMI, hypertension, diabetes, and dyslipidemia were identified as influencing factors for self-monitoring blood pressure behavior.

Objective:To study the epidemic characteristics and clinical symptoms of patients with Hashimoto's thyroiditis (HT) in Shandong Province, and to provide a basis for further optimizing the clinical treatment strategies for HT.Methods:Data on HT patients admitted to Shandong Provincial Center for Disease Control and Prevention from January 2018 to December 2023 were collected. A retrospective analysis was conducted to analyze their epidemiological characteristics, clinical symptoms, and auxiliary examination results.Results:A total of 192 HT patients' data were included, comprising 42 males (21.87%) and 150 females (78.13%). The average age of patients was 40.38 years old, ranging from 9 to 74 years old. Most patients resided in urban areas (129 cases, 67.19%). HT cases occurred throughout the year in every mouth, with higher incidence in June (32 cases, 16.7%) and July (20 cases, 10.4%), lower incidence in March (8 cases, 4.2%) and April (10 cases, 5.2%), and sporadic cases in other months. Based on clinical manifestations, among all HT patients, there were 66 cases (34.38%) of Hashitoxicosis type, 11 cases (5.73%) of pseudothyrotoxicosis type, 7 cases (3.65%) of exophthalmic type, 5 cases (2.60%) of subacute thyroiditis-like type, 3 cases (1.56%) of juvenile type, 35 cases (18.23%) of fibrous type, 39 cases (20.31%) of thyroid adenoma or carcinoma type, and 26 cases (13.54%) of other autoimmune diseases type. Based on disease progression, among all HT patients, there were 61 cases (31.77%) in the hyperthyroid phase, 16 cases (8.33%) in the hyperthyroid-hypothyroid coexisting phase, and 115 cases (59.90%) in the hypothyroid phase. Based on clinical symptoms, among all HT patients,there were 78 cases(40.62%) of neck mass symptoms, 101 cases (52.60%) of digestive system symptoms, and 95 cases (49.48%) of low metabolic symptoms. Laboratory tests revealed that 144 cases had elevated levels of both thyroglobulin antibody and thyroid peroxidase antibody. Color ultrasound examination showed strip-like echoes in the thyroid in 99 cases (51.56%) and grid-like echoes in 43 cases (22.40%). After treatment with antithyroid drugs or appropriate thyroid hormone supplementation, all 192 HT patients experienced symptom relief.Conclusions:HT patients in Shandong Province were predominantly female and urban residents. Common clinical symptoms included anterior neck swelling, constipation, fever, and weight gain. Early detection, diagnosis, and treatment could delay disease progression.