Based on the holistic view of "spleen-vessels-heart-spirit" system， this article explores the pathogenesis and progression of atrial fibrillation. It is proposed that the onset of atrial fibrillation is due to failure of the spleen to transport and disharmony of blood vessels； phlegm and blood stasis obstructing the collaterals and damage to the heart structure are the basis of its pathogenesis； the unclear mind and disorder of body and spirit are the causes of its progression. Based on the characteristics of pathological changes in different stages of the disease， it is proposed that early treatment should focus on restoring the middle jiao， clearing and promoting blood vessels， using modified Yigong Powder （异功散）； during the progression of the disease， treatment should remove blood stasis and phlegm， nourish heart and protect the pulse， using self-prescribed modified Mengshi Tongmai Decoction （礞石通脉汤）； meanwhile， calming mind and stabilizing palpitations， and regulating spirit should be sequentially incorporated， with self-prescribed Jiazao Ningmai Decoction （甲枣宁脉汤） or Shenying Dingji Decoction （参英定悸汤） and modified as appropriate. Clinical treatment should focus on the whole disease course of atrial fibrillation， implementing stage-based treatments to enable early intervention and holistic regulation.

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc), primarily manifesting as motor dysfunctions such as resting tremor, muscle rigidity, and bradykinesia. According to the classical model of basal ganglia motor control, approximately half of the medium spiny neurons (MSNs) in the striatum are D1-MSNs, which constitute the direct pathway. These neurons express D₁-dopamine receptor (D₁R) and substance P, and they mainly participate in the selection, initiation, and execution of movements. The other half are D2-MSNs, which constitute the indirect pathway. These neurons express D₂-dopamine receptor (D₂R) and adenosine 2A receptors and are involved in inhibiting unnecessary movements or terminating ongoing movements, thereby adjusting movement sequences to perform more precise motor behaviors. The direct pathway in the striatum modulates the activity of motor cortex neurons by exciting D1-MSNs through neurotransmitters such as glutamate (Glu), allowing the motor cortex to send signals more freely to the motor system, thus facilitating the generation and execution of specific motor behaviors. Studies using D1-Cre and D2-Cre mice with neurons labeled for D₁R and D₂R have shown that both types of neurons are involved in the execution of movements, with D1-MSNs participating in movement initiation and D2-MSNs in inhibiting actions unrelated to the target movement. These findings suggest that the structural and functional plasticity of D1-MSNs and D2-MSNs in the basal ganglia circuitry enables motor learning and behavioral regulation. Additionally, when SNpc DA neurons begin to degenerate, D1-MSNs are initially affected but do not immediately cause motor impairments. In contrast, when D2-MSNs undergo pathological changes, they are first activated by upstream projecting neurons, leading to the inhibition of most motor behaviors and resulting in motor dysfunction. Therefore, it is hypothesized that motor impairments such as bradykinesia and initiation difficulties are more closely related to the functional activity of D2-MSNs. The extracellular signal-regulated kinase (Erk)/mitogen-activated protein kinase (MAPK) signaling pathway has been identified as a critical modulator in the pathophysiology of PD. Recent findings indicate that Erk/MAPK signaling pathway can mediate DA and Glu signaling in the central nervous system, maintaining normal functional activity of striatal MSNs and influencing the transmission of motor control signals. Within this complex regulatory network, the Erk/MAPK signaling pathway plays a key role in transmitting motor information to downstream neurons, regulating normal movements, avoiding unnecessary movements, and finely tuning motor behaviors. Our laboratory’s previous research found that 4 weeks of aerobic exercise intervention improved motor dysfunction in PD mice by inhibiting the Erk1/2 signaling upstream of striatal MSNs, primarily involving the Erk1/2 signaling in D2-MSNs rather than D1-MSNs. This review summarizes the neurobiological mechanisms of Erk/MAPK signaling pathway in D2-MSNs for the prevention and treatment of motor dysfunction in PD. By exploring the role of this signaling pathway in regulating motor abnormalities and preventing motor dysfunction in the central nervous system of PD, this review provides new theoretical perspectives for related mechanistic research and therapeutic strategies.

Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.

Atherosclerosis is a complex pathological condition resulting from lipid deposition， chronic inflammatory responses， and fibrosis， with a prolonged disease course and multifactorial etiology. Based on the traditional Chinese medicine （TCM） theory of accumulation syndrome， atherosclerosis can be classified under this category， with its pathogenesis involving phlegm， blood stasis， deficiency， and accumulation. This paper proposed a stage-based intervention strategy using the four therapeutic principles of "attacking， supplementing， dispersing， dissipating"， and divided into six stages based on the pathological progression， including the stage of accumulation before formation， the stage of accumulation already formed， the stage of nucleus accumulation， the stage of nucleus accumulation decay， the stage of nucleus accumulation consolidation， and the stage of severe stenosis of nucleus. At different stages， the intervention focuses on reinforcing healthy qi and consolidating the root， tonifying the kidneys and spleen， dispersing and removing turbidity， removing phlegm stagnation， promoting qi circulation， dispersing accumulations and removing stasis， attacking accumulation and expelling stasis， directing the turbid downward and dispersing accumulation， and treatment would be adjusted based on specific symptoms， which provides a theoretical framework for the prevention and treatment of atherosclerosis with TCM.

Premature ejaculation refers to a sexual dysfunction in which men experience a short intravaginal ejaculation latency and a lack of control over ejaculation during sexual activity. The onset of this condition is often accompanied by anxiety and depression, which can seriously affect the quality of the patient′s sexual life and the relationship between partners. Based on the "integration of body and spirit" theory in traditional Chinese medicine, our team believes that this condition is a comorbidity of physical and spiritual factors. We propose that the core pathogenesis of this disease lies in the "loss of form and essence, impairment of spirit, and depression of the mind, "while the primary treatment principle involves "nourishing form and regulating spirit." As a result, a new diagnosis and treatment approach of "four-dimensional integration" is summarized in this study. The disease is treated through the four dimensions of shape, body, spirit, and emotion. Traditional Chinese medicine is used to adjust the shape in cases where the physical form is damaged. For individuals with depression of heart and liver qi, the treatment focuses on soothing the heart and smoothing liver qi, and the modified Wangyou Powder and Xuanzhi Decoction is used. In cases where the heart and kidney function are compromised, the treatment involves nourishing both the heart and kidney while restoring interaction between the heart and the kidney, and modified Jihuo Yansi Elixir is used. To reduce the sensitivity of the glans penis, the patient′s body is washed with a traditional Chinese medicine formula, and a delicate fumigation formula is decocted for external washing. For those who are not in tune with their god, psychological counseling can be used to regulate their spirit and advocate "self-partner" and psychotherapy. If there are issues with intimacy, partners should focus on cooperating during foreplay, sexual intercourse, and post-coital interactions. Overall, the treatment aims to harmonize the body and spirit, addressing both physical and psychological factors through a comprehensive, multi-dimensional approach. This method provides new perspectives and ideas for the clinical diagnosis and treatment of this condition.

Background: Hearing loss (HL) is one of the most common sensory disorders, affecting over 5-8% of the world's population. Approximately half of HL cases are attributed to genetic factors. In hereditary deafness, about 75-80% is inherited through autosomal recessive inheritance, and common pathogenic genes include GJB2 and SLC26A4. Pathogenic variants in the SLC26A4gene are the leading cause of hereditary hearing loss in humans, second only to the GJB2 gene. Variants in the SLC26A4gene cause hearing loss, which can be non-syndromic autosomal recessive deafness (DFNB4, OMIM #600791) associated with enlarged vestibular aqueduct (EVA) or Pendred syndrome (Pendred, OMIM #605646). DFNB4 is characterized by sensorineural hearing loss combined with EVA or less common cochlear malformation defect. Pendred syndrome is characterized by bilateral sensorineural hearing loss with EVA and an iodine defect that can lead to thyroid goiter. Currently, it is known that EVA is associated with variants in the SLC26A4 gene and is a penetrant feature of SLC26A4-related HL. Predominant mutations in these genes differ significantly across populations. For instance, predominant SLC26A4 mutations differ among populations, including p.T416P and c.1001G>A in Caucasians, p.H723R in Japanese and Koreans, and c.919-2A>G in Han Taiwanese and Han Chinese. On the other hand, there has been no study of hearing loss related to SLC26A4 gene variants among Mongolians, which is the basis of our research. Aim: We aimed to identify the characteristics of the SLC26A4 gene variants in Mongolian people with Enlarged vestibular aqueduct and Mondini malformation. Materials and Methods: In 2022-2024, We included 13 people with hearing loss and enlarged vestibular aqueduct, incomplete cochlea (1.5 turns of the cochlea with cystic apex- incomplete partition type II- Mondini malformation) were examined by CT scan of the temporal bone in our study. WES (Whole exome sequencing) analysis was performed in the Genetics genetic-laboratory of the National Taiwan University Hospital. Results: Genetic analysis revealed 26 confirmed pathogenic variants of bi-allelic SLC26A4 gene of 8 different types in 13 cases, and c.919-2A>G variant was dominant with 46% (12/26) in allele frequency, and c.2027T>A (p.L676Q) variant 19% (5/26), c.1318A>T(p.K440X) variant 11% (3/26), c.1229C>T (p.T410M) variant 8% (2/26) ) , c.716T>A (p.V239D), c.281C>T (p.T94I), c.1546dupC, and c.1975G>C (p.V659L) variants were each 4% (1/26)- revealed. Two male children, 11 years old (SLC26A4: c.919-2A>G) and 7 years old (SLC26A4: c.919-2A>G:, SLC26A4: c.2027T>A (p.L676Q))had history of born normal hearing and progressive hearing loss. Conclusions 1. 26 variants of bi-allelic SLC26A4 gene mutation were detected in Mongolian people with EVA and Mondini malformation, and c.919-2A>G was the most dominant allele variant, and rare variants such as c.1546dupC, c.716T>A (p.V239D) were detected. 2. Our study shows that whole-exome sequencing (WES) can identify gene mutations that are not detected by polymerase chain reaction (PCR) or NGS analysis.

Objective: Machine learning (ML) has been reported to have better predictive capability than traditional statistical techniques. The aim of this study was to assess the efficacy of ML algorithms and logistic regression (LR) for predicting depressive symptoms during the COVID-19 pandemic. Methods: Analyses were carried out in a national cross-sectional study involving 21,916 participants. The ML algorithms in this study included random forest (RF), support vector machine (SVM), neural network (NN), and gradient boosting machine (GBM) methods. The performance indices were sensitivity, specificity, accuracy, precision, F1-score, and area under the receiver operating characteristic curve (AUC). Results: LR and NN had the best performance in terms of AUCs. The risk of overfitting was found to be negligible for most ML models except for RF, and GBM obtained the highest sensitivity, specificity, accuracy, precision, and F1-score. Therefore, LR, NN, and GBM models ranked among the best models. Conclusion Compared with ML models, LR model performed comparably to ML models in predicting depressive symptoms and identifying potential risk factors while also exhibiting a lower risk of overfitting.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

This case report explores the therapeutic potential of theta burst stimulation (TBS) for cognitive enhancement in individuals with brain injuries. The study presents a 38-year-old male suffering from an organic mental disorder attributed to a traumatic brain injury (TBI), who demonstrated notable cognitive improvements following an intensive TBS protocol targeting the left dorsal lateral prefrontal cortex. The treatment led to significant enhancements in impulse control, irritability, and verbal comprehension without adverse effects. Neuropsychological assessments and brain imaging post-intervention revealed improvements in short-term memory, abstract reasoning, list-generating fluency, and increased cerebral blood flow in the prefrontal cortex. These findings suggest that TBS, by promoting neural plasticity and reconfiguring neural networks, offers a promising avenue for cognitive rehabilitation in TBI patients. Further research is warranted to optimize TBS protocols and understand the mechanisms underlying its cognitive benefits.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.