Intelligent devices for assessing essential tremor: a comprehensive review.

Essential tremor (ET) stands as the most prevalent movement disorder, characterized by rhythmic and involuntary shaking of body parts. Achieving an accurate and comprehensive assessment of tremor severity is crucial for effectively diagnosing and managing ET. Traditional methods rely on clinical observation and rating scales, which may introduce subjective biases and hinder continuous evaluation of disease progression. Recent research has explored new approaches to quantifying ET. A promising method involves the use of intelligent devices to facilitate objective and quantitative measurements. These devices include inertial measurement units, electromyography, video equipment, and electronic handwriting boards, and more. Their deployment enables real-time monitoring of human activity data, featuring portability and efficiency. This capability allows for more extensive research in this field and supports the shift from in-lab/clinic to in-home monitoring of ET symptoms. Therefore, this review provides an in-depth analysis of the application, current development, potential characteristics, and roles of intelligent devices in assessing ET.

[Research progress in pathogenesis and traditional Chinese medicines treatment of ischemic stroke-related headache].

Headache is a common clinical complication of ischemic stroke. As a precursor of stroke, headache occurs repeatedly in the convalescent period of ischemic stroke, leading to secondary stroke and seriously hindering patients' rehabilitation. Currently, it is believed that the pathogenesis of ischemic stroke-related headache is associated with the abnormal release of vasoactive substances, high platelet aggregation, and stimulation of intracranial pain-sensitive structures. The active ingredients in traditional Chinese medicines(TCM) with the effects of activating blood to resolve stasis and clearing heat to release exterior can protect brain tissue and relieve headache by reducing the release of inflammatory cytokines, alleviating antioxidant stress, inhibiting neuronal apoptosis and so on. This paper introduces the research progress in the potential mechanism and TCM treatment of ischemic stroke-related headache, aiming to provide reference for further research and drug development of this complication.

Cerebrospinal Fluid Changes and Clinical Features of Neurosyphilis Compared with Latent Syphilis Infection in the Central Nervous System: A Cross-Sectional Study.

Purpose: At present, there is no gold standard or unified standard for the diagnosis of neurosyphilis, and the rate of misdiagnosis is high. The diagnosis of neurosyphilis is still challenging. This study compared the clinical indicators between neurosyphilis and latent syphilis infection in the central nervous system. The purpose of this study was to provide evidence for the differential diagnosis and prognosis of patients with neurosyphilis and latent syphilis infection of the central nervous system. Methods: The clinical data of 59 patients with neurosyphilis and 30 patients with latent syphilis infection in the nervous system from 2008 to 2021 were analyzed. The cerebrospinal fluid and serum biochemical markers were evaluated for all patients. Results: CSF-nucleated cells, CSF-TRUST, CSF-totalprotein and CSF-IgG (P<0.001) were significantly different between neurosyphilis and latent syphilis infection in the central nervous system. CSF-TRUST titer was positively correlated with D-D concentration (r = 0.274, P < 0.05), sodion (r =0.251, P < 0.05), respectively. Glucose concentration is the most unreliable in the diagnosis of neurosyphilis (AUC=0.445, P=0.395), and TRUST combined with nucleated cells and total protein is the most accurate in the diagnosis of neurosyphilis (AUC=0.989, P<0.001). Conclusion: The combination of TRUST, nucleated cell count and totalprotein detection in CSF can distinguish the patients with neurosyphilis and latent syphilis infection in the central nervous system, which has a significant diagnostic value.

Ubiquitin ligase RNF125 targets PD-L1 for ubiquitination and degradation.

As a critical immune checkpoint molecule, PD-L1 is expressed at significantly higher levels in multiple neoplastic tissues compared to normal ones. PD-L1/PD-1 axis is a critical target for tumor immunotherapy, blocking the PD-L1/PD-1 axis is recognized and has achieved unprecedented success in clinical applications. However, the clinical efficacy of therapies targeting the PD-1/PD-L1 pathway remains limited, emphasizing the need for the mechanistic elucidation of PD-1/PD-L1 expression. In this study, we found that RNF125 interacted with PD-L1 and regulated PD-L1 protein expression. Mechanistically, RNF125 promoted K48-linked polyubiquitination of PD-L1 and mediated its degradation. Notably, MC-38 and H22 cell lines with RNF125 knockout, transplanted in C57BL/6 mice, exhibited a higher PD-L1 level and faster tumor growth than their parental cell lines. In contrast, overexpression of RNF125 in MC-38 and H22 cells had the opposite effect, resulting in lower PD-L1 levels and delayed tumor growth compared with parental cell lines. In addition, immunohistochemical analysis of MC-38 tumors with RNF125 overexpression showed significantly increased infiltration of CD4+, CD8+ T cells and macrophages. Consistent with these findings, analyses using The Cancer Genome Atlas (TCGA) public database revealed a positive correlation of RNF125 expression with CD4+, CD8+ T cell and macrophage tumor infiltration. Moreover, RNF125 expression was significantly downregulated in several human cancer tissues, and was negatively correlated with the clinical stage of these tumors, and patients with higher RNF125 expression had better clinical outcomes. Our findings identify a novel mechanism for regulating PD-L1 expression and may provide a new strategy to increase the efficacy of immunotherapy.

Do Not Ignore Tuberculosis of the Parotid Gland When Meeting Obvious Infiltration of Neutrophils in a Suspicious Swelling by FNAC.

Parotid gland tuberculosis constantly results in unnecessary medical examinations and surgery because of its similarities in the presentation to neoplasms of the parotid gland. Although parotid gland involvement is extremely rare even in tuberculosis-endemic countries, accurate diagnosis of this clinical entity is of great significance because tuberculous parotitis can be successfully treated medically without surgical therapy. Fine needle aspiration cytology (FNAC) and molecular identification of the parotid swellings are efficient in making a rapid diagnosis. Herein, we report an early misdiagnosis of malignancy from a renal transplantation patient on long-term immunologic inhibitor therapy, who ultimately proved to have tuberculosis of the parotid gland by FNAC and molecular identification. The aim of this study is to describe and analyze the etiologic characteristics, epidemiology, clinical presentations, diagnostic methods, histopathologic findings, and pathogenic mechanisms of these rare infections.

GP73 is a TBC-domain Rab GTPase-activating protein contributing to the pathogenesis of non-alcoholic fatty liver disease without obesity.

The prevalence of non-obese nonalcoholic fatty liver disease (NAFLD) is increasing worldwide with unclear etiology and pathogenesis. Here, we show GP73, a Golgi protein upregulated in livers from patients with a variety of liver diseases, exhibits Rab GTPase-activating protein (GAP) activity regulating ApoB export. Upon regular-diet feeding, liver-GP73-high mice display non-obese NAFLD phenotype, characterized by reduced body weight, intrahepatic lipid accumulation, and gradual insulin resistance development, none of which can be recapitulated in liver-GAP inactive GP73-high mice. Common and specific gene expression signatures associated with GP73-induced non-obese NAFLD and high-fat diet (HFD)-induced obese NAFLD are revealed. Notably, metformin inactivates the GAP activity of GP73 and alleviates GP73-induced non-obese NAFLD. GP73 is pathologically elevated in NAFLD individuals without obesity, and GP73 blockade improves whole-body metabolism in non-obese NAFLD mouse model. These findings reveal a pathophysiological role of GP73 in triggering non-obese NAFLD and may offer an opportunity for clinical intervention.

CXCL8, CXCL9, and CXCL10 serum levels increase in syphilitic patients with seroresistance.

BACKGROUND: Recently, the rise of syphilitic seroresistance brings great confusion to the clinical diagnosis and treatment of syphilis, and no clear diagnostic marker has been found to distinguish syphilitic seroresistance from other progression of syphilis. This study evaluated the serum chemokines levels of CCL2, CXCL8, CXCL9, and CXCL10 and its correlation with blood routine, coagulation, and biochemical indexes in seroresistant syphilitic patients. METHOD: Serum levels of chemokines were quantitatively determined by Flow Cytometric Bead Array (CBA). The results expressed in pg/ml. Clinical parameters were detected and analyzed according to the clinical laboratory standards. A correlation analysis was subsequently performed. RESULTS: The seroresistant syphilitic patients increased significantly serum chemokines levels of CXCL8 (***p < 0.001), CXCL9 (***p < 0.001), and CXCL10 (**p < 0.01) when compared to noninfected individuals, but the CCL2 was not statistically significant, and serum CXCL8 shows a strong association with platelets (r = 0.51, **p = 0.004) and serum CXCL10 was significantly positively related to INR levels (r = 0.49, **p = 0.007). CONCLUSION: Increasing serum abnormalities in CXCL8, CXCL9, and CXCL10 level combining with platelets of peripheral blood and plasmatic INR in syphilis patients may be helpful for the diagnosis of serofast state.

A rare case of pulmonary nocardiosis comorbid with Sjogren's syndrome.

BACKGROUND: Nocardia is an opportunistic pathogen, which occurs in patients with autoimmune diseases and immune dysfunction, and can cause bacteremia and other life-threatening complications. The clinical manifestations of Nocardia pneumonia are similar to tuberculous and other clinical common bacterial pneumonia, but its antibacterial treatments are different and detection methods are unique, which may lead patients to suffer for many years due to clinical misdiagnosis and missed diagnosis. METHODS: Imaging and laboratory examinations were performed for preliminary diagnosis, and next-generation sequencing was used to identify the exact species type of Nocardia in the bronchoalveolar lavage fluid (BALF) of the patient. RESULTS: Imaging and laboratory parameters preliminarily implied that the patient was infected with Nocardia with Sjogren's syndrome (SS), and NGS showed that the strain was N. terpenica. CONCLUSIONS: Accurate etiological diagnosis and corresponding antibiotics are key to improve the prognosis of pulmonary nocardiosis in this case. Nocardia pneumonia is rare in clinical practice; it is of great medical significance to improve the understanding of pulmonary nocardiosis.

HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry.

Responsible for the ongoing coronavirus disease 19 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through binding of the viral spike protein (SARS-2-S) to the cell-surface receptor angiotensin-converting enzyme 2 (ACE2). Here we show that the high-density lipoprotein (HDL) scavenger receptor B type 1 (SR-B1) facilitates ACE2-dependent entry of SARS-CoV-2. We find that the S1 subunit of SARS-2-S binds to cholesterol and possibly to HDL components to enhance viral uptake in vitro. SR-B1 expression facilitates SARS-CoV-2 entry into ACE2-expressing cells by augmenting virus attachment. Blockade of the cholesterol-binding site on SARS-2-S1 with a monoclonal antibody, or treatment of cultured cells with pharmacological SR-B1 antagonists, inhibits HDL-enhanced SARS-CoV-2 infection. We further show that SR-B1 is coexpressed with ACE2 in human pulmonary tissue and in several extrapulmonary tissues. Our findings reveal that SR-B1 acts as a host factor that promotes SARS-CoV-2 entry and may help explain viral tropism, identify a possible molecular connection between COVID-19 and lipoprotein metabolism, and highlight SR-B1 as a potential therapeutic target to interfere with SARS-CoV-2 infection.

Epidemiology and molecular identification of mycoplasma pneumoniae associated with respiratory infections in Zhejiang province, China, 2008-2017.

INTRODUCTION: Mycoplasma pneumoniae is a common cause of respiratory infections in humans. The aim of this study was to investigate the infection of Mycoplasma pneumoniae (MP) in patients with acute respiratory tract infections in Zhejiang Province from 2008 to 2017, and to provide evidence for the early diagnosis and prevention of MP pneumonia. METHODS: MP-DNA was detected in nasopharyngeal swabs of patients with acute respiratory tract infection by real-time fluorescent PCR (TaqMan probe). Statistical analysis and epidemiological investigation were carried out on the test results. RESULTS: There were 10 296 patients with acute respiratory tract infection in Zhejiang Provincial People's Hospital from 2008 to 2017, including 4387 females and 5909 males. A total of 1251 MP-DNA-positive patients were detected, with a total positive rate of 12.2% (1251/10296). Among 1251 patients with MP infection, 571 were female positive, with an average positive rate of 13.0% (571/4387), and 680 were male positive, with a positive rate of 11.5% (680/5909). From 2008 to 2017, the positive rates were 22.8% (33 cases), 20.9% (211 cases), 20.9% (350 cases), 5.5% (70 cases), 11.7% (136 cases), 15.2% (190 cases), 7.8% (94 cases), 5.9% (62 cases), 7.8% (56 cases), and 6.0% (49 cases), respectively. Of 1251 MP-DNA-positive patients, 1243 (99.4%) were younger than 18 years old. CONCLUSIONS: Mycoplasma pneumoniae infection mainly occurs from late summer to autumn and in the age below 18 years, suggesting that early diagnosis and prevention of MP infection in adolescents should be emphasized.

The Mitochondrial Protein MAVS Stabilizes p53 to Suppress Tumorigenesis.

Recent reports have shown the critical role of the mitochondrial antiviral signaling (MAVS) protein in virus-induced apoptosis, but the involvement of MAVS in tumorigenesis is still poorly understood. Herein, we report that MAVS is a key regulator of p53 activation and is critical for protecting against tumorigenesis. We find that MAVS promotes p53-dependent cell death in response to DNA damage. MAVS interacts with p53 and mediates p53 mitochondrial recruitment under genotoxic stress. Mechanistically, MAVS inhibits p53 ubiquitination by blocking the formation of the p53-murine double-minute 2 (MDM2) complex, leading to the stabilization of p53. Notably, compared with their wild-type littermates, MAVS knockout mice display decreased resistance to azoxymethane (AOM) or AOM/dextran sulfate sodium salt (DSS)-induced colon cancer. MAVS expression is significantly downregulated in human colon cancer tissues. These results unveil roles for MAVS in DNA damage response and tumor suppression.

RNF34 functions in immunity and selective mitophagy by targeting MAVS for autophagic degradation.

Viral infection triggers the formation of mitochondrial antiviral signaling protein (MAVS) aggregates, which potently promote immune signaling. Autophagy plays an important role in controlling MAVS-mediated antiviral signaling; however, the exact molecular mechanism underlying the targeted autophagic degradation of MAVS remains unclear. Here, we investigated the mechanism by which RNF34 regulates immunity and mitophagy by targeting MAVS. RNF34 binds to MAVS in the mitochondrial compartment after viral infection and negatively regulates RIG-I-like receptor (RLR)-mediated antiviral immunity. Moreover, RNF34 catalyzes the K27-/K29-linked ubiquitination of MAVS at Lys 297, 311, 348, and 362 Arg, which serves as a recognition signal for NDP52-dependent autophagic degradation. Specifically, RNF34 initiates the K63- to K27-linked ubiquitination transition on MAVS primarily at Lys 311, which facilitates the autophagic degradation of MAVS upon RIG-I stimulation. Notably, RNF34 is required for the clearance of damaged mitochondria upon viral infection. Thus, we elucidated the mechanism by which RNF34-mediated autophagic degradation of MAVS regulates the innate immune response, mitochondrial homeostasis, and infection.

Tumor Microenvironment Regulation by the Endoplasmic Reticulum Stress Transmission Mediator Golgi Protein 73 in Mice.

The unfolded protein response (UPR) signal in tumor cells activates UPR signaling in neighboring macrophages, which leads to tumor-promoting inflammation by up-regulating UPR target genes and proinflammatory cytokines. However, the molecular basis of this endoplasmic reticulum (ER) stress transmission remains largely unclear. Here, we identified the secreted form of Golgi protein 73 (GP73), a Golgi-associated protein functional critical for hepatocellular carcinoma (HCC) growth and metastasis, is indispensable for ER stress transmission. Notably, ER stressors increased the cellular secretion of GP73. Through GRP78, the secreted GP73 stimulated ER stress activation in neighboring macrophages, which then released cytokines and chemokines involved in the tumor-associated macrophage (TAM) phenotype. Analysis of HCC patients revealed a positive correlation of GP73 with glucose-regulated protein 78 (GRP78) expression and TAM density. High GP73 and CD206 expression was associated with poor prognosis. Blockade of GP73 decreased the density of TAMs, inhibited tumor growth, and prolonged survival in two mouse HCC models. Conclusion: Our findings provide insight into the molecular mechanisms of extracellular GP73 in the amplification and transmission of ER stress signals.