Novel SLC12A3 gene mutations and clinical characteristics in two pedigrees with Gitelman syndrome.

OBJECTIVE: Gitelman syndrome (GS) is an autosomal recessive tubulopathy resulting from inactivating mutations in the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride cotransporter (NCC). To date, more than 500 mutations have been identified in the SLC12A3 gene. In this study, we identified two new mutations in the SLC12A3 gene in two Chinese GS pedigrees. DESIGN, PATIENTS AND MEASUREMENTS: The clinical characteristics and laboratory examination of two suspected GS patients in our hospital were analyzed. In addition, two pedigrees including 11 members and 2 patients underwent SLC12A3 gene analysis. RESULTS: Both patients were middle-aged women with characteristics of hypokalemic metabolic alkalosis, hypomagnesemia, low level of urinary calcium and the elevated levels of renin-angiotensin-aldosterone system. So, they were clinically diagnosed as GS. Patient 2 also had type 2 diabetes and Graves' disease. Both patients were found to carry two mutations of SLC12A3 gene by Sanger direct sequencing, which were all compound heterozygous mutations. We identified three mutations in these two Chinese GS pedigrees, one of which was c.179C>T (Thr60Met). The novel c.2159G>T (p. Gly720Val) and c.2675T>C (p. Leu892Pro) mutations were strongly predicted to be pathogenic using four network programs-Polyphen-2, SIFT, Mutation Taster and LRT. CONCLUSIONS: We identified two novel SLC12A3 genetic variant [c.2159G>T (p.Gly720Val) and c.2675T>C (p.Leu892Pro)] in two Chinese GS pedigrees. The discovery of new mutations has enriched the spectrum of SLC12A3 genotypes.

Actinomyces meyeri-induced brain abscess in pregnancy: a case report.

BACKGROUND: Brain abscesses can occur when suppurative, bacterial or protozoan infections spread to the brain. Here, we report a rare case of Actinomyces meyeri-induced brain abscess in a pregnant woman. CASE PRESENTATION: We present the case of a 38-years-old primipara admitted to the emergency department at our hospital with a 4-day history of fever and vomiting. The symptoms worsened rapidly during the 8 h prior to admission, and the patient experienced a sudden loss of consciousness 4 h before arrival to the unit. Brain magnetic resonance imaging revealed abnormal signals in the right parietal-temporal lobe, suggesting the possibility of abscess rupture into the ventricle and sulcus. Right lateral ventricle compression and midline structure deviation to the left were noted. A right temporal-occipital mass with midline shift was detected. Emergency procedures were promptly performed, including craniotomy, removal of the right temporal-occipital mass, decompressive craniectomy, implantation of an intracranial pressure monitoring device, and external ventricular drainage. Cerebrospinal fluid culture indicated infection with Actinomyces meyeri. After administration of antibiotics, including linezolid and meropenem injections, along with treatments to decrease intracranial pressure, the patient's vital signs stabilized. However, the patient developed hydrocephalus, requiring placement of a hydrocephalus shunt several months later. Throughout this period, the patient remained in a coma vigil state, and labor was induced for the fetus. CONCLUSIONS: Although the patient did not present with any apparent predisposing causes for brain abscess, a scout view of CT revealed dental caries. In addition, the occurrence of the brain abscess may have been influenced by the hormonal changes during pregnancy, including increased secretion of estrogen and progesterone, as well as decreased immune function. Early diagnosis and intervention are crucial in such cases. Therefore, it is recommended to seek early medical attention if symptoms such as fever, vomiting, and changes in mental state occur during pregnancy, as the prognosis for both the mother and infant is poor once the abscess ruptures.

Case report: isolated prevotella intermedia causing intracranial infection detected using metagenomic next generation sequencing.

BACKGROUND: Isolated Prevotella intermedia, a rare gram-negative, rod-shaped, anaerobic bacterium, is rarely detected in clinical practice. It has been associated with infections of the oral cavity and female genital tract, but has never been detected in cerebrospinal fluid (CSF) of patients in China. Accurate detection of causative pathogens is still an arduous task owing to the difficult conditions of anaerobic bacterial culture. Isolated Prevotella intermedia can be detected by metagenomic next generation sequencing (mNGS) of the CSF. Correct diagnosis and antibiotic treatment can help patients avoid life-threatening events. CASE PRESENTATION: Herein, we describe the case of a 64-year-old Chinese woman who presented with typical features of meningoencephalitis. Routine CSF culture failed to identify the causative pathogen. Isolated Prevotella intermedia was detected by mNGS, and the patient was treated with antibacterial agents including ceftriaxone, vancomycin, moxifloxacin, meropenem, metronidazole, and linezolid. The patient underwent surgical treatment for abscess of left frontal parietal lobe, which was observed on magnetic resonance imaging (MRI) and was suspected to be caused by Prevotella intermedia. It was further confirmed that it was a secondary infection from the oral cavity, and the possible etiology might have been dental surgery. Treatment was rendered to the patient based on metagenomic test result, and her condition improved after two months. CONCLUSIONS: This case highlights the role of mNGS in accurate diagnosis of patients with central nervous system infection. In particular, mNGS can be used to identify rare pathogens and confirm the diagnosis in patients with unknown etiology.

Association of Tim-4 expression in monocyte subtypes with clinical course and prognosis in acute ischemic stroke patients.

Background: It has been proven that T cell immunoglobin and mucin domain (Tim)-4 and monocytes (Mo) are involved in regulation of immunity, which is important for the recovery of acute ischemic stroke (AIS).Methods: In this study, the expression of Tim-4 in both circulating Mo subtypes and plasma in 32 consecutive AIS patients and 32 control patients was assessed to determine their correlation with the clinical course and prognosis of AIS.Results: It was found that, compared to the control patients, the percentage of Tim-4 expression in overall Mo, classical Mo and non-classical Mo was significantly elevated after 2 and 5 days of stroke (p < 0.05), while it was promoted from 0 to 10 days of stoke in intermediate Mo (p < 0.05). Furthermore, Tim-4 expressions in non-classical Mo and intermediate Mo were obviously correlated with National Institutes of Health Stroke Scale (NIHSS) scores at 2 days of stroke (r = 0.351, p = 0.048; r = 0.358, p = 0.044, respectively). In poor outcome (PO) patients, the expression of Tim-4 in non-classical Mo was remarkably promoted at 2 days of stroke in comparison with non-PO patients (p < 0.05). More importantly, our results revealed a positive correlation between Tim-4 expression in non-classical Mo and interleukin (IL)-6 plasma levels in AIS patients without infection.Conclusion: In summary, our findings proved that Tim-4 expression in non-classical Mo could be an appropriate target for the prediction of the clinical course and prognosis in AIS patients.

MRI radiomics combined with machine learning for diagnosing mild cognitive impairment: a focus on the cerebellar gray and white matter.

Objective: Mild Cognitive Impairment (MCI) is a recognized precursor to Alzheimer's Disease (AD), presenting a significant risk of progression. Early detection and intervention in MCI can potentially slow disease advancement, offering substantial clinical benefits. This study employed radiomics and machine learning methodologies to distinguish between MCI and Normal Cognition (NC) groups. Methods: The study included 172 MCI patients and 183 healthy controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, all of whom had 3D-T1 weighted MRI structural images. The cerebellar gray and white matter were segmented automatically using volBrain software, and radiomic features were extracted and screened through Pyradiomics. The screened features were then input into various machine learning models, including Random Forest (RF), Logistic Regression (LR), eXtreme Gradient Boosting (XGBoost), Support Vector Machines (SVM), K Nearest Neighbors (KNN), Extra Trees, Light Gradient Boosting Machine (LightGBM), and Multilayer Perceptron (MLP). Each model was optimized for penalty parameters through 5-fold cross-validation to construct radiomic models. The DeLong test was used to evaluate the performance of different models. Results: The LightGBM model, which utilizes a combination of cerebellar gray and white matter features (comprising eight gray matter and eight white matter features), emerges as the most effective model for radiomics feature analysis. The model demonstrates an Area Under the Curve (AUC) of 0.863 for the training set and 0.776 for the test set. Conclusion: Radiomic features based on the cerebellar gray and white matter, combined with machine learning, can objectively diagnose MCI, which provides significant clinical value for assisted diagnosis.

MicroRNA-25-5p negatively regulates TXNIP expression and relieves inflammatory responses of brain induced by lipopolysaccharide.

Sepsis is one of the most common causes of death in patients suffering from severe infection or injury. Currently, a specific effective therapy remains to be established. In the present study, miR-25-5p, miR-105, miR-106b-5p, miR-154-3p, miR-20b-5p, miR-295-3p, miR-291-3p, miR-301b, miR-352, and miR-93-5p were predicted to target TXNIP mRNA from the databases of miRDB, Targetscan, and microT-CDS. The luciferase reporter assay confirmed that miR-25-5p negatively regulates TXNIP expression. The ELISA analyses and western blotting demonstrated that miR-25-5p downregulated the production of IL-1ß, IL-6, IL-8, and TNF-α in lipopolysaccharide (LPS)-stimulated cells or rats, as well as the protein levels of TXNIP, NLRP3, and cleaved caspase-1. In addition, miR-25-5p increased the cell viability and decreased the apoptosis in LPS-stimulated CTX TNA2 cells and reduced the abnormal morphology of the brain in LPS-stimulated rats. Besides, miR-25-5p decreased the relative mean fluorescence intensity of DCF in LPS-stimulated CTX TNA2 cell, apoptosis, and protein levels of MnSOD and catalase in LPS-stimulated brains. These findings indicate that miR-25-5p downregulated LPS-induced inflammatory responses, reactive oxygen species production, and brain damage, suggesting that miR-25-5p is a candidate treatment for septic encephalopathy.

Endovascular treatment of traumatic oronasal hemorrhage complicated with progressive acute epidural hemorrhage: A case report.

RATIONALE: Massive oronasal hemorrhage can induce shock and is life-threatening, and early endovascular treatment is the standard of care. Few studies have reported the use of endovascular treatment for acute epidural hemorrhage (AEDH). However, endovascular treatment of oronasal hemorrhage complicated by AEDH has not yet been demonstrated. Many patients with a low to moderate volume of oronasal hemorrhage complicated by AEDH choose conservative treatment but eventually undergo craniotomy due to increased intracranial hemorrhage. PATIENT CONCERNS: A 32-year-old man presented to our hospital with traumatic oronasal hemorrhage complicated by AEDH after being hit by a blunt object. DIAGNOSIS: Computerized tomography suggested progressive AEDH and multiple basilar skull fractures. Emergency cerebral angiography showed rupture of the right middle meningeal artery and a branch of the left maxillary artery causing AEDH and oronasal hemorrhage. INTERVENTIONS: The patient underwent interventional embolization to treat the ruptured intracranial vessels. OUTCOMES: After 23 days, cranial computerized tomography showed remarkable absorption of the right frontal epidural hematoma, with the patient having a Glasgow Coma Scale score of 15. LESSONS: This case provides a valuable treatment for patients with AEDH complicated with oronasal hemorrhage, early interventional embolization may be an effective treatment strategy to prevent further complications and ensure a good patient outcome.

Vertebral artery dissection induced lateral medullary syndrome characterized with severe bradycardia: a case report and review of the literature.

BACKGROUND: Lateral medullary syndrome is the most common type of brainstem infarction. Lateral medullary syndrome results in damage to the corresponding cranial nerve nuclei and the nucleus tractus solitarius, with vertigo, ipsilateral ataxia, crossed sensory disturbances, Horner's sign, bulbar palsy, and other underlying symptoms or signs. However, cases with cardiac arrhythmia and other autonomic dysfunctions as the primary manifestations are less common. Clinically, sudden death occasionally occurs in patients with lateral medullary syndrome, which may be associated with severe cardiac arrhythmia. These patients may suffer in life-threatening arrhythmia and even cardiac arrest, and vital signs should be closely monitored to prevent sudden death. In younger patients, vertebral artery dissection is the most common cause. CASE DESCRIPTION: Here, we present a case of lateral medullary syndrome caused by vertebral artery dissection with severe bradycardia. The patient was a 49-year-old man who was admitted with "sudden onset of numbness in the left limbs and right side of the face for 1 hour". Electrocardiogram (ECG) monitoring showed a repeated heart rate decrease to as low as 23 beats/min, followed by a gradual increase in heart rate to 35-55 beats/min after 2-3 seconds. Head magnetic resonance imaging (MRI) examination revealed right dorsolateral cerebral infarction of the medulla oblongata. Digital subtraction angiography (DSA) revealed a right vertebral artery dissecting aneurysm. We performed an emergency placement of a temporary pacemaker, followed by conservative treatment with platelet aggregation inhibitors, vascular softening agents and improved collateral circulation. Elective spring coil embolization of the vertebral artery dissecting aneurysm and stent implantation were performed. At outpatient follow-up, the patient had a good prognosis. CONCLUSIONS: Clinical management of patients with lateral medullary syndrome should be prioritized, with close cardiac monitoring at the early stages of observation and pacemaker placement and tracheal intubation as required to prevent adverse events.

Serum Exosomal microRNA-27-3p Aggravates Cerebral Injury and Inflammation in Patients with Acute Cerebral Infarction by Targeting PPARγ.

Acute cerebral infarction (ACI) possesses high mortality. Exosomes present in serum have potential application value in ACI diagnosis. This study investigated the mechanism of serum exosomes in ACI. Serum exosomes isolated from ACI patients and normal people were identified and then injected into the established middle cerebral artery occlusion (MCAO) rat model to evaluate cerebral injury and inflammation. Exosomal microRNA (miR)-27-3p expression was detected and interfered to analyze rat cerebral inflammation. The binding relationship between miR-27-3p and PPARγ was predicted and verified. The lipopolysaccharide (LPS)-treated microglia model was established and intervened with miR-27-3p to detect PPARγ, Iba-1, and inflammation-related factor expressions. After overexpressing PPARγ, rat cerebral inflammation was evaluated. The clinical significance of serum exosomal miR-27-3p in ACI was evaluated. Serum exosomes from ACI patients caused exacerbated MCAO rat cerebral injury and poor behavior recovery, as well as promoted cerebral inflammation. Serum exosomal miR-27-3p deepened rat brain inflammation. miR-27-3p targeted PPARγ to promote microglia activation and inflammation-related factor expressions in MCAO rats, and overexpressing PPARγ attenuated MCAO rat cerebral inflammation. Serum exosomal miR-27-3p promised to be a biomarker for ACI. We proved that serum exosomes from ACI patients aggravated ACI patient cerebral inflammation via the miR-27-3p/PPARγ axis.

The effect of metformin on carotid intima-media thickness (CIMT): A systematic review and meta-analysis of randomized clinical trials.

Metformin administration has been reported to influence the carotid intima-media thickness (CIMT) in humans. However, since previously conducted studies have yielded inconsistent results, the exact effect of metformin on CIMT remains unclear. Causes that could lead to inconsistency in reported research could be the duration and dose of the intervention, as well as the sample size. To address this inconsistency, we conducted a systematic review and meta-analysis to evaluate the influence of metformin on CIMT in human subjects. We identified eligible studies by searching several electronic databases (EMBASE, PubMed-MEDLINE, Web of Science and Google Scholar) up to December 12, 2019. Data were pooled using the random-effects model. Combining data from 1087 participants (9 studies), our meta-analysis revealed that the administration of metformin resulted in a significant reduction in CIMT (WMD = -0.049 mm; 95% CI: -0.095, -0.004). Stratified analyses showed that an intervention lasting ≥12 months (WMD: -0.084 mm, 95% CI: -0.145, -0.024) and an intake of metformin ≤1500 mg/day (WMD: -0.081 mm, 95% CI: -0.132, -0.029) resulted in a significantly greater reduction in CIMT. However, an intervention duration of less than 12 months and an intake of metformin ˃1500 mg/day yielded no significant effects on CIMT. The results of the current study confirm that metformin administration is associated with a significant reduction in CIMT. Taking into account that CIMT reflects the burden of atherosclerosis, the clinical utility of metformin might also be related to its anti-atherogenic effects.

Assessment of sleep quality using cardiopulmonary coupling analysis in patients with Parkinson's disease.

Objectives: To assess the sleep quality of patients with Parkinson's disease (PD) and evaluate the effect of cardiopulmonary coupling (CPC) analysis on sleep quality and its correlation with subjective complaints in patients with PD. Methods: Our study included 42 patients with PD and 30 healthy controls. CPC analysis and the Pittsburgh Sleep Quality Index (PSQI) were used to evaluate the sleep quality of subjects. Results: High-frequency coupling (HFC) and sleep efficiency were significantly lower in the PD than in the control group, whereas very low-frequency coupling (VLFC) and sleep latency were significantly higher in the PD than in the control group. PSQI scores were significantly higher in the PD than in the control group (all p < .05). The PSQI score showed a negative correlation with the HFC ratio in the PD group (r = -.478, p = .001). Factors related to the occurrence of PD with poor sleep quality were the unified Parkinson's disease rating scale (UPDRS) score and nocturia. Conclusions: The sleep quality of patients with PD was generally decreased. CPC analysis can reflect the subjective sleep quality of patients with PD and serve as an effective sleep monitoring tool.

Meta-Analysis of Visual Evoked Potential and Parkinson's Disease.

BACKGROUND: Previous studies suggested that visual evoked potential (VEP) was impaired in patients with Parkinson's disease (PD), but the results were inconsistent. METHODS: We conducted a systematic review and meta-analysis to explore whether the VEP was significantly different between PD patients and healthy controls. Case-control studies of PD were selected through an electronic search of the databases PubMed, Embase, and the Cochrane Central Register of Controlled Trials. We calculated the pooled weighted mean differences (WMDs) and 95% confidence intervals (CIs) between individuals with PD and controls using the random-effects model. RESULTS: Twenty case-control studies which met our inclusion criteria were included in the final meta-analysis. We found that the P100 latency in PD was significantly higher compared with healthy controls (pooled WMD = 6.04, 95% CI: 2.73 to 9.35, P=0.0003, n=20). However, the difference in the mean amplitude of P100 was not significant between the two groups (pooled WMD = 0.64, 95% CI: -0.06 to 1.33, P=0.07) based on 10 studies with the P100 amplitude values available. CONCLUSIONS: The higher P100 latency of VEP was observed in PD patients, relative to healthy controls. Our findings suggest that electrophysiological changes and functional defect in the visual pathway of PD patients are important to our understanding of the pathophysiology of visual involvement in PD.

Tim-4 expression increases in ischemic stroke patients and is associated with poor outcome.

T cell immunoglobin and mucin domain (Tim)-4 on monocytes is involved in immune regulation. Here, we investigated Tim-4 expression on circulating monocytes and in plasma of ischemic stroke. Tim-4 expression was significantly increased on day 2 and day 5 after stroke. Furthermore, stroke severity was positively correlated with Tim-4 expression on monocytes or in plasma. Increased Tim-4 expression was related to stroke associated with infection (SAI) on day 2. Up-regulated Tim-4 expression on monocytes or in plasma on day 2 was a risk predictor of outcome. Our findings suggest that Tim-4 can act as a prognostic biomarker of ischemic stroke.

Peripheral lung adenocarcinomas harboring epithelial growth factor receptor mutations with microRNA-135b overexpression are more likely to invade visceral pleura.

Lung adenocarcinoma, characterized by its early and aggressive local invasion and high metastatic potential, is the most frequently observed histological type of non-small-cell lung cancer (NSCLC). Visceral pleural invasion (VPI) caused by peripheral lung adenocarcinomas is closely associated with the poor prognosis of patients with NSCLC. The association between VPI and some clinicopathological characteristics has been observed in the past few decades. However, the molecular mechanism of VPI in lung adenocarcinomas is unknown. In the present, the expression level of microRNA (miR-)135b and epidermal growth factor receptor (EGFR) mutations using the reverse transcription-quantitative polymerase chain reaction and DNA sequencing, respectively. In addition, the present study aimed at exploring the association between the miR-135b level, EGFR mutations and VPI in peripheral lung adenocarcinoma. The results of the present study demonstrated that miR-135b was significantly upregulated in lung adenocarcinoma compared with adjacent normal tissue and positively associated EGFR mutations in peripheral lung adenocarcinoma. Furthermore, it was identified that lung adenocarcinomas with EGFR mutations and miR-135b overexpression were more likely to invade visceral pleura. Taken together, these findings indicate that miR-135b overexpression is positively associated with mutations to EGFR, which may promote the development of peripheral lung adenocarcinomas by the formation of VPI. This indicates that the two factors may serve as prognostic markers and molecular targets for the treatment of peripheral lung adenocarcinomas.