Epilepsy affects over 50 million people worldwide. Drug-resistant epilepsy (DRE) accounts for up to a third of these cases, and neuro-inflammation is thought to play a role in such cases. Despite being a long-debated issue in the field of DRE, the mechanisms underlying neuroinflammation have yet to be fully elucidated. The pro-inflammatory microenvironment within the brain tissue of people with DRE has been probed using single-cell multimodal transcriptomics. Evidence suggests that inflammatory cells and pro-inflammatory cytokines in the nervous system can lead to extensive biochemical changes, such as connexin hemichannel excitability and disruption of neurotransmitter homeostasis. The presence of inflammation may give rise to neuronal network abnormalities that suppress endogenous antiepileptic systems. We focus on the role of neuroinflammation and brain network anomalies in DRE from multiple perspectives to identify critical points for clinical application. We hope to provide an insightful overview to advance the quest for better DRE treatments.
Humans ; Drug Resistant Epilepsy/metabolism* ; Neuroinflammatory Diseases/immunology* ; Animals ; Brain/pathology* ; Nerve Net/pathology*

Objective: To explore the application of manual screening collaborated with the Artificial Intelligence TPS-Assisted Cytologic Screening System in urinary exfoliative cytology and its clinical values. Methods: A total of 3 033 urine exfoliated cytology samples were collected at the Henan People's Hospital, Capital Medical University, Beijing, China. Liquid-based thin-layer cytology was prepared. The slides were manually read under the microscope and digitally presented using a scanner. The intelligent identification and analysis were carried out using an artificial intelligence TPS assisted screening system. The Paris Report Classification System of Urinary Exfoliated Cytology 2022 was used as the evaluation standard. Atypical urothelial cells and even higher grade lesions were considered as positive when evaluating the recognition sensitivity, specificity, and diagnostic accuracy of artificial intelligence-assisted screening systems and human-machine collaborative cytologic screening methods in urine exfoliative cytology. Among the collected cases, there were also 1 100 pathological tissue controls. Results: The accuracy, sensitivity and specificity of the AI-assisted cytologic screening system were 77.18%, 90.79% and 69.49%; those of human-machine coordination method were 92.89%, 99.63% and 89.09%, respectively. Compared with the histopathological results, the accuracy, sensitivity and specificity of manual reading were 79.82%, 74.20% and 95.80%, respectively, while those of AI-assisted cytologic screening system were 93.45%, 93.73% and 92.66%, respectively. The accuracy, sensitivity and specificity of human-machine coordination method were 95.36%, 95.21% and 95.80%, respectively. Both cytological and histological controls showed that human-machine coordination review method had higher diagnostic accuracy and sensitivity, and lower false negative rates. Conclusions: The artificial intelligence TPS assisted cytologic screening system has achieved acceptable accuracy in urine exfoliation cytologic screening. The combination of manual screening and artificial intelligence TPS assisted screening system can effectively improve the sensitivity and accuracy of cytologic screening and reduce the risk of misdiagnosis.
Humans ; Artificial Intelligence ; Urothelium/pathology* ; Cytodiagnosis ; Epithelial Cells/pathology* ; Sensitivity and Specificity ; Urologic Neoplasms/urine*

Male ; Humans ; Prostate/pathology* ; Adenocarcinoma/pathology* ; Giant Cells/pathology*

OBJECTIVE: To examine the impact of COVID-19 pandemic on the epidemic status of imported malaria and national malaria control program in China, so as to provide insights into post-elimination malaria surveillance. METHODS: All data pertaining to imported malaria cases were collected from Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region during the period from January 1, 2018 through December 31, 2021. The number of malaria cases, species of malaria parasites, country where malaria parasite were infected, diagnosis and treatment after returning to China, and response were compared before (from January 1, 2018 to January 22, 2020) and after the COVID-19 pandemic (from January 23, 2020 to December 31, 2021). RESULTS: A total of 2 054 imported malaria cases were reported in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region during the period from January 1, 2018 to December 31, 2021, and there were 1 722 cases and 332 cases reported before and after the COVID-19 pandemic, respectively. All cases were reported within one day after definitive diagnosis. The annual mean number of reported malaria cases reduced by 79.30% in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region after the COVID-19 pandemic (171 cases) than before the pandemic (826 cases), and the number of monthly reported malaria cases significantly reduced in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region since February 2020. There was a significant difference in the constituent ratio of species of malaria parasites among the imported malaria cases in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region before and after the COVID-19 pandemic (χ² = 146.70, P < 0.05), and P. falciparum malaria was predominant before the COVID-19 pandemic (72.30%), while P. ovale malaria (44.28%) was predominant after the COVID-19 pandemic, followed by P. falciparum malaria (37.65%). There was a significant difference in the constituent ratio of country where malaria parasites were infected among imported malaria cases in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region before and after the COVID-19 pandemic (χ² = 13.83, P < 0.05), and the proportion of malaria cases that acquired Plasmodium infections in western Africa reduced after the COVID-19 pandemic that before the pandemic (44.13% vs. 37.95%; χ² = 4.34, P < 0.05), while the proportion of malaria cases that acquired Plasmodium infections in eastern Africa increased after the COVID-19 pandemic that before the pandemic (9.58% vs. 15.36%; χ² = 9.88, P = 0.02). The proportion of completing case investigation within 3 days was significantly lower after the COVID-19 pandemic than before the pandemic (96.69% vs. 98.32%; χ²= 3.87, P < 0.05), while the proportion of finishing foci investigation and response within 7 days was significantly higher after the COVID-19 pandemic than before the pandemic (100.00% vs. 98.43%; χ² = 3.95, P < 0.05). CONCLUSIONS The number of imported malaria cases remarkably reduced in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region of China during the COVID-19 pandemic, with a decreased proportion of completing case investigations within 3 days. The sensitivity of the malaria surveillance-response system requires to be improved to prevent the risk of secondary transmission of malaria due to the sharp increase in the number of imported malaria cases following the change of the COVID-19 containment policy.
Humans ; Pandemics ; China/epidemiology* ; Incidence ; COVID-19/epidemiology* ; Malaria/prevention & control* ; Malaria, Falciparum/epidemiology*

Adipose tissue is a promising target for treating obesity and metabolic diseases. However, pharmacological agents usually fail to effectively engage adipocytes due to their extraordinarily large size and insufficient vascularization, especially in obese subjects. We have previously shown that during cold exposure, connexin43 (Cx43) gap junctions are induced and activated to connect neighboring adipocytes to share limited sympathetic neuronal input amongst multiple cells. We reason the same mechanism may be leveraged to improve the efficacy of various pharmacological agents that target adipose tissue. Using an adipose tissue-specific Cx43 overexpression mouse model, we demonstrate effectiveness in connecting adipocytes to augment metabolic efficacy of the β ₃-adrenergic receptor agonist Mirabegron and FGF21. Additionally, combing those molecules with the Cx43 gap junction channel activator danegaptide shows a similar enhanced efficacy. In light of these findings, we propose a model in which connecting adipocytes via Cx43 gap junction channels primes adipose tissue to pharmacological agents designed to engage it. Thus, Cx43 gap junction activators hold great potential for combination with additional agents targeting adipose tissue.

Aluminum ; Bone Diseases ; Fluorides ; Follow-Up Studies ; Humans ; Radiography

Coal ; Coal Mining ; Dust/analysis* ; Humans ; Male ; Miners ; Occupational Diseases ; Occupational Exposure/adverse effects*

Background/Aims: To determine the value of salivary pepsin in discriminating sub-types of gastroesophageal reflux disease (GERD) and GERD-related disorders. Methods: Overall, 322 patients with different sub-types of GERD and 45 healthy controls (HC) were studied. All patients took Gastroesophageal Reflux Disease Questionnaire (GerdQ) and underwent endoscopy and 24-hour esophageal pH monitoring and manometry. Salivary pepsin concentration (SPC) was detected by using colloidal gold double-antibody immunological sandwich assay. Oral esomeprazole treatment was administrated in the patients with non-erosive reflux disease (NERD) and extra-esophageal symptoms (EES). Results: Compared to HC, patients with erosive esophagitis, NERD, EES, EES plus typical GERD symptoms, or Barrett’s esophagus had a higher prevalence of saliva and SPC (all P < 0.001). There was no significant difference in the positive rate for pepsin in patients with functional heartburn or GERD with anxiety and depression, compared to HC. After esomeprazole treatment, the positive rate and SPC were significantly reduced in NERD (both P < 0.001) and in EES (P = 0.001 and P = 0.002, respectively). Of the 64 NERD patients, 71.9% (n = 46) were positive for salivary pepsin, which was significantly higher than the rate (43.8%, n = 28) of pathological acid reflux as detected by 24-hour esophageal pH monitoring (P = 0.002). Conclusions Salivary pepsin has an important significance for the diagnosis of GERD and GERD-related disorders. Salivary pepsin and 24-hour esophageal pH monitoring may complement with each other to improve the diagnostic efficiency.

BACKGROUND AND PURPOSE: Data on the association between calcium (Ca) and ischemic stroke are sparse and inconsistent. This study aimed to examine Ca intake and serum Ca levels in relation to risk of ischemic stroke. METHODS: The primary analysis included 19,553 participants from the Reasons for Geographic And Racial Differences in Stroke (REGARDS) study. A subcohort was randomly selected to create a case-cohort study (n=3,016), in which serum Ca levels were measured. Ischemic stroke cases were centrally adjudicated by physicians based on medical records. Cox proportional hazards regression for the cohort and weighted Cox proportional hazard regression with robust sandwich estimation method for the case-cohort analysis with adjustment for potential confounders were performed. RESULTS: During a mean 8.3-year follow-up, 808 incident cases of ischemic stroke were documented. Comparing the highest quintile to the lowest, a statistically significant inverse association was observed between total Ca intake and risk of ischemic stroke (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.55 to 0.95; P(linear-trend)=0.183); a restricted cubic spline analysis indicated a threshold effect like non-linear association of total Ca intake with ischemic stroke (P(non-linear)=0.006). In the case-cohort, serum Ca was inversely associated with the risk of ischemic stroke. Compared to the lowest, the highest quintile of serum Ca had a 27% lower risk of ischemic stroke (HR, 0.73; 95% CI, 0.53 to 0.99; P(linear-trend)=0.013). Observed associations were mainly mediated by type 2 diabetes, hypertension, and cholesterol. CONCLUSIONS: These findings suggest that serum Ca has inverse and Ca intake has threshold effect like association with risk of ischemic stroke.
Calcium ; Cholesterol ; Cohort Studies ; Diabetes Mellitus ; Follow-Up Studies ; Hypertension ; Medical Records ; Methods ; Stroke