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Abstract Migraine is a common bi-directional comorbidity of epilepsy, indicating potential complex interactions between the two conditions. However, no previous studies have used brain morphology analysis to assess possible interactions between epilepsy and migraine. Voxel-based morphometry (VBM), surface-based morphometry (SBM), and structural covariance networks (SCNs) can be used to detect morphological changes with high accuracy. We recruited 30 individuals with epilepsy and comorbid migraine without aura (EM), along with 20 healthy controls (HC) and 30 epilepsy controls (EC) without migraine. We used VBM, SBM, and SCN analysis to compare differences in gray matter volume, cortical thickness, and global level and local level graph theory indexes between the EM, EC, and HC groups to investigate structural brain changes in the EM patients. VBM analysis showed that the EM group had gray matter atrophy in the right temporal pole compared with the HC group (p

Abstract Objectives Epilepsy and migraine are common chronic neurological disease. Epidemiologic studies and shared pathophysiology and treatment suggest that these two diseases overlap. However, migraine is often underestimated among patients with epilepsy. This study aimed to evaluate the prevalence of migraine and identify the related influencing factors among adult patients with epilepsy. Methods Adult patients with epilepsy were recruited at the outpatient epilepsy clinic of 13 tertiary hospitals in China from February to September 2022. ID Migraine questionnaire was applied to evaluate for migraine. Both univariable and multivariable logistic regression models were used to explore the influencing factors of migraine. Results A total of 1326 patients with epilepsy were enrolled in this study. The prevalence of migraine among patients with epilepsy was 19.2% (254/1326). In the multivariable analysis, being female (OR = 1.451, 95% CI: 1.068–1.975; p = 0.018), focal and focal to bilateral tonic–clonic seizures (OR = 1.583, 95% CI: 1.090–2.281; p = 0.015), and current seizure attack in the last 3 months (OR = 1.967, 95% CI: 1.282–3.063; p = 0.002) were the influencing factors for migraine. However,

Abstract Background Gynostemma pentaphyllum, an ancient Chinese herbal medicine, serves as a natural source of gypenosides with significant medicinal properties. Basic helix-loop-helix (bHLH) transcription factors play pivotal roles in numerous biological processes, especially in the regulation of secondary metabolism in plants. However, the characteristics and functions of the bHLH genes in G. pentaphyllum remain unexplored, and their regulatory role in gypenoside biosynthesis remains poorly elucidated. Results This study identified a total of 111 bHLH members in G. pentaphyllum (GpbHLHs), categorizing them into 26 subgroups based on shared conserved motif compositions and gene structures. Collinearity analysis illustrated that segmental duplications predominately lead to the evolution of GpbHLHs, with most duplicated GpbHLH gene pairs undergoing purifying selection. Among the nine gypenoside-related GpbHLH genes, two GpbHLHs (GpbHLH15 and GpbHLH58) were selected for further investigation based on co-expression analysis and functional prediction. The expression of these two selected GpbHLHs was dramatically induced by methyl jasmonate, and their nuclear localization was confirmed. Furthermore, yeast one-hybrid and dual-luciferase assays demonstrated that GpbHLH15 and GpbHLH58 could bind to the promoters of the gypenoside biosynthesis pathway genes, such as GpFPS1, GpSS1, and GpOSC1, and activate their promoter activity to varying degrees. Conclusions In conclusion, our findings provide a detailed analysis of the bHLH family and valuable insights into the potential use of GpbHLHs to enhance the accumulation of gypenosides in G. pentaphyllum.

Abstract Artificial intelligence provides an opportunity to try to redefine disease subtypes based on similar pathobiology. Using a machine-learning algorithm (Subtype and Stage Inference) with cross-sectional MRI from 296 individuals with focal epilepsy originating from the temporal lobe (TLE) and 91 healthy controls, we show phenotypic heterogeneity in the pathophysiological progression of TLE. This study was registered in the Chinese Clinical Trials Registry (number: ChiCTR2200062562). We identify two hippocampus-predominant phenotypes, characterized by atrophy beginning in the left or right hippocampus; a third cortex-predominant phenotype, characterized by hippocampus atrophy after the neocortex; and a fourth phenotype without atrophy but amygdala enlargement. These four subtypes are replicated in the independent validation cohort (109 individuals). These subtypes show differences in neuroanatomical signature, disease progression and epilepsy characteristics. Five-year follow-up observations of these individuals reveal differential seizure outcomes among subtypes, indicating that specific subtypes may benefit from temporal surgery or pharmacological treatment. These findings suggest a diverse pathobiological basis underlying focal epilepsy that potentially yields to stratification and prognostication – a necessary step for precise medicine.

The global health threat posed by carbapenem-resistant Klebsiella pneumoniae (CRKP) is exacerbated by the limited availability of effective treatments. Bacteriophages are promising alternatives to conventional antimicrobial agents. However, current phage databases are limited. Thus, identifying and characterizing new phages could provide biological options for the treatment of multi-drug resistant bacterial infections. Here, we report the characterization of a novel lytic phage, vB_KpnP_23, isolated from hospital sewage. This phage exhibited potent activity against carbapenemase-producing CRKP strains and was characterised by an icosahedral head, a retractable tail, and a genome comprising 40,987 base pairs, with a G + C content of 51 %. Capable of targeting and lysing nine different capsule types (K-types) of CRKP, including the clinically relevant ST11-K64, it demonstrated both high bacteriolytic efficiency and stability in various environmental contexts. Crucially, vB_KpnP_23 lacks virulence factors, antimicrobial resistance genes, or tRNA, aligning with the key criteria for therapeutic application. In vitro evaluation of phage-antibiotic combinations revealed a significant synergistic effect between vB_KpnP_23 and meropenem, levofloxacin, or amikacin. This synergy could lead to an 8-fold reduction in the minimum inhibitory concentration (MIC), suggesting that integrated treatments combining this phage with the aforementioned antibiotics may substantially enhance drug effectiveness. This approach not only extends the clinical utility of these antibiotics but also presents a strategic advance in combating antibiotic resistance. Specifically, it underscores the potential of phage-antibiotic combinations as a powerful tool in the treatment of infections caused by CRKP, offering a promising avenue to mitigate the public health challenges of antibiotic-resistant pathogens.

Abstract Purpose This study aimed to characterise the whole-genome structure of two clinical Klebsiella pneumoniae strains co-harbouring mcr-8.1 and tmexCD1-toprJ1, both resistant to colistin and tigecycline. Methods K. pneumoniae strains TGC-02 (ST656) and TGC-05 (ST273) were isolated from urine samples of different patients hospitalised at separate times in 2021. Characterisation involved antimicrobial susceptibility testing (AST), conjugation assays, whole-genome sequencing (WGS), and bioinformatics analysis. Comparative genomic analysis was conducted on mcr-8.1-carrying and tmexCD1-toprJ1-carrying plasmids. Results Both K. pneumoniae isolates displayed a multidrug-resistant phenotype, exhibiting resistance or reduced susceptibility to ampicillin, ampicillin/sulbactam, cefazolin, aztreonam, amikacin, gentamicin, tobramycin, ciprofloxacin, levofloxacin, nitrofurantoin, trimethoprim/sulfamethoxazole, apramycin, tigecycline and colistin. WGS analysis revealed that clinical strain TGC-02 carried the TmexCD1-toprJ1 gene on a 200-Kb IncFII/IncFIB-type plasmid, while mcr-8 was situated on a 146-Kb IncFII-type plasmid. In clinical strain TGC-05, TmexCD1-toprJ1 was found on a 300-Kb IncFIB/IncHI1B/IncR-type plasmid, and mcr-8 was identified on a 137-Kb IncFII/IncFIA-type plasmid. Conjugation experiments assessed the transferability of these plasmids. While transconjugants were not obtained for TGC-05 despite multiple screening with tigecycline or colistin, pTGC-02-tmex and pTGC-02-mcr8 from clinical K. pneumoniae TGC-02 demonstrated self-transferability through conjugation. Notably, the rearrangement of pTGC-02-tmex and pTGC-02-mcr8 via IS26-based homologous recombination was observed. Moreover, the conjugative and fusion plasmids of the transconjugant co-harboured the tmexCD1-toprJ1 gene cluster and mcr-8.1, potentially resulting from IS26-based homologous recombination. Conclusion The emergence of colistin- and tigecycline-resistant K. pneumoniae strains is concerning, and effective surveillance measures should be implemented to prevent further dissemination.

Abstract Objective Observational studies have shown an association between COVID‐19 and epilepsy. However, causality remains unproven. This study aimed to investigate the causative effect of genetically predicted COVID‐19 phenotypes on epilepsy risk using a two‐sample Mendelian randomization (MR) analysis. Methods We retrieved summary‐level datasets for three COVID‐19 phenotypes (COVID‐19 susceptibility, COVID‐19 hospitalization, and COVID‐19 severity) and epilepsy from the genome‐wide association studies conducted by the COVID‐19 Host Genetics Initiative (COVID‐19 HGI) and International League Against Epilepsy (ILAE) consortium, respectively. To analyze the final results, nine MR analytic methods were utilized. The inverse‐variance weighted (IVW) method was chosen as the primary approach for data analysis to evaluate the potential causal effect. Other MR analytic methods (MR‐Egger regression, weighted median estimator, mode based‐estimator, and MR‐PRESSO) were used as a supplement to IVW to ensure the robustness of the results. Results The IVW approach demonstrated no causal association between any genetically predicted COVID‐19 phenotype and the risk of epilepsy [COVID‐19 susceptibility: odds ratio (OR) = 0.99, 95% confidence interval (CI) = 0.86–1.14, p = 0.92; COVID‐19 hospitalization: OR = 1.00, 95% CI = 0.96–1.04, p = 0.95; COVID‐19 severity: OR = 0.99, 95% CI = 0.96–1.01, p = 0.25]. Other MR complementary methods revealed consistent results. Additionally, no evidence for heterogeneity and horizontal pleiotropy was found. Significance This MR study revealed no genetically predicted causal relationship between COVID‐19 phenotypes and epilepsy.

Abstract Neuro‐COVID, a condition marked by persistent symptoms post‐COVID‐19 infection, notably affects various organs, with a particular focus on the central nervous system (CNS). Despite scant evidence of SARS‐CoV‐2 invasion in the CNS, the increasing incidence of Neuro‐COVID cases indicates the onset of acute neurological symptoms early in infection. The Omicron variant, distinguished by heightened neurotropism, penetrates the CNS via the olfactory bulb. This direct invasion induces inflammation and neuronal damage, emphasizing the need for vigilance regarding potential neurological complications. Our multicenter study represents a groundbreaking revelation, documenting the definite presence of SARS‐CoV‐2 in the cerebrospinal fluid (CSF) of a significant proportion of Neuro‐COVID patients. Furthermore, notable differences emerged between RNA‐CSF‐positive and negative patients, encompassing aspects such as blood–brain barrier integrity, extent of neuronal damage, and the activation status of inflammation. Despite inherent limitations, this research provides pivotal insights into the intricate interplay between SARS‐CoV‐2 and the CNS, underscoring the necessity for ongoing research to fully comprehend the virus's enduring effects on the CNS. The findings underscore the urgency of continuous investigation Neuro‐COVID to unravel the complexities of this relationship, and pivotal in addressing the long‐term consequences of COVID‐19 on neurological health.

Abstract Headache is one of the most common symptoms of epilepsy comorbidities. However, the relationship between the epilepsy and headache still needs clarification. Previous studies mostly investigated the overall incidence and clinical features of the headache in patients with the epilepsy. Temporal lobe epilepsy (TLE) and juvenile myoclonic epilepsy (JME) are the common types of focal epilepsy and generalized epilepsy, respectively. Nevertheless, there was no study comparing the clinical features of headache between TLE and JME. This study aimed to analyze the headache features of these two types of epilepsy. Patients with either TLE or JME diagnosed with headache and referred to the West China Hospital of Sichuan University were consecutively recruited from June 2021 to June 2022. The duration of epilepsy was longer than 6 months in these patients. Data on headache and epilepsy were obtained through face-to-face questionnaires. The headache was classified according to the International Classification Headache Disorders-3rd edition (ICHD-III) criteria. χ2-test, t-test, rank-sum test, logistic regression modeling and Mann Whitney test were used to compare the clinical differences of the headache in TLE and JME. A total of 151 TLE patients and 30 JME patients were enrolled in this study. There was no significant difference in the family history of headache, epilepsy durations, headache types, proportion receiving analgesic therapy, the frequency of inter-ictal headache (inter-IH), and the quality of life in epilepsy -10 inventory (QOLIE-10) between the TLE and JME patients. Patients in the TLE group were significantly older (p = 0.004), and a lower percentage of them had a family history of epilepsy (p = 0.007) compared with the JME patients. The proportion of cases with refractory epilepsy was higher in the TLE group than that in the JME group (p

ABSTRACT Objective To assess the efficacy and safety of immunotherapy for LGI1 antibody encephalitis, and consider the predictors of poor outcomes following immunotherapy. Methods We searched PubMed and Embase for articles reporting the immunotherapy data of anti‐LGI1 encephalitis patients. The proportions of patients with poor outcomes (modified Rankin Scale [mRS] score > 2) at 3 months, 12 months, and the last follow‐up, as well as the odds ratio [OR] of predictors were pooled. Results The review included 162 articles with 1066 patients. The proportion of patients with poor functional outcomes was 21% at 3 months, 14% at 12 months, and 14% at the last follow‐up after receiving immunotherapy. The proportion of patients with reported relapse was 16.6%. The mean duration from onset to the first relapse was 15.6 months. Predictors significantly associated with poor outcomes were age (increase of 1 year), the presence of cognitive impairment, and CSF LGI1 antibody positive. We did not find a statistically significant association between the worst mRS score in the acute phase, the presence of faciobrachial dystonic seizures (FBDS), days from symptom onset to immunotherapy, second‐line treatment, maintenance immunotherapy, or follow‐up time and outcomes. Interpretation Although most patients respond to immunotherapy, a minority of patients still have poor outcomes. Advanced age, cognitive impairment, and CSF LGI1 antibody positive are associated with an increased risk of poor outcomes. However, due to the insufficiency of the data, these conclusions need to be interpreted with caution.

Abstract Aim Nurses are key staff in the response to the COVID‐19 epidemic. The aim of present study was to assess Chinese clinical nurses' preparedness levels for COVID‐19 after the outbreak, as well as the associated demographic factors. Design The design was a cross‐sectional survey. Methods We distributed an online questionnaire to nurses from five eastern coastal area hospitals. The questionnaire collected demographic information, and included the nurses' preparedness to respond to COVID‐19 questionnaire (NPR COVID‐19). Results The total mean NPR COVID‐19 score was 200.99 (standard deviation = 33.60), and the psychological approaches subscale had the lowest mean score. Education and training were positively associated with the NPR COVID‐19 score. Nurses' characteristics, such as seniority, job category and educational level, were entered into the NPR COVID‐19 regression model, and seniority (≤5 years) showed the strongest negative association with NPR COVID‐19 scores (standard coefficient = −0.20). Conclusions Chinese nurse's preparedness to respond to COVID‐19 was adequate. Nurses with less than 5 years of work experience, nursing researchers and diploma‐educated nurses reported feeling a low preparedness to respond to COVID‐19. These nurses should receive specific training.

Net primary productivity (NPP), a key indicator of terrestrial ecosystem quality and function, represents the amount of organic matter produced by vegetation per unit area and time. This study utilizes the MOD17A3 NPP dataset (2001–2022) to analyze the spatio-temporal dynamics of NPP in Xinjiang and projects future trends using Theil-Sen trend analysis, the Mann–-Kendall test, and the Hurst Index. By integrating meteorological data, this study employs partial correlation analysis, the Miami model, and residual analysis to explore the driving mechanisms behind NPP changes influenced by climatic factors and human activities. The results indicate that: (1) The average NPP in Xinjiang has increased over the years, displaying a spatial pattern with higher values in the north and west. Regions with increasing NPP outnumber those with declining trends, while 75.18% of the area shows un-certain future trends. (2) Precipitation exhibits a stronger positive correlation with NPP compared to temperature. (3) Climate change accounts for 28.34% of the variation in NPP, while human activities account for 71.66%, making the latter the dominant driving factor. This study aids in monitoring ecological degradation risks in arid regions of China and provides a scientific basis for developing rational coping strategies and ecological restoration initiatives.

Abstract Background Primary liver cancer (PLC) is a highly malignant disease. This study developed an effective and convenient tool to evaluate survival times of patients after hepatectomy, which can provide a reference point for clinical decisions. Methods Clinical and laboratory data of 243 patients with PLC after hepatectomy were collected. Univariate cox regression analysis, Lasso regression analysis and multivariate cox regression analysis were used to determine the best prediction index. Multivariate cox regression analysis was used to construct a survival prediction model. A receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to verify the model. The patients in this model were divided into was divided into high‐risk and low‐risk groups according to the optimal cut‐off value of the ROC curve for different prognostic years. Kaplan–Meier survival analysis and log‐rank test were used to analyse the survival differences between the two groups. Results Tumour size, portal vein thrombosis, distant metastasis, alpha‐fetoprotein and protein induced by vitamin K absence or antagonist‐II levels were independent risk factors for overall survival (OS) after PLC surgery. The area under the concentration‐time curve for 2‐, 3‐ and 4‐year survival of patients was 0.710, 0.825 and 0.919, respectively, with a good calibration of the Hosmer–Lemeshow test (p > 0.05) and net benefit. The mortality rates in patients with 2, 3 and 4 years of survival were 70.59%, 67.83% and 66.67% for the high‐risk group and 21.84%, 22.50% and 22.67% for the low‐risk group, respectively. The mortality rate of the high‐risk group was significantly higher than that of the low‐risk group (p

Neuromyelitis optica spectrum disorder (NMOSD) is a rare demyelinating disease of the central nervous system primarily affecting the optic nerves, spinal cord, and brainstem. Viral infection may trigger NMOSD. Here, we report the case of a 34-year-old female presenting with a range of symptoms including nausea, vomiting, dysphagia, choking, and fatigue with unsteady gait, diplopia, hearing loss, left-sided facial paralysis, breathing difficulties, and hoarseness of voice. Her HBV DNA concentration, as determined by quantitative PCR analysis, exceeded 5×107 IU/ml in serum and 4.48×102 IU/ml in CSF. Next-generation sequencing of CSF revealed 1,528 HBV sequences in DNA analysis and 6 sequences in RNA analysis. Serum aquaporin-4 antibody (AQP4-Ab) titer was 1:10, and the CSF titer was 1:3.2. Brain magnetic resonance imaging showed high signal intensities in the brain stem, medulla oblongata, and left middle cerebellar peduncle with mild restricted-diffusion. The patient received antiviral and hepatoprotective medications before the high-dose methylprednisolone pulse therapy. However, the patient did not respond well to the first-line treatment. Subsequently, the patient received ofatumumab and inebilizumab. Throughout the follow-up period, there was a gradual improvement in her neurological symptoms, with no reactivation of hepatitis B or deterioration of liver function observed. Thereby, to the best of our knowledge, we report the first case of successful treatment with ofatumumab and inebilizumab in a patient with NMOSD concurrent with HBV infection.

Abstract Epilepsy is one of the most common serious chronic neurological diseases affecting people of all ages globally. It is characterized by recurrent seizures. About 50 million people worldwide have epilepsy. Indubitably, people with epilepsy (PWE) may be without access to appropriate treatment. Many studies have examined the molecular mechanisms and clinical aspects of epilepsy; nonetheless, the treatment gap exists in some special areas. In the tropics, the specific geographical and ecological conditions and a lack of medical resources result in neglect or delay of diagnosis for PWE. Herein, we summarized the epidemiology of epilepsy in the tropics and discussed the disease burden and existing problems, aiming to offer a medical environment for patients in need and highlight the importance of reducing the epileptic disease burden in tropical countries.

Rotavirus (RV) is the main pathogen that causes severe diarrhea in infants and children under 5 years of age. No specific antiviral therapies or licensed anti-rotavirus drugs are available. It is crucial to develop effective and low-toxicity anti-rotavirus small-molecule drugs that act on novel host targets. In this study, a new anti-rotavirus compound was selected by ELISA, and cell activity was detected from 453 small-molecule compounds. The anti-RV effects and underlying mechanisms of the screened compounds were explored. In vitro experimental results showed that the small-molecule compound ML241 has a good effect on inhibiting rotavirus proliferation and has low cytotoxicity during the virus adsorption, cell entry, and replication stages. In addition to its in vitro effects, ML241 also exerted anti-RV effects in a suckling mouse model. Transcriptome sequencing was performed after adding ML241 to cells infected with RV. The results showed that ML241 inhibited the phosphorylation of ERK1/2 in the MAPK signaling pathway, thereby inhibiting IκBα, activating the NF-κB signaling pathway, and playing an anti-RV role. These results provide an experimental basis for specific anti-RV small-molecule compounds or compound combinations, which is beneficial for the development of anti-RV drugs.

Background: Epilepsy is one of the most common chronic brain diseases. Almost one-third of patients have drug-resistant epilepsy (DRE). Cannabidiol is being considered as a potential novel drug for treating DRE. Objectives: To investigate long-term efficacy and safety of cannabidiol in treatment of DRE and the differences in cannabidiol treatment among patients with different characteristics. Design: Systematic review and meta-analysis. Data sources and methods: Medline, Embase, and CENTRAL were searched for literature. RevMan5.4 was used for meta-analysis. The Intention-to-treat set and the random effect were used as the main analysis. Subgroup analyses were performed according to age, dose, concomitant antiseizure medications (ASMs), epilepsy syndromes, and study designs. Results: Fifty studies were included in this systematic review. A total of 4791 participants were collected. The responder rates (seizure frequency reduced at least 50%) at 12-, 24-, 48-, 72-, 96-, and 144-week were 0.40 [0.36, 0.45], 0.39 [0.34, 0.44], 0.37 [0.30, 0.44], 0.27 [0.17, 0.37], 0.22 [0.14, 0.30], and 0.38 [0.23, 0.53]. Seizure-free rates were 0.04 [0.03, 0.06], 0.04 [0.03, 0.05], 0.03 [0.02, 0.05], 0.03 [0.02, 0.03], 0.02 [0.01, 0.03], and 0.04 [0.01, 0.06]. Proportion of adverse events were 0.72 [0.61, 0.83], 0.62 [0.42, 0.81], 0.60 [0.41, 0.79], 0.35 [0.14, 0.56], 0.83 [0.75, 0.90], and 0.96 [0.94, 0.99]. The pooled 12-, 24-, 48-, 96-, and 144-week proportion of serious adverse events were 0.15 [0.09, 0.21], 0.23 [0.14, 0.31], 0.10 [0.06, 0.15], 0.31 [0.24, 0.38], and 0.40 [0.35, 0.45]. Subgroup analyses showed that there was no significant difference on efficacy and safety among age subgroups and epilepsy syndromes subgroups. For most periods, there were no significant difference on efficacy among subgroups of dose and concomitant ASMs. However, higher doses and more concomitant ASMs were associated with higher proportion of adverse events. Conclusion: Cannabidiol treatment of DRE has stable efficacy and fewer adverse events in early period. Long-term use may have decreased efficacy and increased adverse events. Dose escalation may not increase efficacy, but may increase adverse events. Furthermore, cannabidiol use may reduce dosage of other ASMs without reducing efficacy, thereby reducing adverse effects. Cannabidiol may have similar effects in various epilepsy syndromes. Trial registration: PROSPERO (CRD42022351250).

Study region: The west bank of Dianchi Lake, China. Study focus: The Soil Conservation Service Curve Number (SCS-CN) model is widely used to simulate rainfall runoff of mountain floods. The determination of the CN parameter within the SCS-CN model is key to accurately simulating runoff. CN is closely related to regional land use, soil type, antecedent moisture conditions and slope. Therefore, this study established an optimized SCS-CN model by comprehensively considering the above factors, particularly the interception of rainfall by vegetation. New hydrological insights for the region: (1) The original CN value resulted in underestimation of surface runoff in the study area [Nash-Sutcliffe Efficiency Coefficient (NSE) = 0.2260], indicating that regional differences reduce the applicability of the original CN value; (2) the optimized model considering the slope, antecedent rainfall, and other single or combined factors generated simulations of runoff that were closer to observations (NSE = 0.6811); the accuracy of the CN value can be effectively improved by combining various factors; however, since the CN had not yet reached the optimal value, simulations remained inaccurate; (3) consideration of interception of rainfall by vegetation in the model greatly improved the accuracy of simulated runoff [NSE = 0.8620]; indicating that the impact of vegetation interception of rainfall on surface runoff cannot be ignored. The results demonstrated that the SCS-CN model can provide more accurate simulations of mountain flood runoff in the study area after considering multiple factors, such as vegetation interception of rainfall.

Background: Depression and anxiety are the most common psychiatric comorbidities in patients with epilepsy (PWE). However, they are often unrecognized and consequently untreated. Objective: The study was conducted to evaluate the prevalence and risk factors of anxiety and depression among Chinese adult PWE. Design: Cross-sectional study. Methods: Adult PWE were recruited from 13 tertiary epilepsy centers from February to September 2022. Generalized Anxiety Disorder-7 and Neurological Disorders Depression Inventory for Epilepsy were applied to evaluate anxiety and depression, respectively. Both univariate and multivariate logistic regression analyses models were performed to explore the risk factors of anxiety and depression. Results: A total of 1326 PWE were enrolled in this study. The prevalence of anxiety and depression was 31.45% and 27.30%, respectively. Being female [odds ratio (OR) = 1.467, 95% CI: 1.134–1.899; p = 0.004], focal and focal to bilateral tonic-clonic seizures (TCSZ) (OR = 1.409, 95% CI: 1.021–1.939; p = 0.036), and seizure occurrence in the last 3 months (OR = 1.445, 95% CI: 1.026–2.044; p = 0.036) were the risk factors for anxiety. Focal and focal to bilateral TCSZ (OR = 1.531, 95% CI: 1.094–2.138; p = 0.013) and seizure occurrence in the last 3 months (OR = 1.644, 95% CI: 1.130–2.411; p = 0.010) were the risk factors for depression. In addition, for every 1-year increment of age, the odds of developing depression were decreased by 3.8% ( p = 4.12e −5 ). Nevertheless, up to 70% of PWE did not receive any treatment for comorbidity. Conclusion: There were approximately 30% of PWE screened positive for anxiety or depression. Both focal and focal to bilateral TCSZ and seizure occurrence in the last 3 months were estimated as risk factors for anxiety and depression. However, the current status of treatment was not optimal.

Rotaviruses (RVs) are a major cause of diarrhea in young children worldwide. The currently available and licensed vaccines contain live attenuated RVs. Optimization of live attenuated RV vaccines or developing non-replicating RV (e.g., mRNA) vaccines is crucial for reducing the morbidity and mortality from RV infections. Herein, a nucleoside-modified mRNA vaccine encapsulated in lipid nanoparticles (LNP) and encoding the VP7 protein from the G1 type of RV was developed. The 5′ untranslated region of an isolated human RV was utilized for the mRNA vaccine. After undergoing quality inspection, the VP7-mRNA vaccine was injected by subcutaneous or intramuscular routes into mice. Mice received three injections in 21 d intervals. IgG antibodies, neutralizing antibodies, cellular immunity, and gene expression from peripheral blood mononuclear cells were evaluated. Significant differences in levels of IgG antibodies were not observed in groups with adjuvant but were observed in groups without adjuvant. The vaccine without adjuvant induced the highest antibody titers after intramuscular injection. The vaccine elicited a potent antiviral immune response characterized by antiviral clusters of differentiation CD8+ T cells. VP7-mRNA induced interferon-γ secretion to mediate cellular immune responses. Chemokine-mediated signaling pathways and immune response were activated by VP7-mRNA vaccine injection. The mRNA LNP vaccine will require testing for protective efficacy, and it is an option for preventing rotavirus infection.

Coordinated regulation of alternative splicing is essential for germ cell development. Here, the authors report that hnRNPH1 interacts with alternative splicing factors PTBP2 and SRSF3 in the germline to regulate pre-mRNA alternative splicing.

Epilepsy is a chronic neurological disorder associated with severe social and psychological effects, and most epilepsy patients often report at least one comorbidity. Accumulating evidence have suggested that lacosamide, a new generation of anti-seizure medications, may exhibit efficacy in the management of both epilepsy and its related comorbidities. Therefore, this narrative review aimed to elucidate the recent advancements regarding the therapeutic role of lacosamide in epilepsy-associated comorbidities. The possible pathophysiological mechanisms between epilepsy and epilepsy-associated comorbidities have been also partially described. Whether lacosamide improves cognitive and behavioral functions in patients with epilepsy has not been conclusively established. Some studies support that lacosamide may alleviate anxiety and depression in epilepsy patients. In addition, lacosamide has been found to be safe and effective in the treatment of epilepsy in people with intellectual disabilities, epilepsy of cerebrovascular etiology, and epilepsy associated with brain tumors. Moreover, lacosamide treatment has demonstrated fewer side effects on other systems. Hence, future larger and higher quality clinical studies are needed to further explore both the safety and efficacy of lacosamide in the treatment of epilepsy-associated comorbidities.

Rotavirus is one of the main pathogens causing severe diarrhea in infants and young children < 5 years of age. The development of the next-generation rotavirus vaccine is of great significance for preventing rotavirus infection and reducing severe mortality. The current study aimed to develop and evaluate the immunogenicity of inactivated rotavirus vaccine (IRV) in rhesus monkeys. Monkeys received two or three IRV injections intramuscularly at a 4-week interval. Neutralizing antibodies, cellular immunity, PBMC gene expression profiling, and immune persistence were evaluated. Three-dose immunization of IRV induced a higher level of neutralizing, IgG and IgA antibodies compared to two-dose immunization. IRV induced IFN-γ secretion to mediate cellular immune responses, including robust pro-inflammatory and antiviral responses. Chemokine-mediated signaling pathways and immune response were broadly activated by IRV injection. The IRV-induced neutralizing antibodies resulting from two doses returned to baseline levels 20 weeks after full immunization, while those resulting from three doses returned to baseline levels 44 weeks after full immunization. Increasing immunization dose and injection number will help to improve IRV immunogenicity and neutralizing antibody persistence.

BackgroundAppendiceal goblet cell carcinoma (aGCC) is a rare neoplasm with mixed endocrine and exocrine features. No paraneoplastic neurological syndromes or autoantibodies have been identified in cases of aGCC or even appendiceal tumors. Amphiphysin-immunoglobulin G (IgG) autoimmunity was first described in stiff-person syndrome with breast cancer. We firstly described the clinical course and pathological findings of a patient with aGCC-associated amphiphysin-IgG autoimmunity.Case presentationA 54-year-old man who developed aGCC was admitted for acute disturbance of consciousness, psychiatric symptoms, cognitive impairment, seizure and hypotension. Amphiphysin-IgG was detected in the patient’s serum and CSF by immunoblotting and tissue-based indirect immunofluorescence assay confirming the diagnosis of definite paraneoplastic amphiphysin-IgG-positive encephalitis. Histopathology revealed amphiphysin protein expression and accompanying immune cell infiltration (predominantly CD20+ B cells, CD3+ and CD8+ T cells) within the tumor tissue, suggesting a possible paraneoplastic origin of amphiphysin-associated paraneoplastic neurological syndromes (PNSs) in this case. Although the patient’s symptoms resolved after high-dose corticosteroid therapy, he experienced recurrence 6 months later, manifesting as paraneoplastic cerebellar dysfunction. Despite treatment with IV cyclophosphamide and oral mycophenolate mofetil, no improvement was noted.ConclusionsThis case suggests that aGCC may trigger amphiphysin-IgG autoimmunity.

The generation and dissemination of antibiotic resistance bacteria (ARB) and antibiotic resistance genes (ARGs) in the environment has become a critical risk to human health. This study is based on a pilot-scale simulated water distribution system to understand the effects of chlorine disinfection treatment (without free chlorine) on ARB and ARGs in biofilms. The hydraulic parameters and pipe materials of the system were simulated based on a drinking water system. The results of the colony counts showed that bacterial multi-antibiotic resistance could be enhanced 13-fold in the biofilms of the pipeline. The use of high-throughput qPCR (HT-qPCR) indicated that the total relative abundance of ARGs in biofilm samples increased significantly (p < 0.05), while the diversity of bacteria was shown to be reduced via taxonomic analysis of the V3–V4 region of 16S rRNA. The prominent types of ARGs were conferred resistance by aminoglycoside and β-lactam after the chlorine disinfection treatment, and antibiotic deactivation was the main mechanism. Phyla Proteobacteria had the highest abundance in both treatment and control groups but decreased from 70.81% (initial biofilm sample) to 26.09% (the sixth-month biofilm sample) in the treatment groups. The results show that the chlorine disinfection plays a role in the risk of development of bacterial antibiotic resistance in pipe networks owing to bacteria in biofilms. This study was the first to investigate the contribution of chlorination without free chlorine to the bacterial community shift and resistome alteration in biofilms at a pilot-test level. HIGHLIGHTS Chlorine disinfection can enhance bacterial multi-antibiotic resistance.; The total relative abundance of ARGs in biofilm samples increased significantly.; The diversity of the treated biofilm bacteria increased.; Antibiotic deactivation was the main mechanism after chlorine disinfection.;

Background: Emotional disorder is an important indicator for assessing the quality of life (QOL) of people with epilepsy (PWE). Depression, somatic symptom disorder (SSD) and anxiety are among the most frequently occurring mental disorders and overlap with each other. Objectives: This study examines the overlap of these three emotional disorders and their effects separately and in combination on the QOL of PWE. Design: Cross-sectional study. Data Sources and Methods: Adults attending our epilepsy clinic between 1 July 2020 and 1 May 2022 were consecutively enrolled. They were screened for depression, SSD, and anxiety by structured interviews, and demographic, epilepsy-related and QOL indicators were collected. Multivariate analysis, propensity score matching (PSM) and stratified analysis were used to explore the effects of their respective and combined effects on QOL. Results: Among the 749 patients, 189 patients (25%) were diagnosed with depression, 183 patients (24%) were diagnosed with SSD, and 157 patients (21%) were diagnosed with anxiety. The frequency of occurrence of each emotional disorder together with other emotional disorders was higher than the frequency of occurrence of an emotional disorder alone. Depression, SSD, and anxiety all had an independent effect on QOL of PWE ( p

Abstract Background Brain magnetic resonance imaging (MRI) rarely reveals structural changes in patients with suspected anti-Tr/DNER encephalitis and thus provides very limited information. Here, we combined structural MRI, functional MRI, and positron emission tomography-computed tomography (PET-CT) findings to characterize this rare disorder in a patient. Case presentation A 43-year-old woman presented with progressive cerebellar ataxia, memory impairment, anxiety, and depression. Anti-Tr antibodies were detected in both her serum (1:10) and cerebrospinal fluid (1:10). A diagnosis of anti-Tr-positive autoimmune cerebellar ataxia was established. The patient’s symptoms were worse, but her brain MRI was normal. Meanwhile, voxel-based morphometry analysis showed bilateral reduced cerebellar volume, especially in the posterior lobe and uvula of the cerebellum and the middle of the left temporal lobe compared with 6 sex- and age-matched healthy subjects (6 females, 43 ± 2 years; p

BackgroundPopulation aging accompanied by multimorbidity imposes a great burden on households and the healthcare system. This study aimed to determine the incidence and determinants of catastrophic health expenditure (CHE) in the households of old people with multimorbidity in China.MethodsData were obtained from the China Health and Retirement Longitudinal Study (CHARLS) conducted in 2018, with 3,511 old people (≥60 years) with multimorbidity responding to the survey on behalf of their households. CHE was identified using two thresholds: ≥10% of out-of-pocket (OOP) health spending in total household expenditure (THE) and ≥40% of OOP health spending in household capacity to pay (CTP) measured by non-food household expenditure. Logistic regression models were established to identify the individual and household characteristics associated with CHE incidence.ResultsThe median values of THE, OOP health spending, and CTP reached 19,900, 1,500, and 10,520 Yuan, respectively. The CHE incidence reached 31.5% using the ≥40% CTP threshold and 45.6% using the ≥10% THE threshold. It increased by the number of chronic conditions reported by the respondents (aOR = 1.293–1.855, p < 0.05) and decreased with increasing household economic status (aOR = 1.622–4.595 relative the highest quartile, p < 0.001). Hospital admissions over the past year (aOR = 6.707, 95% CI: 5.186 to 8.674) and outpatient visits over the past month (aOR = 4.891, 95% CI: 3.822 to 6.259) of the respondents were the strongest predictors of CHE incidence. The respondents who were male (aOR = 1.266, 95% CI: 1.054 to 1.521), married (OR = 1.502, 95% CI: 1.211 to 1.862), older than 70 years (aOR = 1.288–1.458 relative to 60–69 years, p < 0.05), completed primary (aOR = 1.328 relative to illiterate, 95% CI: 1.079 to 1.635) or secondary school education (aOR = 1.305 relative to illiterate, 95% CI: 1.002 to 1.701), lived in a small (≤2 members) household (aOR = 2.207, 95% CI: 1.825 to 2.669), and resided in the northeast region (aOR = 1.935 relative to eastern, 95% CI: 1.396 to 2.682) were more likely to incur CHE.ConclusionMultimorbidity is a significant risk of CHE. Household CHE incidence increases with the number of reported chronic conditions. Socioeconomic and regional disparities in CHE incidence persist in China.

Rhamnolipid biosurfactants are multifunctional compounds that can play an indispensable role in biotechnological, biomedical, and environmental bioremediation-related fields, and have attracted significant attention in recent years. Herein, a novel strain Pseudomonas sp. S1WB was isolated from an oil-contaminated water sample. The biosurfactants produced by this strain have capabilities to reduce surface tension (SFT) at 32.75 ± 1.63 mN/m and emulsified 50.2 ± 1.13 % in liquid media containing 1 % used engine oil (UEO) as the sole carbon source. However, the lowest SFT reduction (28.25 ± 0.21), highest emulsification index (60.15 ± 0.07), and the maximum yields (900 mg/L) were achieved under optimized conditions; where, the glucose/urea and glycerol/urea combinations were found efficient carbon and nitrogen substrates for improved biosurfactants production. Biosurfactants product was characterized using ultra-high performance liquid chromatography-mass spectrometry (UHPLC- MS) and detected various di- rhamnolipids congeners. In addition, the di-rhamnolipids produced by S1WB strain was found highly stable in terms of surface activity and EI indices at different environmental factors i.e. temperature, pH and various NaCl concentrations, where, emulsifying property was found high stable till 30 days of incubation. Moreover, the stain was capable to degrade hydrocarbon at 42.2 ± 0.04 %, and the Gas chromatography- mass spectrometry (GC-MS) profile showed the majority of peak intensities of hydrocarbons have been completely degraded compared to control.

Abstract Background Understanding and identifying the factors responsible for genetic differentiation is of fundamental importance for efficient utilization and conservation of traditional rice landraces. In this study, we examined the spatial genetic differentiation of 594 individuals sampled from 28 locations in Yunnan Province, China, covering a wide geographic distribution and diverse growing conditions. All 594 accessions were studied using ten unlinked target genes and 48 microsatellite loci, and the representative 108 accessions from the whole collection were sampled for resequencing. Results The genetic diversity of rice landraces was quite different geographically and exhibited a geographical decline from south to north in Yunnan, China. Population structure revealed that the rice landraces could be clearly differentiated into japonica and indica groups, respectively. In each group, the rice accessions could be further differentiated corresponded to their geographic locations, including three subgroups from northern, southern and middle locations. We found more obvious internal geographic structure in the japonica group than in the indica group. In the japonica group, we found that genetic and phenotypic differentiation were strongly related to geographical distance, suggesting a pattern of isolation by distance (IBD); this relationship remained highly significant when we controlled for environmental effects, where the likelihood of gene flow is inversely proportional to the distance between locations. Moreover, the gene flow also followed patterns of isolation by environment (IBE) whereby gene flow rates are higher in similar environments. We detected 314 and 216 regions had been differentially selected between Jap-N and Jap-S, Ind-N and Ind-S, respectively, and thus referred to as selection signatures for different geographic subgroups. We also observed a number of significant and interesting associations between loci and environmental factors, which implies adaptation to local environment. Conclusions Our findings highlight the influence of geographical isolation and environmental heterogeneity on the pattern of the gene flow, and demonstrate that both geographical isolation and environment drives adaptive divergence play dominant roles in the genetic differentiation of the rice landraces in Yunnan, China as a result of limited dispersal.

Anti-N-methyl-d-aspartate receptor encephalitis (NMDARe), a common autoimmune encephalitis, can be accompanied by demyelinating disorders, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). To compare the clinical characteristics of patients with different overlapping syndromes, we searched the PubMed database and performed a systematic review. Of the 79 patients with overlapping syndromes, 15 had MS, 18 had aquaporin-4-antibody-positive NMOSD (AQP4-Ab-positive NMOSD), and 46 had MOGAD. Compared with classical NMDARe, overlapping syndromes showed atypical symptoms, such as limb weakness, sensory disturbance, and visual impairments in addition to the main symptoms of NMDARe and a lower ratio of ovarian teratoma. Patients with MOGAD overlap were the youngest, while patients with MS and AQP4-Ab-positive NMOSD overlap tended to be older than patients with classical NMDARe. A majority of patients with NMDARe who overlapped with MS or AQP4-Ab-positive NMOSD were female, but this was not the case for patients overlapped with MOGAD. When NMDARe and demyelinating diseases occurred sequentially, the interval was the longest in patients with NMDARe overlapped with MS. A favorable outcome was observed in patients overlapping with MOGAD, but no robust comparison can be drawn with the patients overlapping with AQP4-Ab-positive NMOSD and MS regarding the small number of available data. The long-term prognosis of overlapping syndromes needs further investigation.

Abstract Human herpes virus 6 (HHV-6) is a ubiquitous and most common pathogen that affects humans. Human herpes virus 6B (HHV-6B) is a wide spread human herpesvirus that infects most people when they are children, establishes latent infections in the central nervous system (CNS), especially in the hippocampus and amygdala, and induces neurologic diseases. HHV-6 can establish a latent infection and be reactivated by various stimuli. Recently, viral genomic DNA of HHV-6B has been detected in surgically removed brain tissues of intractable epilepsy patients, suggesting the involvement of HHV-6B in the pathogenesis of epilepsy. Temporal lobe epilepsy (TLE) has been shown to be closely related with HHV-6B. TLE patients with HHV-6B in their brains suffer from reiterative attacks of febrile seizures and hippocampal sclerosis. However, the mechanisms underlying the contribution of this virus to the development of TLE remains unknown. The direct damage and immune activation caused by the virus are involved in the process of neuron damage, abnormal neural circuit formation and glial cell proliferation. In addition, some cytokines like interleukin-17A (IL-17A), nuclear factor-kappa B (NF-κb), transforming growth factor-β (TGF-β), mitogen-activated protein kinase (MAPK) and phospholipase A2 are up-regulated and involved in the pathological process of TLE. More studies are needed to clarify the mechanisms underlying the link between HHV-6B and epilepsy, and identify biomarkers to recognize different patient groups for anti-inflammatory or immunomodulatory therapies.

Plant-derived agents are powerful bio-pesticides for the eco-friendly control of mosquito vectors and other blood-sucking arthropods. The larval toxicity of beta-carboline alkaloids against the Asian tiger mosquito, Aedes albopictus (Skuse) (Diptera: Culicidae), was investigated under laboratory conditions. The total alkaloid extracts (TAEs) and beta-carboline alkaloids (harmaline, harmine, harmalol, and harman) from Peganum harmala seeds were isolated and tested in this bioassay. All alkaloids were tested either individually or as binary mixtures, using the co-toxicity coefficient (CTC) and Abbott’s formula analysis. The results revealed considerable toxicity of the tested alkaloids against A. albopictus larvae. When all larval instars were exposed to the TAEs at 48 h post-treatment, the mortality of all larval instars varied in a concentration-dependent manner. The second-instar larvae were the most susceptible to different concentrations of TAEs, and the fourth-instar larvae were more tolerant to TAEs than the second-instar larvae. Especially, the third-instar larvae exposed to all alkaloids also showed that all doses resulted in an increased mortality of the third-instar larvae at 48 h post-treatment, and the toxicities of the tested alkaloids in a descending order were TAEs > harmaline > harmine > harmalol, with the LC50 values of 44.54 ± 2.56, 55.51 ± 3.01, 93.67 ± 4.53, and 117.87 ± 5.61 μg/mL at 48 h post-treatment, respectively. In addition, all compounds were also tested individually or in a 1:1 ratio (dose LC25/LC25) as binary mixtures to assess the synergistic toxicity of these binary combinations against the third-instar larvae at 24 and 48 h post-treatment, respectively. The results demonstrated that when tested as a binary mixture, all compounds (especially TAEs, harmaline, and harmine) showed their synergistic effects, exceeding the toxicity of each compound alone. Interestingly, the obtained data further revealed that the TAEs at sublethal doses (LC10 and LC25) could significantly delay the larval development and decrease the pupation and emergence rates of A. albopictus. This phenomenon could be helpful in order to develop more effective control strategies for different notorious vector mosquitoes.

Abstract Objectives This study aimed to assess the health utility of leukemia patients in China using the EQ-5D-5L, compare it with the population norms, and identify the potential factors associated with health utility. Methods A hospital based cross-sectional survey was conducted in three tertiary hospitals from July 2015 to February 2016. A total of 186 patients with leukemia completed the EQ-5D-5L and their health utility scores were calculated using the Chinese value set. EQ-5D-5L utility and dimensions scores of leukemia patients were compared with China’s population norms using Kruskal–Wallis test and chi square test. Potential factors associated with health utility were identified using Tobit regression. Results The mean EQ-5D-5L utility scores of patients with leukemia, grouped by either gender or age, were significantly lower than those of the general population (p

Abstract People with epilepsy (PWE) have an increased suicide prevalence. This study aimed to identify the risk factors for suicidal tendency among PWE in West China. A nested case–control study was designed in a cohort of patients with epilepsy (n = 2087). In total, 28 variates were calculated. In the univariate analysis, unemployment, low income, seizure frequency, seizure-free time, infectious or structural etiology, levetiracetam or phenobarbital use, anxiety, depression, and stigma were associated with suicidal tendency. A multivariate analysis indicated that unemployment (odds ratio [OR] 5.74, 95% confidence interval [CI] 2.13–15.48), levetiracetam use (OR 2.80, 95%CI 1.11–7.05), depression (C-NDDI-E score ≥ 13; OR 3.21, 95%CI 1.26–8.21), and stigma (SSCI score ≥ 16; OR 6.67, 95%CI 1.80–24.69) were independently associated with suicidal tendency. Conditional inference tree analysis indicated that SSCI and C-NDDI-E scores could effectively identify patients with suicidal tendency. Thus, this study suggests that unemployment, levetiracetam use, depression, and stigma are independent risk factors for suicidal tendency in PWE in China.

Abstract An environment co-contaminated with metals and antibiotics ultimately exposes bacteria to these metals and antibiotics simultaneously. This study aims to explore the efficacy of sublethal concentrations of copper ions contaminated with tetracycline regarding antibiotic resistance in a sensitive strain of E. coli K12. The study proved that a copper ions and tetracycline co-contaminated environment could considerably enhance the mutation frequencies of chloramphenicol and polymyxin B resistance in antibiotic susceptible E. coli; however, the equivalent copper ions and tetracycline alone showed weaker effects. Results also demonstrated that an environment co-contaminated with relatively high sublethal concentrations of copper ion and tetracycline co-contaminated environment could induce much higher antibiotic resistance than the low sublethal and control groups. Whole-genome characterization results indicated that variability existed within the genotype and phenotype involved in antibiotic resistance. Additionally, the evolved resistant strains displayed hereditary resistance after 5 round culture cycles in LB broth over 5 days. Results implied that co-contamination with metals and antibiotics environment could strengthen resistance and contribute to the induction and dissemination of antibiotic resistance in metal and antibiotic co-contaminated environment.

Paraneoplastic neurological syndromes (PNSs) are a group of neurological disorders triggered by an underlying remote tumor. Ovarian teratoma (OT) is the most common histologic type of germ cell tumor in females. The most common PNSs associated with OT is anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. However, with the increasing number of new antibodies reported over the last decade, the clinical spectrum of OT-related PNSs is also expanding. Our knowledge of OT-related PNSs is still far from complete. Here, we provide a comprehensive review of the most recent findings in the field of OT-related PNSs, with a particular focus on their clinical and pathological characteristics. Overall, the description of neuronal antibodies in PNSs associated with OT strongly suggests that antibodies may be responsible for the clinical symptoms in some cases. OT-related PNSs are associated with various clinical manifestations, including anti-NMDAR encephalitis, limbic encephalitis, encephalomyelitis, progressive cerebellar syndrome and opsoclonus-myoclonus syndrome. The pathological characteristics of the OT suggest that the mechanism of PNSs is probably due to heteromorphic neurons in the tumor tissue, the ectopic expression of the antigens in neural tissue within the teratomas and patients’ unusual immune response. Despite the severity of the neurological syndromes, most patients with OT-related PNSs showed good neurologic response to early tumor resection combined with immunotherapy. To further advance the management of OT-related PNSs, additional studies are needed to explore this complex topic.

ObjectivesThis study reported a case of overlapping anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and myelin oligodendrocyte glycoprotein (MOG) inflammatory demyelinating disease with human herpesviruses 7 (HHV-7) infection.MethodsThe detailed clinical characteristics, neuroimaging features, and outcomes of the patient were collected. Polymerase chain reaction (PCR), cell-based assay (CBA) and the tissue-based indirect immunofluorescence assay (TBA) were used for diagnosis.ResultsThe clinical manifestations included headache, dizziness, fever, optic neuritis, and epileptic-seizures. Brain magnetic resonance imaging (MRI) showed hyperintensities involving the left frontal, orbital gyrus and bilateral optic nerve with substantial contrast enhancement. Moreover, test for HHV-7 DNA by using the next generation sequencing metagenomics and polymerase chain reaction showed positive result in CSF but not in the serum samples. Anti-HHV-7 IgM and IgG antibodies were detected in both the serum and cerebrospinal fluid. NMDAR antibodies (1:10) were found positive in the patient’s CSF by a cell-based assay, and MOG antibodies were positive in the serum (1:10) and CSF (1:32). The patient appeared to respond well to immune therapy and it was found that the clinical symptoms including epileptic-seizure as well as headache were relieved and cerebral lesions almost disappeared after the treatment. However, his vision was not completely restored even at the 8-month follow-up, especially the vision in his right eye which was more seriously damaged.DiscussionWe report a rare case of MOG antibodies and anti-NMDAR encephalitis overlapping syndrome (MNOS) with HHV-7 infection for the first time. The possibility of MNOS needs be considered when optic neuritis occurs in the patients diagnosed with anti-NMDAR encephalitis. Besides, immunotherapy should be initiated as early as possible to improve the treatment outcomes and facilitate complete cure.

Objective: In recent years, research on microRNAs (miRNAs) associated with coronary artery disease (CAD) has attracted considerable attention. However, findings of these studies on the validity of circulating miRNAs in CAD diagnosis are controversial. A meta-analysis was therefore conducted to determine the potential value of miRNAs as biomarkers in CAD diagnosis. Methods: Relevant documents on miRNAs expression levels in the diagnosis of CAD were searched and collected from Pubmed, Embase, and Web of Science. They were collected from the time of inception of the database till January 31, 2020. A meta-analysis was conducted using Stata14.0 software. Forest maps were studied and a comprehensive evaluation of the diagnostic value of the expression levels of mRNAs in CAD was conducted using statistical indicators such as the summary receiver operating characteristic curve. Results: Overall, 14 studies were included, with 38 data sets, involving 29 miRNAs with 846 cases and 898 controls. The meta-analysis revealed that the average sensitivity and specificity of miRNAs for CAD diagnosis were 0.80 (0.75–0.84) and 0.78 (0.75–0.81), respectively. The positive likelihood, negative likelihood, and diagnostic odds ratios were 3.7 (3.1–4.4), 0.26 (0.21–0.33), and 14 (10–21), respectively, and the area under the curve was 0.85 (0.82–0.88). Subgroup analysis revealed that the accuracy in the Asian population was higher than that in the non-Asian population. Multiple miRNAs may be more diagnostically accurate than single miRNAs. MiRNAs in whole blood were more accurate than those in plasma, serum, and peripheral blood mononuclear cells. The diagnostic performance of the quantitative real-time polymerase chain reaction group was better than that of the qPCR group. Conclusion: According to our study, miRNAs may be a new, non-invasive diagnostic tool for the diagnosis of CAD. As a screening tool in clinical practice, it has potential diagnostic value and is worthy of clinical promotion. Considering the number and quality of the studies included in this meta-analysis, the above conclusion requires more quality research to verify it.

Abstract Background Biosurfactants, being highly biodegradable, ecofriendly and multifunctional compounds have wide applications in various industrial sectors including environmental bioremediation. Surfactin, a member of lipopeptide family, which is considered as one of the most powerful biosurfactants due to its excellent emulsifying activities as well as environmental and therapeutic applications. Therefore, the aim of this study was to investigate the newly isolated bacterial strain S2MT for production of surfactin-like biosurfactants and their potential applications for oil-contaminated soil remediation. Results In this study, the strain S2MT was isolated from lake sediment and was identified as Bacillus nealsonii based on transmitted electron microscopy (TEM) and 16S rRNA ribo-typing. The strain S2MT produced biosurfactant that reduced the surface tension (34.15 ± 0.6 mN/m) and displayed excellent emulsifying potential for kerosene (55 ± 0.3%). Additionally, the maximum biosurfactant product yield of 1300 mg/L was achieved when the composition of the culture medium was optimized through response surface methodology (RSM). Results showed that 2% glycerol and 0.1% NH4NO3 were the best carbon/nitrogen substrates for biosurfactant production. The parameters such as temperature (30 °C), pH (8), agitation (100 rpm), NH4NO3 (0.1%) and NaCl (0.5%) displayed most significant contribution towards surface tension reduction that resulted in enhanced biosurfactant yield. Moreover, the extracted biosurfactants were found to be highly stable at environmental factors such as salinity, pH and temperature variations. The biosurfactants were characterized as cyclic lipopeptides relating to surfactin-like isoforms (C13–C15) using thin-layer chromatography (TLC), Ultra high performance liquid chromatography and mass spectrometry (UHPLC-MS). The crude biosurfactant product displayed up to 43.6 ± 0.08% and 46.7 ± 0.01% remediation of heavy engine-oil contaminated soil at 10 and 40 mg/L concentrations, respectively. Conclusion Present study expands the paradigm of surfactin-like biosurfactants produced by novel isolate Bacillus nealsonii S2MT for achieving efficient and environmentally acceptable soil remediation as compared to synthetic surfactants.

Abstract Traditional rice landraces grown under on‐farm conservation conditions by indigenous farmers are extremely important for future crop improvement. However, little is known about how the natural selection and agriculture practices of indigenous farmers interact to shape and change the population genetics of rice landraces grown under on‐farm conservation conditions during the domestication. In this study, we sequenced DNA from 108 core on‐farm conserved rice landraces collected from the ethnic minority regions of Yunnan, China, including 56 accessions collected in 1980 and 52 accessions collected in 2007 and obtained 2,771,245 of credible SNPs. Our findings show that most genetic diversity was retained during the 27 years of domestication by on‐farm conservation. However, SNPs with marked allele frequency differences were found in some genome regions, particularly enriched in genic regions, indicating changes in genic regions may have played a much more prominent role in the short‐term domestication of 27 years. We identified 186 and 183 potential selective‐sweep regions in the indica and japonica genomes, respectively. We propose that on‐farm conserved rice landraces during the short‐term domestication had a highly polygenic basis with many loci responding to selection rather than a few loci with critical changes in response to selection. Moreover, loci affecting important agronomic traits and biotic or abiotic stress responses have been particularly targeted in selection. A genome‐wide association study identified 90 significant signals for six traits, 13 of which were in regions of selective sweeps. Moreover, we observed a number of significant and interesting associations between loci and environmental factors, which implies adaptation to local environment. Our results provide insights into short‐term evolutionary processes and shed light on the underlying mechanisms of on‐farm conservation.

Abstract Seizures are a common finding in patients with tuberculous meningitis (TBM), and associate with four times increased risk of death and neurological disability, especially in children. It has been reported that brain inflammation, diffuse neuronal injury, and reactive gliosis may all contribute to the pathogenesis of seizures in TBM. Early seizure onset may be associated with meningeal irritation and cerebral oedema; while, the late seizures are usually due to infarction, hydrocephalus, tuberculoma and paradoxical response. Moreover, recurrent uncontrolled seizures can evolve to status epileptics resulting in an increased risk of chronic epilepsy and poor prognosis. Therefore, this review aimed to assess the frequency of seizures in patients with TBM, and discuss the etiologies, mechanisms, and characteristics of seizures in TBM. Besides, we have searched the literature to identify the prognostic factors for chronic epilepsy after TBM.

BackgroundMechanical ventilation (MV) is commonly used in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patients with serious conditions. However, little is known about the potential risk factors and long-term outcomes of anti-NMDAR encephalitis requiring MV, especially prolonged MV.MethodsThe data collected prospectively from 305 patients with anti-NMDAR encephalitis were retrospectively reviewed. The functional outcome was assessed using a modified Rankin scale (mRS) every 3 months.ResultsWe identified 62 (20.3%) patients who required MV. The most common reasons for MV were decreased consciousness and/or status epilepticus (SE). Among 60 patients analyzed, 27 patients required prolonged MV (>15 days). Prolonged MV primarily was based on the younger age, coma, tumor, and severe pneumonia. During the follow-up (median: 28 months, range: 3–87 months), 77% of patients required MV that exhibited a good outcome. In univariate analysis, prolonged MV, higher levels of C-reactive protein (CRP), and neutrophil-to-lymphocyte ratio (NLR) were found to be associated with poor neurological outcome at 6 months. Although the prolonged MV group exhibited a longer time to achieve a good outcome as compared to the short MV group (median duration 6 months vs. 3 months, p = 0.004), no significant difference was observed between the two groups about long-term outcomes.ConclusionIt is important to recognize that most anti-NMDAR encephalitis patients who required MV will achieve a favorable long-term outcomes, despite the longer duration of MV. Our results may help clinicians in the ventilator management of severe anti-NMDAR encephalitis patients.

Background: Moxibustion is increasingly used for treatment of irritable bowel syndrome (IBS). This study investigated the long-term effects of moxibustion for IBS with diarrhea (IBS-D). Methods: Patients with IBS-D were assigned to receive moxibustion or sham moxibustion (52 each, 3× per week, 6 weeks) and were followed up to 24 weeks. The acupoints were bilateral ST25 and ST36, body surface temperatures at acupoints were 43°C ± 1°C and 37°C ± 1°C for the moxibustion and sham groups, respectively. Primary outcome was changes in IBS Adequate Relief (IBS-AR) from baseline to 6 weeks. Secondary outcomes included the following: IBS symptom severity scale (IBS-SSS), Bristol stool form scale (BSS), IBS quality of life (IBS-QOL), and Hospital Anxiety and Depression Scale (HADS). Results: Based on an intention-to-treat analysis, the rate of IBS-AR in the moxibustion group was significantly higher than the sham group at 6 weeks (76.9% versus 42.3%; p 50 points in IBS-SSS of the treatment group was significantly higher than that of the sham ( p

In order to deal with the biochemical metabolic disorder and the lack of end metabolites caused by hereditary metabolic diseases, a quantitative detection method of amino acids and carnitine in human blood and the quality control method of polypeptide drugs were proposed. First, a method for the detection of 10 amino acids and 32 acylcarnitine metabolites in human blood was established and analyzed by liquid chromatography tandem mass spectrometry. Through the experimental research on typical peptide drugs, combined with the classical synthesis process and the PLS-DA model of human body in different regions, the relevant detection methods for the quality control of peptide drugs were established, which provided a reference for the formulation of peptide drug quality standards. The experimental results show that the quantitative detection method proposed in this paper can effectively detect the content of most amino acids and acylcarnitine. The classical detection method achieved a loss of 16.74% smaller mass-to-charge ratio, and based on this, the quantitative standard for polypeptide drug delivery was determined, which verifies the correctness and superiority of the detection method in this paper.

ObjectiveTo address the effects of high dose steroids on in-hospital infection and neurologic outcome in anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis patients.MethodsWe retrospectively reviewed the clinical data of anti-NMDAR encephalitis patients in West China Hospital, the Third Hospital of Mianyang and Mianyang Central Hospital between October 2011 and August 2020. The development of infections, inflammatory factors, neurologic outcome at discharge and risk factors for in-hospital infection were assessed in patients with and without high dose steroid therapy before and after immunotherapy. Least absolute shrinkage and selection operator (LASSO) regression and logistic regression models were established to assess risk factors for in-hospital infection.ResultsA total of 278 patients with anti-NMDAR encephalitis were included in the study. Thirty-four patients received high dose methylprednisolone (IVMP) therapy only, 84 patients received intravenous immunoglobulin (IVIG) therapy, and 160 patients received IVIG and IVMP therapy. Compared with the IVIG group, IVIG + IVMP group had a higher infection rate (64.38% vs 39.29%, P < 0.001), a higher incidence of noninfectious complications (76.25% vs 61.90%, P = 0.018) and a higher modified Rankin Scale (mRS) score at discharge from the hospital (3 vs 2, P < 0.001). Inflammatory indicators, including white blood cell (WBC) count, neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII), were higher (9.93 vs 5.65, 6.94 vs 3.47 and 1.47 vs 0.70, respectively, P < 0.001) in the IVIG + IVMP group than in the IVIG group. Moreover, lymphocyte-to-monocyte ratio (LMR) was lower (2.20 vs 2.54, P = 0.047) in the IVIG + IVMP group. The LASSO model showed that mRS score on admission, seizure, body temperature, uric acid (URIC), cerebrospinal fluid immunoglobulin G (CSF IgG), NLR and LMR were risk factors for in-hospital infection. The prediction model exhibited an area under the curve (AUC) of 0.885.ConclusionsHigh dose steroids therapy was significantly associated with higher in-hospital infectious complication rates and a poor short-term prognosis in relatively severe anti-NMDAR encephalitis patients. The established prediction model might be helpful to reduce the risk of in-hospital infection.

Abstract Background Androgen plays a pivotal role in spermatogenesis, accompanying a question how androgen acts on germ cells in testis since germ cells lack of androgen receptors (AR). Promyelocytic leukemia zinc-finger (PLZF) is essential for maintenance of undifferentiated spermatogonia population which is terminologically called spermatogonia progenitor cells (SPCs). Aims We aim to figure out the molecular connections between androgen and fates of PLZF+ SPCs population. Method Immunohistochemistry was conducted to confirm that postnatal testicular germ cells lacked endogenous AR. Subsequently, total cells were isolated from 5 dpp (day post partum) mouse testes, and dihydrotestosterone (DHT) and/or bicalutamide treatment manifested that Plzf was indirectly regulated by androgen. Then, Sertoli cells were purified to screen downstream targets of AR using ChIP-seq, and gene silence and overexpression were used to attest these interactions in Sertoli cells or SPCs-Sertoli cells co-culture system. Finally, these connections were further verified in vivo using androgen pharmacological deprivation mouse model. Results Gata2 is identified as a target of AR, and β1-integrin is a target of Wilms’ tumor 1 (WT1) in Sertoli cells. Androgen signal negatively regulate β1-integrin on Sertoli cells via Gata2 and WT1, and β1-integrin on Sertoli cells interacts with E-cadherin on SPCs to regulate SPCs fates. Conclusion Androgen promotes differentiation of PLZF+ spermatogonia pool via indirect regulatory pattern.