Development of a short-term prognostic model for anti-N-methyl-D-aspartate receptor encephalitis in Chinese patients.

BACKGROUND: Recognizing the predictors of poor short-term prognosis after first-line immunotherapy in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is essential for individualized treatment strategy. The objective of this study was to ascertain the factors that forecast short-term prognosis in patients with anti-NMDAR encephalitis, develop a prognostic prediction model, and authenticate its efficacy in an external validation cohort. Further, all patients were followed-up long-term to assess the factors of long-term outcome and relapses. METHODS: A prospective enrollment of patients diagnosed with anti-NMDAR encephalitis was conducted across five clinical centers in China from June 2014 to Mar 2022. The enrolled patients were divided into the derivation and validation sets based on enrollment time. The short-term prognostic model was visualized using a nomogram. Further, all patients were followed-up long-term to assess the factors of long-term outcome. RESULTS: This study found that poor short-term prognosis was a risk factor for poor long-term outcome (6-month prognosis, OR 29.792, 95%CI 6.507-136.398, p < 0.001; 12-month prognosis, OR 15.756, 95%CI 3.384-73.075, p < 0.001; 24-month prognosis, OR 5.500, 95%CI 1.045-28.955, p = 0.044). Abnormal behavior or cognitive dysfunction (OR 8.57, 95%CI 1.48-49.79, p = 0.017), consciousness impairment (OR19.32, 95%CI 3.03-123.09, p = 0.002), autonomic dysfunction or central hypoventilation (OR 5.66, 95%CI 1.25-25.75, p = 0.025), CSF pleocytosis (OR 4.33, 95%CI 1.48-12.65, p = 0.007), abnormal EEG (OR 5.48, 95% CI 1.09-27.54, p = 0.039) were independent predictors for a poor short-term prognosis after first-line immunotherapy. A nomogram that incorporated those factors showed good discrimination and calibration abilities. The area under the curve (AUC) for the prognostic model were 0.866 (95%CI: 0.798-0.934) with a sensitivity of 0.761 and specificity of 0.869. CONCLUSION: We established and validated a prognostic model that can provide individual prediction of short-term prognosis after first-line immunotherapy for patients with anti-NMDAR encephalitis. This practical prognostic model may help neurologists to predict the short-term prognosis early and potentially assist in adjusting appropriate treatment timely.

Effect of Comprehensive Nursing Based on Risk Factors in Liver Cancer Patients Accepted Intervention Therapy On Quality of Life and Prognosis.

Objective: To explore the effect of comprehensive nursing measures, based on the risk factors of dementia, in liver cancer patients, who accepted intervention therapy. Methods: 86 patients met the inclusion criteria, and exclusion criteria were divided into an experimental group (EG group) and a control group (CG group). The general baseline data of age, sex, and education level of groups were evaluated before intervention. CG group adopted routine nursing measures, while EG group gave comprehensive nursing measures on the basis of routine nursing measures. Cognitive function, severity, Barthel index (BI), and quality of life were evaluated on admission day, discharge day, and three months after discharge. Results: The scores of cognitive function, mental state, and self-care ability of daily life in the EG group were significantly higher than those in the CG group on the day of discharge and 3 months after discharge. Three months after discharge, the quality of life total score of EG group was significantly higher than that in CG group, and the scores in the family role, language, activity, self-care ability, social role, thinking and social function were also higher than those in CG group (P < .05). Three months after discharge, the readmission rate and retraining rate in the EG group were significantly lower than those in the CG group (P < .05), but there was no significant difference in mortality between the two groups(P > .05). Conclusion: Comprehensive nursing measures based on prognostic factors in patients undergoing interventional therapy for hepatocellular carcinoma can more effectively enhance patient recovery.

Ubiquitin-specific peptidases: Players in bone metabolism.

Osteoporosis is an ageing-related disease, that has become a major public health problem and its pathogenesis has not yet been fully elucidated. Substantial evidence suggests a strong link between overall age-related disease progression and epigenetic modifications throughout the life cycle. As an important epigenetic modification, ubiquitination is extensively involved in various physiological processes, and its role in bone metabolism has attracted increasing attention. Ubiquitination can be reversed by deubiquitinases, which counteract protein ubiquitination degradation. As the largest and most structurally diverse cysteinase family of deubiquitinating enzymes, ubiquitin-specific proteases (USPs), comprising the largest and most structurally diverse cysteine kinase family of deubiquitinating enzymes, have been found to be important players in maintaining the balance between bone formation and resorption. The aim of this review is to explore recent findings highlighting the regulatory functions of USPs in bone metabolism and provide insight into the molecular mechanisms governing their actions during bone loss. An in-deep understanding of USPs-mediated regulation of bone formation and bone resorption will provide a scientific rationale for the discovery and development of novel USP-targeted therapeutic strategies for osteoporosis.

A Magtein®, Magnesium L-Threonate, -Based Formula Improves Brain Cognitive Functions in Healthy Chinese Adults.

Magnesium is one of the most abundant essential minerals in the body. Magnesium supplements mostly have low bioavailability, except magnesium L-threonate. In 2010, a novel magnesium compound, magnesium L-threonate (Magtein®) was identified and was shown to raise the magnesium levels in the brain and neurons effectively. In this double-blind, placebo-controlled study, Magtein®PS, a magnesium L-threonate (Magtein®)- and phosphatidylserine-based formulation additionally containing vitamins C and D, was tested for its cognitive benefits in 109 healthy Chinese adults aged 18-65 years. Subjects were randomly assigned to receive either Magtein®PS or placebo (starch) capsules, at a dose of 2 g/day. "The Clinical Memory Test", the standard test commonly used in Chinese hospitals and academic institutes for cognitive evaluation, was administered before and 30 days after subjects received the supplement. Subjects receiving Magtein®PS showed significant improvements over the control group in all five subcategories of "The Clinical Memory Test" as well as the overall memory quotient scores. The older participants showed more improvement than younger participants. Results indicated significant benefits of Magtein®PS in improving memory and cognition in healthy Chinese adults.

A GRIP-1-EZH2 switch binding to GATA-4 is linked to the genesis of rhabdomyosarcoma through miR-29a.

Terminal differentiation failure is an important cause of rhabdomyosarcoma genesis, however, little is known about the epigenetic regulation of aberrant myogenic differentiation. Here, we show that GATA-4 recruits polycomb group proteins such as EZH2 to negatively regulate miR-29a in undifferentiated C2C12 myoblast cells, whereas recruitment of GRIP-1 to GATA-4 proteins displaces EZH2, resulting in the activation of miR-29a during myogenic differentiation of C2C12 cells. Moreover, in poorly differentiated rhabdomyosarcoma cells, EZH2 still binds to the miR-29a promoter with GATA-4 to mediate transcriptional repression of miR-29a. Interestingly, once re-differentiation of rhabdomyosarcoma cells toward skeletal muscle, EZH2 was dispelled from miR-29a promoter which is similar to that in myogenic differentiation of C2C12 cells. Eventually, this expression of miR-29a results in limited rhabdomyosarcoma cell proliferation and promotes myogenic differentiation. We thus establish that GATA-4 can function as a molecular switch in the up- and downregulation of miR-29a expression. We also demonstrate that GATA-4 acts as a tumor suppressor in rhabdomyosarcoma partly via miR-29a, which thus provides a potential therapeutic target for rhabdomyosarcoma.

The neutrophil percentage-to-albumin ratio is related to the occurrence of diabetic retinopathy.

BACKGROUND: Among patients with diabetic retinopathy (DR), no proof was available to confirm the prognostic significance of the neutrophil percentage-to-albumin ratio (NPAR). We hypothesized that NPAR plays a role in the incidence of DR in diabetic patients. METHODS: We extracted all diabetes mellitus (DM) data from the National Health and Nutrition Examination Survey (NHANES) database between 1999 and 2018, NPAR was expressed as neutrophil percentage/albumin. Multivariable logistic regression and generalized additive model were utilized for the purpose of examining the correction between NPAR levels and DR. Subgroup analysis of the associations between NPAR and DR was carried out to investigate if the impact of the NPAR varied among different subgroups. RESULTS: An aggregate of 5850 eligible participants were included in the present research. The relationship between NPAR levels and DR was positive linear. In the multivariate analysis, following the adjustment for confounders (gender, white blood cell, age, monocyte percent, red cell distribution width, eosinophils percent, bicarbonate, body mass index, iron, glucose, basophils percent, total bilirubin, creatinine, and chloride), higher NPAR was an independent risk factor for DR compared to lower NPAR (OR, 95% CI: 1.18, 1.00-1.39; 1.24, 1.04-1.48). For the purpose of sensitivity analysis, we found a trend of consistency (p for trend: 0.0190). The results of the subgroup analysis revealed that NPAR did not exert any statistically significant interactions with any of the other DR risk variables. CONCLUSIONS: Elevated NPAR is associated with an elevated risk of occurrence of DR in diabetic patients.

Selective recognition of tryptophan by a methylpillar[5]arene-based supramolecular fuorescent probe.

Herein we present a simple fluorescence quenching method to selectively recognise and determine L-tryptophan (L-Trp) out of other 19 natural amino acids. Methylpillar[5]arene (MeP5), which is employed as a macrocyclic fluorescent probe, exhibits fluorescence activity in the solution of poor solvents because of aggregation-induced emission (AIE) effect. Fluorescence quenching of MeP5 in the solution of EtOH/CH2Cl2 (98/2, v/v) was observed upon the addition of L-Trp whereas other 19 natural amino acids did not bring about obvious change in fluorescence intensity. 1H NMR titration, fluorescence spectroscopy, mass spectrometry and theoretical analysis revealed that L-Trp can be encapsulated into the cavity of MeP5 to form a stable 1:1 host-guest inclusion complex which accounts for the quenching characteristics. The proposed procedure in this investigation offers an attractive and promising method for the selective detection of L-Trp in a mixture of natural amino acids.

Validation of the NEOS score in Chinese patients with anti-NMDAR encephalitis.

OBJECTIVE: The performance of anti-NMDAR Encephalitis One-Year Functional Status (NEOS) in predicting the 1-year functional status in Chinese patients with anti-NMDAR encephalitis is unknown. METHODS: We recruited patients with anti-NMDAR encephalitis from the Multicenter and Prospective Clinical Registry Study of Anti-NMDAR Encephalitis in Beijing Area. Patients were followed up for 1 year. We defined the poor functional status as a modified Rankin Scale score of more than 2 and good functional status as a modified Rankin Scale score of no more than 2. We performed a receiver-operator characteristic analysis to assess the discriminatory power of the NEOS score in predicting the 1-year functional status by using the area under the curve (AUC). Calibration was assessed by Pearson correlation coefficient and Hosmer-Lemeshow tests. RESULTS: Among the 111 patients with anti-NMDAR encephalitis recruited from 364 potentially eligible participants, 87 (78.4%) had good functional status at 1 year, whereas the remaining 24 (21.6%) had poor functional status. The AUC of the NEOS score for 1-year poor functional status was 0.86 (95% CI 0.78-0.93, p < 0.001). The increased NEOS was associated with higher risk of 1-year poor functional status in patients with anti-NMDAR encephalitis. CONCLUSIONS: The NEOS score is considered a reliable predictor of the risk of 1-year poor functional status in Chinese patients with anti-NMDAR encephalitis. This score could help to estimate the velocity of clinical improvement in advance. CLINICALTRIALGOV IDENTIFIER: NCT02443350. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in patients with anti-NMDAR encephalitis, the NEOS score predicts 1-year functional status.

Circular RNA expression in isoproterenol hydrochloride-induced cardiac hypertrophy.

Circular RNA (circRNA) is a novel class of noncoding RNAs, and the roles of circRNAs in the development of cardiac hypertrophy remain to be explored. Here, we investigate the potential roles of circRNAs in cardiac hypertrophy. By circRNA sequencing in left ventricular specimens collected from 8-week-old mice with isoproterenol hydrochloride-induced cardiac hypertrophy, we found 401 out of 3323 total circRNAs were dysregulated in the hypertrophic hearts compared with the controls. Of these, 303 circRNAs were upregulated and 98 were downregulated. Moreover, the GO and KEGG analyses revealed that the majority of parental gene of differentially expressed circRNAs were not only related to biological process such as metabolic process and response to stimulus, but also related to pathway such as circulatory system and cardiovascular diseases. On the other hand, total 1974 miRNAs were predicted to binding to these differentially expressed circRNAs, and the possible target mRNAs of those miRNAs were also predicted and analyzed in terms of functional annotation. Finally, we identified that ANF and miR-23a are downstream targets of circRNA wwp1, suggesting that circRNA wwp1 exerts inhibitory roles of cardiac hypertrophy via down-regulation of ANF and miR-23a, which underlying the potential mechanisms whereby circRNA regulates cardiac hypertrophy.

Cytokines/Chemokines: Potential Biomarkers for Non-paraneoplastic Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

Objective: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common type of autoimmune encephalitis. This study focuses on finding new biomarkers to evaluate the clinical condition and provide new directions for treatment. Methods: A total of 44 cytokines/chemokines in the cerebrospinal fluid of 10 non-paraneoplastic patients and nine controls were measured. We selected some of the cytokines/chemokines that significantly increased in patients. Six selected cytokines/chemokines, including IL-10, CXCL10, CCL22, CCL3, IL-7, TNF-α, and three previously reported (IL-2, IL-6, and IL-17A), were measured in seven other patients who provided repeat samples. We compared their levels and explored correlations with severity of disease and antibody titers. Results: The levels of Th1 axis (CXCL10, TNF-α, IFN-γ, CCL3), Th2 axis (CCL1, CCL8, CCL17, CCL22), Treg axis (IL-10), Th17 axis (IL-7), and B cell axis (CXCL13) cytokines, as well as IL-12 p40 and IL-16, were significantly higher in patients compared to those in controls. The level of IL-2 was significantly decreased at the intermediate stage of treatment compared with that before treatment. The severity of disease is positively correlated with levels of CXCL10, CCL3, IL-10, CCL22, and IL-6. The level of CCL3 in the high antibody titer group was greater than that in the low antibody titer group. Conclusion: The pathogenesis of anti-NMDAR encephalitis involves T cell and B cell cytokines. T cells likely assist B cells to produce antibodies. IL-2, CXCL10, CCL3, IL-10, CCL22, and IL-6 may represent new biomarkers in anti-NMDAR encephalitis. Given the lack of research on IL-10, CCL3, and CCL22 in this disease, it will be informative to explore their potential role in pathogenesis in larger studies.

[Value of early enteral nutrition in patients with severe heart failure undergoing mechanical ventilation].

OBJECTIVE: To observe the effect of early enteral nutrition (EEN) on nutritional indicators and clinical outcomes in patients with severe heart failure undergoing mechanical ventilation. METHODS: Thirty-four patients with severe heart failure (grade III-IV of cardiac function) and pulmonary infections undergoing mechanical ventilation admitted to intensive care unit (ICU) of Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine from May 2017 to April 2018 were enrolled. They were randomly divided into EEN group and delayed enteral nutrition (DEN) group. Both groups were given routine treatment, including mechanical ventilation, improvement of cardiac function, anti-infection, protection of vital organ function, regulation of blood sugar and adjustment of electrolyte and acid-base balance. The patients in EEN group received enteral nutrition (EN) within 48 hours after ICU admission, and in DEN group, EN was started after the patients had spent the early stage of stress and had stable vital signs (48 hours after ICU admission). The changes in serum B-type natriuretic peptide (BNP), C-reactive protein (CRP), nutritional indicators and liver function indicators at ICU admission and 7 days after treatment were compared between the two groups. The time needed for patients to reach EN target, duration of mechanical ventilation, length of ICU stay, and the 28-day mortality were recorded, and complications were observed. RESULTS: There was no significant difference in serum BNP, CRP, nutritional indicators or liver function indicators at ICU admission between the two groups. After treatment for 7 days, BNP and CRP in both groups were decreased significantly as compared with those at ICU admission [BNP (ng/L): 592.1±370.9 vs. 2 517.7±1 163.4 in EEN group, 621.9±418.8 vs. 2 251.5±1 006.8 in DEN group; CRP (mg/L): 46.0±19.6 vs. 59.8±22.5 in EEN group, 40.5±18.8 vs. 61.2±24.6 in DEN group, all P < 0.05], pre-albumin (PA) and transferrin (TF) were significantly increased [PA (g/L): 0.18±0.05 vs. 0.15±0.06 in EEN group, 0.17±0.04 vs. 0.12±0.06 in DEN group; TF (g/L): 1.6±0.4 vs. 1.5±0.4 in EEN group, 1.7±0.5 vs. 1.4±0.5 in DEN group, all P < 0.05]. However, there was no significant difference in the above indicators after treatment between the two groups (all P > 0.05). There was no significant change in liver function after treatment in both groups. The EN treatment was successfully completed in both groups. Some patients developed abdominal distension and diarrhea in varying degrees, which were alleviated by slowing down the infusion rate, supplemented by gastrointestinal motility drugs and intestinal flora adjustment drugs. The time needed to reach EN target in EEN group was significantly earlier than that in DEN group (hours: 42.4±10.2 vs. 53.8±17.1, P < 0.05), the duration of mechanical ventilation (days: 14.2±8.7 vs. 13.4±7.9), the length of ICU stay (days: 17.8±6.7 vs. 18.3±5.6) and 28-day mortality [5.9% (1/17) vs. 11.8% (2/17)] showed no significant difference as compared with those in DEN group (all P > 0.05), and it did not increase the incidence of aspiration pneumonia [23.5% (4/17) vs. 17.7% (3/17), P > 0.05]. CONCLUSIONS: EEN could help to achieve nutritional goals as soon as possible, improve the nutritional status of the body, and provide conditions and basis for further treatment of severe heart failure patients.

miR-29a attenuates cardiac hypertrophy through inhibition of PPARδ expression.

Although cardiac hypertrophy is widely recognized as a risk factor that leads to cardiac dysfunction and, ultimately, heart failure, the complex mechanisms underlying cardiac hypertrophy remain incompletely characterized. The nuclear receptor peroxisome proliferator-activated receptor δ (PPARδ) is involved in the regulation of cardiac lipid metabolism. Here, we describe a novel PPARδ-dependent molecular cascade involving microRNA-29a (miR-29a) and atrial natriuretic factor (ANF), which is reactivated in cardiac hypertrophy. In addition, we identify a novel role of miR-29a, in which it has a cardioprotective function in isoproterenol hydrochloride-induced cardiac hypertrophy by targeting PPARδ and downregulating ANF. Finally, we provide evidence that miR-29a reduces the isoproterenol hydrochloride-induced cardiac hypertrophy response, thereby underlining the potential clinical relevance of miR-29a in which it may serve as a potent therapeutic target for heart hypertrophy treatment.

Application of the 2016 diagnostic approach for autoimmune encephalitis from Lancet Neurology to Chinese patients.

BACKGROUND: A unified clinical approach to diagnose autoimmune encephalitis was published in Lancet Neurology in 2016. Purpose of our study is to examine the feasibility and reasonability of the 2016 "A clinical approach to diagnosis of autoimmune encephalitis" in China with a retrospective study. METHODS: We retrospectively collected 95 cases of autoimmune encephalitis and non autoimmune encephalitis cases with detailed clinical data from Beijing Tongren Hospital and the China National Knowledge Infrastructure (CNKI). All cases were analysed stepwise according to the approach in Lancet Neurology to compare the new diagnosis with the final clinical diagnosis. RESULTS: The disease course of these 95 cases ranged from 2 to 540 days. Initial symptoms include fever, headache, seizure, mental and behavioral disorders, memory deterioration and illusion. Based on symptoms and signs when the patient came to the hospital, the sensitivity and specificity of criteria were as follows: possible autoimmune encephalitis (pAE) 84% and 94%, definite autoimmune limbic encephalitis (dALE) 38% and 96%, probable anti-N-methyl-D-aspartate receptor encephalitis (prNMDARE) 49% and 98%. The sensitivities of the above three criteria and the specificity of pAE were low during early disease stage, while the specificities of dALE and prNMDAER remained relatively high in different time periods. CONCLUSIONS: This new autoimmune encephalitis diagnostic approach can recognize possible autoimmune encephalitis. The chances of a case being autoimmune-mediated following classification as autoimmune encephalitis with the new criteria are high. The flowchart is recommended to use as a whole. At the early disease stage, criteria with low sensitivity and high specificity, such as dALE and prNMDARE, lead most cases to enter subsequent diagnosis steps, namely autoantibody detection in the flowchart. Final diagnoses can only be made by autoantibody tests. These factors may make it challenging for clinicians to make diagnosis promptly and to begin immune-modulating therapy immediately. Moreover, the criteria for patients with paraneoplastic syndromes (PNSs) should be considered to avoid diagnosis omission. For Chinese patients, a multi-centre, prospective study on the clinical manifestations, laboratory diagnostic technology, therapy, and prognosis is greatly needed.

[Ocular syndromes in patients with neurobrucellosis].

OBJECTIVE: To investigate the clinical features of ocular syndromes in patients with neurobrucellosis. METHOD: This is a retrospective series case study. The clinical data of 5 patients with neurobrucellosis, who were treated in Department of Neurology, Beijing Tongren Hospital, Captical Medical Uinversity, from May 2009 to January 2015, were collected. Their epidemiological information, clinical manifestation, laboratory and radiologic examination, therapy and prognosis were analyzed. RESULTS: Among the five patients, there were 3 males and 2 females, and their ages ranged from 20 to 67 years. The median age was 25 years. All patients had ever exposed to sheep. 1 patient lived close to a slaughterhouse and 2 patients lived in epidemic areas of brucellosis. 5 patients presented with binocular vision loss, 8 eyes with fundus edema, 3 patients with ophthalmoplegia;4 patients with fever,4 patients with headache,3 patients with neck stiffness,1 patient with movement and sensation disorders. Cerebrospinal fluid (CSF) pressure elevated, white cell number and protein increased with glucose reduction were detected respectively in 3 cases. While, CSF chloride decreased in 2 cases. Serum agglutination test for brucella was positive in 5 patients. Serum brucella culture was positive in 1 patient and CSF brucella culture was positive in 1 patient. Brain magnetic resonance imaging (MRI) showed that the optic nerve was involved in 3 patients,the meninges were involved in 1 patient and the brain white matter was involved in 1 patient. The combination of rifamycin, tetracycline, ceftriaxone sodium or quinolone were given to all patients and showed appreciated effects. CONCLUSIONS: The clinical features of ocular syndromes are atypical in patients with neurobrucellosis. Vision loss and ophthalmoplegia are more common to be seen. Neurobrucellosis should be considered when patients with ocular signs and other system symptoms without a definite diagnosis.

[Increasing pattern of phytoplankton biomass with species richness and tests of sampling and complementary effects].

A total of eighteen common phytoplankton species in China coastal waters were divided into different assemblages to investigate the increasing pattern of the assemblage biomass with species richness. The sampling effect was studied by multiple analysis of variance (MANOVA) method, and the complementary effect was explored by over-yielding analysis, relative yield total (RYT) index, and subset approach. It was shown that the increasing pattern of assemblage biomass with species richness was not unitary. When the species number was lower than 5, the assemblage biomass increased with increasing species richness; when the species number was higher than 5, there were no obvious relationships between assemblage biomass and species richness. A stronger complementary effect was observed inside the assemblage, presenting a hump-shaped variation with increasing species richness. The sampling effect of the assemblages occurred at stable growth phase.

[Effects of species richness on colony biomass and tests of sampling- and complementary effect].

With eight species of unicellular algae cultured in random combinations to construct the assemblages with different degrees of richness, the increase pattern of colony biomass with the change of species richness was investigated, and the sampling effect was detected by using multiple variance analysis (MANOVA) method. Three analysis methods, i. e., over-yielding analysis, relative yield total (RYT) index, and subset approach, were applied to explore the complementary effect, and additive partitioning method was applied to separate the sampling effect and complementary effect quantitatively. The results showed that the colony biomass presented a saturated rise with the increase of species richness, and a strong complementary effect was observed in phytoplankton colonies. At exponential growth phase, some specific algal species affected the colony biomass significantly, but after reaching the stable phase, the biomass was not affected by the presence of given phytoplankton. The sampling effect was generally negative at stable phase, while the complementary effect and net biodiversity effect were always positive.