Preparatory movement state enhances premovement EEG representations for brain-computer interfaces.

OBJECTIVE: Motor-related brain-computer interface (BCI) have a broad range of applications, with the detection of premovement intentions being a prominent use case. However, the electroencephalography (EEG) features during the premovement phase are not distinctly evident and are susceptible to attentional influences. These limitations impede the enhancement of performance in motor-based BCI. The objective of this study is to establish a premovement BCI encoding paradigm that integrates the preparatory movement state and validates its feasibility in improving the detection of movement intentions. Methods. Two button tasks were designed to induce subjects into a preparation state for two movement intentions (left and right) based on visual guidance, in contrast to spontaneous premovement. The low frequency movement-related cortical potentials (MRCPs) and high frequency event-related desynchronization (ERD) EEG data of 14 subjects were recorded. Extracted features were fused and classified using task­related common spatial patterns (TR-CSP) and common spatial patterns (CSP) algorithms. Differences between prepared premovement and spontaneous premovement were compared in terms of time domain, frequency domain, and classification accuracy. RESULTS: In the time domain, MRCPs features reveal that prepared premovement induce lower amplitude and earlier latency on both contralateral and ipsilateral motor cortex compared to spontaneous premovement, with susceptibility to the dominant hand's influence. Frequency domain ERD features indicate that prepared premovement induce lower ERD values bilaterally, and the ERD recovery speed after button press is the fastest. By using the fusion approach, the classification accuracy increased from 78.92% for spontaneous premovement to 83.59% for prepared premovement (p<0.05). Along with the 4.67% improvement in classification accuracy, the standard deviation decreased by 0.95. Significance. The research findings confirm that incorporating a preparatory state into premovement enhances neural representations related to movement. This encoding enhancement paradigm effectively improves the performance of motor-based BCI. Additionally, this concept has the potential to broaden the range of decodable movement intentions and related information in motor-related BCI.

COVID-19-induced acute loss of consciousness in Marchiafava-Bignami disease: a case report.

Among the various manifestations of COVID-19, the neurological implications of SARS-CoV-2 infection are of significant concern. Marchiafava-Bignami disease (MBD), a neurodegenerative disorder, exhibits a clinical spectrum ranging from mild progressive dementia in its chronic form to states of acute coma and varied mortality rates. Acute MBD primarily occurs in chronic alcoholics and malnourished individuals and is characterized by sudden loss of consciousness, seizures, confusion, and psychosis. We herein report a case of MBD presenting as acute loss of consciousness after the development of COVID-19. The patient presented with a history of fever and upper respiratory infection and was diagnosed with SARS-CoV-2 infection. He developed a neurological syndrome characterized by altered consciousness and convulsions, and brain magnetic resonance imaging revealed abnormal signals in the corpus callosum and frontoparietal lobes. Considering his alcohol intake history and the absence of other differential diagnoses, we diagnosed him with acute MBD triggered by COVID-19. After high-dose vitamin B1 and corticosteroid therapy, his clinical symptoms improved. In this case, we observed a temporal sequence between the development of COVID-19 and acute exacerbation of MBD. This case adds to the mounting evidence suggesting the potential effect of SARS-CoV-2 on the neurological system.

Relationship between initial red cell distribution width and ΔRDW and mortality in cardiac arrest patients.

AIMS: There has been a lack of research examining the relationship between red cell distribution width (RDW) and the prognosis of cardiac arrest (CA) patients. The prognostic value of the changes in RDW during intensive care unit (ICU) hospitalization for CA patients has not been investigated. This study aims to investigate the correlation between RDW measures at ICU admission and RDW changes during ICU hospitalization and the prognosis of CA patients and then develop a nomogram that predicts the risk of mortality of these patients. METHODS AND RESULTS: A retrospective cohort study is used to collect clinical characteristics of CA patients (>18 years) that are on their first admission to ICU with RDW data measured from the Medical Information Mart for Intensive Care IV Version 2.0 database. Patients are randomly divided into a development cohort (75%) and a validation cohort (25%). The primary outcome is 30 and 360 day all-cause mortality. ΔRDW is defined as the RDW on ICU discharge minus RDW on ICU admission. A multivariate Cox regression model is applied to test whether the RDW represents an independent risk factor that affects the all-cause mortality of these patients. Meanwhile, the dose-response relationship between the RDW and the mortality is described by restricted cubic spine (RCS). A prediction model is constructed using a nomogram, which is then assessed using receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA). A total of 1278 adult CA patients are included in this study. We found that non-survivors have a higher level of RDW and ΔRDW compared with survivors, and the mortality rate is higher in the high RDW group than in the normal RDW group. The Kaplan-Meier survival curve indicates that patients in the normal RDW group had a higher cumulative survival rate at 30 and 360 days than those in the high RDW group (log-rank test, χ2  = 36.710, χ2  = 54.960, both P values <0.05). The multivariate Cox regression analysis shows that elevated RDW at ICU admission (>15.50%) is an independent predictor of 30 [hazard ratio = 1.451, 95% confidence interval (CI) = 1.181-1.782, P < 0.001] and 360 day (hazard ratio = 1.393, 95% CI = 1.160-1.671, P < 0.001) all-cause mortality among CA patients, and an increase in RDW during ICU hospitalization (ΔRDW ≥ 0.4%) can serve as an independent predictor of mortality among these patients. A non-linear relationship between the RDW measured at ICU admission and the increased risk of mortality rate of these patients is shown by the RCS. This study established and validated a nomogram based on six variables, anion gap, first-day Sequential Organ Failure Assessment score, cerebrovascular disease, malignant tumour, norepinephrine use, and RDW, to predict mortality risk in CA patients. The consistency indices of 30 and 360 day mortality of CA patients in the validation cohort are 0.721 and 0.725, respectively. The nomogram proved to be well calibrated in the validation cohort. DCA curves indicated that the nomogram provided a higher net benefit over a wide, reasonable range of threshold probabilities for predicting mortality in CA patients and could be adapted for clinical decision-making. CONCLUSIONS: Elevated RDW levels on ICU admission and rising RDW during ICU hospitalization are powerful predictors of all-cause mortality for CA patients at 30 and 360 days, and they can be used as potential clinical biomarkers to predict the bad prognosis of these patients. The newly developed nomogram, which includes RDW, demonstrates high efficacy in predicting the mortality of CA patients.

DPA-Zinc around Polyplexes Acts Like PEG to Reduce Protein Binding While Targeting Cancer Cells.

Gene therapy holds great promise as an effective treatment for many diseases of genetic origin. Gene therapy works by employing cationic polymers, liposomes, and nanoparticles to condense DNA into polyplexes via electronic interactions. Then, a therapeutic gene is introduced into target cells, thereby restoring or changing cellular function. However, gene transfection efficiency remains low in vivo due to high protein binding, poor targeting ability, and substantial endosomal entrapment. Artificial sheaths containing PEG, anions, or zwitterions can be introduced onto the surface of gene carriers to prevent interaction with proteins; however, they reduce the cellular uptake efficacy, endosomal escape, targeting ability, thereby, lowering gene transfection. Here, it is reported that linking dipicolylamine-zinc (DPA-Zn) ions onto polyplex nanoparticles can produce a strong hydration water layer around the polyplex, mimicking the function of PEGylation to reduce protein binding while targeting cancer cells, augmenting cellular uptake and endosomal escape. The polyplexes with a strong hydration water layer on the surface can achieve a high gene transfection even in a 50% serum environment. This strategy provides a new solution for preventing protein adsorption while improving cellular uptake and endosomal escape.

Association between inflammatory bowel disease and Parkinson's disease: a prospective cohort study of 468,556 UK biobank participants.

Introduction: Inflammatory Bowel Disease (IBD) and Parkinson's disease (PD) are both chronic, progressive disorders. As such, given the inconclusive results of extensive research on the association between IBD and PD, our study intends to examine this relationship further using the UK Biobank database. Methods: We conducted a prospective cohort study using the Cox proportional hazards model, analyzing data from the UK Biobank to investigate the relationship between IBD and PD, following subjects until PD diagnosis, loss to follow up, death or study termination on 30 June, 2023. Results: The results show that IBD had no effect on the risk of PD (HR: 1.356, 95% CI: 0.941-1.955, p = 0.103), and the effect remained consistent in specific Crohn's disease, ulcerative colitis or unclassified IBD populations. In addition, after sensitivity analysis using propensity matching scores and excluding patients diagnosed with PD 5 or 10 years after baseline, IBD had no effect on the risk of PD. However, in the subgroup analysis, we found that in females (HR: 1.989, 95% CI: 1.032-3.835, p = 0.040), the polygenic risk score was highest (HR: 2.476, 95% CI: 1.401-4.374, p = 0.002), and having ulcerative colitis without hypertension (HR: 2.042, 95% CI: 1.128-3.697, p = 0.018) was associated with an increased risk of PD. Conclusion: In conclusion, over an average follow-up period of 13.93 years, we found no significant association between IBD and PD.

Network Pharmacology-Based Strategy to Investigate the Pharmacologic Mechanisms of Coptidis Rhizoma for the Treatment of Alzheimer's Disease.

Background: Alzheimer's disease (AD) is becoming a more prevalent public health issue in today's culture. The experimental study of Coptidis Rhizoma (CR) and its chemical components in AD treatment has been widely reported, but the principle of multi-level and multi-mechanism treatment of AD urgently needs to be clarified. Objective: This study focuses on network pharmacology to clarify the mechanism of CR's multi-target impact on Alzheimer's disease. Methods: The Phytochemical-compounds of CR have been accessed from the Traditional Chinese Medicine Database and Analysis Platform (TCMSP) and Symmap database or HPLC determination. The values of Oral Bioavailability (OB) ≥ 30% and Drug Like (DL) ≥ 0.18 or blood ingredient were used to screen the active components of CR; the interactive network of targets and compounds were constructed by STRING and Cytoscape platform, and the network was analyzed by Molecular Complex Detection (MCODE); Gene Ontology (GO) function, Kyoto Encyclopedia of Genes and Genomes Pathway (KEGG) and metabolic pathway enrichment of targets were carried out with Metascape, the Database for Annotation, Visualization and Integrated Discovery (DAVID) and MetaboAnalyst platform; Based on CytoHubba, the potential efficient targets were screened by Maximal Clique Centrality (MCC) and Degree, the correlation between potential efficient targets and amyloid ß-protein (Aß), Tau pathology was analyzed by Alzdata database, and the genes related to aging were analyzed by Aging Altas database, and finally, the core targets were obtained; the binding ability between ingredients and core targets evaluated by molecular docking, and the clinical significance of core targets was assessed with Gene Expression Omnibus (GEO) database. Results: 19 active components correspond to 267 therapeutic targets for AD, of which 69 is potentially effective; in module analysis, RELA, TRAF2, STAT3, and so on are the critical targets of each module; among the six core targets, RELA, MAPK8, STAT3, and TGFB1 have clinical therapeutic significance; GO function, including 3050 biological processes (BP), 257 molecular functions (MF), 184 cellular components (CC), whose functions are mainly related to antioxidation, regulation of apoptosis and cell composition; the HIF-1 signaling pathway, glutathione metabolism is the most significant result of 134 KEGG signal pathways and four metabolic pathways, respectively; most of the active components have an excellent affinity in docking with critical targets. Conclusion: The pharmacological target prediction of CR based on molecular network pharmacology paves the way for a multi-level networking strategy. The study of CR in AD treatment shows a bright prospect for curing neurodegenerative diseases.

Prominent Effects of Berbamine Hydrochloride on Alzheimer's Disease Model Mice.

Very few anti-Alzheimer's disease (AD) drugs are clinically available at present due to the complex mechanism of Alzheimer's disease. For the purpose of discovering potential anti-AD drugs in bisbenzylisoquinoline alkaloids, the anti-AD function and the mechanism of the function of berbamine hydrochloride (BBMH) were studied. Three kinds of AD model mice, double transgenic APP/PS1 AD mice, Gal-Alu AD mice induced by the intraperitoneal injection of d-galactose combined with the intragastric administration of aluminum trichloride, and Alu AD-like mice induced by stereotactic brain injection of aluminum trichloride, were administered with BBMH for 40 days at a dosage of 280 mg/kg/d. The effects of BBMH on the learning and memory behavior of the AD mice were studied through the Morris water maze experiment, and the influences of BBMH on the pathological features of AD, including the deposition of Aß, the lesions of pyramidal cells (neurons), and the formation of neurofibrillary tangles, were studied by the immunohistochemical staining, hematoxylin-eosin staining, and silver staining of the brain tissues of the mice. The water maze experiment showed that BBMH could significantly improve the learning and memory abilities of three kinds of treated mice. Immunohistochemical staining showed that BBMH could significantly reduce the deposition of Aß in the brain tissues of treated mice. Hematoxylin-eosin staining showed that BBMH could significantly alleviate the lesions of pyramidal cells in the hippocampal tissue of the mice. Silver staining showed that BBMH could significantly reduce the formation of neurofibrillary tangles in the hippocampal tissue of the mice. These results indicated that BBMH has significant anti-AD effects and the potential as an anti-AD drug. Western blot analysis of the brain tissue of the mice showed that the expression level of calpain, a Ca2+-dependent proteolytic enzyme, was significantly inhibited and the expression level of SelK, a selenoprotein mainly expressed in immune cells, was significantly increased. It is speculated that the anti-AD effect of BBMH is related to the improvement of the phagocytosis of microglial cells in brain tissues and macrophages migrated into the brain as well as the regulation of calcium homeostasis and calcium-dependent proteases in the brain tissues of the mice.

Probiotic in the prevention of ventilator-associated pneumonia in critically ill patients: evidence from meta-analysis and trial sequential analysis of randomized clinical trials.

BACKGROUND: Probiotic might have a role in the prevention of ventilator-associated pneumonia (VAP) among mechanically ventilated patients, but the efficacy and safety remained inconsistent. The aim of this systematic review and meta-analysis was to evaluate the efficacy and safety of probiotic (prebiotic, synbiotic) versus placebo in preventing VAP in critically ill patients undergoing mechanical ventilation. METHODS: PubMed, Embase and the Cochrane library databases were searched to 10 October 2021 without language restriction for randomized or semi-randomized controlled trials evaluating probiotic (prebiotic, synbiotic) vs. placebo in prevention of VAP in critically ill mechanically ventilated patients. The pooled relative risk (RR) along with 95% confidence intervals (CI) were combined using a random-effects model. Furthermore, the trial sequential analysis (TSA) and subgroup analyses were performed. Statistical significance was regarded as P < 0.05. RESULTS: Twenty-three trials involving 5543 patients were eligible for this meta-analysis. The combined RR of decreasing the risk of VAP by probiotic was 0.67 (0.56, 0.81) for all eligible studies, 0.69 (n = 5136; 95% CI = 0.57 to 0.84; P < 0.01) for adults studies and 0.55 (n = 407; 95%CI = 0.31 to 0.99; P = 0.046) for neonates/children studies. Additionally, the above-mentioned positive finding in 20 adults studies was verified by the results of TSA, subgroup analyses and cumulative meta-analysis. Ample evidences demonstrated a 31% decrease in RR of incidence of VAP was noted when prophylactic probiotic therapy was administrated among adult patients. Finally, there were no effects on the ICU/hospital/28-/90-day mortality, bacteremia, CRBSI, diarrhea, ICU-acquired infections, infectious complications, pneumonia, UTI and wound infection between two groups (P > 0.05 for all). CONCLUSIONS: Based on the results of our study, the current evidences suggested that prophylactic administration of probiotic might be utilized as a preventive method for VAP in neonates/children and adults patients who required mechanical ventilation. However, further large, high-quality RCTs are warranted to assess the efficacy and safety of probiotic treatment in critically ill patients, especially for the neonates/children studies and the long-term consequences of this therapy.

Electroencephalogram Analysis of Magnetic Stimulation at Different Acupoints.

Magnetic stimulation has some similarities with acupuncture, and it has broad application prospects because of its non-invasiveness and easy quantification. This paper combines magnetic stimulation technology with electroencephalography to analyze the time-frequency and the brain functional network results elicited by magnetic stimulation at different acupoints. This paper hopes to observe the different effects of stimulating different acupoints on the brain from the perspective of EEG. The EEG signals during magnetic stimulation at ST36, ST40, and GB37 were recorded, respectively. The time-frequency results showed that the magnetic stimulation at ST36 and ST40 on the Foot Yangming Stomach Meridian increased the energy in the left parietal lobe and the right central region, and the energy increased mainly in the theta and alpha bands. However, during the magnetic stimulation at GB37 on the Foot Shaoyang Gallbladder Meridian, the energy in the central region and the frontal lobe increased, and the energy increased mainly in the delta, theta, and alpha bands. Moreover, the energy in the right parietal lobe decreased during magnetic stimulation at GB37. The results of brain functional network were also consistent with time-frequency results. The brain network connections of GB37 stimulation in the central region were significantly less than that of ST36 and ST40 (p < 0.01). In addition, the connections between central region and frontal lobe and the connections between central region and parietal lobe of GB37 stimulation were significantly different from that of ST36 and ST40 (p < 0.01). The above results indicate that ST36 and ST40 on the same meridian have similar effects on the brain, while GB37 on the other meridian has completely different effects from ST36 and ST40. The results of this paper explain the reason why stimulating ST36 and ST40 can treat similar diseases from the perspective of EEG, and also explain that stimulating GB37 has significantly different effects on the brain from that of ST36 and ST40.

Research on the Histological Features and Pathological Types of Gastric Adenocarcinoma With Mucinous Differentiation.

Objective: To discuss the histological features, pathological types, and prognosis of gastric adenocarcinoma with mucinous differentiation. Methods: Specimens of 189 cases of gastric adenocarcinoma with mucinous differentiation were collected for detailed histomorphology, immunohistochemistry, fluorescence in situ hybridization, and follow-up. Results: In accordance with the morphological and histological structural features of the cancer cells as well as the area ratio of the mucus, gastric adenocarcinoma with mucinous differentiation was divided into four types, namely pure mucinous carcinoma, intraductal papillary mucinous carcinoma, signet ring cell type mucinous carcinoma, and mixed cell type mucinous carcinoma. Based on the macroscopic types according to Bormann's classification, pure mucinous carcinoma was mostly Type I, intraductal papillary mucinous carcinoma was mostly Type II, signet ring cell type mucinous carcinoma was mostly Type IV, and mixed cell type mucinous carcinoma was mostly Type III. The 5-year survival rate was 69.2, 64.2, 0, and 31.5%, respectively. There was a statistical difference in the lymph node metastasis rate and survival rate of the four carcinoma types. The invasion features of pure mucinous carcinoma entailed penetrating corrosively in a push-in form, without blood vessel or lymphatic metastasis and with few lymphocytes and lymphatic nodules in the marginal area. Thus, there was little lymph node metastasis and invasion of nerves. The HER2 protein expression rate was 40.2% (76/189), the HER2 gene amplification detected by FISH technology was 16.9% (32/189). Conclusion: The independent histological type, four subtypes, and histopathological classification of gastric mucinous adenocarcinoma are important for the prognosis evaluation and precise treatment of this disease.

Cyclic topology enhances the killing activity of polycations against planktonic and biofilm bacteria.

Bacterial biofilms, as a fortress to protect bacteria, enhance resistance to antibiotics because of their limited penetration, which has become a major threat to current anti-infective therapy. Antimicrobial polycations have received wide attention to kill planktonic bacteria because of their unique antimicrobial mechanism without drug resistance but it is still hard to kill the bacteria in the deep of the biofilm. Unlike linear polymers, the cyclic topology has been demonstrated with enhanced penetration in tissues, which is attributed to the lack of end groups, constrained conformation and a smaller hydrodynamic volume, opening a new sight of polycations in the antibacterial application against biofilms. Here, polycations with different topologies including linear and cyclic polycations were synthesized and their killing activity against planktonic and biofilm bacteria was studied. The experimental results showed the enhanced antibacterial activity of cyclic polycations for planktonic bacteria, which is presumably attributed to their smaller hydrodynamic volume, higher local density of positive charge and more interactions between cation units and the bacterial membrane than their linear analogues. Besides, cyclic polycations exhibit enhanced killing effect for biofilm bacteria and inhibition effect for biofilms with 5-7 times and 2-3 times enhancements than the linear polycations, respectively. Furthermore, an Escherichia coli infection model on mice was established and the therapeutic effects of cyclic and linear polycations were evaluated. Compared with the linear polycations, the cyclic polycations exhibited enhanced antibacterial activity with an ∼4 times increase, promoting the healing of the infected wounds. This work provides a new perspective in the development of antimicrobial polycations, which are promising therapeutic agents to kill planktonic and biofilm bacteria without drug resistance.

Expression of Cyclin D1 gene in ovarian cancer and effect of silencing its expression on ovarian cancer cells based on the Oncomine database.

We aimed to analyze the expression of Cyclin D1 (CCND1) gene in ovarian cancer and the influence of silencing its expression on ovarian cancer cells based on the Oncomine database. The expression of CCND1 gene in ovarian cancer was analyzed by utilizing the relevant information in different tumors and Oncomine database. The correlation between CCDN1 expression level and prognosis of ovarian cancer was analyzed by the online database Kaplan-Meier (kmplot.com). The expression of CCND1 gene in ovarian cancer and the effect of silencing its expression on cancer cells were analyzed by cell experiments. After mining and comprehensively analyzing 7 studies on the differential expression of CCND1 gene in ovarian cancer tissue and normal ovarian tissue included in the Oncomine database, it was found that the median value of CCND1 gene ranked 218.0 (P = 8.03 × 10-6) among all differentially expressed genes, suggesting that CCND1 gene expression in ovarian cancer tissue was higher than that in normal ovarian tissue. Adib Ovarian, Bonome Ovarian and Hendrix Ovarian microarrays revealed that the expression of CCND1 gene in ovarian cancer tissue was significantly higher than that in normal ovarian tissue (P < 0.05). Kaplan-Meier Plotter database showed that the overall survival and progression-free survival of ovarian cancer patients with high CCND1 expression were significantly shorter than those of patients with low CCND1 expression (P < 0.05). The expression levels of CCND1 gene in normal ovarian epithelial cells and SKOV3 ovarian cancer cells were detected by RT-PCR. The expression of CCND1 gene was significantly higher in SKOV3 group than that in control group (P < 0.01). Flow cytometry revealed that the percentage of cells in G0/G1 phase was significantly higher, while that in S phase was lower in SKOV3 + siCCND1 group than the values of SKOV3 and SKOV3 + siNC groups (P < 0.05). The apoptosis rate of ovarian cancer cells was significantly higher in SKOV3 + siCCND1 group than those of SKOV3 and SKOV3 + siNC groups (P < 0.01). CCND1 gene is highly expressed in ovarian cancer tissue and related to prognosis. Preoperative evaluation of CCND1 gene expression in ovarian cancer patients may benefit the assessment of risk and prognosis.

Association of the rs17250932, rs4794067, and rs2240017 polymorphism in the TBX21 gene with autoimmune diseases: A meta-analysis.

OBJECTIVE: To evaluate systematically the association between TBX21 gene polymorphisms (rs17250932, rs2240017, and rs4794067) and the risk of autoimmune diseases in Asian populations. METHODS: The Medline, Web of Science, and Chinese Biomedical Literature Database were used to retrieve eligible studies that were published before July 2020. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were calculated by using the dominant model, heterozygote contrast model, and allelic contrast model. Publication bias was evaluated using contour-enhanced funnel plots and Egger's regression test. Sensitivity analysis was conducted to assess the robustness of this meta-analysis. RESULTS: A total of 12 eligible studies, including 3834 patients and 4824 healthy controls, were recruited in this meta-analysis. The pooled data demonstrated that TBX21 rs2240017 and rs4794067 polymorphisms were significantly associated with the risk of autoimmune diseases in Asian populations in allelic contrast model (OR: 1.456, 95% CI: 1.131-1.875, P = 0.004; OR: 0.766, 95% CI: 0.615-0.954, P = 0.017), heterozygote comparison model (OR: 1.647, 95% CI: 1.239-2.189, P = 0.001; OR: 0.796, 95% CI: 0.634-0.999, P = 0.049), and dominant model (OR: 1.572, 95% CI: 1.194-2.071, P = 0.004; OR: 0.767, 95% CI: 0.607-0.970, P = 0.027). The G allele of rs2240017 may be a risk factor for autoimmune diseases, and the T allele of rs4794067 may increase the risk of autoimmune diseases. However, we failed to find evidence of the association between TBX21 rs17250932 polymorphism and susceptibility to autoimmune diseases. No publication bias was established in this meta-analysis. CONCLUSION: This meta-analysis indicated that TBX21 rs2240017 and rs4794067 polymorphism confer susceptibility to autoimmune diseases, but not rs17250932.

Association of the rs17250932, rs4794067, and rs2240017 polymorphism in the TBX21 gene with autoimmune diseases: A meta-analysis

Objective: To evaluate systematically the association between TBX21 gene polymorphisms (rs17250932, rs2240017, and rs4794067) and the risk of autoimmune diseases in Asian populations. Methods: The Medline, Web of Science, and Chinese Biomedical Literature Database were used to retrieve eligible studies that were published before July 2020. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were calculated by using the dominant model, heterozygote contrast model, and allelic contrast model. Publication bias was evaluated using contour-enhanced funnel plots and Egger’s regression test. Sensitivity analysis was conducted to assess the robustness of this meta-analysis. Results: A total of 12 eligible studies, including 3834 patients and 4824 healthy controls, were recruited in this meta-analysis. The pooled data demonstrated that TBX21 rs2240017 and rs4794067 polymorphisms were significantly associated with the risk of autoimmune diseases in Asian populations in allelic contrast model (OR: 1.456, 95% CI: 1.131–1.875, P = 0.004; OR: 0.766, 95% CI: 0.615–0.954, P = 0.017), heterozygote comparison model (OR: 1.647, 95% CI: 1.239–2.189, P = 0.001; OR: 0.796, 95% CI: 0.634–0.999, P = 0.049), and dominant model (OR: 1.572, 95% CI: 1.194–2.071, P = 0.004; OR: 0.767, 95% CI: 0.607–0.970, P = 0.027). The G allele of rs2240017 may be a risk factor for autoimmune diseases, and the T allele of rs4794067 may increase the risk of autoimmune diseases. However, we failed to find evidence of the association between TBX21 rs17250932 polymorphism and susceptibility to autoimmune diseases. No publication bias was established in this meta-analysis. Conclusion: This meta-analysis indicated that TBX21 rs2240017 and rs4794067 polymorphism confer susceptibility to autoimmune diseases, but not rs17250932 (AU)

Potential use of glutathione as a treatment for Parkinson's disease.

The aim of the present study was to assess the efficacy and safety of glutathione (GSH) for the treatment of Parkinson's disease (PD). The PubMed, Cochrane Library, OvidSP, Web of Science, China Science and Technology Journal Database, Chinese National Knowledge Infrastructure and China Wanfang Standards Database databases were systematically searched from the inception dates to October 1st, 2019, using the key words'glutathione' or 'GSH' and 'Parkinson' or 'Parkinson's disease' or 'PD'. The quality of the included articles was assessed using the bias risk assessment tool of the Cochrane systematic evaluator manual (version 5.1.0). Pooled analysis of the relevant data was performed using RevMan 5.3 software and subgroup analysis was performed to determine the impact of the dosage (300 vs. 600 mg) on the outcome measures. A total of seven randomized controlled trials involving 450 participants were included in the meta-analysis. The results of the present study indicated a statistically significant difference between the GSH and control groups, in terms of the Unified Parkinson's Disease Rating Scale (UPDRS) III [standard mean difference (SMD), -0.48; 95% CI, -(0.88-0.08); P=0.02] and GSH peroxidase (SMD, 1.88; 95% CI, 0.52-3.24; P=0.007). However, the differences in the UPDRS I (SMD, -0.04; 95% CI, -0.25-0.16; P=0.70) and UPDRS II (SMD, 0.03; 95% CI, -0.17-0.24; P=0.77) score and in side effects were not statistically significant between the groups. Subgroup analyses revealed that the dosage (300 vs. 600 mg) was an influencing factor for UPDRS III. The present study demonstrated that GSH may mildly improve motor scores in PD, but not at the expense of increased adverse events.

Non-catecholamine vasopressors in the treatment of adult patients with septic shock-evidence from meta-analysis and trial sequential analysis of randomized clinical trials.

BACKGROUND: Norepinephrine (NE) has currently been the first-choice vasopressor in treating septic shock despite generally insufficient for patients with refractory septic shock. The aim of this update meta-analysis was to assess the safety and efficacy of a combination of non-catecholamine vasopressors (vasopressin/pituitrin/terlipressin/selepressin/angiotensin II) and NE versus NE in managing adult septic shock patients. METHODS: We conducted this study of literatures published from the inception to April 30, 2020, using PubMed, Embase, and the Cochrane Library databases without language restriction. Randomized controlled trials comparing NE with non-catecholamine vasopressors among adult septic shock patients were included in this meta-analysis. Pooled effects of relative risk (RR) or standard mean difference (SMD) and corresponding 95% confidence interval (CI) were calculated using a random-effects model. RESULTS: Twenty-three studies covering 4380 participants were finally enrolled. The combined analysis of non-catecholamine vasopressors resulted in a nonsignificant reduction in 90-day/ICU/hospital mortality except for a decreased in 28-day mortality (n = 4217; RR, 0.92; 95% CI 0.86-0.99; P = 0.02). This favorable result was subsequently verified by the subgroup analyses of low risk of bias studies (RR = 0.91, 95% CI = 0.84 to 0.98; P = 0.02) and catecholamine-resistant refractory shock patients group (RR, 0.84; 95% CI = 0.70-1.00; P = 0.048). The pooled analysis of non-catecholamine vasopressors showed a 14% higher success rate of shock reversal at 6 h, a 29% decreased risk of continuous renal replacement therapy, but a 51% increased risk of hyponatremia and a 2.43 times higher risk of digital ischemia. Besides, the pooled data showed that non-catecholamine vasopressors decreased heart rate (HR) (SMD, - 0.43; 95% CI - 0.66 - - 0.19; P < 0.001), serum creatinine (- 0.15; 95% CI - 0.29 - - 0.01; P = 0.04), and the length of mechanical ventilation (MV) (- 0.19; 95% CI - 0.31 - - 0.07; P < 0.01, but there was no significant difference in other parameters. CONCLUSIONS: Current pooled results suggest that the addition of NE to non-catecholamine vasopressors was associated with a marginally significant reduction in 28-day mortality. Moreover, they were able to shorten the length of MV, improved renal function, decreased HR, and increased the 6-h shock reversal success rate at the expense of increased the risk of hyponatremia and digital ischemia.

[A study on quality of Paridis Rhizoma and consideration on standards of Paridis Rhizoma in Chinese Pharmacopoeia].

Thin layer chromatography, high performance liquid chromatography and multivariate statistical analysis were integrated in current study to provide a basis for the quality evaluation and the standard improvement of Paridis Rhizoma(Chinese name: Chong-lou). The results demonstrated that the primary saponins in the two authorized sources of Paridis Rhizoma were polyphyllinsⅠ, Ⅱ and Ⅶ, while the rhizome of Trillium tschonoskii an adulterant of Paridis Rhizoma was rich of polyphyllin Ⅵ. Therefore, the apparent content of polyphyllin Ⅵ plays a determinant role towards the source authentication of raw materials and decoction slices of Paridis Rhizoma, whose adulterants frequently occur in the market. Moreover, the contents of polyphyllin Ⅵ in the two authorized sources could meet the requirements of Chinese Pharmacopoeia. Therefore, we suggested that polyphyllin Ⅵ should not be omitted from the quality standard of Paridis Rhizoma in the Chinese Pharmacopoeia, and on the other side, polyphyllinsⅠ, Ⅱ and Ⅶ should be the eligible quality indicators. The study aims to sound information and evidences for the quality evaluation of Paridis Rhizoma, and also to provide a theoretical basis for the standard revision of Paridis Rhizoma in the future Chinese Pharmacopoeia.

[Comparative study on quality of decoction pieces of Saposhnikovia divaricata with different growth patterns and years and thinking of standard of decoction pieces of S. divaricata in Chinese Pharmacopoeia].

This study aims to compare the internal chemical composition and appearance indifferent growth patterns and years of Saposhnikovia divaricata decoction pieces,which was applied to explore the effect of growth patterns and years on its quality. The appearance characteristic data of 55 batches of different growth patterns and years of S. divaricata were collected using PANTONE color card.High performance liquid chromatography( HPLC) was used to determine the contents of prim-O-glucosyl-cinmifugin,cimifugin,4-O-ß-D-glucosyl-5-O-methylvisamminol and sec-O-glucosylhamaudol. The content of alcohol soluble extract and water-soluble extract were determined by hot-dip method. The content of volatile oil was determined by steam distillation. The correlation between growth patterns and years and the contents of 4 chromones,extracts and volatile oil were analyzed by modern statistical methods. Also,the method of comprehensively evaluating the quality of Chinese herbal pieces was developed by combining the growth patterns and years,appearance and chemical indexes. MTT assay was used to evaluate the effects on the survival rate of RAW264. 7 cells at four different concentrations of chromones and LPS was used to stimulate well-growing RAW264. 7 cells to establish an inflammatory model. The contents of NO and TNF-α in cell supernatant were detected by NO test kit and ELISA method. The contents of alcohol soluble extracts and water-soluble extracts in different growth patterns and years are: wild productsperennial cultivation>annual cultivation; the contents of four chromones are: wild products>perennial cultivation and annual cultivation. There was no significant difference between the sum of the two indexes in the Pharmacopoeia of perennial cultivation and wild products. 4 chromones showed no toxicity to RAW264. 7 cells at 5 mg·L-1. The release of NO and TNF-α was inhibited by 4 chromones and the anti-inflammatory effect of cimifugin was the best. In summary,there are obvious differences in appearance characteristics,internal quality and effects between different growth patterns and years. It showed that the wild products were superior to the perennial cultivation and the perennial cultivation was superior to the annual cultivation. In order to alleviate the shortage of wild S. divaricata resources,it is suggested that the Chinese Pharmacopoeia standard should increase the character of decoction pieces of perennial cultivation,and properly raise the limit requirement of the sum of the two indexes in the Chinese Pharmacopoeia to ensure the clinical demands and effect.

Photothermal Therapy Nanomaterials Boosting Transformation of Fe(III) into Fe(II) in Tumor Cells for Highly Improving Chemodynamic Therapy.

Chemodynamic therapy based on Fe2+-catalyzed Fenton reaction holds great promise in cancer treatment. However, low-produced hydroxyl radicals in tumor cells constitute its severe challenges because of the fact that Fe2+ with high catalytic activity could be easily oxidized into Fe3+ with low catalytic activity, greatly lowering Fenton reaction efficacy. Here, we codeliver CuS with the iron-containing prodrug into tumor cells. In tumor cells, the overproduced esterase could cleave the phenolic ester bond in the prodrug to release Fe2+, activating Fenton reaction to produce the hydroxyl radical. Meanwhile, CuS could act as a nanocatalyst for continuously catalyzing the regeneration of high-active Fe2+ from low-active Fe3+ to produce enough hydroxyl radicals to efficiently kill tumor cells as well as a photothermal therapy agent for generating hyperthermia for thermal ablation of tumor cells upon NIR irradiation. The results have exhibited that the approach of photothermal therapy nanomaterials boosting transformation of Fe3+ into Fe2+ in tumor cells can highly improve Fenton reaction for efficient chemodynamic therapy. This strategy was demonstrated to have an excellent antitumor activity both in vitro and in vivo, which provides an innovative perspective to Fenton reaction-based chemodynamic therapy.

Dose-dependent neurotoxicity caused by the addition of perineural dexmedetomidine to ropivacaine for continuous femoral nerve block in rabbits.

OBJECTIVE: This study was designed to evaluate the neurotoxicity of dexmedetomidine combined with ropivacaine for continuous femoral nerve block in rabbits. METHODS: Thirty New Zealand rabbits were randomly divided into 5 groups of 6 rabbits each and received a continuous femoral nerve block with saline; 0.25% ropivacaine; or 1, 2, or 3 µg/mL of dexmedetomidine added to 0.25% ropivacaine (Groups A-E, respectively). Sensory and motor function was assessed after the nerve block. The rabbits were anesthetized and killed after 48 hours of a continuous femoral nerve block, and the femoral nerves were removed for light and electron microscopy analyses. RESULTS: The behavior scores were highest in Group A at 2 and 6 hours after injection. The scores were higher in Groups B and C than in Groups D and E at these same time points. All groups showed normal pathological tissues in the femoral nerves under optical microscopy. Under electron microscopy, histological abnormalities were observed only in Group E; none of the other groups exhibited pathological abnormalities. Quantitative analysis of the myelin sheath area revealed no significant difference in the axonal area, total area of the myelin sheath, or ratio of the total axonal area to the total area of the myelin sheath in all groups. CONCLUSION: The lowest doses of dexmedetomidine (1 and 2 µg/mL) combined with 0.25% ropivacaine for continuous femoral nerve block resulted in no neurotoxic lesions, but the higher dose (3 µg/mL) resulted in neurotoxic lesions in this rabbit experimental model.