Risk factors and intervention of caregiver burden in Parkinson's disease: a systematic review and meta-analysis.

PURPOSE: This study summarized characteristics and risk factors of caregiver burden in PD patients and used meta-analysis to verify the effectiveness of the intervention on caregiver burden. METHODS: Systematic review and meta-analysis were conducted. RESULTS: Forty-nine articles that involved 5387 caregivers of patients with PD were included in this study. Results of systematic review indicated that Zarit burden Inventory (ZBI) was the most used scale to measure the caregiver burden. All scales revealed caregivers of PD patients had mild to moderate caregiver burden. For the PD patients with longer disease duration, severer disease severity, more negative emotion and cognition impairment, their caregivers intended to have higher caregiver burden. The caregiver with negative emotion and who spent more time on caregiving indicated higher caregiver burden than the others. The caregiver burden was not improved after deep brain stimulation (DBS). Meta-analysis showed that cognitive behavior therapy and palliative care had no significant effect to reduce caregiver burden in PD patients' caregiver. CONCLUSION: Caregivers of PD patients experienced mild to moderate caregiver burden. Demographic factor, diseased-related factor and negative emotional factor were the risk factors of caregiver burden. Health education and care support for long-term management after DBS surgery should be provided for patients and caregivers to decrease caregiver burden.

Independent risk factors for in-hospital outcome of myasthenic crisis: a prospective cohort study.

Background: Myasthenic crisis (MC) is a life-threatening condition for myasthenia gravis (MG). Therapeutic plasma exchange (TPE) and intravenous immunoglobulin (IVIg) efficaciously treat patients with MC. However, not every MC responds well to rescue therapies, and the determinants for outcome with the evidence from prospective cohorts are still lacking. Objectives: To explore the risk factors for in-hospital outcomes in patients with MC. Methods: Using a national neuromuscular center-based cohort of MG with prospective follow-ups from the crisis to the post-crisis phase, we finally included 90 MC episodes from 76 independent patients who received a standard regimen of rescue therapies. Results: The mean admission age was 52.89 ± 15.72 years. With a female predominance of 63.16% (48/76) and a high proportion of thymoma-associated MG (TMG) of 63.16% (48/76), the overall in-hospital mortality was 2.63% (2/76) and the average duration for mechanical ventilation (MV) use was 17.09 ± 13.36 days (0-53 days). In contrast to the patients with anti-acetylcholine receptor (AChR) antibodies, muscle-specific tyrosine kinase (MuSK)-associated MC exhibited a shorter MV support (5.20 ± 5.07 versus 17.40 ± 13.24 days, p = 0.023), length of intensive care units (ICU) stay (6.00 ± 4.64 versus 19.16 ± 17.54 days, p = 0.046), and hospital stay (16.00 ± 4.12 versus 34.43 ± 20.48 days, p = 0.011). Thymoma [odds ratio (OR): 0.200, 95% confidence interval (CI): 0.058-0.687, p = 0.011], partial pressure of carbon dioxide (PCO2) in blood gas before MV (OR: 1.238, 95% CI: 1.015-1.510, p = 0.035), and pneumonia (OR: 0.204, 95% CI: 0.049-0.841, p = 0.028) were identified as independent risk factors for prolonged MV use. TMG patients with thymoma burden exhibited a notable longer MV use (22.08 ± 17.54 versus 8.88 ± 6.79 days, p = 0.001), a prolonged hospital stay (40.40 ± 26.13 versus 23.67 ± 13.83 days, p = 0.009) compared with non-TMG. Even with complete thymoma resection (R0), TMG exhibited an unfavorable outcome versus non-TMG. Conclusion: With timely rescue therapies and prospective follow-ups, the in-hospital outcome of MCs was substantially improved. Thymoma, PCO2 in blood gas before MV, and pneumonia were identified as independent risk factors for prolonged MV use.

Risk factors for in-hospital outcome of myasthenic crisis Myasthenic crisis (MC) is a life-threatening condition for myasthenia gravis (MG). Therapeutic plasma exchange (TPE) and intravenous immunoglobulin (IVIg) efficaciously treat patients with MC. However, not every MC responds well to rescue therapies, and the determinants for outcome with the evidence from prospective cohorts are still lacking. Using a national neuromuscular center-based cohort of MG with prospective follow-ups from the crisis to the post-crisis phase, we were able to include 90 MC episodes from 76 independent patients who received a standard regimen of rescue therapies. The mean admission age was 52.89±15.72 years. With a female predominance and a high proportion of thymoma-associated MG. The overall in-hospital mortality was 2.63% (2/76) and the average duration for MV use was 17.09±13.36 days (0-53 days). In contrast to the patients with anti-AChR antibodies, MuSK-associated MC exhibited a shorter MV support, length of ICU stay and hospital stay. Thymoma, PCO2 in blood gas before MV, and pneumonia were identified as independent risk factors for prolonged MV use. TMG patients with thymoma burden exhibited a notable longer MV use, a prolonged hospital stay compared with non-TMG. Even with complete thymoma resection (R0), TMG exhibited an unfavorable outcome versus non-TMG. With timely rescue therapies and prospective follow-ups, the in-hospital outcome of MCs was substantially improved. Thymoma, PCO2 in blood gas before MV, and pneumonia.

Clinical outcome and peripheral immune profile of myasthenic crisis with omicron infections: A prospective cohort study.

The impact of Omicron infections on the clinical outcome and immune responses of myasthenia gravis (MG) remained largely unknown. From a prospective multicenter MG cohort (n = 189) with 197 myasthenic crisis (MC), we finally included 41 independent MG patients to classify into two groups: the Omicron Group (n = 13) and the Control Group (n = 28). In this matched cohort study, all-cause mortality was 7.69% (1/13) in Omicron Group and 14.29% (4/28) in Control Group. A higher proportion of elevated serum IL-6 was identified in the Omicron Group (88.89% vs 52.38%, P = 0.049). In addition, the proportions of CD3+CD8+T in lymphocytes and Tregs in CD3+CD4+ T cells were significantly elevated in the Omicron Group (both P = 0.0101). After treatment, the Omicron Group exhibited a marked improvement in MG-ADL score (P = 0.026) and MG-QoL-15 (P = 0.0357). MCs with Omicron infections were associated with elevated serum IL-6 and CD3+CD8+T response. These patients tended to present a better therapeutic response after fast-acting therapies and anti-IL-6 treatment.

Improving the quality of self-management in discharged patients with multiple sclerosis: a best practice implementation project.

OBJECTIVES: This project determined current compliance with best practice recommendations for self-management in patients with multiple sclerosis (MS) and used a web-based intervention to implement strategies to improve the quality of self-management in discharged patients with MS. METHODS: Guided by the JBI Evidence-based Model of Health care, this project applied the 7 phases of the JBI Evidence Implementation Framework to improve the quality of self-management in MS patients. RESULTS: After implementation, compliance significantly improved across all criteria compared with the baseline audit. All patients were assessed to determine their ability to self-manage (Criterion 1). All health care providers were trained to facilitate self-management and behavioral change (Criterion 2). All patients had self-management goals and action plans that were set together by both health care providers and patients (Criteria 3, 5, 6, 7). All patients received education through online patient education courses and were given an education handbook (Criterion 4). The agreed action plan was documented (Criterion 8). All members of the multidisciplinary team coordinated the services required by the patients (Criterion 9) and provided appropriate support to help patients achieve their goals and solve problems through a WeChat group and the communication module on the self-management online platform (Criterion 10). CONCLUSION: This implementation project effectively promoted practice change by enhancing patients' knowledge of self-management and staff awareness of delivering self-management support to MS patients.

Enterococcus faecium R-026 combined with Bacillus subtilis R-179 alleviate hypercholesterolemia and modulate the gut microbiota in C57BL/6 mice.

Probiotics have been demonstrated to lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in individuals with mild hypercholesterolemia. Our previous study found that intervention with Bacillus subtilis R-179 and Enterococcus faecium R-026, well-known probiotics, improved obesity-associated dyslipidemia through ameliorating the gut microbiota, but similar studies on hypercholesterolemia have not been reported to date. Here, we investigated the therapeutic effect of live combined B. subtilis R-179 and E. faecium R-026 (LCBE) in a C57BL/6 mouse model of hypercholesterolemia. A total of 40 mice were administered with a high-cholesterol diet (containing 1.2% cholesterol) to establish a state of hypercholesterolemia for 4 weeks. Then, mice were divided into one model group (group M) and three treatment groups (n = 10 per group), which were administered with LCBE at 0.023 g/mouse/day (group L) or 0.230 g/mouse/day (group H), or atorvastatin 0.010 g/kg/day (group A), for 5 weeks while on a high-cholesterol diet. LCBE at high doses significantly alleviated the symptoms of group M and reduced serum TC, LDL-C, and lipopolysaccharide (LPS). LCBE improved liver steatosis and adipocyte enlargement caused by a high-cholesterol diet. In addition, the administration of LCBE regulated the change in gut microbiota and diversity (Shannon index). Compared with group M, the relative abundance of Actinobacteriota, Colidextribacter, and Dubosiella dramatically decreased in the treatment groups, which were positively correlated with serum TC and LPS. These findings indicated that the mechanism of action of LCBE in treating hypercholesterolemia may be modulation of the gut microbiota. In conclusion, LCBE ameliorated lipid accumulation, reduced inflammation, and alleviated the gut microbiota imbalance in hypercholesterolemic mice. These findings support the probiotic role of LCBE as a clinical candidate for the treatment of hypercholesterolemia.

The gut microbiome: an important factor influencing therapy for pediatric acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most prevalent form of pediatric leukemia. The gut microbiome (GM) is crucial for proper nutrition, immunity, and biological conflict. Since the relationship between ALL and GM is bidirectional, ALL occurrence and treatment are closely related to GM destruction and the development of impaired immunity. Studies have discovered significant GM alterations in patients with ALL, including decreased diversity, that are likely directly caused by the development of ALL. Chemotherapy, antibiotic therapy, and hematopoietic stem cell transplantation (HSCT) are the mainstays of treatment for pediatric ALL. These approaches affect the composition, diversity, and abundance of intestinal microorganisms, which in turn affects therapeutic efficiency and can cause a variety of complications. Modulating the GM can aid the recovery of patients with ALL. This article discusses the various treatment modalities for pediatric ALL and their corresponding effects on the GM, as well as the changes in the GM that occur in children with ALL from diagnosis to treatment. Gaining a greater understanding of the link between ALL and the GM is expected to help improve treatment for pediatric ALL in the future.

Establishment and application of multiplex droplet digital polymerase chain reaction assay for bovine enterovirus, bovine coronavirus, and bovine rotavirus.

Bovine enterovirus (BEV), bovine coronavirus (BCoV), and bovine rotavirus (BRV) are still the major worldwide concerns in the health care of cattle, causing serious economic losses in the livestock industry. It is urgent to establish specific and sensitive methods to detect viruses for the early control of diseases. Droplet digital PCR (ddPCR) has been proposed to effectively detect viral particles, and it does not involve Ct values or standard curves. In this study, we designed specific primers and probes, based on conserved regions of viral genomes, to optimize protocols for a dual ddPCR assay for detecting BCoV and BRV and a multiplex ddPCR assay for BEV, BCoV, and BRV. Sensitivity assays revealed that the lower limit of detection for qPCR was 1,000 copies/µL and for ddPCR for BEV, BCoV, and BRV, 2.7 copies/µL, 1 copy/µL and 2.4 copies/µL, respectively. Studying 82 samples collected from diarrheal calves on a farm, our dual ddPCR method detected BCoV, BRV, and co-infection at rates of 18.29%, 14.63%, and 6.1%, respectively. In contrast, conventional qPCR methods detected BCoV, BRV, and co-infection at rates of 10.98%, 12.2%, and 3.66%, respectively. On the other hand, studying 68 samples from another farm, qPCR detected BCoV, BRV, BEV, and co-infection of BCoV and BEV at rates of 14.49%, 1.45%, 5.80%, and 1.45%, respectively. Our multiplex ddPCR method detected BCoV, BRV, BEV, co-infection of BCoV and BEV, and co-infection of BRV and BEV. at rates of 14.49%, 2.9%, 8.7%, 2.9%, and 1.45%, respectively. Studying 93 samples from another farm, qPCR detected BCoV, BRV, BEV, and co-infection of BCoV and BEV was detected at rates of 5.38%, 1.08%, 18.28%, and 1.08%, respectively. Co-infection of BCoV, BRV, BEV, BCoV, and BEV, and co-infection of BRV and BEV, were detected by multiplex ddPCR methods at rates of 5.38%, 2.15%, 20.45%, 1.08%, and 1.08%, respectively. These results indicated that our optimized dual and multiplex ddPCR methods were more effective than conventional qPCR assays to detect these viral infections.

Identifying causal genes for migraine by integrating the proteome and transcriptome.

BACKGROUND: While previous genome-wide association studies (GWAS) have identified multiple risk variants for migraine, there is a lack of evidence about how these variants contribute to the development of migraine. We employed an integrative pipeline to efficiently transform genetic associations to identify causal genes for migraine. METHODS: We conducted a proteome-wide association study (PWAS) by combining data from the migraine GWAS data with proteomic data from the human brain and plasma to identify proteins that may play a role in the risk of developing migraine. We also combined data from GWAS of migraine with a novel joint-tissue imputation (JTI) prediction model of 17 migraine-related human tissues to conduct transcriptome-wide association studies (TWAS) together with the fine mapping method FOCUS to identify disease-associated genes. RESULTS: We identified 13 genes in the human brain and plasma proteome that modulate migraine risk by regulating protein abundance. In addition, 62 associated genes not reported in previous migraine TWAS studies were identified by our analysis of migraine using TWAS and fine mapping. Five genes including ICA1L, TREX1, STAT6, UFL1, and B3GNT8 showed significant associations with migraine at both the proteome and transcriptome, these genes are mainly expressed in ependymal cells, neurons, and glial cells, and are potential target genes for prevention of neuronal signaling and inflammatory responses in the pathogenesis of migraine. CONCLUSIONS: Our proteomic and transcriptome findings have identified disease-associated genes that may give new insights into the pathogenesis and potential therapeutic targets for migraine.

Effect of boron on cadmium uptake and expression of Cd transport genes at different growth stages of wheat (Triticum aestivum L.).

Boron (B) is an essential microelement for plant growth and has been shown to reduce cadmium (Cd) toxicity in wheat through modulating gene expression. However, there is not enough information about the effects of different applications of B fertilizer on the accumulation of Cd, particularly throughout the wheat growth period. This experiment employed two different B fertilization methods. The soil application method utilized 1.5 mg B kg-1 soil (Cd+B) and foliar application utilized 0.1% (F0.1%), 0.3% (F0.3%), and 0.6% (F0.6%) B concentrations along with 4 mg kg-1 Cd. The results showed that B application in the soil reduced Cd concentrations per plant by 43.9% at the seedling stage, 74.59% in the roots, and 52.11% in the shoots at the elongation stage. At the same time, Cd concentrations in the roots were higher by B application at the anthesis and maturity stages, suggesting that B retains more Cd in the roots. The gray correlation analysis showed that the gray relational coefficients followed the following order: F0.3% > F0.1% > Cd+B > F0.6%. According to quantitative real-time PCR analysis, the six Cd transporters were mostly expressed in the roots at the seedling stage and anthesis stage. In addition, the expression of TCONS1113, TRIAE1060, and TRIAE5370 showed a negative correlation relationship with Cd concentration at the seedling stage, both in roots and shoots. At the anthesis stage, the expression of TCONS1113 and TRIAE5370 in roots was higher in Cd-treated plants compared to B-treated plants, and a similar tendency was noted for the expression of TRIAE5770 and TRIAE1060 in shoots as well. These results suggest that B application could significantly inhibit Cd uptake and translocation by regulating the expression of Cd transporter genes, especially at the seedling stage and the elongation phase in wheat.

Arteannuin B Enhances the Effectiveness of Cisplatin in Non-Small Cell Lung Cancer by Regulating Connexin 43 and MAPK Pathway.

Cisplatin (DDP)-based chemotherapy is the first-line regimen for advanced non-small cell lung cancer (NSCLC) patients. However, advanced NSCLC patients may have innate resistance to DDP or develop resistance during DDP treatment. We investigated a natural compound, arteannuin B (Art B), for its potential effects on DDP resistance in NSCLC. Art B was isolated from Artemisia annua by chromatographic purification and spectral elucidation. The activities of Art B on DDP-mediated effects were examined using in vitro and in vivo assays. We observed significant correlations in T stage, clinical stage, chemotherapy resistance and poor survival of NSCLC patients with low Cx43 expression. Art B enhanced the effectiveness of cisplatin by increasing Cx43 expression in normal and DDP-resistant NSCLC cells. Art B also increased DDP uptake through up-regulating Cx43. The combination of DDP and Art B showed better therapeutic effect than individual treatments both in vitro and in vivo. Art B increased intracellular Fe[Formula: see text] level, promoted calcium influx, and activated gap junction and MAPK pathways, which might contribute to Art B-mediated effects. Art B may serve as a new drug candidate to enhance the antitumor effect of DDP on NSCLC.

Facial Palsy as Initial Symptom in Glycine Receptor Antibody Positive Progressive Encephalomyelitis With Rigidity and Myoclonus: A Case Report.

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare and disabling syndrome characterized by painful spasms, myoclonic jerks, hyperekplexia, brainstem signs, and dysautonomia, which is considered to be a severe form of stiff person spectrum disorder (SPSD) and is mostly associated with glycine receptor antibodies. The PERM has an acute or subacute course, with complex and varied initial symptoms mainly manifest as stiffness and pain. The authors present the case of a male patient admitted for intractable stiffness and paroxysmal myoclonus of the lower extremities preceded by a 5-day history of facial weakness. After admission, his symptoms deteriorated rapidly. He developed progressive generalized hypertonia and painful spasms, which quickly spread to the upper extremities, and he suffered frequent paroxysmal myoclonus. Serum and cerebrospinal fluid (CSF) were tested by a cell-based assay, and both were positive for glycine receptor antibodies (GlyR-Abs). The patient developed complications, such as crushed teeth, lumbar vertebral compression fractures, and psoas major muscle abscess, during rapid disease progression, although he responded well after being treated with intravenous methylprednisolone and immunoglobulin. This report of PERM, initiated as facial palsy followed by acute progression, helps to expand the clinical spectrum of this rare autoimmune disorder and raise awareness of the prevention of complications.

The effect of integrated health care in patients with hypertension and diabetes: a systematic review and meta-analysis.

BACKGROUND: A growing number of studies show that integrated health care provides comprehensive and continuous care to patients with hypertension or diabetes. However, there is still no consensus about the effect of integrated health care on patients with hypertension or diabetes. The objective of this study was to verify the effectiveness of integrated health care for patients with hypertension or diabetes by using a systematic review and meta-analysis. METHODS: The study searched multiple English and Chinese electronic databases. The search period was from database inception to 31 October 2020. Systematic reviews and meta-analyses were conducted after assessing the risk of bias of each study. RESULTS: Sixteen studies that involved 5231 patients were included in this study. The results of the systematic review revealed that systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI) and glycosylated haemoglobin (HbA1c) are commonly used indicators for patients with hypertension or diabetes. Individual models and group- and disease-specific models are the most commonly used models of integrated health care. All the studies were from high-income and middle-income countries. Meta-analysis showed that integrated health care significantly improved SBP, DBP and HbA1c but not BMI. A comparison of interventions lasting 6 and 12 months for diabetes was conducted, and HbA1c was decreased after 12 months. The changes in SBP and DBP were statistically significant after using group- and disease-specific model but not individual models. HbA1c was significantly improved after using group- and disease-specific models and individual models. CONCLUSION: Integrated health care is a useful tool for disease management, and individual models and group- and disease-specific models are the most commonly used models in integrated health care. Group- and disease-specific models are more effective than individual models in the disease management of hypertension patients. The duration of intervention should be considered in the disease management of patients with diabetes, and interventions longer than 12 months are recommended. The income level may affect the model of integrated health care in selecting which disease to intervene, but this point still needs support from more studies.

Telemedicine application in patients with chronic disease: a systematic review and meta-analysis.

BACKGROUND: Telemedicine has been widely used for long-term care and self-management in patients with chronic disease, but there is no consensus regarding the effect of telemedicine on chronic disease management. The aim of this study is to review and analyse the effect of telemedicine on the management of chronic diseases such as hypertension, diabetes, and rheumatoid arthritis using a systematic review and meta-analysis. METHODS: We performed a comprehensive literature search of the Web of Science, PubMed, MEDLINE, EMBASE, CNKI (Chinese database), VIP (Chinese database), WanFang (Chinese database), and SinoMed (Chinese database) databases from their inception until December 31, 2021. The retrieved literature was screened and assessed independently by two authors. We used the risk-of-bias assessment tool recommended by the Cochrane Handbook for Systematic Reviews of Interventions 5.0.2 for assessing literature quality and Revman 5.3 software to conduct the meta-analysis. RESULTS: Fifteen articles were included in this study. The results of the systematic review indicated that telemedicine consultation and telemonitoring are the most commonly used intervention methods. Telemedicine is helpful for improving self-management in patients with rheumatoid arthritis. The results of the meta-analysis showed patients' index of glycosylated hemoglobin (HbA1c) improved after 12 months of intervention (MD = - 0.84; 95% CI = - 1.53, - 0.16; Z = 2.42; P = 0.02), and no significant differences in fasting blood glucose (FBG) levels were observed after 6 months of intervention (MD = - 0.35; 95% CI = - 0.75,0.06; Z = 1.69; P = 0.09). The results also showed that systolic blood pressure (MD = - 6.71; 95% CI = - 11.40, - 2.02; Z = 2.81; P = 0.005) was reduced after 6 months of intervention. CONCLUSION: Telemedicine had a positive effect on the management of diabetes, hypertension, and rheumatoid arthritis, especially when telemedicine consultation and telemonitoring method were used. When telemedicine was used as a disease management tool for patients with diabetes, the optimal intervention time is 12 months. Telemedicine improved the systolic blood pressure in hypertensive patients while also reducing negative emotions and enhancing medication adherence in rheumatoid arthritis patients.

Pneumonia and systemic inflammatory response syndrome as predictors for difficult-/prolonged-weaning after invasive ventilation in myasthenic crisis: A retrospective analysis of a Chinese cohort.

Weaning from invasive mechanical ventilation (MV) represents a pivotal step for myasthenic crisis (MC) patients. The aim was to evaluate the association between the weaning process and clinical outcomes, as well as to determine the independent predictors for difficult-/prolonged-weaning in MC. MC patients requiring invasive MV were recruited from Jan 2014 through Sep 2020. Among 124 consecutive MC patients, we finally included 66 patients (age 48.4 ±â€¯18.7 years, female 45.5%). According to the WIND (Weaning according to a New Definition) classification, these patients were classified into no-weaning (n = 5, 7.6%), short-weaning (n = 13, 19.7%), difficult-weaning (n = 26, 39.4%), and prolonged-weaning group (n = 22, 33.3%). Four-week functional assessment in short-weaning group was more favorable than that in difficult-/prolonged-weaning group (p<0.001). Length of hospital stay (23.0 (15.0-28.0) vs. 37.5 (27.0-54.8), p<0.001), length of ICU stay (17.0 (8.5-22.5) vs. 34.0 (20.3-45.0), p<0.001), duration on ventilation (6.0 (6.0-8.5) vs. 18.0 (13.3-30.0), p<0.001), and time interval from MV to first weaning (6.0 (6.0-8.0) vs. 11.0 (8.0-20.8), p<0.001) in short-weaning group were significantly shorter than those in difficult-/prolonged-weaning group. Short-weaning group had a lower prevalence of pneumonia (23.1% vs. 75.0%) and systemic inflammatory response syndrome (SIRS) (38.5% vs. 85.4%), and a higher value in the lowest hemoglobin level (123.0 ±â€¯12.9 g/L vs. 108.3 ±â€¯18.1 g/L) and the lowest serum albumin level (33.2 ±â€¯3.4 g/L vs. 29.9 ±â€¯4.2 g/L) than difficult-/prolonged-weaning group. Multivariate logistic regression analysis identified pneumonia and the presence of SIRS within one week of MC as independent predictors for difficult-/prolonged-weaning. The weaning process is associated with clinical outcomes in MC patients requiring ventilation. Pneumonia concurrence and the presence of SIRS within one week of MC were identified as independent predictors for difficult-/prolonged-weaning after invasive MV.

Metabolomic and antioxidant enzyme activity changes in response to cadmium stress under boron application of wheat (Triticum aestivum).

Boron (B) has previously been shown to inhibit cadmium (Cd) uptake in wheat. Here, we investigated the physiological response of external B application (C for no B added, B for B added, B+Cd for B and Cd added, B/Cd for B 24 h pretreatment before Cd added, B and Cd were 46.2 µM and 5 µM, respectively) on wheat growth under Cd stress. The results showed that the wheat growth was significantly weaker under Cd treatment, while B application did not significantly improve the wheat growth under Cd stress. However, B application decreased Cd concentrations and malondialdehyde (MDA) concentrations of shoot and root. The key enzyme activities including superoxide dismutase (SOD) and peroxidase (POD) significantly increased under Cd treatments while decreased under B treatments. Further, a total of 198, 680 and 204 of the differential metabolites were isolated between B and C treatment, Cd and C treatment and B+Cd and Cd treatment, respectively. The metabolites with up-accumulation in B application (B+Cd) roots were mainly galactaric acid, citric acid, N6-galacturonyl-L-lysine, D-glucose, while the metabolites with down-accumulation were mainly threoninyl-tryptophan and C16 sphinganine. The differential metabolic pathways were mainly concentrated in linoleic acid metabolism, galactose metabolism, sphingolipid metabolism, glycolysis/gluconeogenesis, propanoate metabolism in diabetic complications between B+Cd treatment and B treatment. The results indicate that B alleviates Cd toxicity in winter wheat by inhibiting Cd uptake, increasing antioxidant enzyme activity and changing metabolites.

Rationale and design of a phase 3b, prospective, randomized, open label, blinded-endpoint, multicenter trial of the efficacy and safety of urokinase thrombolysis comparing with antiplatelet agents for patients with minor stroke.

RATIONALE: Minor ischemic stroke attack has taken a significant part of cerebrovascular disease burden. Benefits of thrombolysis in minor stroke is under debates and the use of urokinase in developing countries needs to be further explored. AIM: TRUST (ThRombolysis of Urokinase for minor STroke) trial was designed to evaluate the efficacy and safety of intravenous urokinase for the treatment of acute minor ischemic stroke. SAMPLE SIZE ESTIMATES: To reach a double-sided type I error rate of 0.05 to test our hypothesis, with ß = 0.80, sample size of 1002 subjects were determined after further adjustment to account for up to 5% nonadherence. METHODS AND DESIGN: TRUST trial was developed with PROBE design, as a multicenter, randomized, open label, single-blind clinical trial with the stage of phase 3b. STUDY OUTCOMES: The proportion of patients retaining full ability of independent living, which is defined as patients scoring 0-1 on modified Rankin Scale score at 90 days. DISCUSSION: TRUST trial may potentially provide promising and affordable thrombolysis for acute minor ischemic stroke in the developing parts of the world.

COVID-19 Vaccination Attitudes With Neuromyelitis Optica Spectrum Disorders: Vaccine Hesitancy and Coping Style.

Background: Vaccination is an important method by which to stop the spread of coronavirus disease 2019 (COVID-19) in a population. Patients with neuromyelitis optica spectrum disorders (NMOSD) have unstable immune function and receive immunosuppressive therapy frequently, so they are hardly to make a decision to receive vaccination. Our study investigated the vaccine hesitancy and coping styles in patients with NMOSD to analyze the relationship between vaccine hesitancy and coping styles, and elucidate the factors influencing vaccine hesitancy. Methods: A convenient sampling method was used to recruit participants. The Adult Vaccine Hesitancy Scale and Medical Coping Modes Questionnaire were used to measure the vaccine hesitancy and coping style of the participants. Pearson correlation, multiple stepwise, linear regression, and one-way analysis of variance were used to analyze the data. Results: A total of 262 NMOSD patients were investigated. The score of vaccine hesitancy in NMOSD patients is lower (21.13 ± 4.355) than 25 points which indicated the patient is not considered to have vaccine hesitancy. The score for vaccine hesitancy was negatively correlated with the confrontation and avoidance coping styles (r = -0.481 and r = 0.423). That adoption of the coping styles of confrontation and avoidance as well as the residence of the patient were predictors of vaccine hesitation in NMOSD patients (R 2(adj) = 0.29, P < 0.001). In addition, the vaccine hesitancy scores of NMOSD patients residing in rural areas were significantly higher than those of patients living in urban areas (P < 0.01). Comparing with each level of education, the scores were not statistically significant in vaccine hesitancy and coping styles (P > 0.05). Conclusions: This study reveals that the NMOSD patients is not considered to have vaccine hesitancy, Patients who tend to adopt confrontation and avoidance coping styles have less vaccine hesitancy. Health authorities and medical specialist teams should strengthen effective vaccination information for patients with NMOSD, such as expert consensus or guidelines through various media to help them with decision-making. The significance of vaccination, the safety and side effects of COVID-19 vaccination and predicting of epidemiological trends of COVID-19 should be emphasized. More attention should be paid to NMOSD patients who living in rural areas.

In-depth peripheral CD4+ T profile correlates with myasthenic crisis.

OBJECTIVE: Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies against neuromuscular junctions. Myasthenic crisis (MC) represents the most severe state of MG with high in-hospital mortality. We aimed to identify immune signatures using in-depth profiling in MC, and to assess the correlations between immune biomarkers with clinical severity longitudinally. METHODS: We studied 181 participants including 57 healthy controls, 96 patients with MG who never experienced crisis and 28 MC patients from December 2018 through June 2020. Follow-up visits occurred prospectively from crisis to 6 months off-mechanical ventilation. The frequencies of 20 CD4+ T subpopulations and 18 serum cytokines were associated with clinical scores using correlations and principal component analysis. RESULTS: Patients in crisis exhibited a proinflammatory CD4+ T response with elevated Th1 (P = 0.026), and Th17 cells (P = 0.032); decreased T follicular helper 2 (Tfh2) cells (P < 0.001), Tnaive in Tfh cells (P < 0.001), ICOS- Tfh cells (P = 0.017), and T central memory in Tfh (P = 0.022) compared with controls, and increased frequencies of Tregs (P = 0.026) and Tfh17 (P = 0.045) compared with non-crisis MG. Cytokine cascade was identified in crisis including the ones associated with Th1 (IL-1ß/2/12p70/18/27/IFN-γ/TNF-α), Th2 (IL-4/5/13), Th17 (IL-6/17A/21/22/23/GM-CSF), Th9 (IL-9), and Treg (IL-10). Longitudinally, seven immune biomarkers including Tregs, IL-2/4/17A/IFN-γ/TNF-α/GM-CSF had significant correlations with MG-activities of daily living score. INTERPRETATION: Vigorous inflammatory CD4+ T signatures were identified in MC and are associated with clinical severity. Future research is needed to explore its potential candidacy for therapeutic intervention and predicting impending crisis.

Neuromyelitis optica spectrum disorder in China: Quality of life and medical care experience.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is considered to be the most common subset of CNS inflammatory demyelinating diseases in China. We aimed to systematically evaluate the impact of NMOSD on Chinese patients' quality of life (QoL), medical care experience, family wellness and social life. METHODS: A cross-sectional survey was performed involving 210 mostly AQP4-IgG-positive NMOSD patients from 25 provinces across China. An established survey instrument specific for NMOSD developed by The Guthy-Jackson Charitable Foundation and the Multiple Sclerosis Quality of Life-54 scale were implemented. Pearson or Spearman Correlation analysis was performed to define the significant determinants of QoL. RESULTS: More than 70% of the participants carried an initial diagnosis other than NMOSD, most of the patients were initially diagnosed with idiopathic optic neuritis (43.6%), multiple sclerosis (19.5%), gastrointestinal disorders (11.0%) and depression (10.0%). The average time elapsed between the first symptoms and accurate NMOSD diagnosis was 2.4 ± 4.9 years. Sixty-one percent of the participants reported NMOSD imposing a great negative impact on their life quality. NMOSD worsened both physical and emotional health (Short Form-36 physical health score: 37.9 ± 43.7, emotional health score: 44.8 ± 44.3). Visual impairment, pain, and bowel and bladder dysfunction were the greatest negative physical determinants of overall QoL. Worsened physical health was associated with diminished emotional health (r = 0.71, p < 0.001), and also with an interference in the ability to work (r = 0.41, p < 0.001). Only a small portion (3.3%) of the patients exhibited psychological resilience (with poor physical health but very robust emotional health). NMOSD significantly influenced the decision to have children in the study cohort, especially in the younger generation (r = -0.476, p < 0.001). Non-specific oral immunosuppressants were the most common preventive treatments, and only 13.9% received rituximab treatment. More than half (55.7%) of the patients reported dissatisfaction with current treatment options. A large proportion (88.1%) of the participants reported health insurance insufficient to pay all disease-related costs. Both concerns about treatment and about financial burden contributed to diminished QoL. CONCLUSIONS: This investigation yields novel insights into the physical, emotional, and socioeconomic impact of NMOSD on Chinese patients, which may afford potentially modifiable aspects of personal or clinical care to improve the patients' QoL, as well as serve as baseline data to reflect how future standard treatments will change patients' life quality.

Donning and doffing of personal protective equipment protocol and key points of nursing care for patients with COVID-19 in ICU.

Coronavirus pandemic is the most important public health event in the world currently. Patients with coronavirus disease 2019 (COVID-19) in a critical state are at risk of progressing rapidly into many serve complications; they require a high level of care from ICU nurses. How to avoid the virus to infect health care worker is also a critical issue. Based on the summarized experience of Chinese health workers, literature review and clinical practice, this article introduced donning and doffing of personal protective equipment (PPE) protocol and some keypoints of nursing critical care in patients with coronavirus disease 2019 (COVID-19): caring of patients requiring intubation and ventilation, venous thromboembolism (VTE) prevention, caring of patients on ECMO, caring for patients requiring enteral nutrition, psychological support and nursing management of COVID-19 ICU. This article introduced a useful protocol of donning and doffing personal protective equipment to protect health care workers, and provided key points for the ICU nurses how to take care of COVID-19 patients.