Iodine Status and Its Influencing Factors in Hospitalized and Healthy Preschool-Age Children.

Iodine is a trace element necessary for synthesizing thyroid hormones. It is especially crucial for the neurodevelopment and intellectual development of children. Preschool-age children admitted to the hospital tend to have more fragile physical and mental health, but few studies demonstrate their iodine status. Our study aimed to investigate the iodine status of hospitalized and healthy preschool-age children and to explore the factors influencing them. From January to December 2021, 426 children aged 3-6 years were admitted to the respiratory department for pneumonia, bronchopneumonia, or bronchiectasis, but they could eat normally and were recruited as hospitalized children. Six hundred ten healthy children aged 3-6 years were included. We collected anthropometric measurements and urine samples from hospitalized and healthy preschool-age children, and iodine status was assessed through urinary iodine concentration (UIC) and urinary iodine/creatinine ratio (UI/Cr). UIC was 40.1 and 166.1 µg/L for hospitalized and healthy preschool-age children, respectively (P < 0.001). Urinary creatinine concentration (UCr) was 0.2 and 0.8 g/L for hospitalized and healthy preschool-age children, respectively (P < 0.001). UIC decreased with increasing height z-scores in hospitalized children (Spearman's rho = -0.11, P = 0.022). A significantly increased risk of UIC < 100 µg/L was found in hospitalized children (OR = 9.1 (6.8, 12.2), P < 0.001) when compared to healthy children. In conclusion, hospitalized preschool-age children are likelier to have iodine insufficiency than healthy preschool-age children, especially those with good linear growth. Measures should be implemented to ensure adequate iodine intake of preschool-age children during hospitalization to avoid affecting their intellectual and physical development. Due to lower UCr in hospitalized children, creatinine is not appropriate for assessing iodine status in hospitalized children.

A novel frameshift mutation in RHAG leads to Rhnull phenotype in a Chinese individual.

BACKGROUND: We recently encountered a Rhnull phenotype proband within one family in the Chinese population. Rhnull is a rare autosomal recessive disorder characterized by the absence of the Rh antigens on the erythrocyte membrane, resulting in chronic hemolytic anemia. This study described the serological and molecular analysis of a Chinese Rhnull proband and his immediate family. METHODS: Red blood cells antigen phenotyping and antibody screening/identification were conducted. RHD, RHCE, and RHAG were analyzed using genomic DNA by polymerase chain reaction and sequence analysis. RESULTS: Serologic tests showed a D-C-E-c-e- phenotype in the proband associated with the suspicion of anti-Rh29 (titer 16). Molecular analyses showed a new mutation (c.406dupA) in exon 3 of RHAG. This duplication introduced a reading frameshift (p.Thr136AsnfsTer21). The RHAG mutation was found in the homozygous state for the proband and heterozygous state for his parents. CONCLUSION: We identified a novel RHAG mutation resulting in the Rhnull phenotype of the regulator type. Inheritance of the novel allele was shown by family study.

Association of anthropometric z score with complications and length of hospital stay in children with severe pneumonia aged 3 months to 5 years.

BACKGROUND: Severe pneumonia in children accounts for a significant healthcare burden, involving prolonged hospitalization and increased risk of complications. The prognosis is closely related to the child's nutrition status. Anthropometric z scores are preferred to evaluate growth levels in children. This study aimed to investigate the association of anthropometric z scores with complications and length of hospital stay (LOS) in children with severe pneumonia. METHODS: This study included 361 hospitalized children aged 3 months to 5 years with severe pneumonia in Tianjin, China. Anthropometry was performed, and anthropometric z scores were calculated. Blood laboratory indices were assessed, and complications and LOS were recorded. RESULTS: The average anthropometric z scores were -0.10 ± 1.15 (body mass index for age z score), 0.00 ± 0.97 (upper arm circumference for age z score [ACAZ]), and -0.14 ± 1.00 (triceps skinfold thickness for age z score [TSAZ]). The prevalence of complications was 73.96% (n = 267), including 82 children with only respiratory complications, 71 with only extrapulmonary complications, and 114 with both. After adjusting for confounding factors, compared with the noncomplication group, only the extrapulmonary complication group had a lower TSAZ (odds ratio [OR] = 0.597; 95% CI = 0.405-0.880; P < 0.05), whereas the respiratory and extrapulmonary complication group had a lower ACAZ (OR = 0.674; 95% CI = 0.469-0.969; P < 0.05) and TSAZ (OR = 0.573; 95% CI = 0.389-0.843; P < 0.05). ACAZ (ß = -0.368; 95% CI = -0.720 to 0.016; P < 0.05) and TSAZ (ß = -1.123; 95% CI = -1.470 to -0.777; P < 0.05) were negatively correlated with LOS. CONCLUSION: ACAZ and TSAZ were associated with complications and LOS of severe pneumonia in children aged 3 months to 5 years.

Nomogram to predict feeding intolerance in critically ill children.

Feed intolerance (FI) is significantly associated with poor prognosis in critically ill patients. This study aimed to understand the characteristics of children with FI and identify the factors predicting FI in critically ill children. This retrospective cohort study was conducted between January 2017 and June 2022 in the Pediatric Intensive Care Unit of a specialized children's hospital. Eighteen factors, including age, body mass index for age z-score (BAZ) < -2, paediatric index of mortality (PIM)3 score, Glasgow coma scale score, mechanical ventilation (MV), enteral nutrition delay, vasoactive drugs, sedatives, sepsis, heart disease, neurological disease, hypokalemia, arterial PH < 7.35, arterial partial pressure of oxygen (PaO2), blood glucose, hemoglobin, total protein, and albumin, were retrieved to predict FI. The outcome was FI during PICU stay. During the study period, a total of 854 children were included, of which 215 children developed FI. Six predictors of FI were selected: PIM3 score, MV, sepsis, hypokalemia, albumin, and PaO2. Multivariate logistic regression analysis showed that higher PIM3 score, MV, sepsis, hypokalemia, and lower PaO2 were independent risk factors for FI, whereas higher albumin was an independent protective factor for FI. The C-index of the predictive nomogram of 0.943 was confirmed at internal validation to be 0.940, indicating a good predictive value of the model. Decision curve analysis shows good clinical applicability of the nomogram in predicting FI.    Conclusion: The nomogram was verified to have a good prediction performance based on discrimination, calibration, and clinical decision analysis. What is Known: • Research has demonstrated that gastrointestinal (GI) dysfunction is not only a fundamental element of Multiple Organ Dysfunction Syndrome (MODS), but also the initiator of MODS. • Previous study has demonstrated a significant association between FI and poor prognosis in critically ill patients. What is New: • We excluded patients with primary gastrointestinal tract disease from our study, and we observed an incidence of FI of 25.2% in the Pediatric Intensive Care Unit (PICU). • Our study revealed that PIM3 score, MV, sepsis, hypokalemia, albumin, and PaO2 are significant predictors of FI.

Clinical characteristics of anti-AChR-MuSK-LRP4 antibody-negative myasthenia gravis in China.

INTRODUCTION/AIMS: Descriptions of the clinical characteristics of anti-AChR-MuSK-LRP4 antibody-negative myasthenia gravis (triple-negative myasthenia gravis, TNMG) are lacking in the current literature. Therefore, we investigated the clinical characteristics of TNMG in Chinese patients. METHODS: We retrospectively analyzed 925 patients with MG registered in the Department of Neuroimmunology, Henan Institute of Medical and Pharmaceutical Sciences from January 2015 to March 2021. RESULTS: One hundred six patients diagnosed with TNMG were included in the study. The average age of onset was 32.4 y, with a male-to-female ratio of 1:1. The age of onset showed a bimodal distribution: 0-9 y and 40-49 y. Adult patients were more likely to have weakness of limb and bulbar muscles (p < .05). Thymic hyperplasia was found in 20.2% of the patients. Younger patients were more likely to relapse. The rate of adult early-onset myasthenia gravis reaching complete stable remission and pharmacological remission was 47.6%, and the prognosis was better than that in juvenile-onset myasthenia gravis (p = .019). Older age of onset was the only risk factor for the development of generalized TNMG from ocular TNMG (R = 1.046, p = .002, 95% confidence interval 1.017-1.077). DISCUSSION: This study showed that the clinical characteristics of patients with TNMG varied among the different age groups. Significant findings included a bimodal distribution of onset age, coexisting thymic hyperplasia, and a generally favorable prognosis.

First donor haemovigilance system at a national level in China: Establishment and improvement.

BACKGROUND AND OBJECTIVES: No systematic study has measured the incidence of adverse reactions (ARs) to blood donation at the national level in China before 2019. The objective of this study was to establish an effective reporting system to collect information on ARs to blood donation in China. MATERIALS AND METHODS: The status of donor haemovigilance (DHV) in blood collection facilities in China was evaluated, and an online DHV system was established to collect data on ARs to blood donation in July 2019. The definitions of ARs were based on the International Society of Blood Transfusion (ISBT) standards. The prevalence and data quality of ARs from 2019 to 2021 were analysed. RESULTS: A standard online reporting system has been established for ARs to blood donation. In total, 61, 62 and 81 participating sites were included in this pilot study in 2019, 2020 and 2021, respectively. From July 2019 to December 2021, 21,502 cases of whole-blood-related ARs and 1114 cases of apheresis platelet-related ARs were reported, with an incidence of 3.8‰ and 2.2‰, respectively. Data completeness for key reporting elements improved from 41.7% (15/36) in 2019 to 74.4% (29/39) in 2020. Data quality analysis for the year 2021 yielded similar results as for 2020. CONCLUSION: The construction and continuous improvement of the blood donor safety monitoring system prompted the establishment of the DHV system. Improvements have been made to the DHV system in China, with a significant increase in sentinels and higher data quality.

Effectiveness of early glucocorticoids in myasthenia gravis: a retrospective cohort study.

Purpose: This study aimed to clarify the effect of early glucocorticoid (GC) application on achieving minimal manifestation (MM) status or better in the treatment of myasthenia gravis (MG) in the early clinical phase. Methods: A retrospective analysis was performed using data from 336 patients with MG who received GC therapy from January 2015 to September 2022 in the Zhengzhou University Henan Institute of Medical and Pharmaceutical Sciences Myasthenia Gravis Biobank (ZMB). Patients were divided into two groups: the early mono-GC group (treated with GC within 6 months of MG onset) and the delayed mono-GC group. Results: Kaplan-Meier analysis showed that the early mono-GC group achieved MM status earlier and more frequently than the delayed mono-GC group (log-rank test, p = 0.0082; hazard ratio [HR], 1.66; p = 0.011). The early mono-GC group had a lower maintenance oral GC dose than the delayed mono-GC group. In multivariate Cox regression analysis, early mono-GC (HR, 1.50; p = 0.043), early-onset MG (EOMG) (HR, 1.74; p = 0.034), and ocular MG (OMG) (HR, 1.90; p = 0.007) were associated with MM status or better. In conclusion, early mono-GC, EOMG, and OMG were positive predictors of treatment goals. In EOMG, OMG, and acetylcholine receptor antibody-positive MG (AChR-MG) subgroups, the maintenance oral GC doses in the early mono-GC group were significantly lower than the doses in the delayed mono-GC group (p < 0.05). Conclusion: Early intervention with GC led to better long-term outcomes and reduced the necessary maintenance dose of oral GC for patients with MG. EOMG and OMG were positive predictors of MM status or better with mono-GC.

Sorting nexin 17 increases low-density lipoprotein receptor-related protein 4 membrane expression: A novel mechanism of acetylcholine receptor aggregation in myasthenia gravis.

Myasthenia gravis (MG) is characterized by autoimmune damage to the postsynaptic membrane of the neuromuscular junction (NMJ) with impaired postsynaptic acetylcholine receptor (AChR) aggregation. Low-density lipoprotein receptor-related protein 4 (LRP4) plays an important role in AChR aggregation at endplate membranes via the Agrin-LRP4-muscle-specific receptor tyrosine kinase (MuSK) cascade. Sorting nexin 17 (SNX17) regulates the degradation and recycling of various internalized membrane proteins. However, whether SNX17 regulates LRP4 remains unclear. Therefore, we examined the regulatory effects of SNX17 on LRP4 and its influence on AChR aggregation in MG. We selected C2C12 myotubes and induced LRP4 internalization via stimulation with anti-LRP4 antibody and confirmed intracellular interaction between SNX17 and LRP4. SNX17 knockdown and overexpression confirmed that SNX17 promoted MuSK phosphorylation and AChR aggregation by increasing cell surface LRP4 expression. By establishing experimental autoimmune MG (EAMG) mouse models, we identified that SNX17 upregulation improved fragmentation of the AChR structure at the NMJ and alleviated leg weakness in EAMG mice. Thus, these results reveal that SNX17 may be a novel target for future MG therapy.

Bio-Inspired New Hydraulic Actuator Imitating the Human Muscles for Mobile Robots.

Limited load capacity is the bottleneck for the practical application of mobile multi-joint legged robots. And improving the efficiency of the drive system is a key factor in improving the load capacity. To improve the efficiency of mobile robots, in this paper, a new kind of actuator that imitates the driving mechanism of human muscles is innovatively designed and validated through experiments. The proposed actuator consists of a single power source and multiple plunger pistons, and imitates the configuration of a human muscle, to improve the efficiency and load capacities. The design proposed here represents a new class of driving methods. The actuator selects the most appropriate combination of the effective areas of plunger pistons like the human muscles, to ensure that the maximal output force aligns with the load force. To validate that the new actuator can improve the efficiency of hydraulic systems of mobile robots, a robotic arm incorporating a prototype of the new actuator was designed. The proposed system was validated through a series of experiments. The experiments show that the bionic actuator can adjust the flow rate of the system input by adjusting the number and size of the motion units involved in the work, and with the change in load force, it changes the output force by recruiting different motion units, which indicates good controllability. The results reported herein reveal that the application of bionics to the design of robotic actuator can significantly improve the efficiency and overall performance of the robots, and this biomimetic approach can be applied to a variety of robots.

Antibodies to Full-Length Agrin Protein in Chinese Patients With Myasthenia Gravis.

This study aimed to establish a cell-based assay (CBA) for the detection of agrin antibodies (Agrin-Ab) to explore the clinical features of agrin antibody-positive Chinese patients with myasthenia gravis (Agrin-MG). We developed a CBA based on the human full-length agrin protein expressed in HEK293T cells for the reliable and efficient detection of Agrin-Ab. Clinical data and serum samples were collected from 1948 MG patients in 26 provinces in China. The demographic and clinical features of Agrin-MG patients were compared with those of other MG patient subsets. Eighteen Agrin-MG cases were identified from 1948 MG patients. Nine patients were Agrin-Ab positive, and nine were AChR-Ab and Agrin-Ab double-positive (Agrin/AChR-MG). Eleven (61.11%) patients were males older than 40 years of age. The initial symptom in 13 (81.25%) cases was ocular weakness. Occasionally, the initial symptom was limb-girdle weakness (two cases) or bulbar muscle weakness (one case). Agrin-MG patients demonstrated slight improvement following treatment with either acetylcholinesterase inhibitor or prednisone; however, the combination of the two drugs could effectively relieve MG symptoms. In China, Agrin-MG demonstrated seropositivity rates of 0.92%. These patients were commonly middle-aged or elderly men. The patients usually presented weakness in the ocular, bulbar, and limb muscles, which may be combined with thymoma. These patients have more severe diseases, although the combination of pyridostigmine and prednisone was usually effective in relieving symptoms.

[Systematic review of efficacy and safety of Angong Niuhuang Pills in adjuvant treatment of cerebral hemorrhage].

To systematically review the efficacy and safety of Angong Niuhuang Pills in adjuvant treatment of cerebral hemorrhage. CNKI, VIP, Wanfang, CBM, PubMed, EMbase, Cochrane Library were retrieved to collect the randomized controlled trial(RCT) from the time of database establishment to November 2020. Two researchers screened out the literatures and extracted the data according to the inclusion and exclusion criteria. RevMan 5.3 software was used for Meta-analysis. A total of 13 RCTs were included, involving 1 196 patients with cerebral hemorrhage, with 599 in the treatment group and 597 in the control group, and all of them were treated with internal medicine. The results of Meta-analysis showed that compared with conventional therapy, the combined administration with Angong Niuhuang Pills could improve the effective rate in patients with cerebral hemorrhage(RR=1.25, 95%CI[1.18, 1.34], P<0.000 01), the National Institutes of Health stroke scale(NIHSS)score(MD=-5.18, 95%CI[-8.12,-2.23], P=0.000 6) and Glasgow coma scale(GCS) score(MD=1.12, 95%CI[0.46, 1.78], P=0.000 9), activity of daily living(ADL)(MD=15.70, 95%CI[14.05, 17.36 ], P<0.000 01), reduce the malondialdehyde(MDA)(MD=-1.73,95%CI[-2.81,-0.64],P=0.002), but with no statistically significant difference in hematoma volume changes between the two groups. In terms of safety, the combined administration with Angong Niuhuang Pills reduced the incidence of adverse reactions compared with the single administration of conventional therapy(RR=0.40, 95%CI[0.28, 0.57], P<0.000 01), with no serious adverse events. The existing clinical study evidences show that Angong Niuhuang Pills had a good effect in adjuvant treatment of cerebral hemorrhage, and can improve the treatment efficacy, activity of daily living and symptoms of neurological deficits, and reduce oxidative stress, with a higher safety. However, the methodological quality of the included studies is not high, so the above conclusions still need to be verified with more high-quality studies.

No correlation between acetylcholine receptor antibody concentration and individual clinical symptoms of myasthenia gravis: A systematic retrospective study involving 67 patients.

OBJECTIVE: To investigate the correlation between acetylcholine receptor antibodies (AChR-Ab) concentration levels and individualized clinical symptoms in patients with AChR myasthenia gravis (AChR-MG) in China. METHODS: ELISA was used to determine the concentration of AChR-Ab in patients with MG. The Myasthenia Gravis Foundation of America (MGFA) Clinical Classification, Quantitative Myasthenia Gravis (QMG) score, and MG-specific activities of daily living (MG-ADL) scoring systems were used to evaluate the clinical status of patients. Spearman correlation analysis was used to determine the correlation between the AChR-Ab concentration and clinical score. The changes in the antibody concentration and clinical score are shown in MGFA-antibody concentration-treatment plots. RESULTS: Autoantibody detection tests were performed in 67 patients, and their clinical scores were recorded. Forty-nine patients received immunosuppressive therapy, 17 patients received pyridostigmine only, and 1 patient under thymectomy without any medication. The AChR-Ab concentration correlated with the MGFA Classification in 5 (29.4%) patients in the pyridostigmine-only group and 15 (30.6%) patients in the immunosuppressive drug group. The changes in the MGFA Classification preceded the changes in the AChR-Ab concentration in 4 (23.5%) patients treated with pyridostigmine and 10 (20.4%) patients on immunosuppressive drugs. In patients on oral non-steroidal immunosuppressants, the AChR-Ab concentration changed by more than 50%, whereas the MGFA Classification did not increase. The AChR-Ab concentration decreased in 17/32 (53.1%) patients after thymectomy, and then increased, whereas the AChR-Ab concentration increased in 15/32 (46.9%) patients and the MGFA Classification decreased in 27/32 (81.8%) patients after thymectomy. The AChR-Ab concentration presented a slight correlation with the corresponding MGFA, QMG, and MG-ADL in patients with thymoma. DISCUSSION: In the Chinese AChR-MG population, the Changes in the AChR-Ab concentration in individuals with AChR-MG did not consistently correlate with the severity of clinical symptoms.

Peripheral blood hsa-circRNA5333-4: A novel biomarker for myasthenia gravis.

In this study, the potential of specific Circular RNAs (circRNAs) as novel peripheral blood biomarkers for myasthenia gravis (MG) was explored. We analyzed circRNAs in the peripheral blood of three normal controls and three MG patients using RNA microarray. Candidate circRNAs were validated in three independent cohorts by Quantitative Real-time polymerase chain reaction (qPCR). Eleven differentially expressed circRNAs were initially identified and four were confirmed in the first independent cohort. Hsa_circ_0076490 and hsa-circ_5333-4 had the largest areas under the curve (AUCs) of the receiver operating characteristics (ROC) and were validated in the second cohort. In the third cohort, hsa-circRNA5333-4 had a larger AUC: 0.864 (95% confidence interval [CI] = 0.801-0.928, P < 0.001), a stronger correlation with the Quantitative Myasthenia Gravis Score (qMG): r = 0.505 (P < 0.001) and was correlated with gender and acetylcholine receptor antibody levels (P < 0.05). So hsa-circRNA5333-4 represents a novel biomarker for the diagnosis and monitoring of MG.

Simulation of a Novel Tubular Microalgae Photobioreactor with Aerated Tangent Inner Tubes: Improvements in Mixing Performance and Flashing-Light Effects.

At present, large-scale and high-efficiency microalgal cultivation is the key to realizing the technology for carbon capture and storage (CCS) and bioresource recovery. Meanwhile, tubular photobioreactors (PBRs) have great potential for microalgal cultivation due to their high productivity. To improve the mixing performance and flashing-light effect, a novel tube PBR with the inner tube tangential to the outer tube was developed, whose radial aeration pores are situated along the length of the inner tube. The direction of aeration, aeration rate, light/dark cycle period (L/D), light-time ratio, average turbulent kinetic energy (TKE), and degree of synergy between the velocity and direction of the light field in the PBR were optimized by a computational fluid dynamics (CFD) simulation and field synergy theory. The results show that a downwards aeration direction of 30° and an aeration rate of 0.7 vvm are the most conducive to reducing the dead zone and improving the light/dark cycle frequency. Compared to the concentric double-tube PBR, the light/dark cycle frequency and light time of the tangent double-tube PBR increased by 78.2% and 36.2% to 1.8 Hz and 47.8%, respectively, and the TKE was enhanced by 48.1% from 54 to 80 cm2·s-2. Meanwhile, field synergy theory can be extended and applied to the design of tubular microalgae PBRs, and the average synergy of the light and velocity gradients across the cross-section increased by 38% to 0.69. The tangential inner tube aeration structure generated symmetrical vertical vortices between the light and dark areas in the PBR, which significantly improved the mixing performance and flashing-light effect. This novel design can provide a more suitable microenvironment for microalgal cultivation and is promising for bioresource recovery applications and improving the yield of microalgae.

[Effect of modified Buyang Huanwu Decoction on hemorrhagic transformation after rt-PA intravenous thrombolysis in patients with super early cerebral infarction].

To study the effect of modified Buyang Huanwu Decoction on the hemorrhagic transformation after intravenous thrombolysis of recombinant tissue type plasminogen activator(rt-PA) in patients with super early(onset time<4. 5 h) cerebral infarction. From March 2016 to July 2018,at the brain disease zone of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,212 cases of super early cerebral infarction were selected and divided into two group according to the randomized complete blocks designs: control group(106 cases) and traditional Chinese medicine group(106 cases). The control group was treated with rt-PA intravenous thrombolysis,while the traditional Chinese medicine group was treated with modified Buyang Huanwu Decoction in addition to the therapy of the control group. Both groups were treated for 14 days. Neurological deficit score,serum matrix metalloproteinase-9(MMP-9),neuron specific enolase(NSE),vascular endothelial growth factor(VEGF) and plasma cellular fibronectin(c-FN) levels,the incidence of hemorrhagic transformation,clinical efficacy and adverse drug reactions before and after treatment were compared between the two groups. According to the findings,at the 14 thday after treatment,the rank sum test of the grade data showed that the clinical efficacy of the traditional Chinese medicine group was better than that of the control group(Z =-2. 033,P = 0. 042); on the basis of χ2 test,the total efficiency of the traditional Chinese medicine group was higher than that of the control group(χ2= 4. 895,P =0. 027); the hemorrhagic transformation rate of the traditional Chinese medicine group was lower than that of the control group within14 days of treatment(χ2= 3. 962,P = 0. 047). MMP-9 levels in the traditional Chinese medicine group were lower than those in the control group at the 3 rd,5 th,7 th,10 th,14 thd after treatment(t =-2. 474,-3. 022,-5. 163,-6. 998,-9. 821; P = 0. 014,0. 003,0,0,0). The improvement of c-FN,NSE,VEGF and NIHSS scores in the traditional Chinese medicine group was superior to that of the control group after 14 days of treatment(t =-2. 343,-3. 187,-2. 129,-3. 105; P = 0. 020,0. 002,0. 034,0. 002). No obvious adverse reactions of modified Buyang Huanwu Decoction were observed during 14 days of treatment. Modified Buyang Huanwu Decoction could reduce the expressions of MMP-9,c-FN,NSE and VEGF after rt-PA intravenous thrombolysis in patients with super early cerebral infarction,and decrease the hemorrhagic transformation rate after thrombolysis,with high safety.

iTRAQ-Based Proteomics Analysis of Plasma of Myasthenia Gravis Patients Treated with Jia Wei Bu Zhong Yi Qi Decoction.

Myasthenia gravis (MG) is an autoimmune disease. A proportion of MG patients did not get satisfactory results after treatment with pyridostigmine and prednisone. Jia Wei Bu Zhong Yi Qi (Jia Wei BZYQ) decoction, a water extract from multiple herbs, has been demonstrated to be effective in the treatment of multiple "Qi deficiency type" diseases including MG in China. In this text, we investigated protein alterations in the plasma from healthy volunteers (C), MG patients without any treatment (T1), MG patients with routine western medical treatment (T2), and MG patients with combined treatments of Jia Wei BZYQ decoction and routine western medicines (T3) and identified some potential proteins involved in the pathogenesis and treatment of MG. iTRAQ (isobaric tags for relative and absolute quantitation) and 2D-LC-MS/MS (two-dimensional liquid chromatography-tandem mass spectrometry technologies) were employed to screen differentially expressed proteins. The identification, quantification, functional annotation, and interaction of proteins were analyzed by matching software and databases. In our project, 618 proteins were identified, among which 447 proteins had quantitative data. The number of differentially expressed proteins was 110, 117, 143, 115, 86, and 158 in T1 vs. C, T2 vs. C, T2 vs. T1, T3 vs. C, T3 vs. T1, and T3 vs. T2 groups, respectively. Functional annotation results showed that many differentially expressed proteins were closely associated with immune responses. For instance, some key proteins such as C-reactive protein, apolipoprotein C-III, apolipoprotein A-II, alpha-actinin-1, and thrombospondin-1 have been found to be abnormally expressed in T3 group compared to T1 group or T2 group. Interaction network analyses also provided some potential biomarkers or targets for MG management.

Clinical characteristics of AChRAb and MuSKAb double seropositive myasthenia gravis patients.

OBJECTIVES: To explore the characteristics of double seropositive myasthenia gravis (DSP-MG). PATIENTS AND METHODS: A literature review of twenty-four cases of DSP-MG including 2 novel cases presented in the current study, was performed. RESULTS: Among 24 reported patients, 7 were male (29.17%) and 17 were female (70.83%). Among 20 patients with known age, the mean age of onset was 37.30 ±â€¯19.50 years, among which the average onset age of the 6 male patients was 53.17 ±â€¯8.98 years, while the average onset age of the remaining 14 female patients was 30.50 ±â€¯18.94 years. Three patients had simple ocular muscle-type MG (14.28%), while 18 (85.71%) had non-ocular muscle-type MG. After administration of penicillide, 1 patient developed DSP-MG. In 9 cases, patients developed DSP-MG after thymectomy, while 5 patients naturally developed DSP-MG. CONCLUSION: Women more frequently developed DSP-MG than men and men were diagnosed at an older age. MG is typically found in the ocular muscles, bulbar and limb muscles.

[Metabolic Characteristics of Leucocyte-deplated and Suspended RBC Produced by Using Lipid Whole Blood During Routine Storage].

OBJECTIVE: To investigate the differences of metabolic pathways of leucocyte-deplated RBCs prepared by using lipid whole blood and nomal blood during routine storage so as to provide some reference for clinical blood use. METHODS: Twenty U whole blood from 20 donors, including 10 U lipid blood and 10 U normal whole blood, were selected for preparing leukodepleted red blood cells, red blood cells were taken from storage bags on day 0, 14 and 35, respectively. Metabolites in the red blood cells were analyzed, red blood cell metabolic extracts were detected by UPLC-MS/MS. The metabolite data of RBC from 2 groups were analyzed by SIMCA-P 13.0 software using OPLS-DA and by SPSS 19.0 using Mann-Whitney U test. Difference of metabolic pathways was described according to different metabolites. RESULTS: The glucose, adenine, pyruvic acid, GSH, GSSG and niacinamide levels on day 0 in lipid RBCs were higher than those in the control group(P<0.05). The glucose, pyruvic acid and GSH levels on day 14 in lipid RBCs were lower than those in the control group (P<0.05), and the levels of adenine, GSSG and niacinamide were higher than that in the control group (P<0.05). The glucose level on day 0 was lower than that in the control group (P<0.05), and the levels of adenine and niacinamide were higher than those in the control group (P<0.05). but the pyruvic acid, GSH and GSSG levels were not significantly different between 2 groups (P>0.05). CONCLUSION: Compared with the normal red blood cells, the energy metabolism pathway decreases in lipid red blood cells within the storage period and pentose phosphate pathway increases.

[Verteporfin inhibits proliferation, invasion and migration of MDA-MB-231 human breast cancer cells by down-regulating the expression of Yes-associated protein].

Objective To investigate the effects of verteporfin on the proliferation, invasion and migration of human breast cancer MDA-MB-231 cells and the underlying mechanism. Methods MDA-MB-231 cells in the logarithmic growth phase were randomly divided into control group and verteporfin treatment group. After MDA-MB-231 cells were treated with (0, 4, 8, 12, 16) µmol/mL verteporfin, the minimal inhibitory concentration was determined by CCK-8 assay. After treatment with 4 µmol/mL verteporfin, the invasion and migration abilities of MDA-MB-231 cells were detected by TranswellTM invasion assay and scratch wound healing assay, respectively. The expression levels of proliferation-associated proteins c-MYC, cyclin D1, Yes-associated protein (YAP), cysteine-rich protein 61 (CYR61) and connective tissue growth factor (CTGF) in MDA-MB-231 cells treated by (0, 4, 8, 12, 16) µmol/mL verteporfin were determined by Western blotting. Results Verteporfin markedly inhibited the proliferation of MDA-MB-231 cells in a dose-dependent manner, and the minimal inhibitory concentration was 4 µmol/mL. The 4 µmol/mL verteporfin significantly inhibited the invasion and migration abilities of MDA-MB-231 cells. Verteporfin inhibited significantly the expressions of c-MYC, cyclin D1, YAP, CYR61 and CTGF. Conclusion Verteporfin significantly inhibits the proliferation, invasion and migration of MDA-MB-231 cells by down-regulating the expressions of YAP and its target genes CYR61 and CTGF.

Cisplatin-induced autophagy protects breast cancer cells from apoptosis by regulating yes-associated protein.

Breast cancer is a common cause of cancer­related deaths in women. Treatment with cisplatin exhibits some therapeutic efficacy. However, treatment optimization is required, and the mechanisms underlying the cisplatin's proapoptotic effects remain unclear. In the present study, we demonstrated that cisplatin induced apoptosis and autophagy in breast cancer cells. Autophagy induced by cisplatin played a protective role in breast cancer cells, which impaired its proapoptotic effect. Mechanistically, for the first time, we found that cisplatin treatment activated the MAPK signaling pathway and promoted autophagy via the ERK signaling pathway. Notably, we found that nuclear translocation of yes-associated protein (YAP) was regulated by cisplatin-induced autophagy, and we identified YAP as a survival input that promoted survival in cisplatin-treated breast cancer cells. These findings revealed that administration of cisplatin along with an autophagy inhibitor is a promising therapeutic strategy for treating breast cancer.