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.

Trajectories of acute gastrointestinal injury grade in critically Ill children.

OBJECTIVE: To investigate the characteristics of different Acute Gastrointestinal Injury (AGI) grading trajectories and examine their impact on prognosis in the Pediatric Intensive Care Unit (PICU). METHODS: This retrospective cohort study was conducted at a large children's hospital in China. The children admitted to the PICU were included. AGI grade was assessed every other day during the initial nine days following PICU admission. RESULTS: A total of 642 children were included, of which 364 children (56.7%) exhibited varying degrees of gastrointestinal dysfunction (AGI grade ≥ 2). Based on the patterns of AGI grading over time, six groups were identified: low-stable group, low-fluctuating group, medium-decreasing group, medium-increasing group, high-decreasing group, high-persistent group. The high-persistent group accounted for approximately 90% of all recorded deaths. Compared to low-stable group, both the medium-increasing and high-persistent groups exhibited positive correlations with length of stay in PICU (PICU LOS) and length of stay (LOS). Compared to low-stable group, the five groups exhibited a negative correlation with the percentage of energy received by enteral nutrition (EN), as well as the protein received by EN. CONCLUSION: This study identified six distinct trajectory groups of AGI grade in critically ill children. The pattern of AGI grade trajectories over time were associated with EN delivery proportions and clinical outcomes.

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.

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.

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.

[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.

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.

Invalidation of mitophagy by FBP1-mediated repression promotes apoptosis in breast cancer.

Fructose-1,6-bisphosphatase 1, a rate-limiting enzyme in gluconeogenesis, was recently shown to be a tumor suppressor. However, the functions of fructose-1,6-bisphosphatase 1 in the regulation of mitophagy and apoptosis remain unknown. Here, we investigated the effects of fructose-1,6-bisphosphatase 1 on mitophagy and apoptosis as well as their underlying mechanisms in breast cancer cells. In this work, the messenger RNA and protein expression of various molecules were determined by quantitative realtime polymerase chain reaction and western blot, respectively. Gene-expression correlations were obtained from The Cancer Genome Atlas Breast Cancer database and analyzed using cBioPortal. The levels of cellular reactive oxygen species and apoptotic index were detected by flow cytometry. The mitochondrial membrane potentials were assessed with a JC-1 fluorescent sensor. Subcellular structures were observed under a transmission electron microscope. The intracellular distribution of translocase of outer membrane 20 was detected by immunofluorescence staining. Protein-protein interactions were analyzed by immunoprecipitation. Our results indicated that fructose-1,6-bisphosphatase 1 expression was negatively correlated with autophagy level in breast cancer. Fructose-1,6-bisphosphatase 1 restrained autophagy activity by increasing the level of p62 and decreasing the levels of LC3 and Beclin 1. Additionally, fructose-1,6-bisphosphatase 1 promoted cell apoptosis by upregulating the levels of intracellular ROS and expression of pro-apoptotic proteins such as cleaved PARP, cleaved Caspase 3, and Bax and downregulating the levels of anti-apoptotic proteins such as PARP, Caspase 3, and Bcl-2. Finally, fructose-1,6-bisphosphatase 1 limited the efficient removal of diseased mitochondria and reduced the messenger RNA and protein expressions of HIF-1α, BNIP3L/NIX, and BNIP3. More importantly, fructose-1,6-bisphosphatase 1 facilitated co-action between Bcl-2 and Beclin 1, which may be important in the mechanism of fructose-1,6-bisphosphatase 1-mediated mitophagy inhibition. In summary, loss of mitophagy by fructose-1,6-bisphosphatase 1-mediated repression promotes apoptosis in breast cancer.

Pyruvate kinase M2 interacts with mammalian sterile 20-like kinase 1 and inhibits tamoxifen-induced apoptosis in human breast cancer cells.

Tamoxifen has been reported to be associated with antagonism of estrogen-mediated cell growth signaling and activation of estrogen receptor-independent apoptosis events. It has been demonstrated that mammalian sterile 20-like kinase 1 is a direct target of Caspases to amplify the apoptotic signaling pathway. Here, we presented that breast cancer MCF-7 and SKBR3 cells under treatment with 4-hydroxytamoxifen displayed decreased level of pyruvate kinase M2. Western blot results also showed that 4-hydroxytamoxifen induced the activity of pro-apoptotic protein Caspase-3 in MCF-7 and SKBR3 cells, as evidenced by the cleavage of mammalian sterile 20-like kinase 1 substrate in a dose-dependent manner. Co-immunoprecipitation and immunofluorescence experiments were performed to clarify the relationship between pyruvate kinase M2 and mammalian sterile 20-like kinase 1. The results indicated that mammalian sterile 20-like kinase 1 was associated with pyruvate kinase M2 in cultured mammalian cells, and the interaction between mammalian sterile 20-like kinase 1 and pyruvate kinase M2 was decreased in response to 4-hydroxytamoxifen treatment. In addition, knockdown of pyruvate kinase M2 upregulated the level of cleaved Caspase-3 and subsequently facilitated the nuclear translocation of mammalian sterile 20-like kinase 1. Our data further supplemented the extensive functions of pyruvate kinase M2 in mediating breast cancer cell viability by substantially abating the mammalian sterile 20-like kinase 1-mediated apoptosis. In summary, our results identified that mammalian sterile 20-like kinase 1 is a novel downstream target of pyruvate kinase M2, and knockdown of pyruvate kinase M2 contributes apoptosis via promoting nuclear translocation of mammalian sterile 20-like kinase 1 by enhancing Caspase-3-dependent cleavage.

Clinical features of patients with Myasthenia gravis from the Henan province, China.

INTRODUCTION: Myasthenia gravis (MG) occurs globally, and many studies have indicated that there are regional differences in epidemiology, biomarkers, and prognosis of MG. METHODS: A total of 478 patients with MG who visited hospitals in the Henan Province between January 2010 and February 2014 were included. Age, gender, age at onset, serum antibody, thymus pathology, treatment information, and Myasthenia Gravis Foundation of America (MGFA) classification were assessed. RESULTS: Compared with previous reports from other areas, we found some differences in MG patients from Henan. The proportion of childhood MG in our study was lower than other reports of Oriental patients with MG. There seems to be an association between onset age, muscle involvement, and acetylcholine receptor antibody levels. Thymectomy improved the symptoms in 78.5% of thymectomy-treated patients. CONCLUSIONS: These differences are likely related to geographical, environmental, and ethnic differences. Understanding these differences will help us to define more specific treatment.

Detection of subsurface trace impurity in polished fused silica with biological method.

Subsurface damage (SSD), especially photoactive impurities, degrades the performance of high energy optics by reduction in the laser induced damage threshold. As the polishing defects are trace content and lie beneath the surface, they are difficult to detect. We herein present a biological method to measure impurities on polished fused silica, based on the intense inhibiting ability about trace level of ceria on enzyme activity. And the enzyme activity is measured in the individual etching solutions of a sequential etching process. Results show that detectability of the biological method satisfies the needs of trace impurity detection with low cost and simple apparatus. Furthermore ceria can be used to tag SSD in lapped and polished optics.

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.

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.

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.

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.

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.

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.

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.