Association between skeletal muscle mass and metabolic syndrome in middle-aged and elderly community residents / 上海预防医学

ObjectiveTo explore the correlation between skeletal muscle mass and metabolic syndrome （MS） disease risk among middle-aged and elderly community residents in Urumqi， and to provide a theoretical basis for understanding the relationship between skeletal muscle mass and MS among middle-aged and elderly community residents in China. MethodsA total of 1 438 community residents ≥ 50 years old were selected as the research subjects from July 2018 to January 2019 in Urumqi. They were selected from a multi-ethnic natural population cohort in Xinjiang. Data were collected through questionnaires， physical examination， bioelectrical impedance analysis （BIA）， laboratory tests， etc. Skeletal muscle mass was evaluated using the limb skeletal muscle mass index （SMI） corrected for body weight； MS was defined as it at least includes three of the following： abdominal obesity， hypertension， hyperglycemia， high triglycerides and low high-density lipoprotein cholesterol. SMI was divided into four quantile arrays of Q1‒Q4. Trend χ2 test was applied to explore whether there was a correlation between SMI changes and MS. A multivariate logistic regression model was used to analyze whether there is a difference in the risk of MS between the higher SMI group （Q2， Q3， Q4） and the reference group Q1. ResultA total of 560 MS patients were detected in this study， with a prevalence rate of 38.94%. Among them， the prevalence rate of MS was 39.16% in males and 38.80% in females. The increase in male SMI grading level is not correlated with the prevalence of MS （trend P>0.05）； After adjusting for confounding factors （model 4）， the increase in SMI was still not related to the prevalence of MS （Ptrend=0.995）. There was no statistical difference in the risk of MS between the lowest quartile group Q1 and the highest quartile group Q4 （OR=1.01， 95%CI： 0.69‒1.78）. The prevalence of MS in women gradually decreased with the increase of SMI grading level （Ptrend<0.001）； After adjusting for confounding factors （model 4）， there was still a correlation between the increase of SMI and the prevalence of MS （Ptrend=0.005）. With the lowest quartile of SMI Q1 as the reference group， the risk of MS in Q2 （OR=0.63， 95%CI： 0.40‒1.00）， Q3 （OR=0.56， 95%CI： 0.34‒0.94）， Q4 （OR=0.42， 95%CI： 0.23‒0.76） decreased. ConclusionAn increase in skeletal muscle mass may be beneficial for preventing MS， especially among middle-aged and elderly female residents. Considering the intensification of aging in China and the close relationship between MS and related comorbidities， managing skeletal muscle mass may contribute to potential MS prevention.

History and Clinical Application of Classic Famous Formula Danggui Sinitang / 中国实验方剂学杂志

Danggui Sinitang is first recorded in the Treatise on Cold Damage written by ZHANG Zhongjing in the Han dynasty. It is composed of Angelicae Sinensis Radix， Cinnamomi Ramulus， Paeoniae Radix Alba， Asari Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Tetrapanacis Medulla， and Jujubae Fructus and serves as a classic formula for treating the syndrome of blood deficiency and cold reversal. This study systematically reviews the records of Danggui Sinitang in ancient Chinese medicine books of various dynasties and the modern clinical applications to probe into the composition， plant species， processing， dosage， decocting method， and indications of Danggui Sinitang， aiming to provide a reference for the development and clinical application of this classic formula. The review of the records showed that there were a variety of records of Danggui Sinitang with different composition， and the composition of this formula listed in the Treatise on Cold Damage has a significant impact on later generations and has been used by medical practitioners throughout history. Although the dosage of some drugs decreased during the Ming and Qing dynasties， the medical practitioners continued to use the original formula. In terms of processing， although there were slight changes in the processing of Angelicae Sinensis Radix， Paeoniae Radix Alba， Glycyrrhizae Radix et Rhizoma， and Tetrapanacis Medulla， the original processing method was inherited. In terms of indications， Danggui Sinitang was designed to treat cold reversal due to blood deficiency and dysentery. Furthermore， it was used to treat headache， convulsive disease， infantile convulsion， and private part adduction in the Ming and Qing dynasties. Nowadays， this formula is mostly used to treat diabetes peripheral neuropathy， rheumatoid arthritis， dysmenorrhea， Raynaud's disease and other diseases. In terms of precautions， ancient physicians believed that Danggui Sinitang should not be taken by pregnant women and should only be used for limb chills caused by blood deficiency and cold coagulation. For limb chills caused by other reasons， this formula should not be used indiscriminately. Modern research has not reported any serious adverse reactions related to this formula. Danggui Sinitang has a definite therapeutic effect. In subsequent research and development， quality control standards of Danggui Sinitang should be established while its safety is ensured， and the related preparations should be developed and applied.

Xuebijing injection, a Chinese patent medicine, against severe pneumonia: Current research progress and future perspectives / 中西医结合学报

Severe pneumonia is one of the most common infectious diseases and the leading cause of sepsis and septic shock. Preventing infection, balancing the patient's immune status, and anti-coagulation therapy are all important elements in the treatment of severe pneumonia. As multi-target agents, Xuebijing injection (XBJ) has shown unique advantages in targeting complex conditions and saving the lives of patients with severe pneumonia. This review outlines progress in the understanding of XBJ's anti-inflammatory, endotoxin antagonism, and anticoagulation effects. From the hundreds of publications released over the past few years, the key results from representative clinical studies of XBJ in the treatment of severe pneumonia were selected and summarized. XBJ was observed to effectively suppress the release of pro-inflammatory cytokines, counter the effects of endotoxin, and assert an anticoagulation effect in most clinical trials, which are consistent with experimental studies. Collectively, this evidence suggests that XBJ could play an important and expanding role in clinical medicine, especially for sepsis, septic shock and severe pneumonia. Please cite this article as: Zhang M, Zheng R, Liu WJ, Hou JL, Yang YL, Shang HC. Xuebijing injection, a Chinese patent medicine, against severe pneumonia: Current research progress and future perspectives. J Integr Med. 2023; 21(5): 413-422.

Revealing the role of gut microbiota in immune regulation and organ damage in sepsis using 16s rRNA and untargeted metabolomics / 中华危重病急救医学

OBJECTIVE@#To analyze the composition and metabolites of gut microbiota in septic rats by fecal 16s rRNA sequencing and untargeted metabolomics, and to preliminarily explore the effect and potential mechanism of gut microbiota and its metabolites on inflammatory response and multiple organ damage in sepsis.@*METHODS@#Ten males healthy male Wistar rats were randomly divided into a sham operated group (Sham group) and sepsis model group (CLP group) using a random number table method, with 5 rats in each group. A rat sepsis model was established by cecal ligation and perforation (CLP) method. The animals were sacrificed 24 hours after modeling, the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in peripheral blood were detected by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was used to observe the pathological changes of lung and kidney tissues, and the pathological scores were evaluated. Fecal samples were collected, and 16s rRNA high-throughput sequencing and non-targeted metabolomics were used to screen microbiota, metabolites and potential signal pathways that may play an important role in disease outcomes. Spearman correlation analysis was conducted to jointly analyze the gut microbiota and non-targeted metabolism.@*RESULTS@#Compared with the Sham group, the degree of pathological damage to lung and kidney tissues in the CLP group was significantly increased (lung tissue score: 3.60±0.80 vs. 0.00±0.00, kidney tissue score: 2.40±0.80 vs. 0.00±0.00, both P < 0.01), the level of IL-6 and TNF-α in peripheral blood significantly increased [TNF-α (ng/L): 248.12±55.98 vs. 143.28±36.57, IL-6 (ng/L): 260.26±39.47 vs. 116.01±26.43, both P < 0.05], the species diversity of intestinal flora of rats in the CLP group was significantly reduced, the relative abundance of Morganella, Bacteroides and Escherichia-Shigella were significantly increased, and the relative abundance of Lachnospiraceae NK4A136, Ruminococcus, Romboutsia and Roseburia were significantly reduced. In addition, the biosynthesis and bile secretion of phenylalanine, tyrosine, and tryptophan in the gut microbiota of the CLP group were significantly increased, while the biosynthesis of secondary bile acids was significantly reduced. There was a significant correlation between differential metabolites and differential microbiota.@*CONCLUSIONS@#Sepsis can cause significant changes in the characteristics of gut microbiota and fecal metabolites in rats, which provides a basis for translational research to seek new targets for the treatment of sepsis.

METTL14 is a chromatin regulator independent of its RNA N6-methyladenosine methyltransferase activity

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.

Mechanism of disordered subcellular localization of TFE3 fusion protein in TFE3 translocation renal cell carcinoma / 现代泌尿外科杂志

【Objective】 To investigate the effects of the loss of exon 1 of TFE3 on nuclear localization of chimeric TFE3 protein in TFE3 translocation renal cell carcinoma (TFE3 tRCC). 【Methods】 The localization of TFE3 protein in TFE3 tRCC and clear cell renal cell carcinoma (ccRCC) were detected with immunochemistry. The exon retention of TFE3 gene in TFE3 tRCC was analyzed in databases and literatures. The plasmids containing TFE3 full-length and different-length of TFE3 exons which were constructed to pCDH-MCS-EGFP-Puro were transfected into HEK293T using Lipo FiterTM. The localization of EGFP protein in HEK293T cells were detected with confocal microscopy. The localization of TFE3 protein and truncated TFE3 protein were detected with Western blotting. The mRNA expression of the downstream genes of TFE3 protein were detected with q-PCR. 【Results】 Strong nuclear signal of TFE3 protein was observed in TFE3 tRCC, whereas TFE3 protein in ccRCC was mainly localized in cytoplasm. The results of fluorescence imaging and Western blotting showed that TFE3 full-length protein was expressed both in nucleus and cytoplasm, and the expression of truncated TFE3 protein was mainly localized in nucleus. The q-PCR analysis demonstrated that the deletion of exon 1 in TFE3 gene led to a higher transcriptional level of targeted genes of TFE3 protein. 【Conclusion】 The loss of exon 1 in TFE3 played a critical role in preventing TFE3 protein from entering the nucleus. In TFE3 tRCC, the loss of exon 1 in TFE3 gene leads to the nuclear localization of TFE3 fusion protein and activation of its downstream target genes. This mechanism promises to uncover the occurrence and development of TFE3 tRCC.

Research advances of various omics analyses in chronic refractory wounds on body surface / 中华烧伤杂志

The diagnosis and treatment of chronic refractory wounds on body surface has always been full of challenges, and it also poses a huge burden on medical care and society. High-throughput sequencing combined with omics analysis can reveal potential mechanisms of chronic wound formation, and identify potential biomarkers related to diagnosis, prognosis, and screening of chronic wound. Combined with multiple levels of omics analysis, the detailed molecular mechanism of chronic wound development can be further explored and understood, so as to provide clues for the formulation of personalized treatment methods and lay a solid foundation for the precision medicine of chronic wounds. Therefore, this review addresses the recent progress of various omics analyses in chronic refractory wounds on body surface.

Dynamic Changes of ROS and Nrf2-Related Factors During Erythroid Development / 中国实验血液学杂志

OBJECTIVE@#To investigate the changes and roles of reactive oxygen species (ROS) and nuclear factor erythroid 2-related factor 2 (Nrf2) related antioxidases during erythroid development.@*METHODS@#Flow cytometry was used to detect the sensibility of peripheral red blood cells of wild-type mice to a strong oxidant hydrogen peroxide (H2O2). Erythroid cells from different developmental stages in bone marrow (BM) were obtained using fluorescence-activated cell sorter and the ROS levels were detected by flow cytometry. RT-qPCR was used to detect the changes of expression levels of Nrf2 and related antioxidases in erythroid cells from different developmental stages in BM. The ROS levels of the peripheral blood and BM nucleated erythrocytes in Nrf2 knockout mice were further examined. The expression level of Nrf2 in erythroid precursors isolated from 14.5 d embryonic liver of wild-type mice during differentiation and culture in vitro was detected.@*RESULTS@#In the peripheral blood of wild-type mice, the ROS level of reticulocytes and mature erythrocytes treated with H2O2 increased about 4 times and 7 times, respectively (P<0.01). In BM erythrocytes, the ROS level gradually decreased as the cells matured (r=0.85), while the expression level of Nrf2 and its related anti-oxidative genes increased (r=0.99). The ROS levels in peripheral blood erythrocytes and BM nucleated erythrocytes of Nrf2 knockout mice were significantly increased compared with wild-type mice (P<0.01). The expression of Nrf2 increased during the early erythroid development after embryonic liver cell sorting (P<0.01).@*CONCLUSION@#The expression levels of Nrf2 and its related factors vary during erythropoiesis. Nrf2 at physiological level plays an important antioxidant role during the erythroid development.

Analysis of NOVA2 gene variant in a child with Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child with Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities (NEDASB).@*METHODS@#A child with NEDASB who presented at the Third Affiliated Hospital of Zhengzhou University in July 2021 was selected as the subject. Peripheral blood samples of the child and her parents were collected and subjected to high-throughput sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child was found to harbor a heterozygous c.820_828delinsCTTCA (p.Thr274Leufs*121) variant of the NOVA2 gene, for which both of her parents were of wild type. The variant was predicted as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics.@*CONCLUSION@#The heterozygous c.820_828delinsCTTCA (p.Thr274Leufs*121) variant of the NOVA2 gene probably underlay the disease in this child. Above finding has enriched the spectrum of NOVA2 gene variants and provided a basis for genetic counseling and prenatal diagnosis for this family.

Progress of research on evaluation indicators and standards about high-speed train comfort / 中华劳动卫生职业病杂志

The rapid development of high-speed railway in China has proposed higher requests for the comfort level of high-speed trains. However, there is no internationally unified evaluation criterion for high-speed train comfort currently, which therefore substantially affects the comparability and standardization of research results for high-speed train comfort. This paper systematically reviews the research literature about evaluation indicators and standards related to high-speed train comfort, and finds that there is currently no unified definition, evaluation indicators, as well as evaluation criterion for high-speed train comfort. Most current evaluation criteria are based on a single indicator. Some indicators are simultaneously developed by different apartments and differ between each other, and there is no comprehensive indicator or criteria for high-speed train comfort, restricting the comparison of high-speed train comfort across regions. It is recommended that the administrative department of high-speed railroad in China should organize experts to establish a unified definition of high-speed train comfort, comprehensive evaluation indicators and relevant judgment criteria for high-speed train comfort, in face of the rapid development and globalization of high-speed trains.

Effects of manipulator operation task and troubleshooting task on blood pressure indexes of oceanauts / 中华劳动卫生职业病杂志

Objective: To explore the characteristics and rules of blood pressure changes in oceanauts during simulated operation of manipulator and troubleshooting tasks with different difficulty. Methods: In July 2020, 8 deep-sea manned submersible oceanauts, 6 males and 2 females, were selected as objects. In the 1∶1 model of Jiaolong deep-sea manned submersible, the oceanauts performed manipulator operation tasks and troubleshooting tasks with different difficulties, measured the continuous blood pressure of the oceanauts, filled in the NASA Task Load Index (NASA-TLX scale) after the completion of a single mission, and the changes of systolic pressure (SBP), diastolic pressure (DBP), mean arterial pressure (MAP) and mental workload were analyzed. Results: In a single task, the SBP, DBP and MAP of the oceanauts increased first and then decreased. The blood pressure values at the third minute were significantly lower than those at the first minute (P<0.01), and those at the fifth minute were significantly higher than those at the third minute (P<0.01). When performing the same task, compared with the quiet state, SBP, DBP and MAP increased when the oceanauts performed low difficulty, high difficulty, high difficulty+2-back manipulator operation task and troubleshooting task (P<0.05). When the task difficulty was the same, the SBP and MAP of oceanauts performing manipulator operation tasks were higher than those of oceanauts performing troubleshooting tasks (P<0.05). Compared with low difficulty tasks, the scores of NASA-TLX scale for oceanauts performing high difficulty manipulator operationtasks were significantly higher (P<0.05). Compared with the low difficulty task and high difficulty task, the scale score of the high difficulty+2-back troubleshooting task was significantly higher (P<0.05). When the task difficulty was the same, the scale scores of low difficulty and high difficulty manipulator operation tasks were significantly higher than those of troubleshooting tasks (P<0.05). SBP, DBP, MAP of No. 1, No. 3, No. 4, No. 5, and No. 7 oceanauts (all of whom had 6 years of diving) were positively correlated with NASA-TLX scale scores (r>0.8, P<0.05) . Conclusion: In the process of manned deep-sea diving, when the oceanauts perform manipulator operation tasks and troubleshooting tasks, with the increase of task difficulty, the mental load of oceanauts increases, and the blood pressure index increases significantly in a short time. At the same time, improving the proficiency of operation can reduce the variation range of blood pressure indexes. Blood pressure can be used as an effective reference to evaluate the difficulty of operation and guide scientific training.

Association between sarcopenia and metabolic syndrome in middle-aged and elderly people in Urumqi， Xinjiang / 上海预防医学

ObjectiveTo obtain the prevalence of sarcopenia in middle-aged and elderly people in Urumqi based on the 2020 updated based on the 2020 updated Consensus Report 2019 of Asian Working Group for Sarcopenia （AWGS2019）， and to further explore the association between sarcopenia and metabolic syndrome （MS）. MethodsA total of 1 438 middle-aged and elderly people （aged≥50 years） in Urumqi from July 2018 to January 2019 were selected as the research subjects. Data were collected by questionnaire survey， physical examination and laboratory test. Skeletal muscle mass，grip strength and 4 m walking speed were used to represent muscle mass， muscle strength and body function， respectively. Bioelectrical impedance analysis （BIA） was used to measure human body components. Based on the diagnostic criteria of sarcopenia recommended by AWGS2019， the prevalence of sarcopenia in people over 50 years old was obtained. Multivariate logistic regression model was used to explore the correlation between sarcopenia and MS in middle-aged and elderly people of different genders. ResultsThere were 194 patients with sarcopenia， with a prevalence of 13.49%. The prevalence was 15.56% in males and 12.12% in females. There was no significant difference in the prevalence of MS between male sarcopenia group （40.45%） and non-sarcopenia group （38.92%）， while the prevalence of MS in female sarcopenia group （39.04%） was higher than that in non-sarcopenia group （27.56%）. Multivariate logistic regression analysis showed that sarcopenia was a related factor of MS. Compared with non-sarcopenia， the risk of MS in male sarcopenia group was higher （OR=2.11，95%CI： 1.15‒3.88 ）. ConclusionSarcopenia increases the risk of MS in middle-aged and elderly people， with a greater risk in men. Fully understanding of sarcopenia is helpful to early identify high-risk groups of MS and prevent the occurrence of MS.

Clinical and genetic characteristics of children with dopa-responsive dystonia caused by tyrosine hydroxylase gene variations / 中华儿科杂志

Objective: To explore the clinical and genetic characteristics of children with dopa-responsive dystonia (DRD) caused by tyrosine hydroxylase (TH) gene variations. Methods: Clinical data of 9 children with DRD caused by TH gene variations diagnosed in the Department of Children Rehabilitation, the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2022 were retrospectively collected and analyzed, including the general conditions, clinical manifestations, laboratory tests, gene variations and follow-up data. Results: Of the 9 children with DRD caused by TH gene variations, 3 were males and 6 were females. The age at diagnosis was 12.0 (8.0, 15.0) months. The initial symptoms of the 8 severe patients were motor delay or degression. Clinical symptoms of the severe patients included motor delay (8 cases), truncal hypotonia (8 cases), limb muscle hypotonia (7 cases), hypokinesia (6 cases), decreased facial expression (4 cases), tremor (3 cases), limb dystonia (3 cases), diurnal fluctuation (2 cases), ptosis (2 cases), limb muscle hypertonia (1 case) and drooling (1 case). The initial symptom of the very severe patient was motor delay. Clinical symptoms of the very severe patient included motor delay, truncal hypotonia, oculogyric crises, status dystonicus, hypokinesia, decreased facial expression, and decreased sleep. Eleven TH gene variants were found, including 5 missense variants, 3 splice site variants, 2 nonsense variants, and 1 insertion variant, as well as 2 novel variants (c.941C>A (p.T314K), c.316_317insCGT (p.F106delinsSF)). Nine patients were followed up for 40 (29, 43) months, and no one was lost to follow-up. Seven of the 8 severe patients were treated by levodopa and benserazide hydrochloride tablets and 1 severe patient was treated by levodopa tablets. All the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets. Although the weight of the patients increased and the drug dosage was not increased, the curative effect remained stable and there was no obvious adverse reaction. One severe patient developed dyskinesia in the early stage of treatment with levodopa and benserazide hydrochloride tablets and it disappeared after oral administration of benzhexol hydrochloride tablets. Until the last follow-up, motor development of 7 severe patients returned to normal and 1 severe patient still had motor delay due to receiving levodopa and benserazide hydrochloride tablets for only 2 months. The very severe patient was extremely sensitive to levodopa and benserazide hydrochloride tablets and no improvement was observed in this patient. Conclusions: Most of the DRD caused by TH gene variations are severe form. The clinical manifestations are varied and easily misdiagnosed. Patients of the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets, and it takes a long time before full effects of treatment become established. Long-term effect is stable without increasing the drug dosage, and no obvious side effect is observed.

HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems / 中华预防医学杂志

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.

Research on a portable shielding-free ultra-low field magnetic resonance imaging system / 生物医学工程学杂志

The portable light-weight magnetic resonance imaging system can be deployed in special occasions such as Intensive Care Unit (ICU) and ambulances, making it possible to implement bedside monitoring imaging systems, mobile stroke units and magnetic resonance platforms in remote areas. Compared with medium and high field imaging systems, ultra-low-field magnetic resonance imaging equipment utilizes light-weight permanent magnets, which are compact and easy to move. However, the image quality is highly susceptible to external electromagnetic interference without a shielded room and there are still many key technical problems in hardware design to be solved. In this paper, the system hardware design and environmental electromagnetic interference elimination algorithm were studied. Consequently, some research results were obtained and a prototype of portable shielding-free 50 mT magnetic resonance imaging system was built. The light-weight magnet and its uniformity, coil system and noise elimination algorithm and human brain imaging were verified. Finally, high-quality images of the healthy human brain were obtained. The results of this study would provide reference for the development and application of ultra-low-field magnetic resonance imaging technology.

EPCs-exos combined with tanshinone Ⅱ_A protect vascular endothelium cells from oxidative damage via PI3K/Akt pathway / 中国中药杂志

This study aims to investigate the molecular mechanism of tanshinone Ⅱ_(A )(TaⅡ_A) combined with endothelial progenitor cells-derived exosomes(EPCs-exos) in protecting the aortic vascular endothelial cells(AVECs) from oxidative damage via the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt) pathway. The AVECs induced by 1-palmitoyl-2-(5'-oxovaleroyl)-sn-glycero-3-phosphocholine(POVPC) were randomly divided into model, TaⅡ_A, EPCs-exos, and TaⅡ_A+EPCs-exos groups, and the normal cells were taken as the control group. The cell counting kit-8(CCK-8) was used to examine the cell proliferation. The lactate dehydrogenase(LDH) cytotoxicity assay kit, Matrigel assay, DCFH-DA fluorescent probe, and laser confocal microscopy were employed to examine the LDH release, tube-forming ability, cellular reactive oxygen species(ROS) level, and endothelial cell skeleton morphology, respectively. The enzyme-linked immunosorbent assay was employed to measure the expression of interleukin(IL)-1β, IL-6, and tumor necrosis factor(TNF)-α. Real-time fluorescence quantitative PCR(qRT-PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of PI3K and Akt. Compared with the control group, the model group showed decreased cell proliferation and tube-forming ability, increased LDH release, elevated ROS level, obvious cytoskeletal disruption, increased expression of IL-1β, IL-6, and TNF-α, and down-regulated mRNA and protein levels of PI3K and Akt. Compared with the model group, TaⅡ_A or EPCs-exos alone increased the cell proliferation and tube-forming ability, reduced LDH release, lowered the ROS level, repaired the damaged skeleton, decreased the expression of IL-1β, IL-6, and TNF-α, and up-regulated the mRNA and protein levels of PI3K and Akt. TaⅡ_A+EPCs-exos outperformed TaⅡ_A or EPCs-exos alone in regulating the above indexes. The results demonstrated that TaⅡ_A and EPCs-exos exerted a protective effect on POVPC-induced AVECs by activating the PI3K/Akt pathway, and the combination of the two had stronger therapeutic effect.

Aucubin combined with ADSCs-exos protects TBHP-induced nucleus pulposus cells via TLR4/NF-κB pathway / 中国中药杂志

This paper aims to investigate the effects and mechanisms of adipose-derived stem cells-exosomes(ADSCs-exos) toge-ther with aucubin in protecting human-derived nucleus pulposus cells(NPCs) from inflammatory injury, senescence, and apoptosis. The tert-butyl hydroperoxide(TBHP)-induced NPCs were assigned into normal, model, aucubin, ADSCs-exos, and aucubin+ADSCs-exos groups. The cell viability was examined by cell counting kit-8(CCK-8), cell proliferation by EdU staining, cell senescence by senescence-associated-β-galactosidase(SA-β-Gal), and cell cycle and apoptosis by flow cytometry. Enzyme-linked immunosorbent assay was employed to examine the expression of interleukin-1β(IL-1β), IL-10, and tumor necrosis factor-α(TNF-α). Real-time fluorescence quantitative PCR and Western blot were employed to determine the mRNA and protein levels of aggregated proteoglycan(aggrecan), type Ⅱ collagen alpha 1(COL2A1), Toll-like receptor 4(TLR4), and nuclear factor-kappa B(NF-κB). The results showed that compared with the model group, the aucubin or ADSCs-exos group showed enhanced viability and proliferation of NPCs, decreased proportion of G_0/G_1 phase cells, increased proportion of S phase cells, reduced apoptosis and proportion of cells in senescence, lowered IL-1β and TNF-α levels, elevated IL-10 level, down-regulated mRNA and protein levels of TLR4 and NF-κB, and up-regulated mRNA and protein levels of aggrecan and COL2A1. Compared with the aucubin or ADSCs-exos group, the aucubin+ADSCs-exos combination further increased the viability and proliferation of NPCs, decreased the proportion of G_0/G_1 phase cells, increased the proportion of S phase cells, reduced the apoptosis and proportion of cells in senescence, lowered the IL-1β and TNF-α levels, elevated the IL-10 level, down-regulated the mRNA and protein levels of TLR4 and NF-κB, and up-regulated the mRNA and protein levels of aggrecan and COL2A1. In summary, both aucubin and ADSCs-exos could exert protective effects by inhibiting inflammatory responses, reducing apoptosis and senescence of NPCs, improving cell viability and proliferation as well as extracellular matrix synthesis, which may be associated with the inhibition of TLR4/NF-κB signaling pathway activation. The combination of both plays a synergistic role in the protective effects.

Noninvasive Tracking of Every Individual in Unmarked Mouse Groups Using Multi-Camera Fusion and Deep Learning / 神经科学通报·英文版

Accurate and efficient methods for identifying and tracking each animal in a group are needed to study complex behaviors and social interactions. Traditional tracking methods (e.g., marking each animal with dye or surgically implanting microchips) can be invasive and may have an impact on the social behavior being measured. To overcome these shortcomings, video-based methods for tracking unmarked animals, such as fruit flies and zebrafish, have been developed. However, tracking individual mice in a group remains a challenging problem because of their flexible body and complicated interaction patterns. In this study, we report the development of a multi-object tracker for mice that uses the Faster region-based convolutional neural network (R-CNN) deep learning algorithm with geometric transformations in combination with multi-camera/multi-image fusion technology. The system successfully tracked every individual in groups of unmarked mice and was applied to investigate chasing behavior. The proposed system constitutes a step forward in the noninvasive tracking of individual mice engaged in social behavior.

A novel homozygous frameshift variant in DNAH8 causes multiple morphological abnormalities of the sperm flagella in a consanguineous Pakistani family / 亚洲男科学杂志(英文版)

Multiple morphological abnormalities of the sperm flagella (MMAF) is a severe form of asthenozoospermia categorized by immotile spermatozoa with abnormal flagella in ejaculate. Whole-exome sequencing (WES) is used to detect pathogenic variants in patients with MMAF. In this study, a novel homozygous frameshift variant (c.6158_6159insT) in dynein axonemal heavy chain 8 (DNAH8) from two infertile brothers with MMAF in a consanguineous Pakistani family was identified by WES. Reverse transcription-polymerase chain reaction (RT-PCR) confirmed DNAH8 mRNA decay in these patients with the DNAH8 mutation. Hematoxylin-eosin staining and transmission electron microscopy revealed highly divergent morphology and ultrastructure of sperm flagella in these patients. Furthermore, an immunofluorescence assay showed the absence of DNAH8 and a reduction in its associated protein DNAH17 in the patients' spermatozoa. Collectively, our study expands the phenotypic spectrum of patients with DNAH8-related MMAF worldwide.

Clinical features and genetic analysis of a child with EAST/SeSAME syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a EAST/SeSAME syndrome child featuring epilepsy, ataxia, sensorineural deafness and intellectual disability.@*METHODS@#A child with EAST/SeSAME syndrome who had presented at the Third Affiliated Hospital of Zhengzhou University in January 2021 was selected as the study object. Peripheral blood samples of the child and her parents were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing.@*RESULTS@#Genetic testing revealed that the child has harbored compound heterozygous variants of the KCNJ10 gene, namely c.557T>C (p.Val186Ala) and c.386T>A (p.Ile129Asn), which were inherited from her mother and father, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted as likely pathogenic (PM1+PM2_Supporting+PP3+PP4; PM1+PM2_Supporting+PM3+PP3+PP4).@*CONCLUSION@#The patient was diagnosed with EAST/SeSAME syndrome due to the compound heterozygous variants of the KCNJ10 gene.