Comparison of genomic prediction methods for early growth traits of Inner Mongolia cashmere goats based on multi trait models.

Inner Mongolia cashmere goat is an excellent livestock breed formed through long-term natural selection and artificial breeding, and is currently a world-class dual-purpose breed producing cashmere and meat. Multi trait animal model is considered to significantly improve the accuracy of genetic evaluation in livestock and poultry, enabling indirect selection between traits. In this study, the pedigree, genotype, environment, and phenotypic records of early growth traits of Inner Mongolia cashmere goats were used to build multi trait animal model., Then three methods including ABLUP, GBLUP, and ssGBLUP wereused to estimate the genetic parameters and genomic breeding values of early growth traits (birth weight, weaning weight, average daily weight gain before weaning, and yearling weight). The accuracy and reliability of genomic estimated breeding value are further evaluated using the five fold cross validation method. The results showed that the heritability of birth weight estimated by three methods was 0.13-0.15, the heritability of weaning weight was 0.13-0.20, heritability of daily weight gain before weaning was 0.11-0.14, and the heritability of yearling weight was 0.09-0.14, all of which belonged to moderate to low heritability. There is a strong positive genetic correlation between weaning weight and daily weight gain before weaning, daily weight gain before weaning and yearling weight, with correlation coefficients of 0.77-0.79 and 0.56-0.67, respectively. The same pattern was found in phenotype correlation among traits. The accuracy of the estimated breeding values by ABLUP, GBLUP, and ssGBLUP methods for birth weight is 0.5047, 0.6694, and 0.7156, respectively; the weaning weight is 0.6207, 0.6456, and 0.7254, respectively; the daily weight gain before weaning was 0.6110, 0.6855, and 0.7357 respectively; and the yearling weight was 0.6209, 0.7155, and 0.7756, respectively. In summary, the early growth traits of Inner Mongolia cashmere goats belong to moderate to low heritability, and the speed of genetic improvement is relatively slow. The genetic improvement of other growth traits can be achieved through the selection of weaning weight. The ssGBLUP method has the highest accuracy and reliability in estimating genomic breeding value of early growth traits in Inner Mongolia cashmere goats, and is significantly higher than that from ABLUP method, indicating that it is the best method for genomic breeding of early growth weight in Inner Mongolia cashmere goats.

Identification of a natural PLA2 inhibitor from the marine fungus Aspergillus sp. c1 for MAFLD treatment that suppressed lipotoxicity by inhibiting the IRE-1α/XBP-1s axis and JNK signaling

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

Identification of the key mechanisms of action of Si-Ni-San in uveitis using bioinformatics and network pharmacology.

BACKGROUND: Uveitis is an eye disease with a high rate of blindness, whose pathogenesis is not completely understood. Si-Ni-San (SNS) has been used as a traditional medicine to treat uveitis in China. However, its mechanism of action remains unclear. This study explored the potential mechanisms of SNS in the treatment of uveitis through network pharmacology and bioinformatics. METHODS: Using R language and Perl software, the active components and predicted targets of SNS, as well as the related gene targets of uveitis, were mined through the Traditional Chinese Medicine Systems Pharmacology, Therapeutic Target, Gene Expression Omnibus, GeneCards, and DrugBank databases. The network diagram of active components and intersection targets was constructed using Cytoscape software and the String database. The CytoNCA plug-in was used to conduct topological analysis on the network diagram and screen out the core compounds and key targets. The genes were analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment. Chemoffice, Pymol, AutoDock, and Vina were used to analyze the molecular docking of key targets and core compounds of diseases through the PubChem database. RESULTS: JUN, RELA, and MAPK may play important roles in the treatment of uveitis by SNS. Kyoto encyclopedia of genes and genomes pathway enrichment analysis showed that core genes were mainly concentrated in MAPK, toll-like receptor, tumor necrosis factor, and nucleotide oligomerization domain-like receptor signaling pathways. In addition, molecular docking results showed that the bioactive compounds (kaempferol, luteolin, naringin, and quercetin) exhibited good binding ability to JUN, RELA, and MAPK. CONCLUSION: Based on these findings, SNS exhibits multi-component and multi-target synergistic action in the treatment of uveitis, and its mechanism may be related to anti-inflammatory and immune regulation.

Analysis of peripheral blood lymphocyte status in low-level-viremia patients with chronic hepatitis B virus infection after nucleos(t)ide analogue treatment / 中华微生物学和免疫学杂志

Objective:To evaluate the status of T, B and NK lymphocytes in peripheral blood of patients with chronic hepatitis B virus(HBV) infection and low-level viremia after nucleos(t)ide analogue (NA) treatment and to provide ideas for solving low-level viremia.Methods:This retrospective study involved 344 patients with chronic HBV infection who had been treated with NAs. They were divided into two groups: low-level viremia group (LLV group) and complete virological response group (CVR group). Clinical data including basic information, biochemistry and coagulation test results, HBV DNA, peripheral blood lymphocyte counts, PD1 and CD28 expression by T lymphocytes, and perforin and granzyme B expression by NK lymphocytes were collected and compared between the two groups. Propensity matching analysis was performed to verify the accuracy of the results.Results:Among the 344 cases, 162 were in the LLV group and 182 in the CVR group. There were no significant differences in disease diagnosis, alanine aminotransferase (ALT), aspartate aminotransferase (AST) or albumin (ALB) level between the two groups ( P>0.05), but the differences in gender and age were statistically significant ( P<0.05). The differences in the counts and percentages of peripheral blood CD3 +, CD4 + and CD8 + T lymphocyte and CD4 + /CD8 + ratios between the two groups were not statistically significant ( P>0.05), but the expression of PD1 and CD28 by peripheral blood CD3 +, CD4 + and CD8 + T lymphocytes was higher in the LLV group than in the CVR group ( P<0.05). The count of peripheral blood CD19 + B lymphocytes in the LLV group was higher than that in the CVR group ( P>0.05), and the percentage of peripheral blood CD19 + B lymphocytes was also higher in the LLV group ( P<0.05). The count of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of perforin in the LLV group were lower than those in the CVR group ( P>0.05). The percentage of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of granzyme B in the LLV group were lower than those in the CVR group ( P<0.05). After propensity score matching, 108 cases in the LLV group and 108 cases in the CVR group showed no significant differences in basic information ( P>0.05); the percentage of CD4 + T lymphocytes and CD4 + /CD8 + ratio in peripheral blood T lymphocyte subsets were higher in the LLV group than in the CVR group, while the percentage of CD8 + lymphocytes was lower in the LLV group ( P<0.05); the expression of PD1 and CD28 by CD3 +, CD4 + and CD8 + T lymphocytes remained higher in the LLV group ( P<0.05); the differences in the counts and percentages of peripheral blood CD19 + B lymphocytes as well as CD16 + CD56 + NK lymphocytes between the two groups were not statistically significant ( P>0.05); no significant difference in the expression of perforin by CD16 + CD56 + NK lymphocytes was found between the two groups ( P>0.05), and the expression of granzyme B remained lower in the LLV group ( P<0.05). Conclusions:Abnormal number and function of T lymphocytes and decreased function of NK lymphocytes might be related to the development of LLV in patients with chronic HBV infection after treatment. Therefore, in addition to adjusting NAs, targeting of T and NK lymphocytes might also be a feasible measure for future LLV treatment.

Research on mild cognitive impairment diagnosis based on Bayesian optimized long-short-term neural network model / 生物医学工程学杂志

The recurrent neural network architecture improves the processing ability of time-series data. However, issues such as exploding gradients and poor feature extraction limit its application in the automatic diagnosis of mild cognitive impairment (MCI). This paper proposed a research approach for building an MCI diagnostic model using a Bayesian-optimized bidirectional long short-term memory network (BO-BiLSTM) to address this problem. The diagnostic model was based on a Bayesian algorithm and combined prior distribution and posterior probability results to optimize the BO-BiLSTM network hyperparameters. It also used multiple feature quantities that fully reflected the cognitive state of the MCI brain, such as power spectral density, fuzzy entropy, and multifractal spectrum, as the input of the diagnostic model to achieve automatic MCI diagnosis. The results showed that the feature-fused Bayesian-optimized BiLSTM network model achieved an MCI diagnostic accuracy of 98.64% and effectively completed the diagnostic assessment of MCI. In conclusion, based on this optimization, the long short-term neural network model has achieved automatic diagnostic assessment of MCI, providing a new diagnostic model for intelligent diagnosis of MCI.

The correlation between diamine oxidase and T helper cells 17/regulatory T cell immune balance in rheumatoid arthritis / 中华风湿病学杂志

Objective:To investigate the changes of intestinal mucosal barrier function related indexes [diamine oxidase and secretory immunoglobulin A (sIgA)] in peripheral blood of patients with rheumatoid arthritis (RA) and their correlation with peripheral immune function.Methods:A total of 40 patients with RA who admitted to the Rheumatology and Immunology department of the Second Hospital of the Shanxi Medical University were enrolled. We collected their clinical and laboratory data, and selected 20 age and gender matched people as the control group. Enzyme-linked immunosorbnent assay (ELISA) was used to detect the level of DAO and sIgA in the peripheral blood, the lymphocytes and CD4 + T subsets were detected by flow cytometry. Then t-test, rank sum test and correlation analysis were conducted for statistical analysis. Results:① The level of DAO in patients with RA was higher than that of healthy controls [205(164, 251) ng/ml vs 364 (276, 483) ng/ml, Z=-4.48, P<0.001], while the level of sIgA was decreased [3.64 (2.76, 4.83)×10 5 ng/ml vs 6.83 (4.80, 9.44)×10 5, Z=-3.84, P<0.001]. ② The absolute number of B and CD4 + T cells were increased in RA, the difference were statistically significant, but the absolute number of T, natural killer cells (NK) and CD8 + T cells were not significantly different between the two groups. For CD4 + T subsets, the absolute number of T helper cells (Th)1 and Treg cells in RA group were significantly decreased than healthy controls, but there were no statistical significant difference in the number of Th2 and Th17 cells. ③ The level of DAO was positively correlated with absolute number of Th17 cells in patients with RA ( r=0.36 P=0.038), and positively correlated with age and white blood cell count ( r=0.40, P=0.021; r=0.40, P=0.020), but no significant correlation among other indicators were found. ④ The serum sIgA level of RA patients in antimutated citrullinated vimentin antibody (MCV), antiperinuclear factor (APF) and antikeratin antibody (AKA) positive group were higher than those in the negative group [3.99(2.99, 5.58)×10 5 ng/ml vs 2.73(2.29, 3.05)×10 5 ng/ml, Z=-2.55, P=0.011; 5.49 (3.26, 5.70)×10 5 ng/ml vs 3.12 (2.29, 4.04)×10 5 ng/ml, Z=-2.28, P=0.023; 4.07 (3.19, 5.65)×10 5 ng/ml vs 2.88 (2.24, 3.86)×10 5 ng/ml, Z=-2.42, P=0.016], while there was no significant difference in DAO level between groups. ⑤ The DAO level of RA patients with pulmonary interstitial fibrosis was significantly higher than that in the group without pulmonary interstitial fibrosis [421 (216, 528) ng/ml vs 191 (150, 223) ng/ml, Z=-2.81, P=0.005], while there were no significant differences in DAO and sIgA levels among other groups. Conclusion:In RA patients with inte-stinal mucosal barrier impairment, the DAO level is increased, while the sIgA is decreased, and in addition, elevated peripheral blood Th17 may be involved in the process of intestinal mucosal barrier impairment.

Study on the long-term effect of three bone graft materials after periodontal regeneration / 国际生物医学工程杂志

Objective:To evaluate the medium and long term clinical effect of three bone graft materials on periodontitis after periodontal regeneration.Methods:Initially, 16 patients with periodontitis after periodontal regeneration in Tianjin Stomatological Hospital from July 2017 to November 2018 were divided into three groups: Bio-Oss ( n=6), Bio-Gene ( n=5) and Bone 3(n=5) according to the differences in bone materials. Clinical and radiological results were evaluated at pre-surgery, post-6 months, and post-4 years. Results:The 6-month and 4-year clinical follow-up showed that, the depth of exploration (PD) and clinical attachment loss (CAL) of patients in the three groups were lower than those before operation (all P<0.05), and the changes of PD (ΔPD) and CAL (ΔCAL) were not statistically significant (all P>0.05). There was no statistically significant difference in gingival recession (GR) between the three groups (all P>0.05), and there was no statistically significant difference in the change of GR (ΔGR) between the groups (all P>0.05). From 6 months to 4 years after operation, there was no significant difference among ΔGR, ΔPD and ΔCAL groups (all P>0.05). At 6 months and 4 years after operation, the residual alveolar bone height (RBH%) of the three groups was significantly higher than that before operation (all P<0.05), and there was no significant difference between the two groups (all P>0.05); From 6 months to 4 years after operation, there was no significant difference in RBH% between the groups (all P>0.05). Conclusions:Three kinds of bone graft materials have significant clinical effects on periodontitis after periodontal regeneration, which can provide a reference for the selection of clinical regeneration materials.

A physical restraint device to facilitate rehabilitation in critically ill patients / 中华危重病急救医学

Physical restraints are widely used in hospitalized and critically ill patients, especially in intensive care unit (ICU), to prevent adverse events such as the accidental removal of various monitoring leads, therapeutic tubes, and self-injury or injury to others due to delirium and irritation. The existing restraint measures directly bind the upper limbs of the patients to the hospital bed, which often brings psychological harm to the patients and leads to disuse muscular atrophy. Early rehabilitation therapy can help improve the prognosis of patients, but it is difficult to be widely used in ICU due to being heavily dependent on nursing and rehabilitation physicians. A novel restraint device to facilitate rehabilitation training for critically ill patients was designed by the medical staff from the department of critical care medicine of Beijing Tiantan Hospital, Capital Medical University and obtained the National Utility Model Patent of China (ZL 2020 2 2492749.6). The device is mainly composed of a cross beam and a locking device whose two ends are connected by a rocker arm, an upper limb stopper and an upper body stopper. The upper limb and body restraint provide restrictions on the movement of the head, the upper limb, and the upper body. The angle limiter prevents the patient from pulling out the treatment tube by himself, and at the same time retains the ability to grasp the crossbar and rotate it, and the sliding block further increases the activity space, to meet the exercise of the patient's upper limb muscle strength. Carrying out physical rehabilitation training as early as possible during ICU treatment can relieve the patient's resistance to passive restraint, reduce the incidence of disuse muscle atrophy, eliminate the potential hidden dangers of medical disputes, and ultimately improve the prognosis of patients.

Effect of Rab4A degradation by MiR-496 on the progression of gastric cancer / 国际外科学杂志

Objective:To study the effect and mechanism of Rab4A knockout expression on proliferation, migration and invasion of gastric cancer cells. Methods:The expression of Rab4A in four human gastric cancer cell lines MGC-803, SGC-790, MKN45 and AGS was detected by Western blot. Rab4A was knocked out in AGS cells with the highest expression level, and untransfected gastric cancer cells were used as control group. Cell proliferation, migration and invasion were detected by CCK8 and Transwell assay, respectively. Western blot analysis was used to investigate the expression changes of epidermal growth factor receptor (EGFR), downstream pathway proteins AKT and β-catenin induced by Rab4A knockout. The interaction between Rab4A and MiR- 496 was detected by dual luciferase reporter gene, and the effect of MiR- 496 transfection on Rab4A expression was detected by qPCR and Western blot. GraphPad Prism 9 software was used for data analysis, t-test was used for comparison between the two groups, and normal distribution measurement data were expressed as mean ± standard deviation ( ± s). Results:The expression of Rab4A was the highest in AGS cells, and the knockdown of Rab4A inhibited the proliferation, migration and invasion of AGS cells ( P<0.05). In Rab4A knockout gastric cancer cells, the surface expression of epidermal growth factor receptor (EGFR) was significantly decreased, and the expression of downstream pathway proteins p-AKT and β-catenin was also inhibited ( P<0.05). The luciferase reporter showed that MiR- 496 could bind the 3′UTR of Rab4A. In addition, MiR- 496 down-regulated the expression of Rab4A in AGS cells( P<0.05). Conclusion:The expression of Rab4A is inhibited by MiR- 496, and the proliferation, migration and invasion of gastric cancer cells can be inhibited by down-regulating the surface expression of EGFR after inhibiting Rab4A expression.

Oxygen Metabolism-induced Stress Response Underlies Heart-brain Interaction Governing Human Consciousness-breaking and Attention / 神经科学通报·英文版

Neuroscientists have emphasized visceral influences on consciousness and attention, but the potential neurophysiological pathways remain under exploration. Here, we found two neurophysiological pathways of heart-brain interaction based on the relationship between oxygen-transport by red blood cells (RBCs) and consciousness/attention. To this end, we collected a dataset based on the routine physical examination, the breaking continuous flash suppression (b-CFS) paradigm, and an attention network test (ANT) in 140 immigrants under the hypoxic Tibetan environment. We combined electroencephalography and multilevel mediation analysis to investigate the relationship between RBC properties and consciousness/attention. The results showed that RBC function, via two independent neurophysiological pathways, not only triggered interoceptive re-representations in the insula and awareness connected to orienting attention but also induced an immune response corresponding to consciousness and executive control. Importantly, consciousness played a fundamental role in executive function which might be associated with the level of perceived stress. These results indicated the important role of oxygen-transport in heart-brain interactions, in which the related stress response affected consciousness and executive control. The findings provide new insights into the neurophysiological schema of heart-brain interactions.

Predictive Value of Pelvic MRI Combined with SCC-Ag on Lymphatic Metastasis in Cervical Cancer / 肿瘤防治研究

Objective To discuss the clinicopathological characteristics of cervical cancer patients with lymphatic metastasis, to evaluate lymph node metastasis in cervical cancer patients by combining pelvic MRI enlarged lymph nodes and SCC-Ag, and to analyze the prognostic value of the model. Methods We retrospectively analyzed the data of 124 patients with cervical cancer. The predictive model was established based on the result. Results The depth of interstitial infiltration, serum SCC-Ag change value before and after treatment, lymph node enlargement showed by pelvic MRI, D2-40 and Ki67 were independent risk factors for lymph node metastasis of cervical cancer (P < 0.05). The prediction model of lymph node metastasis: L=the serum SCC-Ag change value+7.127×lymph node enlargement showed by pelvic MRI+5.386×D2-40+5.135×the depth of interstitial infiltration+19.457×Ki67; the sensitivity was 78.6% and specificity was 79.2%. Conclusion The cervical cancer patients with L≥20.8261 should be noticed. Doctors should give them individualized neoadjuvant treatment, and ensure adequate surgical scope. The above lymphatic prediction model has predictive value for preoperative lymph node metastasis.

Large fluctuations of the fusion intermediate help SARS-CoV-2 capture host cell membranes

Cell entry by SARS-CoV-2 is accomplished by the S2 subunit of the spike S protein on the virion surface by capture of the host cell membrane and fusion with the viral envelope. Capture and fusion require the prefusion S2 to transit to its potent, fusogenic form, the fusion intermediate (FI). However, the FI structure is unknown, detailed computational models of the FI are unavailable, and the mechanisms and timing of membrane capture and fusion are not established. Here, we constructed a full-length model of the CoV-2 FI by extrapolating from known CoV-2 pre- and postfusion structures. In atomistic and coarse-grained molecular dynamics simulations the FI was remarkably flexible and executed large bending and extensional fluctuations due to three hinges in the C-terminal base. Simulations suggested a host cell membrane capture time of [~] 2 ms. Isolated fusion peptide simulations identified an N-terminal helix that directed and maintained binding to the membrane but grossly underestimated the binding time, showing that the fusion peptide environment is radically altered when attached to its host fusion protein. The large configurational fluctuations of the FI generated a substantial exploration volume that aided capture of the target membrane, and may set the waiting time for fluctuation-triggered refolding of the FI that draws the viral envelope and host cell membrane together for fusion. These results describe the FI as a machinery designed for efficient membrane capture and suggest novel potential drug targets. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=117 SRC="FIGDIR/small/439051v3_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@1374b59org.highwire.dtl.DTLVardef@133d21forg.highwire.dtl.DTLVardef@127f2ddorg.highwire.dtl.DTLVardef@1b9ab8f_HPS_FORMAT_FIGEXP M_FIG C_FIG

Effect of Modified Bazhentang on Nutritional Status and Immune Function of Gastric Cancer Patients with Neoadjuvant Chemotherapy / 中国实验方剂学杂志

Objective:To observe the effect of modified Bazhentang on the nutritional status and immune function of patients with Qi and blood deficiency syndrome in neoadjuvant chemotherapy （NAC） for gastric cancer. Method:One hundred and ten patients were randomly divided into observation group and control group with 55 cases each. Both groups accepted FOLFOX6 protocol. Patients in control group took Jianpi Shengxue tablets orally， 3 tablets/time， 3 times/day. Patients in observation group received modified Bazhentang， 1 dose/day. The course of treatment was six weeks in both groups. Before and after treatment， scores were graded according to patient generated-subjective global assessment （PG-SGA）， Qi and blood deficiency syndrome， and the Revised Piper Fatigue Scale （PFS-R）. Levels of serum total protein （TB）， albumin （ALB）， prealbumin （PAB）， CD4⁺， CD8⁺， helper T lymphocyte 17 （Th17）， regulatory T cell （Treg）， immunoglobulin G （IgG）， IgM， and IgA were detected before and after therapy. Body mass index （BMI） and fat free mass index （FFMI） were measured before and after treatment. Weight loss was recorded， and the acute or subacute toxicity of anticancer drugs was evaluated. Result:The degree of malnutrition in the observation group was lower than that in the control group （<italic>Z</italic>=2.401，<italic>P</italic><0.01）. The levels of TB， ALB and PAB in the observation group were higher than those in the control group （<italic>P</italic><0.01）. The CD4⁺， Treg and CD4⁺/CD8⁺ levels in the observation group were higher than those in the control group （<italic>P</italic><0.01）. The CD8⁺， Th17 and Th17/Treg levels were lower than those in the control group （<italic>P</italic><0.01）. Besides， the levels of IgM and IgA in the observation group were higher than those in the control group （<italic>P</italic><0.01）. The PG-SGA score and weight loss in the observation group were lower than those in the control group （<italic>P</italic><0.01）. The BMI and FFMI data of the observation group were higher than those of the control group （<italic>P</italic><0.05）. The scores of PFS-R and Qi-blood deficiency syndrome were lower than those of the control group （<italic>P</italic><0.01）. The incidence of nausea and vomiting in the observation group was 45.45% （25/55）， lower than 65.45% （36/55） in the control group （<italic>χ</italic>²=4.452，<italic>P</italic><0.05）. Conclusion:Modified Bazhentang can be used to assist gastric cancer patients with NAC， which can improve nutritional status and immune function， promote immune balance， reduce clinical symptoms and fatigue， and reduce chemotherapy toxicity and side effects， so it is worthy of clinical use.

Clinical Application of Screening Cell Combination Method in the Prediction of Red Blood Cell Alloantibody / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical application of screening cell combination method in the prediction of red blood cell alloantibody, so as to provide basis for clinical diagnosis.@*METHODS@#From October 2018 to April 2020, 9 680 samples were screened with automatic blood group instrument, 79 patients with positive alloantibodies were identified by 4 sets of screening cells from different manufacturers (referred to as combined method). At the same time, cell panel Panocell-16 was used for comparative analysis. Meanwhile, the combined method was also used to identify the antibodies of 20 samples from National Center for Clinical Laboratories external quality assessment (EQA) in China and 12 samples from WHO EQA.@*RESULTS@#The 79 alloantibodies included anti-Mia antibody (7 cases), anti-M antibody (13 cases), anti-Le@*CONCLUSION@#The combined method can identify the alloantibodies of red blood cells in Chinese population. The screening cells can be used for screening of irregular antibodies without wasting reagents at the same time.

The correlation between T helper 17 cell/regulatory T cell imbalance and cytokines in patients with immunoglobulin G4-related disease / 中华风湿病学杂志

Objective:To investigate the characteristics of lymphocyte subsets in peripheral blood of patients with immunoglobulin G4-related disease (IgG4-RD) and the correlation between T helper 17 cell (Th17)/regulatory T cells (Treg) cell imbalance and cytokines.Methods:A total of 31 patients with IgG4-RD who were admitted to the Rheumatology and Immunology Department of the Second Hospital of Shanxi Medical University from January 2016 to June 2020 were included. We collected their clinical and laboratory data, and selected 30 age and sex matched healthy people as the control group. Flow cytometry was used to detect the percentage and absolute number of lymphocyte subsets [T, B, natural killer cell (NK), CD4 +T, CD8 +T] and CD4 +T subsets [Th1, Th2, Th17, CD4 +CD25 +forkhead box protein 3 (Foxp3) +Treg] in peripheral blood of IgG4-RD patients and healthy controls. The serum interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-γ levels in the IgG4-RD patients were measured by cytometric bead array (CBA). Correlation between Th17/Treg ratio and disease-related indicators was also analyzed. We used χ2 test, Mann-Whitney U test and Spearman correlation analysis for statistical analysis. Results:① The percentage of CD4 +T cells in the peripheral blood of IgG4-RD patients was higher than that of healthy controls [45.00%(33.97%, 51.48%) vs 39.36%(33.78%, 43.30%), Z=-2.142, P<0.05]. ② The percentage and absolute number of Th17 cells was increased in IgG4-RD patients [1.13%(0.70%, 1.55%) vs 0.77%(0.43%, 1.07%), Z=-2.229, P<0.05; 7.90(5.20, 12.23) cells/μl vs 5.60(3.12, 8.47) cells/μl, Z=-2.568, P<0.05], while the percentage of Treg cells was decreased [3.37%(2.82%, 5.65%) vs 4.96%(4.18%, 6.34%), Z=-2.986, P<0.01]. But the number of Treg cells showed no difference between the two groups. ③ Th17/Treg ratio was significantly increased in IgG4-RD patients [0.29(0.16, 0.46) vs 0.15(0.08, 0.23), Z=-3.119, P<0.01], and it was positively correlated with IgG4-RD response index score ( r=0.491, P<0.01). ④ Serum IL-6 [13.72(9.29, 26.06) pg/ml vs 2.23(1.94, 3.10) pg/ml, Z=-4.815, P<0.01], IL-10 [5.46(4.28, 15.38) pg/ml vs 1.81(1.59, 2.02) pg/ml, Z=-5.298, P<0.01], TNF-α [4.25(1.47, 7.26) pg/ml vs 1.15(1.05, 1.45) pg/ml, Z=-3.146, P<0.01] and IFN-γ [3.89(1.76, 6.61) pg/ml vs 1.41(1.24, 1.65) pg/ml, Z=-3.172, P<0.01] in IgG4-RD group were significantly higher than those in healthy control group. Moreover, Th17/Treg ratio was negatively correlated with IL-2 level ( r=-0.554, P<0.05). Conclusion:Th17/Treg disorder exists in IgG4-RD patients, and it is related to disease activity, indicating that Th17/Treg imbalance may be an important mechanism in IgG4-RD. IL-2 plays an important role in regulating Th17/Treg balance and may be a potential immunotherapy target in future.

Risk factors for hospitalization of pregnant women with influenza A / 中华传染病杂志

Objective:To investigate the influencing factors of hospitalization for pregnant women with influenza A.Methods:From December 2018 to February 2019, 261 pregnant women with influenza A were admitted to Beijing Ditan Hospital, Capital Medical University. The clinical data of age, gestational period, underlying diseases, time from onset to treatment, white blood cell count and lymphocyte count of these patients were collected. Data of out-patients were compared with those of inpatients. Chi-square test and multivariate logistic regression were used to analyze the influencing factors of hospitalization in pregnant women with influenza A.Results:Among the 261 cases of pregnancy with influenza A, 36 cases (13.79%) were hospitalized, of which 10 (27.78%) were hospitalized due to severe influenza complications, the other 26 cases (72.22%) were hospitalized due to pregnancy related adverse events. The proportions of hospitalized patients with age ≥30 years old, gestational period ≥28 weeks, combined with underlying diseases and lymphocyte count <1×10 9/L were 75.00%(27/36), 83.33%(30/36), 16.67%(6/36) and 50.00%(18/36), respectively, which were significantly higher than those of out-patients (47.11%(106/225), 35.56%(80/225), 0.89%(2/225) and 13.22%(16/121), respectively; χ2=9.66, 29.05, 26.00 and 22.12, respectively, all P<0.05). The proportions of inpatients and out-patients with white blood cell count ≥4×10 9/L were 97.22%(35/36) and 97.52%(118/121), respectively, and there was no significant difference ( χ2=0.01, P=0.921). Multivariate logistic regression analysis showed that age ≥30 years (odds ratio ( OR)=5.181, 95% confidence interval ( CI) 1.628-16.489, P=0.005), gestational period ≥28 weeks ( OR=11.054, 95% CI 3.233-37.796, P<0.01), lymphocyte count <1×10 9/L ( OR=6.864, 95% CI 2.237-20.729, P=0.001), and time from onset to treatment <24 h ( OR=0.076, 95% CI 0.012-0.468, P=0.005) were the influencing factors for hospitalization of pregnant women with influenza A. Conclusion:Age ≥30 years old, gestational period ≥28 weeks, lymphocyte count <1×10 9/L and time from onset to treatment <24 h are the influencing factors for hospitalization of pregnant women with influenza A.

LYN′s effects on the migration and invasion of gastric cancer cells through Wnt/ β-catenin signaling pathway / 国际外科学杂志

Objective:To explore the effects of LYN on the biological behaviors of gastric cancer cells, such as migration and invasion, and analyze the regulatory mechanism of Wnt/ β-catenin signaling. Methods:Gastric and paracancerous tissue samples from gastric cancer patients admitted to the Affiliated Hospital of Chengde Medical University from Oct. 2017 to May 2018 were selected to detect the expression level of LYN in clinically collected gastric cancer and paracancerous tissue samples by qRT-PCR.Gastric cancer AGS cells were used as experimental subjects, and shRNA-LYN was transfected into gastric cancer AGS cells using Lipofectamine 2000 as experimental group (Sh-LYN group), and untransfected cells as control group (NC group). LYN mRNA expression in AGS cells before and after transfection was detected by qRT-PCR.Transwell detected cell migration and invasion. Cell apoptosis was detected by TUNEL.Western Blot analysis was performed to detect proteins related to the Wnt/β-catenin signaling pathway and to study its regulatory mechanism.Measurement data were expressed as ( Mean± SD), and independent sample t test was used for comparison between the two groups. P<0.05 was considered statistically significant. Results:LYN mRNA expression was significantly up-regulated in gastric cancer tissues ( t=11.04, P<0.001).Sh-LYN transfected gastric cancer cells could make LYN protein expression lower than that of the normal control group( F=961.26, P=0.016).After transfection, migration and invasion of cells in the sh-LYN group were inhibited, and the apoptosis rate of cells in the sh-LYN group was significantly higher than that in the normal control group ( t=3.437, 4.450, P=0.011, 0.026) .Western Blot results: sh-LYN reduced the expression of Wnt3 and β-catenin significantly when compared with the normal control group.The detection of downstream proteins showed that after LYN knockdown, the expression of EMT epithelial labeled E-cadherin was increased, and EMT mesenchymal labeled N-cardherin and vimentin were down-regulated. The other related proteins snail 1 and snail 2 were also down-regulated. Conclusion:LYN knockdown inhibits migration and invasion of gastric cancer cells and induces apoptosis in gastric cancer cells, a process associated with the Wnt/ β-catenin signaling pathway.

Design and application of a push-pull adjustable artificial dead space / 中华危重病急救医学

Using artificial dead space to correct hypocapnia or induce hypercapnia is of particular significance for diagnosing and treating specific neurocritical diseases. At present, the above purpose is mainly achieved by adding an extension tube between the Y-type connector of the ventilator and the artificial airway in clinical practice. However, its volume is often fixed and cannot adapt to the individualized diagnosis and treatment in different clinical scenarios. The research group led by Professor Zhou Jianxin from the department of critical care medicine of Beijing Tiantan Hospital, Capital Medical University, has designed an artificial dead cavity with adjustable volume based on years of research in the respiratory field and has been granted a national utility model patent (patent number: ZL 2020 2 0496413.4). The artificial dead chamber is simple in structure, composed of a barrel body, a piston head, and a push-pull rod. By freely adjusting the size of the artificial dead chamber volume, it can accurately regulate the target carbon dioxide, correct the spontaneous hyperventilation, terminate intractable hiccup, and shorten the operation time of asphyxia test in clinical diagnosis of brain death while correcting hypocapnia or inducing hypercapnia. It has the advantages of solid reliability, convenient operation, and low production cost, which significantly facilitates scientific research and clinical diagnosis and treatment.

Health Condition and Test Availability as Predictors of Adults' Mental Health during the COVID-19 Pandemic

BackgroundResearch identifying adults mental health during the COVID-19 pandemic relies solely on demographic predictors without examining adults health status during the COVID-19 pandemic as a potential predictor. MethodsAn online survey of 669 adults in Malaysia was conducted during May 2-8, 2020, six weeks after a Movement Control Order (MCO) was issued. FindingsAdults health condition had curvilinear relationships (horizontally reversed J-shaped) with insomnia, anxiety, depression and distress. Reported test availability for COVID-19 (from "strongly disagree" to "strongly agree") also had curvilinear relationships (horizontally reversed J-shaped) with anxiety and depression. Younger adults reported worse mental health, but people from various religions and ethnic groups did not differ significantly in reported mental health. InterpretationAdults with worse health conditions had more mental health problems, especially adults at the lower end of the health spectrum. Test availability negatively predicted anxiety and depression, especially for adults experiencing poor COVID-19 test availability. The significant predictions of health condition and COVID-19 test availability suggest a new direction for the literature to identify psychiatric risk factors directly from health related variables during a pandemic. FundingTsinghua University-INDITEX Sustainable Development Fund (Project No. TISD201904).

Who do not wash their hands during the Covid-19 pandemic? Social media use as a potential predictor

This study predicts handwashing behavior during the Covid-19 pandemic. An analysis of 674 adults in Malaysia identifies their time spent on social media per day as a key predictor of handwashing. The association between time spent on social media and handwashing substantially depends on gender and the number of children in the same household. Additional predictors include age and health condition. This study helps identify specific target groups for health communication on hand hygiene via peoples use of social media, which can be a key channel for health communication campaigns during a pandemic.