Population genomics reveals that a missense mutation in EDNRB2 contributes to white plumage color in pigeons.

Plumage color is an important economic trait for breed feature identification and consumer's requirements in pigeons. The domestic pigeon has multiple types of plumage color, thereby providing a unique opportunity to identify the genetic basis of plumage coloration. White feather color is common for meat and medicinal use. To investigate the genetic variation associated with white plumage color in pigeons, we use genome resequencing and population genomics to identify the genomic regions with strong selective signature between pigeons with brown and white plumage color. Meanwhile, we obtained some candidate genes with melanin or melanosome biosynthesis in selected regions. Finally, we identified a missense mutation p.E256K in the EDNRB2 completely associated with white plumage color. These findings provide a basis for genetic variation in pigeons with plumage color phenotype.

Meta-synthesis of qualitative research on the experience of kinesiophobia in patients with cardiac rehabilitation / 中华护理杂志

Objective To systematically review and synthesize the psychological experience of kinesiophobia in patients with cardiac rehabilitation.Methods PubMed,Web of science,Journals@Ovid,Embase,CINAHL,PsycINFO,Cochrane Library,CNKI,SinoMed,WanFang Database,Vip Database,American Heart Association,European Society of Cardiology and American Association of Cardiovascular and Pulmonary Rehabilitation were searched to collect qualitative research on the psychological experience of cardiac rehabilitation patients with kinesiophobia.The retrieval time was from the establishment of the databases to Jun 2023.The literature was evaluated using the Australian JBI Quality Evaluation Criteria for Qualitative Research in Evidence-based Health Care Centres(2016),and the results were consolidated using an aggregative integration approach.Results A total of 45 results were extracted from 14 studies.Similar results were summarized into 10 groups,and 3 integrated results were synthesized as followed.Kinesiophobia was influenced by many factors;kinesiophobia affects the life experience of patients;strategies to reduce the level of kinesiophobia.Conclusion Nurses should pay more attention to psychological experience of kinesiophobia,and take the corresponding intervention measures to help patients overcome the psychological barriers of kinesiophobia,perfect personalized exercise programs,and improve the level of physical activity.

Construction of microfluidic organ-on-a-chip and its application in simulating subchondral bone remodeling / 中华创伤杂志

Objective:To construct a microfluidic organ-on-a-chip and evaluate its capability in simulating subchondral bone remodeling during the progression of osteoarthritis.Methods:The chip′s main body was designed based on the microfluidic technology and cell co-culture technique. MC3T3-E1 cells were cultured adherently within the cell seeding micro-chamber, with the culture medium perfused at a flow rate of 0.5 ml/min at the bottom of the micro-chamber. Evaluation metrics were as follows: (1) Assessment of the microfluidic organ-on-a-chip: The growth culture medium was perfused and simulation experiments were conducted to test the concentration differences and equilibrium times of the fluid inside and at the bottom of the cell seeding micro-chamber at various time points; live-dead staining was performed to observe the biocompatibility of cells cultured continuously for 3 days and 7 days at a set flow rate, which was divided into 3-day and 7-day groups. (2) Osteogenic potential of the microfluidic organ-on-a-chip: The osteogenic induction medium was perfused, and ALP staining and PCR were performed to compare the number of the black alkaline phosphatase (ALP)-positive cells and the expression levels of osteogenesis-related marker genes including osteoblast-specific transcription factor 2 (RUNX2), type I collagen (COL1A1), bone morphogenetic protein-2 (BMP-2), and osteocalcin (OCN) under static, 3-day and 7-day perfusion conditions, which was divided into static non-induced, static-induced and perfusion-induced groups. (3) Characterization of morphology and size, and biocompatibility of extracellular vesicles (EVs) of three osteoblast subtypes: Three different subtypes of osteoblasts were obtained [endothelial-type osteoblasts (EnOB)-EVs, stromal-type osteoblasts (StOB)-EVs and mineralizing-type osteoblasts (MinOB)-EVs]. Their morphology and size were obtained through transmission electron microscopy and particle size analysis. Growth medium containing EVs of three different cell subtypes was perfused, and cell proliferation/apoptosis assay was performed to compare the biocompatibility of the addition of different EVs concentrations (1, 1.25, 2.5, and 5 μg/ml) for 24 hours, which was categorized into the EnOB-EVs group, StOB-EVs group and MinOB-EVs group. (4) Osteogenic effect of EVs from three subtypes of osteoblasts: Osteogenic induction media containing EVs from three different osteoblast subtypes were perfused for 3 days, and ALP staining and PCR were performed to compare the number of black ALP-positive cells and the expression levels of osteogenesis-related marker genes including RUNX2, COL1A1, BMP-2, and OCN, which was divided into non-EVs group, EnOB-EVs group, StOB-EVs group and MinOB-EVs group.Results:(1) Evaluation of the microfluidic organ-on-a-chip: Simulation results showed that the concentration in the top layer of the upper chamber reached more than 95% of that in the lower chamber and that the concentration in the bottom layer was about 96.5% of that in the lower chamber after 12 hours of continuous perfusion, reaching an equilibrium state of the concentration difference between the upper and lower chambers. The results of live-dead staining showed that the chip was biocompatible at a flow rate of 0.5 ml/min, and the cell survival rate at 3 and 7 days of perfusion was (99.48±0.12)% and (97.07±1.05)% ( P<0.01). (2) ALP staining results showed that at 3 days, the perfusion-induced group showed the highest number of black ALP-positive cells, followed by the static-induced group, and the least in the static non-induced group. At 7 days, the static-induced group had the highest number of black ALP-positive cells, followed by the perfusion-induced group, and the least in the static non-induced group. PCR results indicated that at 3 days, the expression levels of RUNX2, COL1A1, BMP-2, and OCN were 1.00±0.03, 1.00±0.12, 1.00±0.01, and 1.00±0.02 respectively in the static non-induced group; 1.80±0.04, 4.05±0.37, 9.80±1.94, and 4.38±0.89 respectively in the static-induced group, and 2.45±0.23, 5.48±0.42, 91.50±4.56, and 10.82±4.96 respectively in the perfusion-induced group ( P<0.01). At 7 days, the expression levels of RUNX2 was 1.00±0.01 in the static non-induced group, 1.46±0.46 in the static-induced group, and 1.11±0.08 in the perfusion-induced group ( P>0.05); the expression levels of COL1A1, BMP-2, and OCN were 1.00±0.03, 1.00±0.13, and 1.00±0.09 respectively in the static non-induced group, 9.38±0.25, 14.27±4.35, and 84.01±4.02 respectviely in the static-induced group, and 2.39±0.08, 133.64±8.87, and 86.64±8.36 respectively in the perfusion-induced group ( P<0.01). When comparing the static non-induced, static-induced, and perfusion-induced groups at both 3 and 7 days, the perfusion-induced group demonstrated the strongest osteogenic capability. (3) Characterization of morphology and size and biocompatibility of EVs from three osteoblast subtypes: Under the transmission electron microscope, EVs from EnOB-EVs, StOB-EVs, and MinOB-EVs all exhibited a typical saucer-shaped morphology. The particle sizes of EnOB-EVs, StOB-EVs, and MinOB-EVs were (91.3±14.7)nm, (106.0±16.0)nm, and (68.1±10.7)nm, respectively. Cell proliferation/apoptosis assay results indicated that the optimal administration concentration of EnOB-EVs, StOB-EVs, and MinOB-EVs was all 1.25 μg/mL. (4) Validation of osteogenic effect of the microfluidic organ-on-a-chip on three types of EVs: ALP staining results showed that the non-EVs group had the fewest black ALP-positive cells, followed by the EnOB-EVs group, then the StOB-EVs group, and the MinOB-EVs group had the most. PCR results showed that the expression levels of RUNX2, COL1A1, BMP-2, and OCN were 1.00±0.01, 1.00±0.03, 1.00±0.02, and 1.00±0.02 respectively in the non-EVs group, 1.95±0.11, 6.78±2.04, 7.99±0.57, and 6.93±3.83 repectively in the EnOB-EVs group, 0.79±0.12, 5.68±1.53, 12.59±3.15, and 25.59±0.95 respectively in the StOB-EVs group, and 0.68±0.10, 4.36±0.69, 18.75±3.21, and 34.74±3.98 repectively in the MinOB-EVs group ( P<0.01). Compared with the non-EVs group, EnOB-EVs group, StOB-EVs group, and MinOB-EVs group, the MinOB-EVs group showed the most significant osteogenic effect. Conclusions:The microfluidic organ-on-a-chip constructed using microfluidic technology and cell co-culture techniques is capable of maintaining the normal growth of MC3T3-E1 cells, enhancing their proliferation and osteogenic induction differentiation. EVs released by osteoblasts at different stages possess osteogenic effects and can accelerate the bone sclerosis in the remodeling of subchondral bone during the progression of osteoarthritis.

Correlation between hemoglobin level and diabetic retinopathy in patients with type 2 diabetes mellitus / 中华内分泌代谢杂志

Objective:To evaluate the relationship between hemoglobin(Hb) level and the risk of diabetic retinopathy(DR) in patients with type 2 diabetes mellitus(T2DM).Methods:This study was a prospective cohort study. A total of 1 730 T2DM patients without DR, who received regular management at the Li′s Clinic in Taiwan, China starting from 2002, were selected as the study population. All patients underwent annual dilated fundus examination by professional ophthalmologists. General patient information and laboratory results were collected and analyzed. Based on the occurrence of DR during patient follow-up, patients were divided into the DR group and the non-DR(NDR) group. The impact of Hb levels on DR was explored using a generalized linear mixed model, and the relationship between Hb levels and DR was studied using Cox proportional hazards regression model.Results:After an average follow-up of 9.79 years, 481 patients with DR were detected. Compared with NDR group, DR group displayed a longer course of diabetes, higher rates of cataract, insulin use, and anemia, and higher systolic blood pressure, HbA 1C, and UACR as well as lower Hb. The results of the generalized linear mixed model showed a negative correlation between Hb and the occurrence of DR( β=-0.015, P<0.001). The Cox proportional hazards regression model showed that, after adjusting for confounding variables and based on quartiles of average Hb levels during follow-up, the risk of developing DR increased by 56.9% in the Q1 group(Hb≤127 g/L) compared to the Q4 group(Hb≥142 g/L). The cumulative risk plot showed that, after adjusting for confounding variables, the Q1 group had the highest cumulative risk of developing DR, and the difference was statistically significant( P<0.05). Conclusion:Hb was negatively correlated with DR, and the lower Hb levels were associated with the occurrence of DR, independent of other influencing factors.

Advance in the application of recombinase polymerase amplification-lateral flow strips technology in the diagnosis of pathogenic microorganisms / 中华检验医学杂志

Recombinase polymerase amplification (RPA) is a newly developed isothermal amplification technology with high sensitivity and specificity. The combination of RPA and lateral flow strips (LFS) enables rapid identification of target genes. This technique has been widely used in medicine, food, botany, and other fields. This review generalizes the use of RPA-LFS technology for the diagnosing pathogenic microorganisms, providing a reference for point-of-care diagnosis of pathogenic microorganisms.

Stigma and related factors in family members of patients with mental disorders / 中国心理卫生杂志

Objective:To explore stigma and related factors among family members of patients with mental disorders in psychiatric hospitals.Methods:Totally 1 365 family members of inpatients with mental disorders were-surveyed,and were assessed with the Perceived Devaluation-Discrimination Scale and a self-made demographic characteristics questionnaire.Results:The screening rate of stigma among the patient's family members was 61.5％.Males(OR=2.26,95％CI:1.06-5.01),age group of 18-29 years(OR=1.91,95％CI:1.15-3.20),monthly income ≥500 yuan(P＜0.05),disease duration of 0.5-＜lyear(OR=3.14,95％CI:1.66-6.03),care for patients within＜lyear(P＜0.05),teachers(OR=2.32,95％CI:1.24-3.44),self-employed person(OR=1.63,95％CI:1.02-2.24),civil servants(OR=1.77,95％CI:1.09-2.45),schizophrenia(OR=1.87,95％CI:1.32-2.42),affective disorders(OR=1.52,95％CI:1.03-2.016)were the main riskfactors of stigma.Conclusions:Family members of patients with mental disorders generally have a severe stigma,especially of patients with schizophrenia and affective disorders.

Mediating effect of avoidant personality between chronic rhinitis and depressive symptoms in college freshman / 中华行为医学与脑科学杂志

Objective:To explore the influence of chronic rhinitis on depressive symptoms of college freshmen and the mediating effect of avoidant personality.Methods:A cluster sampling method was used to survey 8 079 college freshmen from April 2018 to October 2018 using the Beck depression inventory and the avoidant personality diagnosis questionnaire based on DSM-Ⅳ.SPSS 25.0 software was used for descriptive statistics and Spearman correlation analysis, and the macro program PROCESS version 3.3 was used for the mediating effect.Results:(1) The detection rates of chronic rhinitis, avoidant personality and depressive symptoms were 22.90% (1 850/8 079), 19.22% (1 553/8 079) and 6.28% (507/8 079). The scores for avoidant personality disorder and depressive symptoms were 1.00 (0, 3.00) and 1.00 (0, 4.00), respectively. (2) The chronic rhinitis, avoidant personality and depressive symptoms were positively correlated ( rchronic rhinitis-avoidant personality=0.094, rchronic rhinitis-depressive symptoms=0.095, ravoidant personality-depressive symptoms=0.416, all P<0.001). (3) Chronic rhinitis could positively predict depressive symptoms ( β=1.113, P<0.001). (4) Avoidant personality played a mediating role between chronic rhinitis and depressive symptoms ( β=1.094, P<0.001), and accounted for 44.92%(0.500/1.113) of the total effect. Conclusion:Chronic rhinitis directly affect the depressive symptoms of college freshmen, and indirectly affect the depressive symptoms of college freshmen through the mediating role of avoidant personality.

The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylatedIgG1 in naive but not antigen-experienced vaccinees

The onset of severe SARS-CoV-2 infection is characterized by the presence of afucosylated IgG1 responses against the viral spike (S) protein, which can trigger exacerbated inflammatory responses. Here, we studied IgG glycosylation after BNT162b2 SARS-CoV-2 mRNA vaccination to explore whether vaccine-induced S protein expression on host cells also generates afucosylated IgG1 responses. SARS-CoV-2 naive individuals initially showed a transient afucosylated anti-S IgG1 response after the first dose, albeit to a lower extent than severely ill COVID-19 patients. In contrast, previously infected, antigen-experienced individuals had low afucosylation levels, which slightly increased after immunization. Afucosylation levels after the first dose correlated with low fucosyltransferase 8 (FUT8) expression levels in a defined plasma cell subset. Remarkably, IgG afucosylation levels after primary vaccination correlated significantly with IgG levels after the second dose. Further studies are needed to assess efficacy, inflammatory potential, and protective capacity of afucosylated IgG responses. One sentence summaryA transient afucosylated IgG response to the BNT162b2 mRNA vaccine was observed in naive but not in antigen-experienced individuals, which predicted antibody titers upon the second dose.

Relapse risk analysis in anti-aquaporin 4-IgG positive neuromyelitis optica spectrum disorders patients treated with immunosuppressant / 中华神经科杂志

Objective:To investigate the relapse risk factors of anti-aquaporin 4 (AQP4)-IgG positive neuromyelitis optica spectrum disorders (NMOSD) patients treated with immunosuppressant.Methods:Data (from January 2011 to June 2021) of AQP4-IgG positive NMOSD patients treated with immunosuppressant for longer than 5 years from MSNMObase, a hospital-based electronic registry for multiple sclerosis and related disorders in Peking Union Medical College Hospital, were collected. Clinical features and risk factor differences between patients with and without relapse under the immunosuppressive therapy were analyzed.Results:One hundred and twelve patients with AQP4-IgG positive NMOSD were included, 105 (93.8%) of which were female. The disease onset age was (34.9±11.3) years, 13(11.6%) had an older disease onset age than 50 years (late onset), and the disease duration was 8.1 (6.6, 11.4) years. Sixty-four (57.1%) patients had relapse, and the proportion of late onset patients was significantly lower in relapse group than in non-relapse group [4/64(6.3%) vs 9/48(18.8%), χ2=4.18, P=0.041]. Compared with those without relapse, both the annualized relapse rate (ARR) before treatment [1.07 (0.36, 2.25) vs 0.34 (0, 1.11), Z=2.92, P=0.003] and the proportion of patients with relapse before treatment [54/64(84.4%) vs 33/48(68.8%), χ2=3.86, P=0.049] were significantly higher for patients in relapse group. Multivariate Logistic regression analysis revealed the relapse risk of late-onset patients was lower than that of early-onset patients ( HR=0.26, 95% CI 0.10-0.73, P=0.010) and patients with higher ARR before treatment showed a higher risk of relapse under the immunosuppressive therapy ( HR=1.55,95% CI 1.26-1.91, P<0.001). Conclusion:AQP4-IgG positive NMOSD patients with younger disease onset age than 50 years or with frequent relapses before treatment had a higher relapse risk under the immunosuppressive therapy, and they may need highly effective treatments.

Short-term effects of extended adventitial inversion with graft eversion anastomosis technique in the root treatment of acute type A aortic dissection / 中国胸心血管外科临床杂志

@#Objective    To evaluate the short-term therapeutic effect of extended adventitial inversion with graft eversion anastomosis technique in the root treatment of acute type A aortic dissection (ATAAD). Methods    From November 2019 to July 2020, 28 patients with ATAAD were treated by extended adventitial inversion with graft eversion anastomosis technique in the Department of Cardiovascular Surgery, Dalian Municipal Central Hospital, including 19 males and 9 females, aged 60.11±11.11 years. The intima of the ascending aorta was trimed to 5 mm above the sinotubular junction. The adventitia of the ascending aorta was longitudinally cut to the reserved intima margin along the junction of the three aortic valves. The extended adventitial inversion was sutured continuously, no coronary sinus was sutured over the aortic annulus, and the left and right coronary sinus was sutured above the coronary ostium. The anastomotic graft was everted and inserted into the aortic lumen, and the everted graft was continuously sutured at the level of sinotubular junction which was 5 mm away from the edge of graft. Results    There was no intraoperative death, intractable root hemorrhage, residual root false lumen, root dilatation, anastomotic hematoma or other complications. There was no recurrence of the pain in the back of all patients, and the results of the CT angiography were not significantly changed. In 22 patients with no regurgitation, only 1 (4.55%) patient had a mild regurgitation. In 6 patients with mild aortic regurgitation, the disappearance rate of regurgitation was 50.0% (3/6). Conclusion    The treatment of extended adventitial inversion with graft eversion anastomosis technique in the root treatment of aortic dissection eliminates the residual dissection at the root. The anastomotic hemorrhage is prevented, the root structure of aortic dissection is reconstructed and strengthened, the root function is restored, and the possible expansion of the root is prevented. The short-term results are satisfactory.

Evaluation of 3D printing technology before transcatheter aortic valve replacement surgery / 中国胸心血管外科临床杂志

@#Aortic valve disease is one of the major diseases threatening human health. Transcatheter aortic valve replacement (TAVR) is a new treatment for aortic disease. Preoperative evaluation is of great significance to the successful operation and the long-term quality of life of patients. The 3D printing technology can fully simulate the cardiac anatomy of patients, create personalized molds for patients, improve surgical efficiency, reduce surgical time and surgical trauma, and thus achieve better surgical results. In this review, the relevant literatures were searched, and the evaluation effect of 3D printing technology on the operation of TAVR was reviewed, so as to provide clinical reference.

Expression of miR-101-3p in Gastric Cancer and Its Effects on Invasion, Metastasis, and Angiogenesis of Gastric Cancer Cells by Targeting STC-1 Gene to Regulate PI3K/AKT Signaling Pathway / 肿瘤防治研究

Objective To explore the expression of miR-101-3p in gastric cancer and its mechanism on the invasion, metastasis, and angiogenesis of gastric cancer cells by targeting the STC-1 gene to regulate the PI3K/AKT signaling pathway. Methods qRT-PCR was used to detect the expression of miR-101-3p and STC-1 mRNA in gastric cancer tissues and BGC-823 cell and analyze the relationship between miR-101-3p expression and patients' clinical pathological factors. The cells were transfected with miRNA mimics and plasmids separately or in combination with LipofectamineTM 2000. TargetScanHuman prediction and dual-luciferase assay were used to verify the targeted regulation of miR-101-3p on STC-1. The effect and possible mechanism of miR-101-3p targeting the STC-1 gene on the invasion, metastasis, and angiogenesis of cancer cells were verified by scratch test, Transwell chamber test, Matrigel in vitro tube forming test, and Western blot assay. The development of the transplanted tumor was detected by nude mouse tumorigenicity test. Results The expression of STC-1 in gastric cancer tissues was higher than that in normal tissues. Compared with normal gastric tissues and GES-1 cells, miR-101-3p was down-regulated, and STC-1 mRNA was up-regulated in gastric cancer tissues and BGC-823 cell. The level of miR-101-3p was negatively correlated with the level of STC-1, and significantly correlated with the degree of tumor differentiation, TNM stage, and lymph node metastasis (P < 0.05). miR-101-3p directly targeted STC-1. The overexpression of miR-101-3p inhibited STC-1 expression and downregulated the expression of p-PI3K/PI3K, p-AKT/AKT, MMP-2, MMP-9, VEGF, and Ang2, consequently, inhibited tumor cell invasion, metastasis, and angiogenesis and reduced the size and weight of the transplanted tumors (P < 0.05). Conclusion miR-101-3p is down-regulated in gastric cancer and can target the STC-1 gene to regulate the PI3K/AKT signaling pathway and inhibit the invasion, metastasis, and angiogenesis of BGC-823 gastric cancer cells and the development of transplanted tumors in vivo.

Clinical trials of inhalation in pediatric population in China / 中国临床药理学与治疗学

AIM: To investigate the characteristics of clinical trials of inhalation in pediatric population in China. METHODS: The pediatric clinical trials of inhaled drugs in China registered on the www.Chinadrugtrials.org.cn and Clinical Trials in USA respectively until November 20, 2021 were reviewed. The characteristics of pediatric clinical trials of inhaled drugs including the clinical trial phases, drug indications and classificatio etc. were analyzed. RESULTS: There were 21 pediatric clinical trials of inhaled drugs registered on the www.Chinadrugtrials.org.cn, accounted for 8.9%(21/235) of inhalation clinical trials in all populations. 47.6% of them were generic drugs, mainly focusing on expectorants for Phlegm symptoms and inhaled preparations for asthma, which accounting for 71.4%(15/21). There were 34 pediatric clinical trials of inhaled drugs registered on the Clinical Trials in USA, the drug indications of which were mainly asthma and anesthesia, accounting for 76.5%(26/34). CONCLUSION: The pediatric clinical trials of inhalations in China started later, and the total number is small compared to adults, mainly focusing on generic drugs. We should pay attention to the research and development of new inhalation drugs, standardizing and promoting the clinical trials of inhaled drugs in pediatric population actively.

Antibacterial Effect of Chitosan-Modified Fe3O4 Nanozymes on Acinetobacter baumannii.

The aim of this study was to determine whether the antibacterial activity of chitosan-modified Fe3O4 (CS@Fe3O4) nanomaterials against Acinetobacter baumannii (A. baumannii) is mediated through changes in biofilm formation and reactive oxygen species (ROS) production. For this purpose, the broth dilution method was used to examine the effect of CS@Fe3O4 nanoparticles on bacterial growth. The effects of CS@Fe3O4 nanoparticles on biofilm formation were measured using a semi-quantitative crystal violet staining assay. In addition, a bacterial ROS detection kit was used to detect the production of ROS in bacteria. The results showed that CS@Fe3O4 nanoparticles had a significant inhibitory effect on the colony growth and biofilm formation of drug-resistant A. baumannii (p < 0.05). The ROS stress assay revealed significantly higher ROS levels in A. baumannii subjected to CS@Fe3O4 nanoparticle treatment than the control group (p < 0.05). Thus, we demonstrated for the first time that CS@Fe3O4 nanoparticles had an inhibitory effect on A. baumannii in vitro, and that the antibacterial effect of CS@Fe3O4 nanoparticles on drug-resistant A. baumannii was more significant than on drug-sensitive bacteria. Our findings suggest that the antibacterial mechanism of CS@Fe3O4 nanoparticles is mediated through inhibition of biofilm formation in drug-resistant bacteria, as well as stimulation of A. baumannii to produce ROS. In summary, our data indicate that CS@Fe3O4 nanoparticles could be used to treat infections caused by drug-resistant A. baumannii.

Immunoglobulin G1 Fc glycosylation as an early hallmark of severe COVID-19

BackgroundImmunoglobulin G1 (IgG1) effector functions are impacted by the structure of fragment crystallizable (Fc) tail-linked N-glycans. Low fucosylation levels on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein specific (anti-S) IgG1 has been described as a hallmark of severe coronavirus disease 2019 (COVID-19) and may lead to activation of macrophages via immune complexes thereby promoting inflammatory responses, altogether suggesting involvement of IgG1 Fc glycosylation modulated immune mechanisms in COVID-19. MethodsIn this prospective, observational single center cohort study, IgG1 Fc glycosylation was analyzed by liquid chromatography - mass spectrometry following affinity capturing from serial plasma samples of 159 SARS-CoV-2 infected patients. FindingsAt baseline close to disease onset, anti-S IgG1 glycosylation was highly skewed when compared to total plasma IgG1. A rapid, general reduction in glycosylation skewing was observed during the disease course. Low anti-S IgG1 galactosylation and sialylation as well as high bisection were early hallmarks of disease severity, whilst high galactosylation and sialylation and low bisection were found in patients with low disease severity. In line with these observations, anti-S IgG1 glycosylation correlated with various inflammatory markers. InterpretationAssociation of low galactosylation, sialylation as well as high bisection with disease severity suggests that Fc-glycan modulated interactions contribute to disease mechanism. Further studies are needed to understand how anti-S IgG1 glycosylation may contributes to disease mechanism and to evaluate its biomarker potential. FundingThis project received funding from the European Commissions Horizon2020 research and innovation program for H2020-MSCA-ITN IMforFUTURE, under grant agreement number 721815. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSAntibody glycosylation against the spike (S) protein of patients infected with severe acute respiratory syndrome SARS-CoV-2 has been reported as a potentially important determinant of COVID-19 disease severity. Studies have hitherto focused on afucosylation, a modification on immunoglobulin G1 (IgG) Fc-tail-linked N-glycans that enhances effector functions. Most of these studies featured limited sample numbers or were imperfectly matched with respect to demographic and other important confounding factors. Our lab has contributed to some of these studies, and we additionally searched for research articles on PubMed and Google Scholar from January 2020 to October 2021. To date, only two groups studied anti-S IgG1 glycosylation, which resulted in overall three publications found. However, none of these groups found a severity marker between hospitalized non-ICU and ICU patients or studied dynamic changes. Instead, exclusively fucosylation at the first available timepoint has been associated with disease severity between severely ill inpatients and mild outpatients. Added value of this studyIn this prospective, observational single center cohort study, we investigated the severity marker potential of anti-S IgG1 glycosylation in severe and mild hospitalized COVID-19 cases, and correlated these findings with numerous inflammation and clinical markers. Our study reveals low galactosylation and sialylation as well as high bisection on anti-S IgG1 as early hallmarks of severe COVID-19, after correction for age and sex effects. In line with these observations, anti-S IgG1 glycosylation correlated with many inflammatory markers. As days since onset is one of the major confounders of anti-S IgG1 glycosylation due to its highly dynamic nature, we additionally confirmed our findings in time-matched patient subgroups. We believe anti-S IgG1 glycosylation may be applicable for patient stratification upon hospitalization. Implications of all the available evidenceDemographic factors as well as temporal differences should be taken into consideration when analyzing IgG1 glycosylation of COVID-19 patients. Anti-S IgG1 glycosylation is highly dynamic, but is a promising early severity marker in COVID-19.

The correlation analysis between depression status and progression of knee osteoarthritis / 中国医师进修杂志

Objective:To investigate whether knee osteoarthritis has an impact on the patient′s depression and whether it′s progression will affect the patient′s depression, and to provide a reference for clinical work.Methods:Patients diagnosed with osteoarthritis in Dalian Central Hospital from 2016 to 2019 were divided into 4 groups according to Kellgren-Lawrence staging, and the patients were scored on WOMAC scale, AKSS clinical scale, and AKSS. The score of the scale and the score of the HAMD scale were collected and statistically analyzed using SPSS 17.0.Results:χ2 test was used to show that there was no difference in the gender composition of patients in different stages ( P<0.05). The AKSS clinical scale score, AKSS functional scale score, WOMAC scale score and HAMD scale score were statistically analyzed for each stage. The results showed that the average AKSS clinical scores of patients in each stage were as follows: stage Ⅰ: (90.01 ± 8.41) points; stage Ⅱ: (79.98 ± 10.93) points; stage Ⅲ: (71.78 ± 13.64) points; stage Ⅳ: (54.18 ± 12.58) points. The AKSS functional scores were as follows, stage Ⅰ: 100 points; stage Ⅱ: 80 points; stage Ⅲ: 70 points; stage Ⅳ: 45 points; the average WOMAC scale scores of patients in each stage were as follows, stage Ⅰ: (28.69 ± 19.22) points ; stage Ⅱ: (49.43 ± 22.69) points; stage Ⅲ (70.13 ± 24.84) points; stage Ⅳ: (107.79 ± 24.39) points. The average HAMD scale scores of patients in each stage were as follows, stage Ⅰ: (4.89 ± 3.42) points; stage Ⅱ: (7.65 ± 4.20) points; Stage Ⅲ: (9.05 ± 5.03) points; stage Ⅳ: (12.35 ± 5.41) points. The analysis showed that there were significant statistical differences in the scale scores between each period ( P<0.05). There was a correlation between the patient′s depression status and the patient′s age, pain, and joint function, and there were statistical differences ( P<0.05). Conclusions:There is a significant correlation between depression and pain and function in patients with knee osteoarthritis. The progress of the osteoarthritis course will aggravate the patient′s depression state. Conversely, the patient′s depression state can also aggravate the symptoms of osteoarthritis patients and affect the clinical efficacy of the patients.

Establishment of real-time fluorescent quantitative PCR for detection of torque teno virus types 7, 8 and 10 / 中华微生物学和免疫学杂志

Objective:To establish a real-time fluorescent quantitative PCR for the detection of torque teno virus types 7 (TTV7), 8 (TTV8) and 10 (TTV10) and analyze its performance in clinical sample detection.Methods:Specific primers were designed based on the gene sequences of TTV7, TTV8 and TTV10 in GenBank. Recombinant plasmids of pMD19-T-TTV7, pMD19-T-TTV8 and pMD19-T-TTV10 were constructed and used as positive standard control to establish a real-time fluorescent quantitative PCR based on FAM-Eclipse probe method. The specificity and sensitivity of the established method were evaluated. Moreover, it was validated in terms of clinical sample detection.Results:The standard curve equations of the real-time fluorescent quantitative PCR for detecting TTV7, TTV8 and TTV10 were y=-0.340 2 x+ 114.780 0 ( R2=0.998 8), y=-0.351 1 x+ 114.940 0 ( R2=0.995 3) and y=-0.348 9 x+ 115.020 0 ( R2=0.991 7), respectively, and there was no cross-reaction with other viruses. The detection sensitivity of the established method for TTV7, TTV8 and TTV10 were 108 copies/μl, 84 copies/μl and 98 copies/μl, and the positive detection rates in clinical pediatric serum samples were 10.9%, 2.1% and 4.3%, respectively. Conclusions:The established real-time fluorescent quantitative PCR for detection of TTV7, TTV8 and TTV10 was featured by strong specificity and high sensitivity, which could be used for rapid TTV detection in clinical serum samples.

Ferritin nanoparticle based SARS-CoV-2 RBD vaccine induces persistent antibody response and long-term memory in mice

Since the outbreak of COVID-19, over 200 vaccine candidates have been documented and some of them have advanced to clinical trials with encouraging results. However, the antibody persistence over 3 months post immunization and the long-term memory have been rarely reported. Here, we report that a ferritin nanoparticle based SARS-CoV-2 RBD vaccine induced in mice an efficient antibody response which lasts for at least 7 months post immunization. Significantly higher number of memory B cells were maintained and a significantly higher level of recall response was induced upon antigen challenge. Thus, we believe our current study provide the first information about the long-term antibody persistence and memory response of a COVID-19 vaccine. This information would be also timely useful for the development and evaluation of other vaccines.

Comparative Ubiquitome Analysis under Heat Stress Reveals Diverse Functions of Ubiquitination in Saccharina japonica.

Ubiquitination is a major post-translational modification involved in nearly all aspects of eukaryotic biology. Previous RNA-Seq studies showed that ubiquitination plays essential roles in the heat tolerance of Saccharina japonica, but to date, large-scale profiling of the ubiquitome in S. japonica has not been reported. To better understand the regulatory roles of ubiquitination in heat responses of S. japonica, we investigated its ubiquitome under normal and heat stress by the combination of affinity enrichment and high-resolution liquid chromatography-tandem mass spectroscopy analysis. Altogether, 3305 lysine ubiquitination sites in 1562 protein groups were identified. After normalization, 152 lysine ubiquitination sites in 106 proteins were significantly upregulated and 208 lysine ubiquitination sites in 131 proteins were significantly downregulated in response to heat stress. Protein annotation and functional analysis suggested that ubiquitination modulates a variety of essential cellular and physiological processes, including but not limited to the ubiquitin-26S proteasome system, ribosome, carbohydrate metabolism, and oxidative phosphorylation. Our results provide a global view of the heat response ubiquitome in S. japonica, and could facilitate future studies on the physiological roles of these ubiquitination-related proteins.

Assisting Scalable Diagnosis Automatically via CT Images in the Combat against COVID-19

Introductory paragraphThe pandemic of coronavirus Disease 2019 (COVID-19) caused enormous loss of life globally. 1-3 Case identification is critical. The reference method is using real-time reverse transcription PCR (rRT-PCR) assays, with limitations that may curb its prompt large-scale application. COVID-19 manifests with chest computed tomography (CT) abnormalities, some even before the onset of symptoms. We tested the hypothesis that application of deep learning (DL) to the 3D CT images could help identify COVID-19 infections. Using the data from 920 COVID-19 and 1,073 non-COVID-19 pneumonia patients, we developed a modified DenseNet-264 model, COVIDNet, to classify CT images to either class. When tested on an independent set of 233 COVID-19 and 289 non-COVID-19 patients. COVIDNet achieved an accuracy rate of 94.3% and an area under the curve (AUC) of 0.98. Application of DL to CT images may improve both the efficiency and capacity of case detection and long-term surveillance.