Primary drug resistance among HIV-1 patients in Hubei Province in 2020-2022 / 公共卫生与预防医学

Objective To investigate the prevalence of primary drug resistance among HIV-1 patients in Hubei Province from 2020 to 2022, and to provide corresponding basis and data support for HIV antiviral therapy (ART) in Hubei Province. Methods During 2020-2022, plasma samples of HIV-1 infected patients before ART were collected., Patients’ demographic data and baseline laboratory test data were also collected. HIV-1 pol region was amplified by in-house method for sub-type typing and drug-resistant mutation site analysis. Results The pol gene sequence was successfully amplified in 242 of 285 cases, with a success rate of 84.9%. CRF07_BC was the predominant HIV-1 sub-type, accounting for 47.11% (114/242), followed by CRF01_AE, accounting for 25.21% (61/242), sub-type B, accounting for 14.16% (35/242), and CRF55_01B, accounting for 4.13% (10/242). The primary resistance rate was 6.20% (15/242). The mutation site of nucleoside reverse transcriptase inhibitors (NRTIs) was mainly M184V, and the mutation sites of non-nucleoside reverse transcriptase inhibitors (NNRTIs) were mainly E138A/G/EG and V179E. These different mutation sites led to different degrees of drug resistance to 12 drugs. The incidence of drug resistance mutation of CRF55_01B sub-type was significantly higher than that of other sub-types. Conclusion The primary drug resistance rate of HIV-1 infected patients is at a slightly high level in Hubei Province, and close monitoring of primary drug resistance and mutation sites should be strengthened before ART, especially for CRF55_01B sub-type.

Challenges in the study of self-assembled aggregates in decoction of traditional Chinese medicine: A preliminary review / 药学学报

Decoction is the most commonly used dosage form in the clinical treatment of traditional Chinese medicine (TCM). During boiling, the violent movement of various active ingredients in TCM creates molecular forces such as hydrogen bonding, π-π stacking, hydrophobic interactions and electrostatic interactions, which results in the formation of self-assembled aggregates in decoction (SADs), including particles, gels, fibers, etc. It was found that SADs widely existed in decoction with biological activities superior to both effective monomers and their physical mixtures, providing a new idea to reveal the pharmacodynamic material basis of Chinese herbal medicine from the perspective of component interactions-phase structure. Recently, SADs have become a novel focus of research in TCM. This paper reviewed their relevant studies in recent years and found some issues to be concerned in the research, such as the polydispersity of decoction system, instability of active ingredient interactions during boiling, uncertainty of the aggregates self-assembly rules, and stability, purity, yield of the products. In this regard, some solutions and new ideas were presented for the integrated development and clinical application of SADs.

Cell-type annotation with accurate unseen cell-type identification using multiple references.

The recent advances in single-cell RNA sequencing (scRNA-seq) techniques have stimulated efforts to identify and characterize the cellular composition of complex tissues. With the advent of various sequencing techniques, automated cell-type annotation using a well-annotated scRNA-seq reference becomes popular. But it relies on the diversity of cell types in the reference, which may not capture all the cell types present in the query data of interest. There are generally unseen cell types in the query data of interest because most data atlases are obtained for different purposes and techniques. Identifying previously unseen cell types is essential for improving annotation accuracy and uncovering novel biological discoveries. To address this challenge, we propose mtANN (multiple-reference-based scRNA-seq data annotation), a new method to automatically annotate query data while accurately identifying unseen cell types with the aid of multiple references. Key innovations of mtANN include the integration of deep learning and ensemble learning to improve prediction accuracy, and the introduction of a new metric that considers three complementary aspects to distinguish between unseen cell types and shared cell types. Additionally, we provide a data-driven method to adaptively select a threshold for identifying previously unseen cell types. We demonstrate the advantages of mtANN over state-of-the-art methods for unseen cell-type identification and cell-type annotation on two benchmark dataset collections, as well as its predictive power on a collection of COVID-19 datasets. The source code and tutorial are available at https://github.com/Zhangxf-ccnu/mtANN.

Biotransformation of gallate esters by a pH-stable tannase of mangrove-derived yeast Debaryomyces hansenii.

Introduction: Tannase is a crucial enzyme that finds wide applications in the pharmaceutical industry, feed processing, and beverage manufacturing. Although extensive studies have been conducted on tannases from fungi and bacteria, reports on tannases exhibiting favorable pH stability are relatively limited. Methods: In this study, a tannin-degrading strain Debaryomyces hansenii was screened to induce tannase production, and the corresponding tannase coding gene TANF was successfully cloned and expressed in Yarrowia lipolytica. SDS-PAGE analysis revealed that the purified TanF tannase had a molecular weight of approximately 70 kDa. Results and Discussion: The enzyme demonstrated optimal activity at 40°C and retained over 80% of its activity in the range of 35°C-60°C. Of particular interest, TanF exhibited remarkable enzyme activity at pH 5.0 and retained more than 70% of its relative activity across a wide pH range of 3.0-8.0. Furthermore, TanF exhibited broad substrate specificity for gallate esters. The final gallic acid production by TanF from tannic acid achieved 18.32 g/L. Therefore, the excellent properties TanF has been demonstrated to be an efficient tool for the preparation of gallic acid.

Novel Therapeutic Potential of Retinoid-Related Orphan Receptor α in Cardiovascular Diseases.

The retinoid-related orphan receptor α (RORα) is one subfamily of nuclear hormone receptors (NRs). This review summarizes the understanding and potential effects of RORα in the cardiovascular system and then analyzes current advances, limitations and challenges, and further strategy for RORα-related drugs in cardiovascular diseases. Besides regulating circadian rhythm, RORα also influences a wide range of physiological and pathological processes in the cardiovascular system, including atherosclerosis, hypoxia or ischemia, myocardial ischemia/reperfusion injury, diabetic cardiomyopathy, hypertension, and myocardial hypertrophy. In terms of mechanism, RORα was involved in the regulation of inflammation, apoptosis, autophagy, oxidative stress, endoplasmic reticulum (ER) stress, and mitochondrial function. Besides natural ligands for RORα, several synthetic RORα agonists or antagonists have been developed. This review mainly summarizes protective roles and possible mechanisms of RORα against cardiovascular diseases. However, there are also several limitations and challenges of current research on RORα, especially the difficulties on the transformability from the bench to the bedside. By the aid of multidisciplinary research, breakthrough progress on RORα-related drugs to combat cardiovascular disorder may appear.

Causal association between interleukin and constipation: A Mendelian randomization analysis / 西安交通大学学报(医学版)

【Objective】 To explore the causal association between interleukin (IL) level and constipation by using two-sample Mendelian randomization. 【Methods】 Analyses were performed based on the data from gene-wide association studies (GWAS). Both interleukin and constipation data were obtained from European populations. IL as an exposure variable was obtained from two GWAS data sets: ⅰ. from a genetic map of the human plasma proteome containing 3 301 samples; ⅱ. from a GWAS data set on 90 circulating proteins, containing 30 931 samples. Constipation as an outcome variable was obtained from two GWAS data sets: ⅰ. from Finngene, containing 26919 cases and 282235 controls; ⅱ. from UKBiobank, containing a total of 3 328 cases and 459682 controls. Single nucleotide polymorphisms strongly associated with exposure variables were used as instrumental variables, with inverse variance weighted (IVW) as the main analysis method, MR-egger regression and weighted median method as supplementary evidence for IVW results, and horizontal pleiotropy and heterogeneity were tested to ensure the stability of the results. 【Results】 In both of the two different outcome variables GWAS data, IVW analysis results showed that decreased level of IL-17 receptor C was associated with an increased risk of constipation, with ORs of 0.956 (95% CI: 0.916-0.997, P=0.036‖Finngene) and 0.998 (95% CI: 0.997-0.999, P=0.040‖ukb). Increased level of IL-18 was associated with an increased risk of constipation, with ORs of 1.055 (95% CI: 1.008-1.104, P=0.022‖Finngene) and 1.001 (95% CI: 1.000-1.002, P=0.044‖ukb); while in the Finngene data, the IVW results also suggested that increased levels of IL-2 receptor alpha subunit α and decreased levels of IL-10 and IL-17 were associated with an increased risk of constipation, with ORs of 1.054 (95% CI: 1.001-1.110, P=0.049), 0.945 (95% CI: 0.896-0.996, P=0.035) and 0.934 (95% CI: 0.896-0.997, P=0.040). 【Conclusion】 IL-17 receptor C, IL-18, IL-2 receptor alpha subunit α, IL-10, and IL-17 were causally associated with the risk of constipation.

Associations between maternal parenting styles and preschool children s quality of life in Chengdu / 中国学校卫生

Objective@#To investigate the association between maternal parenting styles and quality of life among preschools，to provide a scientific theoretical basis for interventions targeting at prmoting early life health.@*Methods@#From May to July, 2021, a stratified cluster sampling method was used to enroll 4 233 child mother dyads from 14 preschools in Chengdu. An online questionnaire survey was administered to collect socio demographic information, maternal parenting styles, and children s quality of life.@*Results@#The overall score of quality of life was (80.17±9.81) among preschool children in Chengdu. In the multivariate linear regression models, maternal emotional warmth were significantly associated with higher scores in emotional functioning, social functioning, school functioning, psychosocial health summary score, and total scores ( β coefficients in the high level group were 2.63 , 4.95 , 12.05, 6.54,4.88, P <0.05). In contrast, both maternal rejection and overprotection were significantly associated with lower scores in physical functioning, emotional functioning, social functioning, school functioning, psychosocial health summary score, and the total scores of children s quality of life (for rejection: β coefficients in the high level group were -9.39, -10.82, -7.12 , -6.04 , -8.00, and -8.35 , respectively; for overprotection: β coefficients in the high level group were -6.71, -5.85, -3.08 , -2.39 , -3.77, and - 4.51 , respectively， P <0.05). The associations between high level of maternal rejection and children s emotional functioning showed significant gender differences( β =-3.23, P <0.05).@*Conclusion@#Maternal parenting style has a significant impact on children s quality of life. Interventions targeting at maternal parenting styles may be beneficial to improve the quality of life in preschool children.

Analysis on influencing factors on loneliness in the elderly aged 60 and above in China / 中华流行病学杂志

Objective: To analyze the influential factors of loneliness in the elderly aged ≥60 years in China. Methods: Data used in this study were obtained from participants aged ≥60 years from the China Longitudinal Aging Social Survey, with a sample size of 7 593. Loneliness was measured with loneliness scale, and the influence of subjective and objective factors on loneliness and their interaction were analyzed with stepwise linear regression model and simple slope test. SPSS 25.0 was used for statistical analysis. PROCESS 3.3 macro program was used for simple slope test. Results: A total of 8 926 participants were included. Among the objective factors, the elderly with poor family network have a higher level of loneliness (P<0.05), and community provision of elderly care services could reduce the loneliness of the elderly (P<0.05). Elderly people with subjective aging age ≤60 years old and poor social adaptation and emotional perception have higher levels of loneliness (all P<0.05). Subjective aging age plays a negative regulatory role in the impact of community elderly care services on loneliness (P<0.05), Social adaptation and emotional perception play a negative regulatory role in the impact of family network on loneliness (P<0.05). Conclusions: Elderly people aged ≥60 years of feeling of loneliness was affected by both subjective and objective factors and subjective factors play an important regulatory role in the influence of objective factors on elderly people's feeling of loneliness in China. Therefore, while creating a good aging environment to provide strong external support for the elderly, the subjective initiative of the elderly should also be fully mobilized, to alleviate the loneliness of the elderly from these two aspects.

Medication rules of Chinese herbal compound prescriptions for treating angina in national patent database based on multiple data mining / 中国中药杂志

This study explored the medication rules of Chinese herbal compound prescriptions for the treatment of angina based on the Chinese herbal compound patents in the patent database of the China National Intellectual Property Administration. The data of eligible Chinese herbal compound patents for the treatment of angina were collected from the patent database of the China National Intellectual Property Administration from database inception to November 10, 2022, and subjected to data modeling, analysis of main syndromes, medication frequency analysis, cluster analysis, association rule analysis, and data visualization by using Excel 2021, IBM SPSS Statistics 26.0, IBM SPSS Modeler 18.0, Cytoscape 3.9.1, and Rstudio R 4.2.2.2 to explore the medication rules for angina. The study included 636 pieces of patent data for angina that met the inclusion criteria, involving 815 drugs, with a total frequency of 6 586. The most common main syndromes were blood stasis obstructing the heart syndrome(222, 34.91%) and Qi deficiency and blood stasis syndrome(112, 17.61%). The top 10 most frequently used drugs were Salviae Miltiorrhizae Radix et Rhizoma, Chuanxiong Rhizoma, Notoginseng Radix et Rhizoma, Astragali Radix, Angelicae Sinensis Radix, Carthami Flos, Glycyrrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, Borneolum Syntheticum, and Corydalis Rhizoma. High-frequency drugs included blood-activating and stasis-resolving drugs(1 197, 18.17%) and deficiency-tonifying drugs(809, 12.28%). Cluster analysis identified eight drug combinations, including five new prescriptions suitable for clinical use and new drug development, and three drug pairs. The core drug combination of Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Carthami Flos was identified through the complex co-occurrence network analysis of Chinese medicines. Association rule analysis yielded a total of 17 rules, including 13 drug pairs and 4 tripartite combinations. Common drug pairs included Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma(support degree 25.79%, confidence coefficient 69.49%, lift 1.30) and Salviae Miltiorrhizae Radix et Rhizoma-Notoginseng Radix et Rhizoma(support degree 22.01%, confidence coefficient 61.95%, lift 1.16). Common tripartite combinations included Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Astragali Radix(support degree 10.85%, confidence coefficient 73.40%, lift 1.37) and Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Notoginseng Radix et Rhizoma(support degree 10.69%, confidence coefficient 79.07%, lift 1.48). The results showed that the underlying pathogenesis of angina involved blood stasis obstructing the heart and Qi deficiency and blood stasis. The overall nature of the disease was characterized as asthenia in origin and sthenia in superficiality. In the prescription formulation, blood-activating and stasis-resolving drugs, such as Salviae Miltiorrhizae Radix et Rhizoma, Chuanxiong Rhizoma, and Carthami Flos were often used to resolve the excess manifestation, which were combined with tonifying drugs such as Astragali Radix, Angelicae Sinensis Radix, Glycyrrhizae Radix et Rhizoma, and Ginseng Radix et Rhizoma to reinforce the deficiency. The syndrome, pathogenesis, disease nature, and medication were consistent with clinical practice. Additionally, the new compound prescriptions and drug combinations derived from the multiple data mining in this study could provide references and insights for the clinical diagnosis and treatment of angina and the development of new drugs.

Intravenous Hemostats: Foundation, Targeting, and Controlled-Release.

Uncontrollable blood loss is the greatest cause of mortality in prehospital patients and the main source of disability and death in hospital care. Compared with external hemostats, intravenous hemostats are more appropriate for preventing and treating uncontrolled bleeding in vivo and large bleeding on the body surface. This Review initially establishes intravenous hemostats' response basis, including the coagulation mechanism, fibrinolytic pathway, and protein corona. Second, the study of advancement of intravenous hemostat targeting was expanded from two perspectives, cellular hemostatic agents and synthetic hemostatic agents. Meanwhile, after discussing the progress of controlled-release intravenous hemostats with platelets as the stimuli, this Review offers insight into the possibility of controlled-release intravenous hemostats with microenvironment as the stimuli, combining the studies of controlled-release targeted thrombolysis.

Inferring Gene Co-Expression Networks by Incorporating Prior Protein-Protein Interaction Networks.

Inferring gene co-expression networks from high-throughput gene expression data is an important task in bioinformatics. Many gene networks often exhibit modular structures. Although several Gaussian graphical model-based methods have been developed to estimate gene co-expression networks by incorporating the modular structural prior, none of them takes into account the modular structures captured by the prior networks (e.g., protein interaction networks). In this study, we propose a novel prior network-dependent gene network inference (pGNI) method to estimate gene co-expression networks by integrating gene expression data and prior protein interaction network data. The underlying modular structure is learned from both sets of data. Through simulation studies, we demonstrate the feasibility and effectiveness of our method. We also apply our method to two real datasets. The modular structures in the networks estimated by our method are biological significant.

Association of normal weight obesity with carotid atherosclerosis and peripheral arterial stiffness / 西安交通大学学报(医学版)

【Objective】 To investigate the association of normal weight obesity （NWO） with carotid atherosclerosis （CAS） and peripheral arterial stiffness （PAS） in persons received physical examination. 【Methods】 A total of 1 894 people with normal BMI （18.5-23.9 kg/m2） were consecutively enrolled for this study. All these people had completed body fat measurement， carotid artery ultrasound examination and peripheral arterial stiffness detection. Then they were divided into control group， CAS group， PAS group， and CAS + PAS group according to the test results mentioned above. Clinical data were compared between different groups to assess the baseline situation. Besides， Multivariate Logistic regression analysis was performed to determine independent risk factors for atherosclerosis. 【Results】 The proportion of NWO in CAS group， PAS group， and CAS + PAS group was significantly higher than that in normal group （P<0.05）. Univariate analysis results showed that NWO was correlated with greater risks of both CAS and PAS （P<0.05）. However， multiple factors analysis suggested that NWO was not associated with PAS， but with CAS （OR=1.286， 95% CI： 1.032-1.603， P<0.05）. 【Conclusion】 NWO is closely related to the occurrence of CAS and may be an independent risk factor for CAS. Attention should be paid to the body fat mass of the NWO population. Early intervention is needed to prevent the occurrence of CAS in these people.

Application of LAg-avidity EIA in the estimate of HIV-1 incidence among key surveillance populations in Hubei Province / 公共卫生与预防医学

Objective Limiting antigen avidity enzyme immunoassay (LAg-Avidity EIA) was applied to calculate the HIV-1 incidence of new HIV infections among men who have sex with men(MSM), drug users(DUS), female sex workers(FSW) and male patients in sexually transmitted diseases clinics(STD) in 2017-2020 of Hubei. Methods HIV-1 antibody positive samples were collected from four key groups in the national HIV sentinel surveillance from 2017 to 2020, and tested by the LAg-Avidity EIA to estimate the annual new infection rate of each group. Results The prevalence of MSM was 2.90%, 4.48%, 3.63 and 2.78% from 2017-2020, respectively, which was the highest among the four groups. The rate of late diagnosis increased from 16.67% in 2017 to 28.81% in 2020.The incidence of MSM was 1.64%(0.85%-2.44%),1.41%(0.59%-2.23%),1.46% (0.71%-2.21%) and 0.96%(0.34%-1.57%), respectively, and the difference was not statistically significant (χ2=1.491, P=0.684). The prevalence of STD from 2017-2020 was 0.03%, 0.01%, 0.06% and 0.08%, respectively, with the incidence was 0.09% (-0.06%-0.25%), 0.10(-0.06%-0.26%), 0.26% (0.02%-0.50%) and 0.04%(-0.07%-0.15%). The prevalence and incidence among FSW remains very low, while the prevalence of DUS fluctuated slightly, but no new infections have been detected. Conclusion The incidence of new HIV infection among MSM in Hubei province from 2017-2020 is relatively high compared with other key groups, but the overall trend is declining, thus the intervention of MSM should be further strengthened and expand the coverage of testing in key populations.

Plant developmental stage drives the differentiation in ecological role of the maize microbiome.

BACKGROUND: Plants live with diverse microbial communities which profoundly affect multiple facets of host performance, but if and how host development impacts the assembly, functions and microbial interactions of crop microbiomes are poorly understood. Here we examined both bacterial and fungal communities across soils, epiphytic and endophytic niches of leaf and root, and plastic leaf of fake plant (representing environment-originating microbes) at three developmental stages of maize at two contrasting sites, and further explored the potential function of phylloplane microbiomes based on metagenomics. RESULTS: Our results suggested that plant developmental stage had a much stronger influence on the microbial diversity, composition and interkingdom networks in plant compartments than in soils, with the strongest effect in the phylloplane. Phylloplane microbiomes were co-shaped by both plant growth and seasonal environmental factors, with the air (represented by fake plants) as its important source. Further, we found that bacterial communities in plant compartments were more strongly driven by deterministic processes at the early stage but a similar pattern was for fungal communities at the late stage. Moreover, bacterial taxa played a more important role in microbial interkingdom network and crop yield prediction at the early stage, while fungal taxa did so at the late stage. Metagenomic analyses further indicated that phylloplane microbiomes possessed higher functional diversity at the early stage than the late stage, with functional genes related to nutrient provision enriched at the early stage and N assimilation and C degradation enriched at the late stage. Coincidently, more abundant beneficial bacterial taxa like Actinobacteria, Burkholderiaceae and Rhizobiaceae in plant microbiomes were observed at the early stage, but more saprophytic fungi at the late stage. CONCLUSIONS: Our results suggest that host developmental stage profoundly influences plant microbiome assembly and functions, and the bacterial and fungal microbiomes take a differentiated ecological role at different stages of plant development. This study provides empirical evidence for host exerting strong effect on plant microbiomes by deterministic selection during plant growth and development. These findings have implications for the development of future tools to manipulate microbiome for sustainable increase in primary productivity. Video Abstract.

Sirtuin 3 deficiency exacerbates diabetic cardiomyopathy via necroptosis enhancement and NLRP3 activation.

Sirtuin 3 (SIRT3) is a potential therapeutic target for cardiovascular, metabolic, and other aging-related diseases. In this study, we investigated the role of SIRT3 in diabetic cardiomyopathy (DCM). Mice were injected with streptozotocin (STZ, 60 mg/kg, ip) to induce diabetes mellitus. Our proteomics analysis revealed that SIRT3 expression in the myocardium of diabetic mice was lower than that of control mice, as subsequently confirmed by real-time PCR and Western blotting. To explore the role of SIRT3 in DCM, SIRT3-knockout mice and 129S1/SvImJ wild-type mice were injected with STZ. We found that diabetic mice with SIRT3 deficiency exhibited aggravated cardiac dysfunction, increased lactate dehydrogenase (LDH) level in the serum, decreased adenosine triphosphate (ATP) level in the myocardium, exacerbated myocardial injury, and promoted myocardial reactive oxygen species (ROS) accumulation. Neonatal rat cardiomyocytes were transfected with SIRT3 siRNA, then exposed to high glucose (HG, 25.5 mM). We found that downregulation of SIRT3 further increased LDH release, decreased ATP level, suppressed the mitochondrial membrane potential, and elevated oxidative stress in HG-treated cardiomyocytes. SIRT3 deficiency further raised expression of necroptosis-related proteins including receptor-interacting protein kinase 1 (RIPK1), RIPK3, and cleaved caspase 3, and upregulated the expression of inflammation-related proteins including NLR family pyrin domain-containing protein 3 (NLRP3), caspase 1 p20, and interleukin-1ß both in vitro and in vivo. Collectively, SIRT3 deficiency aggravated hyperglycemia-induced mitochondrial damage, increased ROS accumulation, promoted necroptosis, possibly activated the NLRP3 inflammasome, and ultimately exacerbated DCM in the mice. These results suggest that SIRT3 can be a molecular intervention target for the prevention and treatment of DCM.

β-lactam antibiotics detection using microcolumn gel technology / 中国输血杂志

【Objective】 To develop an assay to determine β-lactam antibiotics using microcolumn gels and to study the β-lactam antibiotics present in the blood of patients and their clinical significances. 【Methods】 446 patients with a history of taking β-lactam antibiotics from January 2019 to June 2019 were randomly selected from Trauma Emergency Center, Department of Arthrosis, Department of Spine and Department of Bone Oncology of our hospital, and 4 mL(per capita) venous blood was collected. Irregular antibody screening, anti-globulin detection and drug antibody determination were performed by microcolumn gel method. The data of gender, age, disease, blood transfusion history and medication were collected. The test results and clinical data were retrospective analyzed. 【Results】 The yielding rate of antibody was 0.45%(2/446) in patients with a history of taking β -lactam antibiotics. 16.38%(73/446) of the samples were positive in direct antiglobulin test, and 64.38%(47/73) of them did not agglutinate with RBCs treated with drugs. The yielding rate of specific antibodies against drug was 4.93%(22/446), and the titer ranged from 2 to 128(8). 1 case of auto-IgM antibody, 1 case of blood group related antibody and 2 cases of non-specific protein adsorption were detected. The yielding rate of drug antibody in patients with blood transfusion history reached to 12.10 %(22/124), so it was also high in patients with bone tumor. 【Conclusion】 Direct antiglobulin assay is helpful for the detection of β-lactam antibodies. The negative results of antibody screening cannot completely exclude the presence of drug antibodies. The yielding rate of drug antibody can be greatly improved by specific drug antibody detection, and it was higher in transfused patients relative to non-transfused one.

A retrospective analysis of 2 728 HIV antibody screening positive samples / 公共卫生与预防医学

Objective To analyze the positive results of HIV antibody screening in the laboratory of AIDS confirmation center of Hubei Provincial Center for Disease Control and Prevention from 2014 to 2020, and to provide a basis for improving detection strategies. Methods A total of 2 728 primary screening positive specimens received by the laboratory of Hubei confirmation center from 2014 to 2020 were retested with two reagents. Specimens with at least one reactive result were confirmed with western blot (WB). The samples with uncertain or negative WB results were further confirmed by nucleic acid quantitative detection. The test results were analyzed retrospectively. Results A total of 2 297 specimens with positive retest results were confirmed by WB, with a positive rate of 93.47%. The highest proportion of patients was from medical institutions. The positive rate detected by 4 diagnostic kits was apparently higher in S/CO＞10 cases than that in S/CO≤10, and the difference was statistically significant (P 5 000cps / ml, and 12 cases were TND. 13 of the 30 WB negative samples had nucleic acid test results＞5 000CPs/mL . Conclusions The coverage of HIV screening laboratories in hospitals at all levels should be further increased to find more HIV infected persons. The anti-HIV ELISA S/CO ratio is correlated with the positive results confirmed by western blot. Therefore, ELISA S/CO ratio can be used to predict anti-HIV antibody positivity. For samples with uncertain or negative WB detection, supplemental nucleic acid test should be carried out timely for early diagnosis.

Survey of Rehabilitation Nursing Management of Neurogenic Bladder and Clinical Application of Intermittent Catheterization in Guangdong, China / 中国康复理论与实践

Objective:To investigate the knowledgement and clinical application of neurogenic bladder and intermittent catheterization among nurses in Guangdong. Methods:From December, 2020 to January, 2021, 241 nurses in Guangdong were investigated with a questionnaire designed by ourselves. Results:The score was low in understanding the neurogenic bladder rehabilitation nursing management and intermittent catheterization through self-assessment. The awareness was deficient in the complication and risk management of neurogenic bladder. Although there were a lot of patients with dysuria in clinical practice, 67.2% of nurses still used indwelling catheter, and only 24.1% used intermittent catheterization. Only 9.9% nurses thought that patients with dysuria were treated positively by doctors. Most of nurses would like to participate in the training and nursing alliance in neurogenic bladder rehabilitation nursing management and intermittent catheterization, and manage patients with neurogenic bladder after discharge. Conclusion:The knowledge of guidelines related with neurogenic bladder and intermittent catheterization among nurses is insufficient, and is not applied in clinical practice. More work should be done to improve the knowledge and standardization of management of neurogenic bladder.

Alterations in thymocyte populations under conditions of endotoxin tolerance / 中华医学杂志(英文版)

BACKGROUND@#Endotoxin tolerance (ET) is a protective phenomenon in which pre-treatment with a tolerance dose of lipopolysaccharide (LPS) leads to dramatically elevated survival. Accumulating evidence has shown that peripheral T cells contribute to the induction of ET. However, what happens to T cell development in the thymus under ET conditions remains unclear. The purpose of this study was to analyze the alterations in thymocyte populations (double-positive [DP] and single-positive [SP] cells) under ET conditions.@*METHODS@#Mice were intraperitoneally injected with LPS at a concentration of 5 mg/kg to establish an LPS tolerance model and were divided into two groups: a group examined 72 h after LPS injection (72-h group) and a group examined 8 days after LPS injection (8-day group). Injection of phosphate-buffered saline was used as a control (control group). Changes in thymus weight, cell counts, and morphology were detected in the three groups. Moreover, surface molecules such as CD4, CD8, CD44, CD69, and CD62L were analyzed using flow cytometry. Furthermore, proliferation, apoptosis, cytokine production, and extracellular signal-regulated kinase (ERK) pathway signaling were analyzed in thymocyte populations. The polymorphism and length of the T-cell receptor (TCR) β chain complementarity-determining region 3 (CDR3) were analyzed using capillary electrophoresis DNA laser scanning analysis (ABI 3730).@*RESULTS@#Thymus weight and cell counts were decreased in the early stage but recovered by the late stage in a murine model of LPS-induced ET. Moreover, the proportions of DP cells (control: 72.130 ± 4.074, 72-h: 10.600 ± 3.517, 8-day: 84.770 ± 2.228), CD4+ SP cells (control: 15.770 ± 4.419, 72-h: 44.670 ± 3.089, 8-day: 6.367 ± 0.513), and CD8+ SP cells (control: 7.000 ± 1.916, 72-h: 34.030 ± 3.850, 8-day: 5.133 ± 0.647) were obviously different at different stages of ET. The polymorphism and length of TCR β chain CDR3 also changed obviously, indicating the occurrence of TCR rearrangement and thymocyte diversification. Further analysis showed that the expression of surface molecules, including CD44, CD69, and CD62L, on thymocyte populations (DP and SP cells) were changed to different degrees. Finally, the proliferation, apoptosis, cytokine production, and ERK pathway signaling of thymocyte populations were changed significantly.@*CONCLUSION@#These data reveal that alterations in thymocyte populations might contribute to the establishment of ET.

Potential role of aberrant mucosal immune response to SARS-CoV-2 in pathogenesis of IgA Nephropathy

Aberrant mucosal immunity has been suggested to play a pivotal role in pathogenesis of IgA nephropathy (IgAN), the most common form of glomerulonephritis worldwide. The outbreak of severe acute respiratory syndrome coronavirus (SARS-CoV-2), the causal pathogen of coronavirus disease 2019 (COVID-19), has become a global concern. However, whether the mucosal immune response caused by SARS-CoV-2 influences the clinical manifestations of IgAN patients remains unknown. Here we tracked the SARS-CoV-2 anti-receptor binding domain (RBD) antibody levels in a cohort of 88 COVID-19 patients. We found that 52.3% of the COVID-19 patients produced more SARS-CoV-2 anti-RBD IgA than IgG or IgM, and the levels of the IgA were stable during 4-41 days of infection. Among these IgA-dominated COVID-19 patients, we found a severe COVID-19 patient concurrent with IgAN. The renal function of the patient declined presenting with increased serum creatinine during the infection and till 7 months post infection. This patient predominantly produced anti-RBD IgA as well as total IgA in the serum compared to that of healthy controls. The analysis of the IgA-coated microbiota as well as proinflammatory cytokine IL-18, which was mainly produced in the intestine, reveals intestinal inflammation, although no obvious gastrointestinal symptom was reported. The mucosal immune responses in the lung are not evaluated due to the lack of samples from respiratory tract. Collectively, our work highlights the potential adverse effect of the mucosal immune response towards SARS-CoV-2, and additional care should be taken for COVID-19 patients with chronic diseases like IgAN.